ID BMP1_HUMAN Reviewed; 986 AA. AC P13497; A8K6F5; B2RN46; D3DSR0; Q13292; Q13872; Q14874; Q99421; Q99422; AC Q99423; Q9UL38; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 21-FEB-2001, sequence version 2. DT 02-OCT-2024, entry version 244. DE RecName: Full=Bone morphogenetic protein 1; DE Short=BMP-1; DE EC=3.4.24.19; DE AltName: Full=Mammalian tolloid protein; DE Short=mTld; DE AltName: Full=Procollagen C-proteinase; DE Short=PCP; DE Flags: Precursor; GN Name=BMP1; Synonyms=PCOLC; 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 BMP1-3). RC TISSUE=Skin; RX PubMed=8643539; DOI=10.1073/pnas.93.10.5127; RA Li S.W., Sieron A.L., Fertala A., Hojima Y., Arnold W.V., Prockop D.J.; RT "The C-proteinase that processes procollagens to fibrillar collagens is RT identical to the protein previously identified as bone morphogenic protein- RT 1."; RL Proc. Natl. Acad. Sci. U.S.A. 93:5127-5130(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BMP1-1). RX PubMed=3201241; DOI=10.1126/science.3201241; RA Wozney J.M., Rosen V., Celeste A.J., Mitsock L.M., Whitters M.J., RA Kriz R.W., Hewick R.M., Wang E.A.; RT "Novel regulators of bone formation: molecular clones and activities."; RL Science 242:1528-1534(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BMP1-4; BMP1-5 AND BMP1-6). RC TISSUE=Placenta; RX PubMed=9500680; DOI=10.1007/s001090050202; RA Janitz M., Heiser V., Boettcher U., Landt O., Lauster R.; RT "Three alternatively spliced variants of the gene coding for the human bone RT morphogenetic protein-1."; RL J. Mol. Med. 76:141-146(1998). RN [4] RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS BMP1-3 AND BMP1-7). RC TISSUE=Placenta; RX PubMed=7798260; DOI=10.1016/s0021-9258(18)31672-7; RA Takahara K., Lyons G.E., Greenspan D.S.; RT "Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are RT encoded by alternatively spliced transcripts which are differentially RT expressed in some tissues."; RL J. Biol. Chem. 269:32572-32578(1994). 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BMP1-5). RC TISSUE=Placenta; 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BMP1-3). RC TISSUE=Brain; 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 [8] RP DISULFIDE BOND AT 183-CYS--CYS-186. RX PubMed=11283002; DOI=10.1074/jbc.m010814200; RA Garrigue-Antar L., Barker C., Kadler K.E.; RT "Identification of amino acid residues in bone morphogenetic protein-1 RT important for procollagen C-proteinase activity."; RL J. Biol. Chem. 276:26237-26242(2001). RN [9] RP SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND MUTAGENESIS OF RP 119-ARG--ARG-120. RX PubMed=12637569; DOI=10.1074/jbc.m213021200; RA Leighton M., Kadler K.E.; RT "Paired basic/Furin-like proprotein convertase cleavage of Pro-BMP-1 in the RT trans-Golgi network."; RL J. Biol. Chem. 278:18478-18484(2003). RN [10] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [11] RP FUNCTION (ISOFORM BMP1-3), AND SUBCELLULAR LOCATION (ISOFORM BMP1-3). RX PubMed=21453682; DOI=10.1016/j.bbrc.2011.03.109; RA Grgurevic L., Macek B., Mercep M., Jelic M., Smoljanovic T., Erjavec I., RA Dumic-Cule I., Prgomet S., Durdevic D., Vnuk D., Lipar M., Stejskal M., RA Kufner V., Brkljacic J., Maticic D., Vukicevic S.; RT "Bone morphogenetic protein (BMP)1-3 enhances bone repair."; RL Biochem. Biophys. Res. Commun. 408:25-31(2011). RN [12] RP FUNCTION. RX PubMed=31152061; DOI=10.1074/jbc.ra119.007806; RA Rosell-Garcia T., Paradela A., Bravo G., Dupont L., Bekhouche M., RA Colige A., Rodriguez-Pascual F.; RT "Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and RT ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain."; RL J. Biol. Chem. 294:11087-11100(2019). RN [13] RP FUNCTION. RX PubMed=32636307; DOI=10.1126/scisignal.aba3880; RA Anastasi C., Rousselle P., Talantikite M., Tessier A., Cluzel C., RA Bachmann A., Mariano N., Dussoyer M., Alcaraz L.B., Fortin L., Aubert A., RA Delolme F., El Kholti N., Armengaud J., Fournie P., Auxenfans C., RA Valcourt U., Goff S.V., Moali C.; RT "BMP-1 disrupts cell adhesion and enhances TGF-beta activation through RT cleavage of the matricellular protein thrombospondin-1."; RL Sci. Signal. 13:0-0(2020). RN [14] RP FUNCTION. RX PubMed=33169406; DOI=10.1002/jper.20-0354; RA Wang J., Xie X., Muench N.A., Massoudi D., Xu C., Greenspan D.S., RA Feng J.Q.; RT "Proteinase bone morphogenetic protein 1, but not tolloid-like 1, plays a RT dominant role in maintaining periodontal homeostasis."; RL J. Periodontology 92:1018-1029(2021). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=33206546; DOI=10.1152/ajpcell.00012.2020; RA N'Diaye E.N., Cook R., Wang H., Wu P., LaCanna R., Wu C., Ye Z., RA Seshasayee D., Hazen M., Lin W., Tyagi T., Hotzel I., Tam L., Newman R., RA Roose-Girma M., Wolters P.J., Ding N.; RT "Extracellular BMP1 is the major proteinase for COOH-terminal proteolysis RT of type I procollagen in lung fibroblasts."; RL Am. J. Physiol. 320:162-174(2021). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 121-321 IN COMPLEX WITH ZINC RP IONS, ZINC-BINDING SITES, COFACTOR, ACTIVE SITE, AND DISULFIDE BONDS. RX PubMed=18824173; DOI=10.1016/j.jmb.2008.09.029; RA Mac Sweeney A., Gil-Parrado S., Vinzenz D., Bernardi A., Hein A., RA Bodendorf U., Erbel P., Logel C., Gerhartz B.; RT "Structural basis for the substrate specificity of bone morphogenetic RT protein 1/tolloid-like metalloproteases."; RL J. Mol. Biol. 384:228-239(2008). RN [17] RP VARIANT [LARGE SCALE ANALYSIS] HIS-45. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [18] RP VARIANT OI13 ARG-12, CHARACTERIZATION OF VARIANT OI13 ARG-12, AND RP INVOLVEMENT IN OI13. RX PubMed=22482805; DOI=10.1016/j.ajhg.2012.02.026; RA Asharani P.V., Keupp K., Semler O., Wang W., Li Y., Thiele H., Yigit G., RA Pohl E., Becker J., Frommolt P., Sonntag C., Altmuller J., Zimmermann K., RA Greenspan D.S., Akarsu N.A., Netzer C., Schonau E., Wirth R., RA Hammerschmidt M., Nurnberg P., Wollnik B., Carney T.J.; RT "Attenuated BMP1 function compromises osteogenesis, leading to bone RT fragility in humans and zebrafish."; RL Am. J. Hum. Genet. 90:661-674(2012). RN [19] RP VARIANT OI13 LEU-249, AND CHARACTERIZATION OF VARIANT OI13 LEU-249. RX PubMed=22052668; DOI=10.1002/humu.21647; RA Martinez-Glez V., Valencia M., Caparros-Martin J.A., Aglan M., Temtamy S., RA Tenorio J., Pulido V., Lindert U., Rohrbach M., Eyre D., Giunta C., RA Lapunzina P., Ruiz-Perez V.L.; RT "Identification of a mutation causing deficient BMP1/mTLD proteolytic RT activity in autosomal recessive osteogenesis imperfecta."; RL Hum. Mutat. 33:343-350(2012). RN [20] RP VARIANT OI13 VAL-270, AND CHARACTERIZATION OF VARIANT OI13 VAL-270. RX PubMed=25402547; DOI=10.1002/humu.22731; RA Cho S.Y., Asharani P.V., Kim O.H., Iida A., Miyake N., Matsumoto N., RA Nishimura G., Ki C.S., Hong G., Kim S.J., Sohn Y.B., Park S.W., Lee J., RA Kwun Y., Carney T.J., Huh R., Ikegawa S., Jin D.K.; RT "Identification and in vivo functional characterization of novel compound RT heterozygous BMP1 variants in osteogenesis imperfecta."; RL Hum. Mutat. 36:191-195(2015). CC -!- FUNCTION: Metalloprotease that plays key roles in regulating the CC formation of the extracellular matrix (ECM) via processing of various CC precursor proteins into mature functional enzymes or structural CC proteins (PubMed:33206546). Thereby participates in several CC developmental and physiological processes such as cartilage and bone CC formation, muscle growth and homeostasis, wound healing and tissue CC repair (PubMed:32636307, PubMed:33169406). Roles in ECM formation CC include cleavage of the C-terminal propeptides from procollagens such CC as procollagen I, II and III or the proteolytic activation of the CC enzyme lysyl oxidase LOX, necessary to formation of covalent cross- CC links in collagen and elastic fibers (PubMed:31152061, CC PubMed:33206546). Additional substrates include matricellular CC thrombospondin-1/THBS1 whose cleavage leads to cell adhesion disruption CC and TGF-beta activation (PubMed:32636307). CC {ECO:0000269|PubMed:31152061, ECO:0000269|PubMed:32636307, CC ECO:0000269|PubMed:33169406, ECO:0000269|PubMed:33206546}. CC -!- FUNCTION: [Isoform BMP1-3]: Plays an important role in bone repair by CC acting as a coactivator of BMP7. {ECO:0000269|PubMed:21453682}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Cleavage of the C-terminal propeptide at Ala-|-Asp in type I CC and II procollagens and at Arg-|-Asp in type III.; EC=3.4.24.19; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU01211, ECO:0000269|PubMed:18824173}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE- CC ProRule:PRU01211, ECO:0000269|PubMed:18824173}; CC -!- ACTIVITY REGULATION: Activity is increased by the procollagen C- CC endopeptidase enhancer protein. CC -!- SUBUNIT: Interacts with POSTN, the interaction promotes deposition on CC the extracellular matrix. {ECO:0000250}. CC -!- INTERACTION: CC P13497; P13497: BMP1; NbExp=4; IntAct=EBI-489827, EBI-489827; CC P13497; Q9H2X0: CHRD; NbExp=2; IntAct=EBI-489827, EBI-947551; CC P13497; P20908: COL5A1; NbExp=2; IntAct=EBI-489827, EBI-2464511; CC P13497; O14793: MSTN; NbExp=3; IntAct=EBI-489827, EBI-8542977; CC P13497; Q15113: PCOLCE; NbExp=3; IntAct=EBI-489827, EBI-8869614; CC P13497-2; P07585: DCN; NbExp=2; IntAct=EBI-12509497, EBI-9663608; CC P13497-2; P97299: Sfrp2; Xeno; NbExp=2; IntAct=EBI-12509497, EBI-15892646; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network CC {ECO:0000269|PubMed:12637569}. Secreted, extracellular space, CC extracellular matrix {ECO:0000269|PubMed:12637569}. Secreted CC {ECO:0000269|PubMed:33206546}. Note=Co-localizes with POSTN in the CC Golgi. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform BMP1-3]: Secreted CC {ECO:0000269|PubMed:21453682}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=BMP1-3; CC IsoId=P13497-1; Sequence=Displayed; CC Name=BMP1-1; CC IsoId=P13497-2; Sequence=VSP_005461, VSP_005462; CC Name=BMP1-2; CC IsoId=P13497-7; Sequence=Not described; CC Name=BMP1-4; CC IsoId=P13497-3; Sequence=VSP_005463, VSP_005464; CC Name=BMP1-5; CC IsoId=P13497-4; Sequence=VSP_005465, VSP_005466; CC Name=BMP1-6; CC IsoId=P13497-5; Sequence=VSP_005467, VSP_005468; CC Name=BMP1-7; CC IsoId=P13497-6; Sequence=VSP_005469, VSP_005470; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- PTM: Proteolytically activated in the trans-Golgi network by furin- CC like/paired basic proprotein convertases, cleavage is not required for CC secretion. {ECO:0000269|PubMed:12637569}. CC -!- DISEASE: Osteogenesis imperfecta 13 (OI13) [MIM:614856]: An autosomal CC recessive form of osteogenesis imperfecta, a disorder of bone formation CC characterized by low bone mass, bone fragility and susceptibility to CC fractures after minimal trauma. Disease severity ranges from very mild CC forms without fractures to intrauterine fractures and perinatal CC lethality. Extraskeletal manifestations, which affect a variable number CC of patients, are dentinogenesis imperfecta, hearing loss, and blue CC sclerae. OI13 is characterized by normal teeth, faint blue sclerae, CC severe growth deficiency, severe bone deformity, and recurrent CC fractures affecting both upper and lower limbs. CC {ECO:0000269|PubMed:22052668, ECO:0000269|PubMed:22482805, CC ECO:0000269|PubMed:25402547}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform BMP1-4]: May be produced at very low levels due CC to a premature stop codon in the mRNA, leading to nonsense-mediated CC mRNA decay. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform BMP1-5]: May be produced at very low levels due CC to a premature stop codon in the mRNA, leading to nonsense-mediated CC mRNA decay. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform BMP1-6]: May be produced at very low levels due CC to a premature stop codon in the mRNA, leading to nonsense-mediated CC mRNA decay. {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; U50330; AAA93462.1; -; mRNA. DR EMBL; M22488; AAA51833.1; -; mRNA. DR EMBL; Y08723; CAA69973.1; -; mRNA. DR EMBL; Y08724; CAA69974.1; -; mRNA. DR EMBL; Y08725; CAA69975.1; -; mRNA. DR EMBL; L35278; AAC41703.1; -; mRNA. DR EMBL; L35279; AAC41710.1; -; mRNA. DR EMBL; AK291620; BAF84309.1; -; mRNA. DR EMBL; CH471080; EAW63698.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63703.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63704.1; -; Genomic_DNA. DR EMBL; BC136679; AAI36680.1; -; mRNA. DR CCDS; CCDS34856.1; -. [P13497-2] DR CCDS; CCDS6026.1; -. [P13497-1] DR PIR; A37278; BMHU1. DR PIR; A58788; A58788. DR PIR; B58788; B58788. DR RefSeq; NP_001190.1; NM_001199.3. [P13497-2] DR RefSeq; NP_006120.1; NM_006129.4. [P13497-1] DR RefSeq; XP_011542919.1; XM_011544617.1. DR RefSeq; XP_016869227.1; XM_017013738.1. DR PDB; 3EDG; X-ray; 1.27 A; A=121-321. DR PDB; 3EDH; X-ray; 1.25 A; A=121-321. DR PDB; 6BSL; X-ray; 1.45 A; A/B=121-321. DR PDB; 6BSM; X-ray; 2.33 A; A=121-320. DR PDB; 6BTN; X-ray; 2.05 A; A/B=121-321. DR PDB; 6BTO; X-ray; 2.05 A; A/B=121-321. DR PDB; 6BTP; X-ray; 1.93 A; A/B=121-320. DR PDB; 6BTQ; X-ray; 1.75 A; A/B=121-321. DR PDBsum; 3EDG; -. DR PDBsum; 3EDH; -. DR PDBsum; 6BSL; -. DR PDBsum; 6BSM; -. DR PDBsum; 6BTN; -. DR PDBsum; 6BTO; -. DR PDBsum; 6BTP; -. DR PDBsum; 6BTQ; -. DR AlphaFoldDB; P13497; -. DR SMR; P13497; -. DR BioGRID; 107117; 145. DR DIP; DIP-33403N; -. DR ELM; P13497; -. DR IntAct; P13497; 108. DR MINT; P13497; -. DR STRING; 9606.ENSP00000305714; -. DR BindingDB; P13497; -. DR ChEMBL; CHEMBL3898; -. DR GuidetoPHARMACOLOGY; 2333; -. DR MEROPS; M12.005; -. DR GlyConnect; 1045; 5 N-Linked glycans (2 sites). DR GlyCosmos; P13497; 5 sites, 4 glycans. DR GlyGen; P13497; 7 sites, 4 N-linked glycans (2 sites), 1 O-linked glycan (2 sites). DR iPTMnet; P13497; -. DR PhosphoSitePlus; P13497; -. DR BioMuta; BMP1; -. DR DMDM; 13124688; -. DR jPOST; P13497; -. DR MassIVE; P13497; -. DR PaxDb; 9606-ENSP00000305714; -. DR PeptideAtlas; P13497; -. DR ProteomicsDB; 52914; -. [P13497-1] DR ProteomicsDB; 52915; -. [P13497-2] DR ProteomicsDB; 52916; -. [P13497-3] DR ProteomicsDB; 52917; -. [P13497-4] DR ProteomicsDB; 52918; -. [P13497-5] DR ProteomicsDB; 52919; -. [P13497-6] DR Pumba; P13497; -. DR Antibodypedia; 2912; 354 antibodies from 37 providers. DR DNASU; 649; -. DR Ensembl; ENST00000306349.13; ENSP00000306121.8; ENSG00000168487.20. [P13497-2] DR Ensembl; ENST00000306385.10; ENSP00000305714.5; ENSG00000168487.20. [P13497-1] DR Ensembl; ENST00000471755.5; ENSP00000428665.1; ENSG00000168487.20. [P13497-4] DR Ensembl; ENST00000520970.5; ENSP00000428332.1; ENSG00000168487.20. [P13497-2] DR Ensembl; ENST00000521385.5; ENSP00000430406.1; ENSG00000168487.20. [P13497-5] DR GeneID; 649; -. DR KEGG; hsa:649; -. DR MANE-Select; ENST00000306385.10; ENSP00000305714.5; NM_006129.5; NP_006120.1. DR UCSC; uc003xbb.4; human. [P13497-1] DR AGR; HGNC:1067; -. DR CTD; 649; -. DR DisGeNET; 649; -. DR GeneCards; BMP1; -. DR HGNC; HGNC:1067; BMP1. DR HPA; ENSG00000168487; Low tissue specificity. DR MalaCards; BMP1; -. DR MIM; 112264; gene. DR MIM; 614856; phenotype. DR neXtProt; NX_P13497; -. DR OpenTargets; ENSG00000168487; -. DR Orphanet; 314029; High bone mass osteogenesis imperfecta. DR Orphanet; 216812; Osteogenesis imperfecta type 3. DR PharmGKB; PA25377; -. DR VEuPathDB; HostDB:ENSG00000168487; -. DR eggNOG; KOG3714; Eukaryota. DR GeneTree; ENSGT00940000157176; -. DR HOGENOM; CLU_005140_0_0_1; -. DR InParanoid; P13497; -. DR OMA; RTVQTIN; -. DR OrthoDB; 2873870at2759; -. DR PhylomeDB; P13497; -. DR TreeFam; TF314351; -. DR BRENDA; 2.7.11.4; 2681. DR BRENDA; 3.4.24.19; 2681. DR BRENDA; 3.4.24.21; 2681. DR PathwayCommons; P13497; -. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR Reactome; R-HSA-2214320; Anchoring fibril formation. DR Reactome; R-HSA-2243919; Crosslinking of collagen fibrils. DR Reactome; R-HSA-8963896; HDL assembly. [P13497-3] DR SignaLink; P13497; -. DR SIGNOR; P13497; -. DR BioGRID-ORCS; 649; 9 hits in 1159 CRISPR screens. DR ChiTaRS; BMP1; human. DR EvolutionaryTrace; P13497; -. DR GeneWiki; Bone_morphogenetic_protein_1; -. DR GenomeRNAi; 649; -. DR Pharos; P13497; Tchem. DR PRO; PR:P13497; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; P13497; protein. DR Bgee; ENSG00000168487; Expressed in stromal cell of endometrium and 158 other cell types or tissues. DR ExpressionAtlas; P13497; baseline and differential. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0031982; C:vesicle; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central. DR GO; GO:0008237; F:metallopeptidase activity; NAS:UniProtKB. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0001502; P:cartilage condensation; TAS:ProtInc. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0030199; P:collagen fibril organization; TAS:Reactome. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IBA:GO_Central. DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW. DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:MGI. DR GO; GO:0016485; P:protein processing; IBA:GO_Central. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR CDD; cd00041; CUB; 5. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd04281; ZnMc_BMP1_TLD; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 2.10.25.10; Laminin; 2. DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 5. DR InterPro; IPR015446; BMP_1/tolloid-like. DR InterPro; IPR000859; CUB_dom. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR049883; NOTCH1_EGF-like. DR InterPro; IPR001506; Peptidase_M12A. DR InterPro; IPR006026; Peptidase_Metallo. DR InterPro; IPR035914; Sperma_CUB_dom_sf. DR InterPro; IPR034036; ZnMP_TLD/BMP1. DR PANTHER; PTHR24255; COMPLEMENT COMPONENT 1, S SUBCOMPONENT-RELATED; 1. DR PANTHER; PTHR24255:SF34; CUB AND SUSHI DOMAIN-CONTAINING PROTEIN 3 ISOFORM X1; 1. DR Pfam; PF01400; Astacin; 1. DR Pfam; PF00431; CUB; 5. DR Pfam; PF07645; EGF_CA; 1. DR Pfam; PF14670; FXa_inhibition; 1. DR PIRSF; PIRSF001199; BMP_1/tolloid-like; 1. DR PRINTS; PR00480; ASTACIN. DR SMART; SM00042; CUB; 5. DR SMART; SM00181; EGF; 2. DR SMART; SM00179; EGF_CA; 2. DR SMART; SM00235; ZnMc; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 5. DR PROSITE; PS51864; ASTACIN; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 2. DR PROSITE; PS01180; CUB; 5. DR PROSITE; PS01186; EGF_2; 2. DR PROSITE; PS50026; EGF_3; 2. DR PROSITE; PS01187; EGF_CA; 2. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Chondrogenesis; KW Cleavage on pair of basic residues; Cytokine; Developmental protein; KW Differentiation; Disease variant; Disulfide bond; EGF-like domain; KW Extracellular matrix; Glycoprotein; Golgi apparatus; Growth factor; KW Hydrolase; Metal-binding; Metalloprotease; Methylation; Osteogenesis; KW Osteogenesis imperfecta; Protease; Proteomics identification; KW Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT PROPEP 23..120 FT /evidence="ECO:0000269|PubMed:12637569" FT /id="PRO_0000028889" FT CHAIN 121..986 FT /note="Bone morphogenetic protein 1" FT /id="PRO_0000028890" FT DOMAIN 121..320 FT /note="Peptidase M12A" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211" FT DOMAIN 322..434 FT /note="CUB 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DOMAIN 435..546 FT /note="CUB 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DOMAIN 547..588 FT /note="EGF-like 1; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 591..703 FT /note="CUB 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DOMAIN 704..743 FT /note="EGF-like 2; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 747..859 FT /note="CUB 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DOMAIN 860..976 FT /note="CUB 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT REGION 83..125 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 85..106 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 214 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT BINDING 213 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT BINDING 217 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT BINDING 223 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT MOD_RES 934 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9WVM6" FT MOD_RES 937 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9WVM6" FT CARBOHYD 91 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 142 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 332 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 363 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 599 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 163..319 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT DISULFID 183..205 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT DISULFID 185..186 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01211, FT ECO:0000269|PubMed:18824173" FT DISULFID 322..348 FT /evidence="ECO:0000250" FT DISULFID 375..397 FT /evidence="ECO:0000250" FT DISULFID 435..461 FT /evidence="ECO:0000250" FT DISULFID 488..510 FT /evidence="ECO:0000250" FT DISULFID 551..563 FT /evidence="ECO:0000250" FT DISULFID 559..572 FT /evidence="ECO:0000250" FT DISULFID 574..587 FT /evidence="ECO:0000250" FT DISULFID 591..617 FT /evidence="ECO:0000250" FT DISULFID 644..666 FT /evidence="ECO:0000250" FT DISULFID 707..718 FT /evidence="ECO:0000250" FT DISULFID 714..727 FT /evidence="ECO:0000250" FT DISULFID 729..742 FT /evidence="ECO:0000250" FT DISULFID 747..773 FT /evidence="ECO:0000250" FT DISULFID 800..822 FT /evidence="ECO:0000250" FT DISULFID 860..890 FT /evidence="ECO:0000250" FT DISULFID 917..939 FT /evidence="ECO:0000250" FT VAR_SEQ 245..302 FT /note="QEYNFLKMEPQEVESLGETYDFDSIMHYARNTFSRGIFLDTIVPKYEVNGVK FT PPIGQR -> VLHSSLLLLSCGSRNGASFPCSLESSTHQALCWTGLFLRPSPFPRLPLA FT APRTLRAGV (in isoform BMP1-4)" FT /evidence="ECO:0000303|PubMed:9500680" FT /id="VSP_005463" FT VAR_SEQ 303..986 FT /note="Missing (in isoform BMP1-4)" FT /evidence="ECO:0000303|PubMed:9500680" FT /id="VSP_005464" FT VAR_SEQ 589..622 FT /note="AACGGFLTKLNGSITSPGWPKEYPPNKNCIWQLV -> GCYDLQVGKPLLWD FT RHCFRLSTHGPEMLGTALRG (in isoform BMP1-5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9500680" FT /id="VSP_005465" FT VAR_SEQ 623..986 FT /note="Missing (in isoform BMP1-5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9500680" FT /id="VSP_005466" FT VAR_SEQ 703..823 FT /note="DKDECSKDNGGCQQDCVNTFGSYECQCRSGFVLHDNKHDCKEAGCDHKVTST FT SGTITSPNWPDKYPSKKECTWAISSTPGHRVKLTFMEMDIESQPECAYDHLEVFDGRDA FT KAPVLGRFCG -> VLEGAGDRHSHLSGLELLLCPHALVDTVPAPPSALHGDTHAHTHT FT HVHTHCPIAQETCRGPPLGASRLSPQGPGHLTLAPQEGSYLDFWDTHRGDPKPRRRRKS FT LKTFSLTPATFRGIWAL (in isoform BMP1-7)" FT /evidence="ECO:0000305" FT /id="VSP_005469" FT VAR_SEQ 703..730 FT /note="DKDECSKDNGGCQQDCVNTFGSYECQCR -> EKRPALQPPRGRPHQLKFRV FT QKRNRTPQ (in isoform BMP1-1)" FT /evidence="ECO:0000303|PubMed:3201241" FT /id="VSP_005461" FT VAR_SEQ 703..717 FT /note="DKDECSKDNGGCQQD -> GGELFGLLGHPPRRP (in isoform FT BMP1-6)" FT /evidence="ECO:0000303|PubMed:9500680" FT /id="VSP_005467" FT VAR_SEQ 718..986 FT /note="Missing (in isoform BMP1-6)" FT /evidence="ECO:0000303|PubMed:9500680" FT /id="VSP_005468" FT VAR_SEQ 731..986 FT /note="Missing (in isoform BMP1-1)" FT /evidence="ECO:0000303|PubMed:3201241" FT /id="VSP_005462" FT VAR_SEQ 824..986 FT /note="Missing (in isoform BMP1-7)" FT /evidence="ECO:0000305" FT /id="VSP_005470" FT VARIANT 12 FT /note="G -> R (in OI13; the mutation leads to severely FT reduced post-translational N-glycosylation of the protein FT and impairs protein secretion; leads to both reduced FT secretion and subsequent reduced processing of the FT substrates CHRD and COL1A1; dbSNP:rs318240762)" FT /evidence="ECO:0000269|PubMed:22482805" FT /id="VAR_069096" FT VARIANT 45 FT /note="D -> H (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036141" FT VARIANT 249 FT /note="F -> L (in OI13; leads to a protein with deficient FT procollagen IC-terminal propeptide proteolytic activity; FT dbSNP:rs398122891)" FT /evidence="ECO:0000269|PubMed:22052668" FT /id="VAR_067224" FT VARIANT 270 FT /note="M -> V (in OI13; partial loss of activity; FT dbSNP:rs786205219)" FT /evidence="ECO:0000269|PubMed:25402547" FT /id="VAR_072248" FT VARIANT 719 FT /note="V -> I (in dbSNP:rs11996036)" FT /id="VAR_051584" FT MUTAGEN 119..120 FT /note="RR->AA: Doesn't abolish secretion." FT /evidence="ECO:0000269|PubMed:12637569" FT CONFLICT 748 FT /note="D -> N (in Ref. 4; AAC41710)" FT /evidence="ECO:0000305" FT CONFLICT 934 FT /note="R -> S (in Ref. 4; AAC41710)" FT /evidence="ECO:0000305" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:6BTP" FT HELIX 126..128 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 131..133 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 134..139 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 145..161 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 165..168 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 173..180 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:6BSL" FT STRAND 194..201 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 208..219 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 224..226 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 230..232 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 234..236 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 238..240 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 246..249 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:3EDH" FT TURN 274..277 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:3EDH" FT STRAND 285..290 FT /evidence="ECO:0007829|PDB:3EDH" FT HELIX 307..316 FT /evidence="ECO:0007829|PDB:3EDH" SQ SEQUENCE 986 AA; 111249 MW; F89201913AC3CBEA CRC64; MPGVARLPLL LGLLLLPRPG RPLDLADYTY DLAEEDDSEP LNYKDPCKAA AFLGDIALDE EDLRAFQVQQ AVDLRRHTAR KSSIKAAVPG NTSTPSCQST NGQPQRGACG RWRGRSRSRR AATSRPERVW PDGVIPFVIG GNFTGSQRAV FRQAMRHWEK HTCVTFLERT DEDSYIVFTY RPCGCCSYVG RRGGGPQAIS IGKNCDKFGI VVHELGHVVG FWHEHTRPDR DRHVSIVREN IQPGQEYNFL KMEPQEVESL GETYDFDSIM HYARNTFSRG IFLDTIVPKY EVNGVKPPIG QRTRLSKGDI AQARKLYKCP ACGETLQDST GNFSSPEYPN GYSAHMHCVW RISVTPGEKI ILNFTSLDLY RSRLCWYDYV EVRDGFWRKA PLRGRFCGSK LPEPIVSTDS RLWVEFRSSS NWVGKGFFAV YEAICGGDVK KDYGHIQSPN YPDDYRPSKV CIWRIQVSEG FHVGLTFQSF EIERHDSCAY DYLEVRDGHS ESSTLIGRYC GYEKPDDIKS TSSRLWLKFV SDGSINKAGF AVNFFKEVDE CSRPNRGGCE QRCLNTLGSY KCSCDPGYEL APDKRRCEAA CGGFLTKLNG SITSPGWPKE YPPNKNCIWQ LVAPTQYRIS LQFDFFETEG NDVCKYDFVE VRSGLTADSK LHGKFCGSEK PEVITSQYNN MRVEFKSDNT VSKKGFKAHF FSDKDECSKD NGGCQQDCVN TFGSYECQCR SGFVLHDNKH DCKEAGCDHK VTSTSGTITS PNWPDKYPSK KECTWAISST PGHRVKLTFM EMDIESQPEC AYDHLEVFDG RDAKAPVLGR FCGSKKPEPV LATGSRMFLR FYSDNSVQRK GFQASHATEC GGQVRADVKT KDLYSHAQFG DNNYPGGVDC EWVIVAEEGY GVELVFQTFE VEEETDCGYD YMELFDGYDS TAPRLGRYCG SGPPEEVYSA GDSVLVKFHS DDTITKKGFH LRYTSTKFQD TLHSRK //