ID COMP_HUMAN Reviewed; 757 AA. AC P49747; B4DKJ3; O14592; Q16388; Q16389; Q2NL86; Q8N4T2; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 14-OCT-2008, sequence version 2. DT 04-NOV-2026, entry version 228. DE RecName: Full=Cartilage oligomeric matrix protein {ECO:0000305}; DE Short=COMP; DE AltName: Full=Thrombospondin-5; DE Short=TSP5; DE Flags: Precursor; GN Name=COMP {ECO:0000312|HGNC:HGNC:2227}; 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] (ISOFORM 1), AND VARIANTS ASP-50; TRP-51; RP GLY-109; GLY-224 AND PRO-285. RC TISSUE=Cartilage; RX PubMed=7713493; DOI=10.1006/geno.1994.1649; RA Newton G., Weremowicz S., Morton C.C., Copeland N.G., Gilbert D.J., RA Jenkins N.A., Lawler J.; RT "Characterization of human and mouse cartilage oligomeric matrix protein."; RL Genomics 24:435-439(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ASP-50; TRP-51; RP GLY-109; GLY-224 AND PRO-285. RA Hashimoto Y., Mori H.; RT "Human comp cDNA with 5 SNIPs."; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary; 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 [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 326-344, VARIANT EDM1 TYR-342, AND RP VARIANT PSACH ARG-328. RX PubMed=7670472; DOI=10.1038/ng0795-330; RA Briggs M.D., Hoffman S.M.G., King L.M., Olsen A.S., Mohrenweiser H., RA Leroy J.G., Mortier G.R., Rimoin D.L., Lachman R.S., Gaines E.S., RA Cekleniak J.A., Knowlton R.G., Cohn D.H.; RT "Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in RT the cartilage oligomeric matrix protein gene."; RL Nat. Genet. 10:330-336(1995). RN [8] RP PROTEIN SEQUENCE OF 80-89, SUBUNIT, CALCIUM-BINDING, AND CHARACTERIZATION RP OF VARIANT PSACH ASP-469 DEL. RX PubMed=10852928; DOI=10.1074/jbc.m909780199; RA Chen H., Deere M., Hecht J.T., Lawler J.; RT "Cartilage oligomeric matrix protein is a calcium-binding protein, and a RT mutation in its type 3 repeats causes conformational changes."; RL J. Biol. Chem. 275:26538-26544(2000). RN [9] RP PROTEIN SEQUENCE, CALCIUM-BINDING, INTERACTION WITH COLLAGEN I; COLLAGEN II RP AND COLLAGEN IX, CHARACTERIZATION OF VARIANT PSACH ASP-469 DEL, AND RP CHARACTERIZATION OF VARIANT EDM1 TYR-361. RX PubMed=11084047; DOI=10.1074/jbc.m009512200; RA Thur J., Rosenberg K., Nitsche D.P., Pihlajamaa T., Ala-Kokko L., RA Heinegaard D., Paulsson M., Maurer P.; RT "Mutations in cartilage oligomeric matrix protein causing RT pseudoachondroplasia and multiple epiphyseal dysplasia affect binding of RT calcium and collagen I, II, and IX."; RL J. Biol. Chem. 276:6083-6092(2001). RN [10] RP INTERACTION WITH FN1. RX PubMed=12225811; DOI=10.1016/s0945-053x(02)00015-x; RA Di Cesare P.E., Chen F.S., Moergelin M., Carlson C.S., Leslie M.P., RA Perris R., Fang C.; RT "Matrix-matrix interaction of cartilage oligomeric matrix protein and RT fibronectin."; RL Matrix Biol. 21:461-470(2002). RN [11] RP INTERACTION WITH MATN1; MATN3 AND MATN4. RX PubMed=15075323; DOI=10.1074/jbc.m403778200; RA Mann H.H., Oezbek S., Engel J., Paulsson M., Wagener R.; RT "Interactions between the cartilage oligomeric matrix protein and RT matrilins. Implications for matrix assembly and the pathogenesis of RT chondrodysplasias."; RL J. Biol. Chem. 279:25294-25298(2004). RN [12] RP FUNCTION, AND INTERACTION WITH ITGB3 AND ITGA5. RX PubMed=16051604; DOI=10.1074/jbc.m504778200; RA Chen F.-H., Thomas A.O., Hecht J.T., Goldring M.B., Lawler J.; RT "Cartilage oligomeric matrix protein/thrombospondin 5 supports chondrocyte RT attachment through interaction with integrins."; RL J. Biol. Chem. 280:32655-32661(2005). RN [13] RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=16542502; DOI=10.1186/ar1922; RA Koelling S., Clauditz T.S., Kaste M., Miosge N.; RT "Cartilage oligomeric matrix protein is involved in human limb development RT and in the pathogenesis of osteoarthritis."; RL Arthritis Res. Ther. 8:R56-R56(2006). RN [14] RP INTERACTION WITH ADAMTS12. RX PubMed=16611630; DOI=10.1074/jbc.m513433200; RA Liu C.-J., Kong W., Xu K., Luan Y., Ilalov K., Sehgal B., Yu S., RA Howell R.D., Di Cesare P.E.; RT "ADAMTS-12 associates with and degrades cartilage oligomeric matrix RT protein."; RL J. Biol. Chem. 281:15800-15808(2006). RN [15] RP INTERACTION WITH ACAN; HEPARIN; HEPARAN SULFATE AND CHONDROITIN SULFATE. RX PubMed=17588949; DOI=10.1074/jbc.m611390200; RA Chen F.-H., Herndon M.E., Patel N., Hecht J.T., Tuan R.S., Lawler J.; RT "Interaction of cartilage oligomeric matrix protein/thrombospondin 5 with RT aggrecan."; RL J. Biol. Chem. 282:24591-24598(2007). RN [16] RP FUNCTION, AND DOMAINS. RX PubMed=17993464; DOI=10.1074/jbc.m704035200; RA Gagarina V., Carlberg A.L., Pereira-Mouries L., Hall D.J.; RT "Cartilage oligomeric matrix protein protects cells against death by RT elevating members of the IAP family of survival proteins."; RL J. Biol. Chem. 283:648-659(2008). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP PROTEOLYTIC CLEAVAGE BY ADAMTS4 AND ADAMTS1. RX PubMed=39672391; DOI=10.1016/j.matbio.2024.12.005; RA de Groot R., Folgado P.B., Yamamoto K., Martin D.R., Koch C.D., Debruin D., RA Blagg S., Minns A.F., Bhutada S., Ahnstroem J., Larkin J., Aspberg A., RA Oennerfjord P., Apte S.S., Santamaria S.; RT "Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 RT generates a neoepitope associated with osteoarthritis and other forms of RT degenerative joint disease."; RL Matrix Biol. 135:106-124(2025). RN [19] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH CALCIUM IONS, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-742. RX PubMed=19276170; DOI=10.1096/fj.08-128090; RA Tan K., Duquette M., Joachimiak A., Lawler J.; RT "The crystal structure of the signature domain of cartilage oligomeric RT matrix protein: implications for collagen, glycosaminoglycan and integrin RT binding."; RL FASEB J. 23:2490-2501(2009). RN [20] RP VARIANTS PSACH SER-459 DEL; TYR-468 AND TYR-472. RX PubMed=7670471; DOI=10.1038/ng0795-325; RA Hecht J.T., Nelson L.D., Crowder E., Wang Y., Elder F.F.B., Harrison W.R., RA Francomano C.A., Prange C.K., Lennon G.G., Deere M., Lawler J.; RT "Mutations in exon 17B of cartilage oligomeric matrix protein (COMP) cause RT pseudoachondroplasia."; RL Nat. Genet. 10:325-329(1995). RN [21] RP VARIANT EDM1 LYS-523. RX PubMed=9021009; RX DOI=10.1002/(sici)1096-8628(19970211)68:4<396::aid-ajmg4>3.3.co;2-r; RA Ballo R., Briggs M.D., Cohn D.H., Knowlton R.G., Beighton P.H., RA Ramesar R.S.; RT "Multiple epiphyseal dysplasia, ribbing type: a novel point mutation in the RT COMP gene in a South African family."; RL Am. J. Med. Genet. 68:396-400(1997). RN [22] RP VARIANT EDM1 SER-371, AND VARIANT PSACH 513-VAL--LYS-516 DEL. RX PubMed=9184241; DOI=10.1111/j.1399-0004.1997.tb02458.x; RA Susic S., McGrory J., Ahier J., Cole W.G.; RT "Multiple epiphyseal dysplasia and pseudoachondroplasia due to novel RT mutations in the calmodulin-like repeats of cartilage oligomeric matrix RT protein."; RL Clin. Genet. 51:219-224(1997). RN [23] RP VARIANTS PSACH, VARIANTS EDM1 SER-453 AND ARG-585, AND VARIANT PSACH RP GLU-440. RX PubMed=9463320; DOI=10.1086/301713; RA Briggs M.D., Mortier G.R., Cole W.G., King L.M., Golik S.S., RA Bonaventure J., Nuytinck L., de Paepe A., Leroy J.G., Biesecker L., RA Lipson M., Wilcox W.R., Lachman R.S., Rimoin D.L., Knowlton R.G., RA Cohn D.H.; RT "Diverse mutations in the gene for cartilage oligomeric matrix protein in RT the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum."; RL Am. J. Hum. Genet. 62:311-319(1998). RN [24] RP VARIANTS PSACH AND EDM1, VARIANTS PSACH ASN-290; VAL-349; GLY-387; GLY-473 RP AND ASN-518, AND VARIANT EDM1 VAL-361. RX PubMed=9921895; DOI=10.1007/s004390050883; RA Ikegawa S., Ohashi H., Nishimura G., Kim K.C., Sannohe A., Kimizuka M., RA Fukushima Y., Nagai T., Nakamura Y.; RT "Novel and recurrent COMP (cartilage oligomeric matrix protein) mutations RT in pseudoachondroplasia and multiple epiphyseal dysplasia."; RL Hum. Genet. 103:633-638(1998). RN [25] RP VARIANTS PSACH ARG-328; ASP-372 DEL; 391-PRO--ASP-394 DELINS VAL; ARG-440; RP SER-459 DEL; TYR-468; ASP-469 DEL AND TYR-472, AND VARIANTS EDM1 TYR-342; RP TYR-361; 367-ARG-GLY-368 DEL AND TYR-408. RX PubMed=9452026; DOI=10.1002/humu.1380110105; RA Loughlin J., Irven C., Mustafa Z., Briggs M.D., Carr A., Lynch S.-A., RA Knowlton R.G., Cohn D.H., Sykes B.; RT "Identification of five novel mutations in cartilage oligomeric matrix RT protein gene in pseudoachondroplasia and multiple epiphyseal dysplasia."; RL Hum. Mutat. Suppl. 1:S10-S17(1998). RN [26] RP VARIANT PSACH GLY-482. RX PubMed=9452063; DOI=10.1002/humu.1380110142; RA Susic S., Ahier J., Cole W.G.; RT "Pseudoachondroplasia due to the substitution of the highly conserved RT Asp482 by Gly in the seventh calmodulin-like repeat of cartilage oligomeric RT matrix protein."; RL Hum. Mutat. Suppl. 1:S125-S127(1998). RN [27] RP VARIANT PSACH ARG-348. RX PubMed=11746045; DOI=10.1002/ajmg.10062; RA Unger S., Koerkkoe J., Krakow D., Lachman R.S., Rimoin D.L., Cohn D.H.; RT "Double heterozygosity for pseudoachondroplasia and spondyloepiphyseal RT dysplasia congenita."; RL Am. J. Med. Genet. 104:140-146(2001). RN [28] RP VARIANT PSACH ASP-719. RX PubMed=11746044; DOI=10.1002/ajmg.10067; RA Mabuchi A., Haga N., Ikeda T., Manabe N., Ohashi H., Takatori Y., RA Nakamura K., Ikegawa S.; RT "Novel mutation in exon 18 of the cartilage oligomeric matrix protein gene RT causes a severe pseudoachondroplasia."; RL Am. J. Med. Genet. 104:135-139(2001). RN [29] RP VARIANTS EDM1 ARG-276; ALA-420 AND MET-585. RX PubMed=11565064; DOI=10.1086/324023; RA Czarny-Ratajczak M., Lohiniva J., Rogala P., Kozlowski K., Peraelae M., RA Carter L., Spector T.D., Kolodziej L., Seppaenen U., Glazar R., RA Krolewski J., Latos-Bielenska A., Ala-Kokko L.; RT "A mutation in COL9A1 causes multiple epiphyseal dysplasia: further RT evidence for locus heterogeneity."; RL Am. J. Hum. Genet. 69:969-980(2001). RN [30] RP VARIANTS PSACH SER-234; GLY-290; ARG-299; TYR-326; 341-GLU-ASP-342 DEL; RP 350-ASN--ASP-372 DEL; VAL-378; ARG-387; 402-GLY--GLY-404 DELINS VAL-CYS; RP ARG-440; ASN-446; SER-448; ASP-473 DEL; HIS-473; ASN-475; GLY-482; GLY-507; RP GLY-511; GLY-515; ILE-529; ARG-585 AND SER-719, VARIANTS EDM1 GLU-167; RP ARG-276; LEU-298; ASP-311; GLY-317; GLY-326; PHE-348; SER-371; TYR-371; RP ASN-374; ASN-376; ASN-385; ASP-385 DEL; TYR-385; HIS-397; ARG-404; TYR-410; RP LYS-415; GLU-427; 430-CYS--SER-432 DELINS LEU-TRP-CYS; GLU-457 DEL; ASP-473 RP INS; ASP-501; LYS-523; MET-585; PRO-718 AND TRP-718, AND VARIANT ARG-756. RX PubMed=21922596; DOI=10.1002/humu.21611; RA Jackson G.C., Mittaz-Crettol L., Taylor J.A., Mortier G.R., Spranger J., RA Zabel B., Le Merrer M., Cormier-Daire V., Hall C.M., Offiah A., RA Wright M.J., Savarirayan R., Nishimura G., Ramsden S.C., Elles R., RA Bonafe L., Superti-Furga A., Unger S., Zankl A., Briggs M.D.; RT "Pseudoachondroplasia and multiple epiphyseal dysplasia: A 7-year RT comprehensive analysis of the known disease genes identify novel and RT recurrent mutations and provides an accurate assessment of their relative RT contribution."; RL Hum. Mutat. 33:144-157(2012). RN [31] RP VARIANTS CTS2 GLU-66 AND TRP-718, CHARACTERIZATION OF VARIANTS CTS2 GLU-66 RP AND TRP-718, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=32686688; DOI=10.1038/s41467-020-17378-z; RA Li C., Wang N., Schaeffer A.A., Liu X., Zhao Z., Elliott G., Garrett L., RA Choi N.T., Wang Y., Wang Y., Wang C., Wang J., Chan D., Su P., Cui S., RA Yang Y., Gao B.; RT "Mutations in COMP cause familial carpal tunnel syndrome."; RL Nat. Commun. 11:3642-3642(2020). RN [32] RP ERRATUM OF PUBMED:32686688. RX PubMed=32747625; DOI=10.1038/s41467-020-17845-7; RA Li C., Wang N., Schaeffer A.A., Liu X., Zhao Z., Elliott G., Garrett L., RA Choi N.T., Wang Y., Wang Y., Wang C., Wang J., Chan D., Su P., Cui S., RA Yang Y., Gao B.; RT "Author Correction: Mutations in COMP cause familial carpal tunnel RT syndrome."; RL Nat. Commun. 11:3931-3931(2020). CC -!- FUNCTION: Plays a role in the structural integrity of cartilage via its CC interaction with other extracellular matrix proteins such as the CC collagens and fibronectin. Can mediate the interaction of chondrocytes CC with the cartilage extracellular matrix through interaction with cell CC surface integrin receptors (PubMed:16051604, PubMed:16542502). Could CC play a role in the pathogenesis of osteoarthritis (PubMed:16542502). CC Potent suppressor of apoptosis in both primary chondrocytes and CC transformed cells. Suppresses apoptosis by blocking the activation of CC caspase-3 and by inducing the IAP family of survival proteins (BIRC3, CC BIRC2, BIRC5 and XIAP) (PubMed:17993464). Essential for maintaining a CC vascular smooth muscle cells (VSMCs) contractile/differentiated CC phenotype under physiological and pathological stimuli. Maintains this CC phenotype of VSMCs by interacting with ITGA7 (By similarity). CC {ECO:0000250|UniProtKB:P35444, ECO:0000269|PubMed:16051604, CC ECO:0000269|PubMed:16542502, ECO:0000269|PubMed:17993464}. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC Evidence={ECO:0000269|PubMed:10852928, ECO:0000269|PubMed:11084047, CC ECO:0000269|PubMed:19276170}; CC Note=Binds 11-14 calcium ions per subunit. CC {ECO:0000269|PubMed:19276170}; CC -!- SUBUNIT: Pentamer; disulfide-linked (PubMed:32686688). Exists in a more CC compact conformation in the presence of calcium and shows a more CC extended conformation in the absence of calcium (PubMed:19276170). CC Interacts with ITGB3, ITGA5 and FN1. Binding to FN1 requires the CC presence of divalent cations (Ca(2+), Mg(2+) or Mn(2+)). The greatest CC amount of binding is seen in the presence of Mn(2+) (PubMed:12225811, CC PubMed:16051604). Interacts with MATN1, MATN3, MATN4 and ACAN CC (PubMed:15075323, PubMed:17588949). Binds heparin, heparan sulfate and CC chondroitin sulfate. EDTA dimishes significantly its binding to ACAN CC and abolishes its binding to MATN3, MATN4 and chondroitin sulfate CC (PubMed:17588949). Interacts with collagen I, II and IX, and CC interaction with these collagens is dependent on the presence of zinc CC ions (PubMed:11084047). Interacts with ADAMTS12 (PubMed:16611630). CC Interacts with ITGA7 (By similarity). {ECO:0000250|UniProtKB:P35444, CC ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:12225811, CC ECO:0000269|PubMed:15075323, ECO:0000269|PubMed:16051604, CC ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:17588949, CC ECO:0000269|PubMed:19276170, ECO:0000269|PubMed:32686688}. CC -!- INTERACTION: CC P49747; P58397: ADAMTS12; NbExp=3; IntAct=EBI-2531022, EBI-9028051; CC P49747; P29972: AQP1; NbExp=3; IntAct=EBI-2531022, EBI-745213; CC P49747; O00244: ATOX1; NbExp=3; IntAct=EBI-2531022, EBI-10179267; CC P49747; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2531022, EBI-3867333; CC P49747; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2531022, EBI-16439278; CC P49747; Q7Z417: NUFIP2; NbExp=3; IntAct=EBI-2531022, EBI-1210753; CC P49747; P32242: OTX1; NbExp=7; IntAct=EBI-2531022, EBI-740446; CC P49747; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-2531022, EBI-744081; CC P49747; P13608: ACAN; Xeno; NbExp=2; IntAct=EBI-2531022, EBI-6259246; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000269|PubMed:32686688}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P49747-1; Sequence=Displayed; CC Name=2; CC IsoId=P49747-2; Sequence=VSP_055758; CC -!- TISSUE SPECIFICITY: Abundantly expressed in the chondrocyte CC extracellular matrix, and is also found in bone, tendon, ligament and CC synovium and blood vessels. Increased amounts are produced during late CC stages of osteoarthritis in the area adjacent to the main defect. CC {ECO:0000269|PubMed:16542502, ECO:0000269|PubMed:32686688}. CC -!- DEVELOPMENTAL STAGE: Present during the earliest stages of limb CC maturation and is later found in regions where the joints develop. CC {ECO:0000269|PubMed:16542502}. CC -!- DOMAIN: The cell attachment motif mediates the attachment to CC chondrocytes. It mediates the induction of both the IAP family of CC survival proteins and the antiapoptotic response. CC {ECO:0000269|PubMed:17993464}. CC -!- DOMAIN: The TSP C-terminal domain mediates interaction with FN1 and CC ACAN. {ECO:0000269|PubMed:17993464}. CC -!- DOMAIN: Each of the eight TSP type-3 repeats binds two calcium ions. CC The TSP C-terminal domain binds three calcium ions. CC {ECO:0000269|PubMed:17993464}. CC -!- PTM: Proteolytically cleaved by metalloproteases ADAMTS4 and ADAMTS1 CC with ADAMTS4 showing more potent activity. CC {ECO:0000269|PubMed:39672391}. CC -!- DISEASE: Multiple epiphyseal dysplasia 1 (EDM1) [MIM:132400]: A CC generalized skeletal dysplasia associated with significant morbidity. CC Joint pain, joint deformity, waddling gait, and short stature are the CC main clinical signs and symptoms. Radiological examination of the CC skeleton shows delayed, irregular mineralization of the epiphyseal CC ossification centers and of the centers of the carpal and tarsal bones. CC Multiple epiphyseal dysplasia is broadly categorized into the more CC severe Fairbank and the milder Ribbing types. The Fairbank type is CC characterized by shortness of stature, short and stubby fingers, small CC epiphyses in several joints, including the knee, ankle, hand, and hip. CC The Ribbing type is confined predominantly to the hip joints and is CC characterized by hands that are normal and stature that is normal or CC near-normal. {ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:11565064, CC ECO:0000269|PubMed:21922596, ECO:0000269|PubMed:7670472, CC ECO:0000269|PubMed:9021009, ECO:0000269|PubMed:9184241, CC ECO:0000269|PubMed:9452026, ECO:0000269|PubMed:9463320, CC ECO:0000269|PubMed:9921895}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Pseudoachondroplasia (PSACH) [MIM:177170]: A skeletal CC dysplasia usually manifesting in the second year of life and CC characterized by moderate to severe disproportionate short stature, CC deformity of the lower limbs, brachydactyly, ligamentous laxity, and CC degenerative joint disease. {ECO:0000269|PubMed:10852928, CC ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:11746044, CC ECO:0000269|PubMed:11746045, ECO:0000269|PubMed:21922596, CC ECO:0000269|PubMed:7670471, ECO:0000269|PubMed:7670472, CC ECO:0000269|PubMed:9184241, ECO:0000269|PubMed:9452026, CC ECO:0000269|PubMed:9452063, ECO:0000269|PubMed:9463320, CC ECO:0000269|PubMed:9921895}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Carpal tunnel syndrome 2 (CTS2) [MIM:619161]: An autosomal CC dominant form of carpal tunnel syndrome, a condition characterized by CC entrapment of the median nerve within the carpal tunnel. Symptoms CC include burning pain and paresthesias involving the ventral surface of CC the hand and fingers which may radiate proximally. Impairment of CC sensation in the distribution of the median nerve and thenar muscle CC atrophy may occur. This condition may be associated with repetitive CC occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid CC arthritis. {ECO:0000269|PubMed:32686688}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB86501.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L32137; AAA57253.1; -; mRNA. DR EMBL; AB086984; BAC53888.1; -; mRNA. DR EMBL; AK296586; BAG59205.1; -; mRNA. DR EMBL; AC003107; AAB86501.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471106; EAW84737.1; -; Genomic_DNA. DR EMBL; BC110847; AAI10848.1; -; mRNA. DR EMBL; BC125092; AAI25093.1; -; mRNA. DR EMBL; S79499; AAB35269.1; -; Genomic_DNA. DR EMBL; S79500; AAB35270.1; -; Genomic_DNA. DR CCDS; CCDS12385.1; -. [P49747-1] DR RefSeq; NP_000086.2; NM_000095.3. [P49747-1] DR PDB; 3FBY; X-ray; 3.15 A; A/B/C=225-757. DR AlphaFoldDB; P49747; -. DR MDposit; P49747; -. DR SMR; P49747; -. DR BioGRID; 107706; 15. DR ComplexPortal; CPX-1791; Thrombospondin 5 complex. DR FunCoup; P49747; 662. DR IntAct; P49747; 21. DR NDEx; IQUERY-CP-COMP; 5 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000222271; -. DR DrugBank; DB01373; Calcium. DR GlyConnect; P49747; 7 N-Linked glycans (2 sites). DR GlyCosmos; P49747; 2 sites, 18 glycans. DR GlyGen; P49747; 4 sites, 18 N-linked glycans (2 sites), 2 O-linked glycans (2 sites). DR iPTMnet; P49747; -. DR PhosphoSitePlus; P49747; -. DR BioMuta; COMP; -. DR DMDM; 209572601; -. DR jPOST; P49747; -. DR MassIVE; P49747; -. DR PaxDb; 9606-ENSP00000222271; -. DR PeptideAtlas; P49747; -. DR ProteomicsDB; 4464; -. DR ProteomicsDB; 56060; -. [P49747-1] DR Antibodypedia; 15160; 440 antibodies from 33 providers. DR DNASU; 1311; -. DR Ensembl; ENST00000222271.7; ENSP00000222271.2; ENSG00000105664.12. [P49747-1] DR Ensembl; ENST00000425807.1; ENSP00000403792.1; ENSG00000105664.12. [P49747-2] DR GeneID; 1311; -. DR KEGG; hsa:1311; -. DR MANE-Select; ENST00000222271.7; ENSP00000222271.2; NM_000095.3; NP_000086.2. DR UCSC; uc002nke.4; human. [P49747-1] DR AGR; HGNC:2227; -. DR ClinPGx; PA26744; -. DR CTD; 1311; -. DR DisGeNET; 1311; -. DR GeneCards; COMP; -. DR GeneReviews; COMP; -. DR HGNC; HGNC:2227; COMP. DR HPA; ENSG00000105664; Tissue enriched (blood). DR MalaCards; COMP; -. DR MIM; 132400; phenotype. DR MIM; 177170; phenotype. DR MIM; 600310; gene. DR MIM; 619161; phenotype. DR OpenTargets; ENSG00000105664; -. DR Orphanet; 93308; Multiple epiphyseal dysplasia type 1. DR Orphanet; 750; Pseudoachondroplasia. DR VEuPathDB; HostDB:ENSG00000105664; -. DR eggNOG; ENOG502QRK8; Eukaryota. DR GeneTree; ENSGT00940000162169; -. DR InParanoid; P49747; -. DR OMA; ACCNAHP; -. DR OrthoDB; 14563at2759; -. DR PAN-GO; P49747; 1 GO annotation based on evolutionary models. DR PhylomeDB; P49747; -. DR PathwayCommons; P49747; -. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR Reactome; R-HSA-3000178; ECM proteoglycans. DR SignaLink; P49747; -. DR Agora; ENSG00000105664; -. DR BioGRID-ORCS; 1311; 12 hits in 1142 CRISPR screens. DR ChiTaRS; COMP; human. DR EvolutionaryTrace; P49747; -. DR GeneWiki; Cartilage_oligomeric_matrix_protein; -. DR GenomeRNAi; 1311; -. DR Pharos; P49747; Tbio. DR PRO; PR:P49747; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P49747; protein. DR Bgee; ENSG00000105664; Expressed in tibia and 136 other cell types or tissues. DR ExpressionAtlas; P49747; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0140149; C:non-collagenous component of interstitial matrix; TAS:GO_Central. DR GO; GO:1990341; C:thrombospondin complex; TAS:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB. DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB. DR GO; GO:0005201; F:extracellular matrix structural constituent; IBA:GO_Central. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL. DR GO; GO:0043394; F:proteoglycan binding; IDA:MGI. DR GO; GO:0009887; P:animal organ morphogenesis; TAS:ProtInc. DR GO; GO:1990079; P:cartilage homeostasis; IDA:UniProtKB. DR GO; GO:0007155; P:cell adhesion; IEA:InterPro. DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl. DR GO; GO:0060173; P:limb development; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0035989; P:tendon development; IBA:GO_Central. DR CDD; cd00054; EGF_CA; 2. DR CDD; cd16077; TSP-5cc; 1. DR FunFam; 2.10.25.10:FF:000346; Cartilage oligomeric matrix protein; 1. DR FunFam; 4.10.1080.10:FF:000004; Cartilage oligomeric matrix protein; 1. DR FunFam; 2.10.25.10:FF:000025; Thrombospondin 3; 1. DR FunFam; 2.10.25.10:FF:000027; Thrombospondin 3; 1. DR FunFam; 2.60.120.200:FF:000002; Thrombospondin 3; 1. DR FunFam; 4.10.1080.10:FF:000001; Thrombospondin 3; 1. DR FunFam; 1.20.5.10:FF:000001; thrombospondin-3 isoform X2; 1. DR Gene3D; 1.20.5.10; -; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.10.25.10; Laminin; 4. DR Gene3D; 4.10.1080.10; TSP type-3 repeat; 2. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR000742; EGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR049883; NOTCH1_EGF-like. DR InterPro; IPR003367; Thrombospondin_3-like_rpt. DR InterPro; IPR017897; Thrombospondin_3_rpt. DR InterPro; IPR008859; Thrombospondin_C. DR InterPro; IPR039081; TSP-5_CC. DR InterPro; IPR024665; TSP/COMP_CC. DR InterPro; IPR046970; TSP/COMP_CC_sf. DR InterPro; IPR028974; TSP_type-3_rpt. DR PANTHER; PTHR10199:SF88; CARTILAGE OLIGOMERIC MATRIX PROTEIN; 1. DR PANTHER; PTHR10199; THROMBOSPONDIN; 1. DR Pfam; PF11598; COMP; 1. DR Pfam; PF07645; EGF_CA; 2. DR Pfam; PF02412; TSP_3; 5. DR Pfam; PF05735; TSP_C; 1. DR SMART; SM00181; EGF; 4. DR SMART; SM00179; EGF_CA; 3. DR SUPFAM; SSF58006; Assembly domain of cartilage oligomeric matrix protein; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF103647; TSP type-3 repeat; 3. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 3. DR PROSITE; PS01187; EGF_CA; 2. DR PROSITE; PS51234; TSP3; 8. DR PROSITE; PS51236; TSP_CTER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Calcium; Cell adhesion; KW Direct protein sequencing; Disease variant; Disulfide bond; Dwarfism; KW EGF-like domain; Extracellular matrix; Glycoprotein; Heparin-binding; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..757 FT /note="Cartilage oligomeric matrix protein" FT /id="PRO_0000035857" FT DOMAIN 87..126 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 127..179 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 180..222 FT /note="EGF-like 3; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 225..267 FT /note="EGF-like 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT REPEAT 268..300 FT /note="TSP type-3 1" FT REPEAT 301..336 FT /note="TSP type-3 2" FT REPEAT 337..359 FT /note="TSP type-3 3" FT REPEAT 360..395 FT /note="TSP type-3 4" FT REPEAT 396..418 FT /note="TSP type-3 5" FT REPEAT 419..456 FT /note="TSP type-3 6" FT REPEAT 457..492 FT /note="TSP type-3 7" FT REPEAT 493..528 FT /note="TSP type-3 8" FT DOMAIN 532..746 FT /note="TSP C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00635" FT REGION 22..86 FT /note="COMP N-terminal" FT REGION 298..503 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 527..757 FT /note="Mediates cell survival and induction of the IAP FT family of survival proteins" FT MOTIF 367..369 FT /note="Cell attachment site" FT /evidence="ECO:0000255" FT COMPBIAS 334..346 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 352..370 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 467..476 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 77..78 FT /note="Cleavage; by ADAMTS4" FT CARBOHYD 121 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 742 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19276170" FT DISULFID 69 FT /note="Interchain" FT /evidence="ECO:0000305|PubMed:19276170" FT DISULFID 72 FT /note="Interchain" FT /evidence="ECO:0000305|PubMed:19276170" FT DISULFID 91..102 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 96..111 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 114..125 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 131..142 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 136..151 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 154..178 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 184..197 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 191..206 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 209..221 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 229..243 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 237..253 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 255..266 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 282..287 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 292..312 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 328..348 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 351..371 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 387..407 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 410..430 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 448..468 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 484..504 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT DISULFID 520..741 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000269|PubMed:19276170" FT VAR_SEQ 129..181 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055758" FT VARIANT 50 FT /note="E -> D" FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2" FT /id="VAR_016254" FT VARIANT 51 FT /note="L -> W" FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2" FT /id="VAR_016255" FT VARIANT 66 FT /note="V -> E (in CTS2; reduced secretion in tendon cells; FT no effect on secretion in chondrocytes; disrupted FT pentamerization; induced ER stress; dbSNP:rs2055205599)" FT /evidence="ECO:0000269|PubMed:32686688" FT /id="VAR_085230" FT VARIANT 109 FT /note="A -> G" FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2" FT /id="VAR_016257" FT VARIANT 167 FT /note="G -> E (in EDM1; dbSNP:rs763887855)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066789" FT VARIANT 224 FT /note="R -> G" FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2" FT /id="VAR_016258" FT VARIANT 234 FT /note="P -> S (in PSACH; dbSNP:rs557483957)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066790" FT VARIANT 276 FT /note="P -> R (in EDM1; dbSNP:rs1311845746)" FT /evidence="ECO:0000269|PubMed:11565064, FT ECO:0000269|PubMed:21922596" FT /id="VAR_026239" FT VARIANT 285 FT /note="R -> P" FT /evidence="ECO:0000269|PubMed:7713493, ECO:0000269|Ref.2" FT /id="VAR_016261" FT VARIANT 290 FT /note="D -> G (in PSACH; dbSNP:rs1568556118)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066791" FT VARIANT 290 FT /note="D -> N (in PSACH; mild form)" FT /evidence="ECO:0000269|PubMed:9921895" FT /id="VAR_007614" FT VARIANT 298 FT /note="S -> L (in EDM1; phenotypic features overlapping FT with mild PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066792" FT VARIANT 299 FT /note="G -> R (in PSACH; dbSNP:rs2145903238)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_007615" FT VARIANT 311 FT /note="A -> D (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066793" FT VARIANT 317 FT /note="D -> G (in EDM1; atypical form)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066794" FT VARIANT 326 FT /note="D -> G (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066795" FT VARIANT 326 FT /note="D -> Y (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066796" FT VARIANT 328 FT /note="C -> R (in PSACH; mild form; dbSNP:rs137852653)" FT /evidence="ECO:0000269|PubMed:7670472, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007616" FT VARIANT 341..342 FT /note="Missing (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066797" FT VARIANT 342 FT /note="D -> Y (in EDM1; Fairbank type; dbSNP:rs137852652)" FT /evidence="ECO:0000269|PubMed:7670472, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007617" FT VARIANT 348 FT /note="C -> F (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066798" FT VARIANT 348 FT /note="C -> R (in PSACH; dbSNP:rs137852656)" FT /evidence="ECO:0000269|PubMed:11746045" FT /id="VAR_017102" FT VARIANT 349 FT /note="D -> V (in PSACH; mild form)" FT /evidence="ECO:0000269|PubMed:9921895" FT /id="VAR_007618" FT VARIANT 350..372 FT /note="Missing (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066799" FT VARIANT 361 FT /note="D -> V (in EDM1; Fairbank type)" FT /evidence="ECO:0000269|PubMed:9921895" FT /id="VAR_007619" FT VARIANT 361 FT /note="D -> Y (in EDM1; binds less calcium)" FT /evidence="ECO:0000269|PubMed:11084047, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007620" FT VARIANT 367..368 FT /note="Missing (in EDM1)" FT /evidence="ECO:0000269|PubMed:9452026" FT /id="VAR_007621" FT VARIANT 371 FT /note="C -> S (in EDM1; Fairbank type)" FT /evidence="ECO:0000269|PubMed:21922596, FT ECO:0000269|PubMed:9184241" FT /id="VAR_007622" FT VARIANT 371 FT /note="C -> Y (in EDM1; dbSNP:rs1057521130)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066800" FT VARIANT 372 FT /note="Missing (in PSACH)" FT /evidence="ECO:0000269|PubMed:9452026" FT /id="VAR_007623" FT VARIANT 374 FT /note="D -> N (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066801" FT VARIANT 374 FT /note="Missing (in PSACH; mild form)" FT /id="VAR_007624" FT VARIANT 376 FT /note="D -> N (in EDM1; dbSNP:rs1555791556)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066802" FT VARIANT 378 FT /note="D -> V (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066803" FT VARIANT 381 FT /note="R -> C (in dbSNP:rs3179763)" FT /id="VAR_046796" FT VARIANT 385 FT /note="D -> N (in EDM1; atypical form; dbSNP:rs1601054715)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066804" FT VARIANT 385 FT /note="D -> Y (in EDM1; atypical form; dbSNP:rs1601054715)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066805" FT VARIANT 385 FT /note="Missing (in EDM1; dbSNP:rs2145901379)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066806" FT VARIANT 387 FT /note="C -> G (in PSACH; mild form)" FT /evidence="ECO:0000269|PubMed:9921895" FT /id="VAR_007625" FT VARIANT 387 FT /note="C -> R (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066807" FT VARIANT 391..394 FT /note="PNSD -> V (in PSACH)" FT /evidence="ECO:0000269|PubMed:9452026" FT /id="VAR_007626" FT VARIANT 397 FT /note="D -> H (in EDM1; dbSNP:rs1479804676)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066808" FT VARIANT 402..404 FT /note="GIG -> VC (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066809" FT VARIANT 404 FT /note="G -> R (in EDM1; dbSNP:rs2055168912)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066810" FT VARIANT 408 FT /note="D -> Y (in EDM1)" FT /evidence="ECO:0000269|PubMed:9452026" FT /id="VAR_007627" FT VARIANT 410 FT /note="C -> Y (in EDM1; phenotype overlapping with mild FT PSACH; dbSNP:rs2145901300)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066811" FT VARIANT 415 FT /note="N -> K (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066812" FT VARIANT 420 FT /note="D -> A (in EDM1)" FT /evidence="ECO:0000269|PubMed:11565064" FT /id="VAR_026240" FT VARIANT 427 FT /note="G -> E (in EDM1; dbSNP:rs2145901034)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066813" FT VARIANT 430..432 FT /note="CDS -> LWC (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066814" FT VARIANT 440 FT /note="G -> E (in PSACH; mild form; dbSNP:rs2145900919)" FT /evidence="ECO:0000269|PubMed:9463320" FT /id="VAR_007628" FT VARIANT 440 FT /note="G -> R (in PSACH; dbSNP:rs1601053997)" FT /evidence="ECO:0000269|PubMed:21922596, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007629" FT VARIANT 446 FT /note="D -> N (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066815" FT VARIANT 448 FT /note="C -> S (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066816" FT VARIANT 453 FT /note="N -> S (in EDM1; Fairbank type; dbSNP:rs28936668)" FT /evidence="ECO:0000269|PubMed:9463320" FT /id="VAR_007630" FT VARIANT 457 FT /note="Missing (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066817" FT VARIANT 459 FT /note="Missing (in PSACH; severe form; dbSNP:rs2145900868)" FT /evidence="ECO:0000269|PubMed:7670471, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007631" FT VARIANT 468 FT /note="C -> Y (in PSACH; severe form; dbSNP:rs137852651)" FT /evidence="ECO:0000269|PubMed:7670471, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007632" FT VARIANT 469 FT /note="Missing (in PSACH; severe form; MUT3 mutant; most FT common mutation; binds less calcium and causes misfolding FT of the protein; greatly reduced interaction with ACAN; FT reduced interaction with collagen)" FT /evidence="ECO:0000269|PubMed:10852928, FT ECO:0000269|PubMed:11084047, ECO:0000269|PubMed:9452026" FT /id="VAR_007633" FT VARIANT 472 FT /note="D -> Y (in PSACH; severe form; dbSNP:rs137852650)" FT /evidence="ECO:0000269|PubMed:7670471, FT ECO:0000269|PubMed:9452026" FT /id="VAR_007634" FT VARIANT 473 FT /note="D -> DD (in EDM1)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066818" FT VARIANT 473 FT /note="D -> G (in PSACH; severe form; dbSNP:rs28936669)" FT /evidence="ECO:0000269|PubMed:9921895" FT /id="VAR_007635" FT VARIANT 473 FT /note="D -> H (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066819" FT VARIANT 473 FT /note="Missing (in PSACH; severe form; dbSNP:rs193922900)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_007636" FT VARIANT 475 FT /note="D -> N (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066820" FT VARIANT 482 FT /note="D -> G (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596, FT ECO:0000269|PubMed:9452063" FT /id="VAR_007637" FT VARIANT 501 FT /note="G -> D (in EDM1; dbSNP:rs1555791425)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066821" FT VARIANT 507 FT /note="D -> G (in PSACH; dbSNP:rs2145900497)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066822" FT VARIANT 511 FT /note="D -> G (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066823" FT VARIANT 513..516 FT /note="Missing (in PSACH; mild form)" FT /evidence="ECO:0000269|PubMed:9184241" FT /id="VAR_007638" FT VARIANT 515 FT /note="D -> G (in PSACH)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066824" FT VARIANT 518 FT /note="D -> N (in PSACH; mild form; dbSNP:rs1359984033)" FT /evidence="ECO:0000269|PubMed:9921895" FT /id="VAR_007639" FT VARIANT 523 FT /note="N -> K (in EDM1; Ribbing type; dbSNP:rs137852654)" FT /evidence="ECO:0000269|PubMed:21922596, FT ECO:0000269|PubMed:9021009" FT /id="VAR_007640" FT VARIANT 529 FT /note="T -> I (in PSACH; dbSNP:rs312262903)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066825" FT VARIANT 585 FT /note="T -> M (in PSACH; mild form and EDM1; FT dbSNP:rs312262900)" FT /evidence="ECO:0000269|PubMed:11565064, FT ECO:0000269|PubMed:21922596" FT /id="VAR_007641" FT VARIANT 585 FT /note="T -> R (in EDM1 and PSACH; dbSNP:rs312262900)" FT /evidence="ECO:0000269|PubMed:21922596, FT ECO:0000269|PubMed:9463320" FT /id="VAR_007642" FT VARIANT 718 FT /note="R -> P (in EDM1; dbSNP:rs149551600)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066826" FT VARIANT 718 FT /note="R -> W (in EDM1 and CTS2; reduced secretion in FT tendon cells and chondrocytes; dbSNP:rs28936368)" FT /evidence="ECO:0000269|PubMed:21922596, FT ECO:0000269|PubMed:32686688" FT /id="VAR_066827" FT VARIANT 719 FT /note="G -> D (in PSACH; severe; dbSNP:rs137852655)" FT /evidence="ECO:0000269|PubMed:11746044" FT /id="VAR_017103" FT VARIANT 719 FT /note="G -> S (in PSACH; dbSNP:rs312262904)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066828" FT VARIANT 756 FT /note="Q -> R (in a patient with multiple epiphyseal FT dysplasia; dbSNP:rs61752496)" FT /evidence="ECO:0000269|PubMed:21922596" FT /id="VAR_066829" FT CONFLICT 256 FT /note="A -> R (in Ref. 1; AAA57253 and 2; BAC53888)" FT /evidence="ECO:0000305" FT CONFLICT 340 FT /note="D -> Y (in Ref. 7; AAB35270)" FT /evidence="ECO:0000305" FT STRAND 232..234 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 241..245 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 251..255 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 259..265 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 272..274 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 285..287 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 291..295 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 310..312 FT /evidence="ECO:0007829|PDB:3FBY" FT TURN 314..317 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 327..331 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 342..344 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 346..348 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 364..367 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 369..371 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 401..403 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 405..407 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 424..426 FT /evidence="ECO:0007829|PDB:3FBY" FT TURN 428..430 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 443..445 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:3FBY" FT TURN 466..468 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 470..473 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 475..477 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 479..481 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 495..500 FT /evidence="ECO:0007829|PDB:3FBY" FT TURN 503..506 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 511..513 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 515..517 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 532..540 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 551..554 FT /evidence="ECO:0007829|PDB:3FBY" FT TURN 555..558 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 559..562 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 567..588 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 596..605 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 608..617 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 625..627 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 636..641 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 648..655 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 656..658 FT /evidence="ECO:0007829|PDB:3FBY" FT TURN 661..663 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 664..669 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 681..689 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 690..692 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 694..701 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 704..708 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 716..728 FT /evidence="ECO:0007829|PDB:3FBY" FT STRAND 732..741 FT /evidence="ECO:0007829|PDB:3FBY" FT HELIX 748..754 FT /evidence="ECO:0007829|PDB:3FBY" SQ SEQUENCE 757 AA; 82860 MW; A0B73AADB39FBC7B CRC64; MVPDTACVLL LTLAALGASG QGQSPLGSDL GPQMLRELQE TNAALQDVRE LLRQQVREIT FLKNTVMECD ACGMQQSVRT GLPSVRPLLH CAPGFCFPGV ACIQTESGAR CGPCPAGFTG NGSHCTDVNE CNAHPCFPRV RCINTSPGFR CEACPPGYSG PTHQGVGLAF AKANKQVCTD INECETGQHN CVPNSVCINT RGSFQCGPCQ PGFVGDQASG CQRRAQRFCP DGSPSECHEH ADCVLERDGS RSCVCAVGWA GNGILCGRDT DLDGFPDEKL RCPERQCRKD NCVTVPNSGQ EDVDRDGIGD ACDPDADGDG VPNEKDNCPL VRNPDQRNTD EDKWGDACDN CRSQKNDDQK DTDQDGRGDA CDDDIDGDRI RNQADNCPRV PNSDQKDSDG DGIGDACDNC PQKSNPDQAD VDHDFVGDAC DSDQDQDGDG HQDSRDNCPT VPNSAQEDSD HDGQGDACDD DDDNDGVPDS RDNCRLVPNP GQEDADRDGV GDVCQDDFDA DKVVDKIDVC PENAEVTLTD FRAFQTVVLD PEGDAQIDPN WVVLNQGREI VQTMNSDPGL AVGYTAFNGV DFEGTFHVNT VTDDDYAGFI FGYQDSSSFY VVMWKQMEQT YWQANPFRAV AEPGIQLKAV KSSTGPGEQL RNALWHTGDT ESQVRLLWKD PRNVGWKDKK SYRWFLQHRP QVGYIRVRFY EGPELVADSN VVLDTTMRGG RLGVFCFSQE NIIWANLRYR CNDTIPEDYE THQLRQA //