ID   MMP13_HUMAN             Reviewed;         471 AA.
AC   P45452; A8K846; B2RCZ3; Q6NWN6;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   27-MAR-2024, entry version 221.
DE   RecName: Full=Collagenase 3;
DE            EC=3.4.24.-;
DE   AltName: Full=Matrix metalloproteinase-13;
DE            Short=MMP-13;
DE   Flags: Precursor;
GN   Name=MMP13;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Mammary carcinoma;
RX   PubMed=8207000; DOI=10.1016/s0021-9258(19)89457-7;
RA   Freije J.M.P., Diez-Itza I., Balbin M., Sanchez L.M., Blasco R.,
RA   Tolivia J., Lopez-Otin C.;
RT   "Molecular cloning and expression of collagenase-3, a novel human matrix
RT   metalloproteinase produced by breast carcinomas.";
RL   J. Biol. Chem. 269:16766-16773(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=9562863; DOI=10.1016/s0171-2985(98)80046-6;
RA   Willmroth F., Peter H.H., Conca W.;
RT   "A matrix metalloproteinase gene expressed in human T lymphocytes is
RT   identical with collagenase 3 from breast carcinomas.";
RL   Immunobiology 198:375-384(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Esophagus, and Synovium;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-390.
RG   NIEHS SNPs program;
RL   Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PROTEIN SEQUENCE OF 20-27 AND 104-118, PROPEPTIDE, AUTOCATALYTIC
RP   PROCESSING, CATALYTIC ACTIVITY, FUNCTION, GLYCOSYLATION AT ASN-117,
RP   SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND INTERACTION WITH TIMP1;
RP   TIMP2 AND TIMP3.
RX   PubMed=8576151; DOI=10.1074/jbc.271.3.1544;
RA   Knaeuper V., Lopez-Otin C., Smith B., Knight G., Murphy G.;
RT   "Biochemical characterization of human collagenase-3.";
RL   J. Biol. Chem. 271:1544-1550(1996).
RN   [7]
RP   PARTIAL PROTEIN SEQUENCE, PROPEPTIDE, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=8663255; DOI=10.1074/jbc.271.29.17124;
RA   Knaeuper V., Will H., Lopez-Otin C., Smith B., Atkinson S.J., Stanton H.,
RA   Hembry R.M., Murphy G.;
RT   "Cellular mechanisms for human procollagenase-3 (MMP-13) activation.
RT   Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to
RT   generate active enzyme.";
RL   J. Biol. Chem. 271:17124-17131(1996).
RN   [8]
RP   FUNCTION.
RX   PubMed=8603731; DOI=10.1016/0014-5793(95)01539-6;
RA   Fosang A.J., Last K., Knaeuper V., Murphy G., Neame P.J.;
RT   "Degradation of cartilage aggrecan by collagenase-3 (MMP-13).";
RL   FEBS Lett. 380:17-20(1996).
RN   [9]
RP   INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=8798568; DOI=10.1074/jbc.271.38.23577;
RA   Borden P., Solymar D., Sucharczuk A., Lindman B., Cannon P., Heller R.A.;
RT   "Cytokine control of interstitial collagenase and collagenase-3 gene
RT   expression in human chondrocytes.";
RL   J. Biol. Chem. 271:23577-23581(1996).
RN   [10]
RP   TISSUE SPECIFICITY, AND INDUCTION BY TGFB1.
RX   PubMed=9056642;
RX   DOI=10.1002/(sici)1097-0177(199703)208:3<387::aid-aja9>3.0.co;2-e;
RA   Johansson N., Saarialho-Kere U., Airola K., Herva R., Nissinen L.,
RA   Westermarck J., Vuorio E., Heino J., Kaehaeri V.M.;
RT   "Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes,
RT   periosteal cells, and osteoblasts during human fetal bone development.";
RL   Dev. Dyn. 208:387-397(1997).
RN   [11]
RP   DOMAIN, CATALYTIC ACTIVITY, AUTOCATALYTIC PROCESSING, FUNCTION, INTERACTION
RP   WITH TIMP1; TIMP2 AND TIMP3, AND ACTIVITY REGULATION.
RX   PubMed=9065415; DOI=10.1074/jbc.272.12.7608;
RA   Knaeuper V., Cowell S., Smith B., Lopez-Otin C., O'Shea M., Morris H.,
RA   Zardi L., Murphy G.;
RT   "The role of the C-terminal domain of human collagenase-3 (MMP-13) in the
RT   activation of procollagenase-3, substrate specificity, and tissue inhibitor
RT   of metalloproteinase interaction.";
RL   J. Biol. Chem. 272:7608-7616(1997).
RN   [12]
RP   INVOLVEMENT IN MDST, AND VARIANT MDST GLY-207.
RX   PubMed=24648384; DOI=10.1002/ajmg.a.36431;
RA   Bonafe L., Liang J., Gorna M.W., Zhang Q., Ha-Vinh R., Campos-Xavier A.B.,
RA   Unger S., Beckmann J.S., Le Bechec A., Stevenson B., Giedion A., Liu X.,
RA   Superti-Furga G., Wang W., Spahr A., Superti-Furga A.;
RT   "MMP13 mutations are the cause of recessive metaphyseal dysplasia, Spahr
RT   type.";
RL   Am. J. Med. Genet. A 164A:1175-1179(2014).
RN   [13]
RP   PHOSPHORYLATION AT TYR-366.
RX   PubMed=25171405; DOI=10.1016/j.cell.2014.06.048;
RA   Bordoli M.R., Yum J., Breitkopf S.B., Thon J.N., Italiano J.E. Jr.,
RA   Xiao J., Worby C., Wong S.K., Lin G., Edenius M., Keller T.L., Asara J.M.,
RA   Dixon J.E., Yeo C.Y., Whitman M.;
RT   "A secreted tyrosine kinase acts in the extracellular environment.";
RL   Cell 158:1033-1044(2014).
RN   [14]
RP   INVOLVEMENT IN MDST.
RX   PubMed=24781753; DOI=10.1038/ejhg.2014.76;
RA   Li D., Weber D.R., Deardorff M.A., Hakonarson H., Levine M.A.;
RT   "Exome sequencing reveals a nonsense mutation in MMP13 as a new cause of
RT   autosomal recessive metaphyseal anadysplasia.";
RL   Eur. J. Hum. Genet. 23:264-266(2015).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 265-471 IN COMPLEX WITH CALCIUM,
RP   AND DISULFIDE BOND.
RX   PubMed=8969305; DOI=10.1006/jmbi.1996.0661;
RA   Gomis-Rueth F.-X., Gohlke U., Betz M., Knaeuper V., Murphy G.,
RA   Lopez-Otin C., Bode W.;
RT   "The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its
RT   C-terminal haemopexin-like domain.";
RL   J. Mol. Biol. 264:556-566(1996).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 104-271 IN COMPLEXES WITH
RP   SYNTHETIC INHIBITORS; CALCIUM AND ZINC, PROPEPTIDE, AND AUTOCATALYTIC
RP   PROCESSING.
RX   PubMed=10074939; DOI=10.1038/6657;
RA   Lovejoy B., Welch A.R., Carr S., Luong C., Broka C., Hendricks R.T.,
RA   Campbell J.A., Walker K.A., Martin R., Van Wart H., Browner M.F.;
RT   "Crystal structures of MMP-1 and -13 reveal the structural basis for
RT   selectivity of collagenase inhibitors.";
RL   Nat. Struct. Biol. 6:217-221(1999).
RN   [17]
RP   STRUCTURE BY NMR OF 104-274 IN COMPLEX WITH CALCIUM AND ZINC.
RX   PubMed=10926524; DOI=10.1006/jmbi.2000.3988;
RA   Zhang X., Gonnella N.C., Koehn J., Pathak N., Ganu V., Melton R.,
RA   Parker D., Hu S.I., Nam K.Y.;
RT   "Solution structure of the catalytic domain of human collagenase-3 (MMP-13)
RT   complexed to a potent non-peptidic sulfonamide inhibitor: binding
RT   comparison with stromelysin-1 and collagenase-1.";
RL   J. Mol. Biol. 301:513-524(2000).
RN   [18]
RP   STRUCTURE BY NMR OF 104-268 IN COMPLEX WITH CALCIUM AND ZINC, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=10986126; DOI=10.1006/jmbi.2000.4082;
RA   Moy F.J., Chanda P.K., Chen J.M., Cosmi S., Edris W., Levin J.I.,
RA   Powers R.;
RT   "High-resolution solution structure of the catalytic fragment of human
RT   collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor.";
RL   J. Mol. Biol. 302:671-689(2000).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 104-271 IN COMPLEX WITH CALCIUM
RP   AND ZINC, COFACTOR, AND CATALYTIC ACTIVITY.
RX   PubMed=15780611; DOI=10.1016/j.bmcl.2005.02.038;
RA   Blagg J.A., Noe M.C., Wolf-Gouveia L.A., Reiter L.A., Laird E.R.,
RA   Chang S.P., Danley D.E., Downs J.T., Elliott N.C., Eskra J.D.,
RA   Griffiths R.J., Hardink J.R., Haugeto A.I., Jones C.S., Liras J.L.,
RA   Lopresti-Morrow L.L., Mitchell P.G., Pandit J., Robinson R.P.,
RA   Subramanyam C., Vaughn-Bowser M.L., Yocum S.A.;
RT   "Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced
RT   selectivity over MMP-14.";
RL   Bioorg. Med. Chem. Lett. 15:1807-1810(2005).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 104-274 IN COMPLEX WITH CALCIUM
RP   AND ZINC, COFACTOR, AND CATALYTIC ACTIVITY.
RX   PubMed=15734645; DOI=10.1016/j.chembiol.2004.11.014;
RA   Engel C.K., Pirard B., Schimanski S., Kirsch R., Habermann J., Klingler O.,
RA   Schlotte V., Weithmann K.U., Wendt K.U.;
RT   "Structural basis for the highly selective inhibition of MMP-13.";
RL   Chem. Biol. 12:181-189(2005).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 104-270 IN COMPLEX WITH CALCIUM
RP   AND ZINC, COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION IN CARTILAGE
RP   DEGRADATION.
RX   PubMed=17623656; DOI=10.1074/jbc.m703286200;
RA   Johnson A.R., Pavlovsky A.G., Ortwine D.F., Prior F., Man C.F.,
RA   Bornemeier D.A., Banotai C.A., Mueller W.T., McConnell P., Yan C.,
RA   Baragi V., Lesch C., Roark W.H., Wilson M., Datta K., Guzman R., Han H.K.,
RA   Dyer R.D.;
RT   "Discovery and characterization of a novel inhibitor of matrix
RT   metalloprotease-13 that reduces cartilage damage in vivo without joint
RT   fibroplasia side effects.";
RL   J. Biol. Chem. 282:27781-27791(2007).
RN   [22]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 104-268 IN COMPLEX WITH TIMP2;
RP   CALCIUM AND ZINC, AND INTERACTION WITH TIMP2.
RX   PubMed=17196980; DOI=10.1016/j.jmb.2006.11.072;
RA   Maskos K., Lang R., Tschesche H., Bode W.;
RT   "Flexibility and variability of TIMP binding: X-ray structure of the
RT   complex between collagenase-3/MMP-13 and TIMP-2.";
RL   J. Mol. Biol. 366:1222-1231(2007).
RN   [23]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 104-274 IN COMPLEX WITH CALCIUM
RP   AND ZINC, CATALYTIC ACTIVITY, COFACTOR, AND FUNCTION.
RX   PubMed=19422229; DOI=10.1021/jm801394m;
RA   Monovich L.G., Tommasi R.A., Fujimoto R.A., Blancuzzi V., Clark K.,
RA   Cornell W.D., Doti R., Doughty J., Fang J., Farley D., Fitt J., Ganu V.,
RA   Goldberg R., Goldstein R., Lavoie S., Kulathila R., Macchia W.,
RA   Parker D.T., Melton R., O'Byrne E., Pastor G., Pellas T., Quadros E.,
RA   Reel N., Roland D.M., Sakane Y., Singh H., Skiles J., Somers J.,
RA   Toscano K., Wigg A., Zhou S., Zhu L., Shieh W.C., Xue S., McQuire L.W.;
RT   "Discovery of potent, selective, and orally active carboxylic acid based
RT   inhibitors of matrix metalloproteinase-13.";
RL   J. Med. Chem. 52:3523-3538(2009).
RN   [24]
RP   X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 104-270 IN COMPLEX WITH CALCIUM
RP   AND ZINC, CATALYTIC ACTIVITY, AND COFACTOR.
RX   PubMed=20005097; DOI=10.1016/j.bmcl.2009.11.081;
RA   Schnute M.E., O'Brien P.M., Nahra J., Morris M., Howard Roark W.,
RA   Hanau C.E., Ruminski P.G., Scholten J.A., Fletcher T.R., Hamper B.C.,
RA   Carroll J.N., Patt W.C., Shieh H.S., Collins B., Pavlovsky A.G.,
RA   Palmquist K.E., Aston K.W., Hitchcock J., Rogers M.D., McDonald J.,
RA   Johnson A.R., Munie G.E., Wittwer A.J., Man C.F., Settle S.L.,
RA   Nemirovskiy O., Vickery L.E., Agawal A., Dyer R.D., Sunyer T.;
RT   "Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify
RT   highly selective matrix metalloproteinase-13 inhibitors for the treatment
RT   of osteoarthritis.";
RL   Bioorg. Med. Chem. Lett. 20:576-580(2010).
RN   [25]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 104-267 IN COMPLEX WITH CALCIUM
RP   AND ZINC, CATALYTIC ACTIVITY, COFACTOR, AND FUNCTION.
RX   PubMed=20726512; DOI=10.1021/jm100669j;
RA   Becker D.P., Barta T.E., Bedell L.J., Boehm T.L., Bond B.R., Carroll J.,
RA   Carron C.P., Decrescenzo G.A., Easton A.M., Freskos J.N.,
RA   Funckes-Shippy C.L., Heron M., Hockerman S., Howard C.P., Kiefer J.R.,
RA   Li M.H., Mathis K.J., McDonald J.J., Mehta P.P., Munie G.E., Sunyer T.,
RA   Swearingen C.A., Villamil C.I., Welsch D., Williams J.M., Yu Y., Yao J.;
RT   "Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl
RT   sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer,
RT   arthritis, and cardiovascular disease.";
RL   J. Med. Chem. 53:6653-6680(2010).
RN   [26]
RP   X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) OF 104-272 IN COMPLEX WITH CALCIUM
RP   AND ZINC, COFACTOR, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND FUNCTION.
RX   PubMed=22689580; DOI=10.1074/jbc.m112.380782;
RA   Devel L., Beau F., Amoura M., Vera L., Cassar-Lajeunesse E., Garcia S.,
RA   Czarny B., Stura E.A., Dive V.;
RT   "Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of
RT   matrix metalloproteases and other metzincins.";
RL   J. Biol. Chem. 287:26647-26656(2012).
RN   [27]
RP   X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 103-274 IN COMPLEX WITH CALCIUM
RP   AND ZINC, COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=23810497; DOI=10.1016/j.bmcl.2013.05.089;
RA   De Savi C., Waterson D., Pape A., Lamont S., Hadley E., Mills M.,
RA   Page K.M., Bowyer J., Maciewicz R.A.;
RT   "Hydantoin based inhibitors of MMP13--discovery of AZD6605.";
RL   Bioorg. Med. Chem. Lett. 23:4705-4712(2013).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 104-471 OF MUTANT ALA-223 IN
RP   COMPLEX WITH CALCIUM AND ZINC, COFACTOR, DISULFIDE BOND, MUTAGENESIS OF
RP   GLU-223, ACTIVE SITE, AND SUBUNIT.
RX   PubMed=23913860; DOI=10.1096/fj.13-233601;
RA   Stura E.A., Visse R., Cuniasse P., Dive V., Nagase H.;
RT   "Crystal structure of full-length human collagenase 3 (MMP-13) with
RT   peptides in the active site defines exosites in the catalytic domain.";
RL   FASEB J. 27:4395-4405(2013).
RN   [29]
RP   VARIANT SEMDM SER-75, CHARACTERIZATION OF VARIANT SEMDM SER-75, AND
RP   FUNCTION IN BONE DEVELOPMENT.
RX   PubMed=16167086; DOI=10.1172/jci22900;
RA   Kennedy A.M., Inada M., Krane S.M., Christie P.T., Harding B.,
RA   Lopez-Otin C., Sanchez L.M., Pannett A.A.J., Dearlove A., Hartley C.,
RA   Byrne M.H., Reed A.A.C., Nesbit M.A., Whyte M.P., Thakker R.V.;
RT   "MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type
RT   (SEMD(MO).";
RL   J. Clin. Invest. 115:2832-2842(2005).
RN   [30]
RP   VARIANTS MANDP1 SER-74; THR-91 AND ASN-232, AND FUNCTION IN BONE
RP   DEVELOPMENT.
RX   PubMed=19615667; DOI=10.1016/j.ajhg.2009.06.014;
RA   Lausch E., Keppler R., Hilbert K., Cormier-Daire V., Nikkel S.,
RA   Nishimura G., Unger S., Spranger J., Superti-Furga A., Zabel B.;
RT   "Mutations in MMP9 and MMP13 determine the mode of inheritance and the
RT   clinical spectrum of metaphyseal anadysplasia.";
RL   Am. J. Hum. Genet. 85:168-178(2009).
CC   -!- FUNCTION: Plays a role in the degradation of extracellular matrix
CC       proteins including fibrillar collagen, fibronectin, TNC and ACAN.
CC       Cleaves triple helical collagens, including type I, type II and type
CC       III collagen, but has the highest activity with soluble type II
CC       collagen. Can also degrade collagen type IV, type XIV and type X. May
CC       also function by activating or degrading key regulatory proteins, such
CC       as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling,
CC       cartilage degradation, bone development, bone mineralization and
CC       ossification. Required for normal embryonic bone development and
CC       ossification. Plays a role in the healing of bone fractures via
CC       endochondral ossification. Plays a role in wound healing, probably by a
CC       mechanism that involves proteolytic activation of TGFB1 and degradation
CC       of CCN2. Plays a role in keratinocyte migration during wound healing.
CC       May play a role in cell migration and in tumor cell invasion.
CC       {ECO:0000269|PubMed:16167086, ECO:0000269|PubMed:17623656,
CC       ECO:0000269|PubMed:19422229, ECO:0000269|PubMed:19615667,
CC       ECO:0000269|PubMed:20726512, ECO:0000269|PubMed:22689580,
CC       ECO:0000269|PubMed:23810497, ECO:0000269|PubMed:8207000,
CC       ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:8603731,
CC       ECO:0000269|PubMed:8663255, ECO:0000269|PubMed:9065415}.
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000269|PubMed:10074939, ECO:0000269|PubMed:10926524,
CC         ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
CC         ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
CC         ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
CC         ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
CC         ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
CC         ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305};
CC       Note=Can bind about 5 Ca(2+) ions per subunit.
CC       {ECO:0000269|PubMed:10074939, ECO:0000269|PubMed:10926524,
CC       ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
CC       ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
CC       ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
CC       ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
CC       ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
CC       ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:10074939, ECO:0000269|PubMed:10926524,
CC         ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
CC         ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
CC         ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
CC         ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
CC         ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
CC         ECO:0000269|PubMed:23913860};
CC       Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:10074939,
CC       ECO:0000269|PubMed:10926524, ECO:0000269|PubMed:10986126,
CC       ECO:0000269|PubMed:15734645, ECO:0000269|PubMed:15780611,
CC       ECO:0000269|PubMed:17196980, ECO:0000269|PubMed:17623656,
CC       ECO:0000269|PubMed:19422229, ECO:0000269|PubMed:20005097,
CC       ECO:0000269|PubMed:20726512, ECO:0000269|PubMed:22689580,
CC       ECO:0000269|PubMed:23810497, ECO:0000269|PubMed:23913860};
CC   -!- ACTIVITY REGULATION: Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by
CC       acetohydroxamic acid and other zinc chelators.
CC       {ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:8576151,
CC       ECO:0000269|PubMed:9065415}.
CC   -!- SUBUNIT: Monomer. Interacts with TIMP1, TIMP2 and TIMP3. Binds (via the
CC       C-terminal region) to collagen. {ECO:0000269|PubMed:10926524,
CC       ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
CC       ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
CC       ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
CC       ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
CC       ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
CC       ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8576151,
CC       ECO:0000269|PubMed:8969305, ECO:0000269|PubMed:9065415}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000305|PubMed:8576151}. Secreted
CC       {ECO:0000269|PubMed:8576151}.
CC   -!- TISSUE SPECIFICITY: Detected in fetal cartilage and calvaria, in
CC       chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal
CC       end of ribs undergoing ossification, as well as in osteoblasts and
CC       periosteal cells below the inner periosteal region of ossified ribs.
CC       Detected in chondrocytes from in joint cartilage that have been treated
CC       with TNF and IL1B, but not in untreated chondrocytes. Detected in T
CC       lymphocytes. Detected in breast carcinoma tissue.
CC       {ECO:0000269|PubMed:8207000, ECO:0000269|PubMed:8798568,
CC       ECO:0000269|PubMed:9056642, ECO:0000269|PubMed:9562863}.
CC   -!- INDUCTION: Up-regulated by TNF and IL1B. {ECO:0000269|PubMed:8798568,
CC       ECO:0000269|PubMed:9056642}.
CC   -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC       binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC       dissociation of the cysteine from the zinc ion upon the activation-
CC       peptide release activates the enzyme (By similarity). {ECO:0000250}.
CC   -!- DOMAIN: The C-terminal region binds to collagen.
CC       {ECO:0000269|PubMed:9065415}.
CC   -!- PTM: The proenzyme is activated by removal of the propeptide; this
CC       cleavage can be effected by other matrix metalloproteinases, such as
CC       MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage
CC       can also be autocatalytic, after partial maturation by another protease
CC       or after treatment with 4-aminophenylmercuric acetate (APMA) (in
CC       vitro).
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:8576151}.
CC   -!- PTM: Tyrosine phosphorylated by PKDCC/VLK.
CC       {ECO:0000269|PubMed:25171405}.
CC   -!- DISEASE: Spondyloepimetaphyseal dysplasia, Missouri type (SEMDM)
CC       [MIM:602111]: A bone disease characterized by moderate to severe
CC       metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening
CC       of the lower limbs with bowing of the femora and/or tibiae, coxa vara,
CC       genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal
CC       changes improve with age. {ECO:0000269|PubMed:16167086}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111]: A bone
CC       development disorder characterized by skeletal anomalies that resolve
CC       spontaneously with age. Clinical characteristics are evident from the
CC       first months of life and include slight shortness of stature and a mild
CC       varus deformity of the legs. Patients attain a normal stature in
CC       adolescence and show improvement or complete resolution of varus
CC       deformity of the legs and rhizomelic micromelia.
CC       {ECO:0000269|PubMed:19615667}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Metaphyseal dysplasia, Spahr type (MDST) [MIM:250400]: An
CC       autosomal recessive, rare disease characterized by moderate short
CC       stature, mild genua vara, and radiographic signs of metaphyseal
CC       dysplasia, but no biochemical signs of rickets.
CC       {ECO:0000269|PubMed:24648384, ECO:0000269|PubMed:24781753}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/mmp13/";
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DR   EMBL; X75308; CAA53056.1; -; mRNA.
DR   EMBL; X81334; CAA57108.1; -; mRNA.
DR   EMBL; AK292211; BAF84900.1; -; mRNA.
DR   EMBL; AK315341; BAG37740.1; -; mRNA.
DR   EMBL; AY741163; AAU13907.1; -; Genomic_DNA.
DR   EMBL; BC067522; AAH67522.1; -; mRNA.
DR   EMBL; BC067523; AAH67523.1; -; mRNA.
DR   EMBL; BC074807; AAH74807.1; -; mRNA.
DR   EMBL; BC074808; AAH74808.1; -; mRNA.
DR   CCDS; CCDS8324.1; -.
DR   PIR; A53711; A53711.
DR   RefSeq; NP_002418.1; NM_002427.3.
DR   PDB; 1EUB; NMR; -; A=104-274.
DR   PDB; 1FLS; NMR; -; A=104-268.
DR   PDB; 1FM1; NMR; -; A=104-268.
DR   PDB; 1PEX; X-ray; 2.70 A; A=265-471.
DR   PDB; 1XUC; X-ray; 1.70 A; A/B=104-274.
DR   PDB; 1XUD; X-ray; 1.80 A; A/B=104-274.
DR   PDB; 1XUR; X-ray; 1.85 A; A/B=104-274.
DR   PDB; 1YOU; X-ray; 2.30 A; A/B=104-271.
DR   PDB; 1ZTQ; X-ray; 2.00 A; A/B/C/D=104-268.
DR   PDB; 2D1N; X-ray; 2.37 A; A/B=104-269.
DR   PDB; 2E2D; X-ray; 2.00 A; A=104-268.
DR   PDB; 2OW9; X-ray; 1.74 A; A/B=104-270.
DR   PDB; 2OZR; X-ray; 2.30 A; A/B/C/D/E/F/G/H=104-270.
DR   PDB; 2PJT; X-ray; 2.80 A; A/B/C/D=104-268.
DR   PDB; 2YIG; X-ray; 1.70 A; A/B=104-274.
DR   PDB; 3ELM; X-ray; 1.90 A; A/B=104-274.
DR   PDB; 3I7G; X-ray; 1.95 A; A/B=104-274.
DR   PDB; 3I7I; X-ray; 2.21 A; A/B=104-274.
DR   PDB; 3KEC; X-ray; 2.05 A; A/B=105-267.
DR   PDB; 3KEJ; X-ray; 2.30 A; A/B=104-270.
DR   PDB; 3KEK; X-ray; 1.97 A; A/B=104-270.
DR   PDB; 3KRY; X-ray; 1.90 A; A/B/C/D=104-267.
DR   PDB; 3LJZ; X-ray; 2.00 A; A/B/C/D=104-267.
DR   PDB; 3O2X; X-ray; 1.90 A; A/B/C/D=105-267.
DR   PDB; 3TVC; X-ray; 2.43 A; A=104-272.
DR   PDB; 3WV1; X-ray; 1.98 A; A/B=104-274.
DR   PDB; 3WV2; X-ray; 2.30 A; A/B=104-274.
DR   PDB; 3WV3; X-ray; 1.60 A; A/B=104-274.
DR   PDB; 3ZXH; X-ray; 1.30 A; A/B=104-274.
DR   PDB; 456C; X-ray; 2.40 A; A/B=104-271.
DR   PDB; 4A7B; X-ray; 2.20 A; A/B=104-272.
DR   PDB; 4FU4; X-ray; 2.85 A; A/B=104-471, C/D=25-50.
DR   PDB; 4FVL; X-ray; 2.44 A; A/B=104-471, C/D=31-50.
DR   PDB; 4G0D; X-ray; 2.54 A; A/B/C/D=104-471, W/X/Y/Z=25-50.
DR   PDB; 4JP4; X-ray; 1.43 A; A/B=103-274.
DR   PDB; 4JPA; X-ray; 2.00 A; A/B=103-274.
DR   PDB; 4L19; X-ray; 1.66 A; A/B=104-274.
DR   PDB; 5B5O; X-ray; 1.20 A; A/B=103-274.
DR   PDB; 5B5P; X-ray; 1.60 A; A/B=103-274.
DR   PDB; 5BOT; X-ray; 1.85 A; A/B=104-274.
DR   PDB; 5BOY; X-ray; 2.03 A; A/B=104-274.
DR   PDB; 5BPA; X-ray; 1.79 A; A/B=104-274.
DR   PDB; 5UWK; X-ray; 1.60 A; A/B=104-274.
DR   PDB; 5UWL; X-ray; 2.55 A; A/B=104-274.
DR   PDB; 5UWM; X-ray; 1.62 A; A/B=104-274.
DR   PDB; 5UWN; X-ray; 3.20 A; A/B/C/D/E=104-274.
DR   PDB; 7JU8; X-ray; 2.00 A; A/B=104-274.
DR   PDB; 830C; X-ray; 1.60 A; A/B=104-271.
DR   PDBsum; 1EUB; -.
DR   PDBsum; 1FLS; -.
DR   PDBsum; 1FM1; -.
DR   PDBsum; 1PEX; -.
DR   PDBsum; 1XUC; -.
DR   PDBsum; 1XUD; -.
DR   PDBsum; 1XUR; -.
DR   PDBsum; 1YOU; -.
DR   PDBsum; 1ZTQ; -.
DR   PDBsum; 2D1N; -.
DR   PDBsum; 2E2D; -.
DR   PDBsum; 2OW9; -.
DR   PDBsum; 2OZR; -.
DR   PDBsum; 2PJT; -.
DR   PDBsum; 2YIG; -.
DR   PDBsum; 3ELM; -.
DR   PDBsum; 3I7G; -.
DR   PDBsum; 3I7I; -.
DR   PDBsum; 3KEC; -.
DR   PDBsum; 3KEJ; -.
DR   PDBsum; 3KEK; -.
DR   PDBsum; 3KRY; -.
DR   PDBsum; 3LJZ; -.
DR   PDBsum; 3O2X; -.
DR   PDBsum; 3TVC; -.
DR   PDBsum; 3WV1; -.
DR   PDBsum; 3WV2; -.
DR   PDBsum; 3WV3; -.
DR   PDBsum; 3ZXH; -.
DR   PDBsum; 456C; -.
DR   PDBsum; 4A7B; -.
DR   PDBsum; 4FU4; -.
DR   PDBsum; 4FVL; -.
DR   PDBsum; 4G0D; -.
DR   PDBsum; 4JP4; -.
DR   PDBsum; 4JPA; -.
DR   PDBsum; 4L19; -.
DR   PDBsum; 5B5O; -.
DR   PDBsum; 5B5P; -.
DR   PDBsum; 5BOT; -.
DR   PDBsum; 5BOY; -.
DR   PDBsum; 5BPA; -.
DR   PDBsum; 5UWK; -.
DR   PDBsum; 5UWL; -.
DR   PDBsum; 5UWM; -.
DR   PDBsum; 5UWN; -.
DR   PDBsum; 7JU8; -.
DR   PDBsum; 830C; -.
DR   AlphaFoldDB; P45452; -.
DR   BMRB; P45452; -.
DR   SMR; P45452; -.
DR   BioGRID; 110465; 34.
DR   STRING; 9606.ENSP00000260302; -.
DR   BindingDB; P45452; -.
DR   ChEMBL; CHEMBL280; -.
DR   DrugBank; DB02049; 2-{4-[4-(4-Chloro-Phenoxy)-Benzenesulfonyl]-Tetrahydro-Pyran-4-Yl}-N-Hydroxy-Acetamide.
DR   DrugBank; DB01996; 3-Methylpyridine.
DR   DrugBank; DB03033; 4-methoxybenzenesulfinate.
DR   DrugBank; DB07827; 4-{[1-METHYL-2,4-DIOXO-6-(3-PHENYLPROP-1-YN-1-YL)-1,4-DIHYDROQUINAZOLIN-3(2H)-YL]METHYL}BENZOIC ACID.
DR   DrugBank; DB08388; 5-(2-ETHOXYETHYL)-5-[4-(4-FLUOROPHENOXY)PHENOXY]PYRIMIDINE-2,4,6(1H,3H,5H)-TRIONE.
DR   DrugBank; DB08561; BENZYL 6-BENZYL-5,7-DIOXO-6,7-DIHYDRO-5H-[1,3]THIAZOLO[3,2-C]PYRIMIDINE-2-CARBOXYLATE.
DR   DrugBank; DB08490; CTS-1027.
DR   DrugBank; DB06423; Endostatin.
DR   DrugBank; DB02697; Hydroxyaminovaline.
DR   DrugBank; DB00786; Marimastat.
DR   DrugBank; DB04759; PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-(3-METHYL-BENZYLAMIDE).
DR   DrugBank; DB04760; PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-(4-FLUORO-3-METHYL-BENZYLAMIDE).
DR   DrugBank; DB04761; PYRIMIDINE-4,6-DICARBOXYLIC ACID BIS-[(PYRIDIN-3-YLMETHYL)-AMIDE].
DR   DrugBank; DB07013; TERT-BUTYL 4-({[4-(BUT-2-YN-1-YLAMINO)PHENYL]SULFONYL}METHYL)-4-[(HYDROXYAMINO)CARBONYL]PIPERIDINE-1-CARBOXYLATE.
DR   DrugBank; DB02071; WAY-151693.
DR   DrugCentral; P45452; -.
DR   GuidetoPHARMACOLOGY; 1637; -.
DR   MEROPS; M10.013; -.
DR   GlyCosmos; P45452; 2 sites, No reported glycans.
DR   GlyGen; P45452; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; P45452; -.
DR   PhosphoSitePlus; P45452; -.
DR   BioMuta; MMP13; -.
DR   DMDM; 1168998; -.
DR   MassIVE; P45452; -.
DR   PaxDb; 9606-ENSP00000260302; -.
DR   PeptideAtlas; P45452; -.
DR   ProteomicsDB; 55677; -.
DR   Antibodypedia; 18066; 1203 antibodies from 40 providers.
DR   DNASU; 4322; -.
DR   Ensembl; ENST00000260302.8; ENSP00000260302.3; ENSG00000137745.13.
DR   GeneID; 4322; -.
DR   KEGG; hsa:4322; -.
DR   MANE-Select; ENST00000260302.8; ENSP00000260302.3; NM_002427.4; NP_002418.1.
DR   UCSC; uc001phl.4; human.
DR   AGR; HGNC:7159; -.
DR   CTD; 4322; -.
DR   DisGeNET; 4322; -.
DR   GeneCards; MMP13; -.
DR   HGNC; HGNC:7159; MMP13.
DR   HPA; ENSG00000137745; Tissue enriched (urinary).
DR   MalaCards; MMP13; -.
DR   MIM; 250400; phenotype.
DR   MIM; 600108; gene.
DR   MIM; 602111; phenotype.
DR   neXtProt; NX_P45452; -.
DR   OpenTargets; ENSG00000137745; -.
DR   Orphanet; 1040; Metaphyseal anadysplasia.
DR   Orphanet; 2501; Metaphyseal chondrodysplasia, Spahr type.
DR   Orphanet; 93356; Spondyloepimetaphyseal dysplasia, Missouri type.
DR   PharmGKB; PA30871; -.
DR   VEuPathDB; HostDB:ENSG00000137745; -.
DR   eggNOG; KOG1565; Eukaryota.
DR   GeneTree; ENSGT00940000157450; -.
DR   InParanoid; P45452; -.
DR   OMA; MEAGYPR; -.
DR   OrthoDB; 391167at2759; -.
DR   PhylomeDB; P45452; -.
DR   TreeFam; TF315428; -.
DR   BRENDA; 3.4.24.17; 2681.
DR   BRENDA; 3.4.24.35; 2681.
DR   BRENDA; 3.4.24.65; 2681.
DR   BRENDA; 3.4.24.B4; 2681.
DR   PathwayCommons; P45452; -.
DR   Reactome; R-HSA-1442490; Collagen degradation.
DR   Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR   Reactome; R-HSA-8941332; RUNX2 regulates genes involved in cell migration.
DR   SignaLink; P45452; -.
DR   SIGNOR; P45452; -.
DR   BioGRID-ORCS; 4322; 13 hits in 1160 CRISPR screens.
DR   ChiTaRS; MMP13; human.
DR   EvolutionaryTrace; P45452; -.
DR   GeneWiki; Matrix_metallopeptidase_13; -.
DR   GenomeRNAi; 4322; -.
DR   Pharos; P45452; Tchem.
DR   PRO; PR:P45452; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P45452; Protein.
DR   Bgee; ENSG00000137745; Expressed in periodontal ligament and 44 other cell types or tissues.
DR   ExpressionAtlas; P45452; baseline and differential.
DR   GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR   GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR   GO; GO:0060349; P:bone morphogenesis; IDA:UniProtKB.
DR   GO; GO:0030574; P:collagen catabolic process; IDA:UniProtKB.
DR   GO; GO:0001958; P:endochondral ossification; IEA:Ensembl.
DR   GO; GO:0022617; P:extracellular matrix disassembly; IMP:UniProtKB.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0003417; P:growth plate cartilage development; IEA:Ensembl.
DR   GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR   GO; GO:1904645; P:response to amyloid-beta; TAS:ARUK-UCL.
DR   CDD; cd00094; HX; 1.
DR   CDD; cd04278; ZnMc_MMP; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.110.10.10; Hemopexin-like domain; 1.
DR   InterPro; IPR000585; Hemopexin-like_dom.
DR   InterPro; IPR036375; Hemopexin-like_dom_sf.
DR   InterPro; IPR018487; Hemopexin-like_repeat.
DR   InterPro; IPR018486; Hemopexin_CS.
DR   InterPro; IPR033739; M10A_MMP.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001818; Pept_M10_metallopeptidase.
DR   InterPro; IPR021190; Pept_M10A.
DR   InterPro; IPR021158; Pept_M10A_Zn_BS.
DR   InterPro; IPR006026; Peptidase_Metallo.
DR   InterPro; IPR002477; Peptidoglycan-bd-like.
DR   InterPro; IPR036365; PGBD-like_sf.
DR   PANTHER; PTHR10201:SF165; COLLAGENASE 3; 1.
DR   PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1.
DR   Pfam; PF00045; Hemopexin; 4.
DR   Pfam; PF00413; Peptidase_M10; 1.
DR   Pfam; PF01471; PG_binding_1; 1.
DR   PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR   PRINTS; PR00138; MATRIXIN.
DR   SMART; SM00120; HX; 4.
DR   SMART; SM00235; ZnMc; 1.
DR   SUPFAM; SSF50923; Hemopexin-like domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF47090; PGBD-like; 1.
DR   PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR   PROSITE; PS00024; HEMOPEXIN; 1.
DR   PROSITE; PS51642; HEMOPEXIN_2; 4.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; P45452; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Collagen degradation; Direct protein sequencing;
KW   Disease variant; Disulfide bond; Dwarfism; Extracellular matrix;
KW   Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Phosphoprotein;
KW   Protease; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:8576151"
FT   PROPEP          20..103
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000269|PubMed:8576151"
FT                   /id="PRO_0000028788"
FT   CHAIN           104..471
FT                   /note="Collagenase 3"
FT                   /id="PRO_0000028789"
FT   REPEAT          281..330
FT                   /note="Hemopexin 1"
FT   REPEAT          331..377
FT                   /note="Hemopexin 2"
FT   REPEAT          379..427
FT                   /note="Hemopexin 3"
FT   REPEAT          428..471
FT                   /note="Hemopexin 4"
FT   REGION          176..246
FT                   /note="Interaction with TIMP2"
FT   REGION          263..284
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          268..471
FT                   /note="Interaction with collagen"
FT   MOTIF           94..101
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        223
FT                   /evidence="ECO:0000305|PubMed:23913860"
FT   BINDING         96
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /note="in inhibited form"
FT                   /evidence="ECO:0000250"
FT   BINDING         128
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         162
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         172
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         174
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         179
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         180
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         182
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         184
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         187
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         194
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         196
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         198
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         200
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         202
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         203
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         205
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         205
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="3"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         222
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         226
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         232
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         240
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860"
FT   BINDING         291
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         293
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         335
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         337
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         383
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         385
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         432
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="4"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   BINDING         434
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="5"
FT                   /evidence="ECO:0000269|PubMed:10926524,
FT                   ECO:0000269|PubMed:10986126, ECO:0000269|PubMed:15734645,
FT                   ECO:0000269|PubMed:15780611, ECO:0000269|PubMed:17196980,
FT                   ECO:0000269|PubMed:17623656, ECO:0000269|PubMed:19422229,
FT                   ECO:0000269|PubMed:20005097, ECO:0000269|PubMed:20726512,
FT                   ECO:0000269|PubMed:22689580, ECO:0000269|PubMed:23810497,
FT                   ECO:0000269|PubMed:23913860, ECO:0000269|PubMed:8969305"
FT   MOD_RES         366
FT                   /note="Phosphotyrosine; by PKDCC"
FT                   /evidence="ECO:0000303|PubMed:25171405"
FT   CARBOHYD        117
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8576151"
FT   CARBOHYD        152
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        284..471
FT                   /evidence="ECO:0000269|PubMed:23913860,
FT                   ECO:0000269|PubMed:8969305"
FT   VARIANT         2
FT                   /note="H -> L (in dbSNP:rs554797)"
FT                   /id="VAR_011971"
FT   VARIANT         74
FT                   /note="F -> S (in MANDP1; dbSNP:rs121909498)"
FT                   /evidence="ECO:0000269|PubMed:19615667"
FT                   /id="VAR_063432"
FT   VARIANT         75
FT                   /note="F -> S (in SEMDM; abnormal intracellular
FT                   autoactivation and autodegradation within the ER/Golgi
FT                   resulting in the secretion of small and inactive fragments;
FT                   dbSNP:rs121909497)"
FT                   /evidence="ECO:0000269|PubMed:16167086"
FT                   /id="VAR_032753"
FT   VARIANT         91
FT                   /note="M -> T (in MANDP1; dbSNP:rs121909499)"
FT                   /evidence="ECO:0000269|PubMed:19615667"
FT                   /id="VAR_063433"
FT   VARIANT         207
FT                   /note="W -> G (in MDST; dbSNP:rs140059558)"
FT                   /evidence="ECO:0000269|PubMed:24648384"
FT                   /id="VAR_073418"
FT   VARIANT         232
FT                   /note="H -> N (in MANDP1; dbSNP:rs121909500)"
FT                   /evidence="ECO:0000269|PubMed:19615667"
FT                   /id="VAR_063434"
FT   VARIANT         390
FT                   /note="D -> G (in dbSNP:rs17860568)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_020534"
FT   MUTAGEN         223
FT                   /note="E->A: Abolishes enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:23913860"
FT   CONFLICT        147
FT                   /note="D -> G (in Ref. 3; BAF84900)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        278
FT                   /note="P -> L (in Ref. 5; AAH67523)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        438
FT                   /note="N -> D (in Ref. 3; BAG37740)"
FT                   /evidence="ECO:0000305"
FT   HELIX           33..36
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   HELIX           38..41
FT                   /evidence="ECO:0007829|PDB:4G0D"
FT   STRAND          44..48
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          109..111
FT                   /evidence="ECO:0007829|PDB:3ZXH"
FT   STRAND          114..122
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          127..129
FT                   /evidence="ECO:0007829|PDB:3I7I"
FT   HELIX           131..146
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:3O2X"
FT   STRAND          152..159
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          162..168
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          173..175
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          180..183
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          186..188
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          191..193
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   TURN            194..197
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          199..202
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          207..215
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   HELIX           216..228
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          235..237
FT                   /evidence="ECO:0007829|PDB:1EUB"
FT   STRAND          241..243
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          249..251
FT                   /evidence="ECO:0007829|PDB:3KRY"
FT   HELIX           256..266
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          269..271
FT                   /evidence="ECO:0007829|PDB:5B5O"
FT   STRAND          291..296
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          299..304
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          307..311
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          313..316
FT                   /evidence="ECO:0007829|PDB:1PEX"
FT   STRAND          319..322
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   HELIX           323..326
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          335..340
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   HELIX           341..343
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          345..350
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          353..358
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          367..369
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   HELIX           370..373
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          384..387
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   TURN            389..391
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          393..398
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          401..406
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   TURN            407..410
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   HELIX           420..423
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          432..437
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          440..445
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          448..453
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   TURN            454..457
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   STRAND          458..464
FT                   /evidence="ECO:0007829|PDB:4FVL"
FT   HELIX           465..469
FT                   /evidence="ECO:0007829|PDB:4FVL"
SQ   SEQUENCE   471 AA;  53820 MW;  E110F50628B57B60 CRC64;
     MHPGVLAAFL FLSWTHCRAL PLPSGGDEDD LSEEDLQFAE RYLRSYYHPT NLAGILKENA
     ASSMTERLRE MQSFFGLEVT GKLDDNTLDV MKKPRCGVPD VGEYNVFPRT LKWSKMNLTY
     RIVNYTPDMT HSEVEKAFKK AFKVWSDVTP LNFTRLHDGI ADIMISFGIK EHGDFYPFDG
     PSGLLAHAFP PGPNYGGDAH FDDDETWTSS SKGYNLFLVA AHEFGHSLGL DHSKDPGALM
     FPIYTYTGKS HFMLPDDDVQ GIQSLYGPGD EDPNPKHPKT PDKCDPSLSL DAITSLRGET
     MIFKDRFFWR LHPQQVDAEL FLTKSFWPEL PNRIDAAYEH PSHDLIFIFR GRKFWALNGY
     DILEGYPKKI SELGLPKEVK KISAAVHFED TGKTLLFSGN QVWRYDDTNH IMDKDYPRLI
     EEDFPGIGDK VDAVYEKNGY IYFFNGPIQF EYSIWSNRIV RVMPANSILW C
//