BMP1_HUMAN
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 03-AUG-2022, entry version 233.
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:33169406, PubMed:32636307). 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;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01211,
CC 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=2; 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 connective tissue disorder
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, borderline osteoporosis, severe bone
CC deformity, and recurrent fractures affecting both upper and lower
CC limbs. {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}.
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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; 142.
DR DIP; DIP-33403N; -.
DR ELM; P13497; -.
DR IntAct; P13497; 55.
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 GlyGen; P13497; 5 sites, 4 N-linked glycans (2 sites).
DR iPTMnet; P13497; -.
DR PhosphoSitePlus; P13497; -.
DR BioMuta; BMP1; -.
DR DMDM; 13124688; -.
DR EPD; P13497; -.
DR jPOST; P13497; -.
DR MassIVE; P13497; -.
DR MaxQB; P13497; -.
DR PaxDb; P13497; -.
DR PeptideAtlas; P13497; -.
DR PRIDE; 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 Antibodypedia; 2912; 309 antibodies from 36 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 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; 170905at2759; -.
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 1079 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 156 other tissues.
DR ExpressionAtlas; P13497; baseline and differential.
DR Genevisible; P13497; HS.
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; cd04281; ZnMc_BMP1_TLD; 1.
DR Gene3D; 2.60.120.290; -; 5.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR029837; BMP-1.
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; IPR001506; Peptidase_M12A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR InterPro; IPR034036; ZnMP_TLD/BMP1.
DR PANTHER; PTHR45645:SF24; PTHR45645:SF24; 1.
DR Pfam; PF01400; Astacin; 1.
DR Pfam; PF00431; CUB; 5.
DR Pfam; PF07645; EGF_CA; 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; SSF49854; SSF49854; 5.
DR SUPFAM; SSF57184; SSF57184; 1.
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; Reference proteome; Repeat; Secreted;
KW 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 BMP1-
FT 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 I C-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
