ID   BMP1_MOUSE              Reviewed;         991 AA.
AC   P98063; Q6NZM2;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 2.
DT   27-MAR-2024, entry version 192.
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;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryo;
RX   PubMed=8174772; DOI=10.1006/dbio.1994.1133;
RA   Fukagawa M., Noboru S., Hogan B.L.M., Jones C.M.;
RT   "Embryonic expression of mouse bone morphogenetic protein-1 (BMP-1), which
RT   is related to the Drosophila dorsoventral gene tolloid and encodes a
RT   putative astacin metalloendopeptidase.";
RL   Dev. Biol. 163:175-183(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; 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   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=8951074; DOI=10.1242/dev.122.11.3587;
RA   Suzuki N., Labosky P.A., Furuta Y., Hargett L., Dunn R., Fogo A.B.,
RA   Takahara K., Peters D.M., Greenspan D.S., Hogan B.L.;
RT   "Failure of ventral body wall closure in mouse embryos lacking a
RT   procollagen C-proteinase encoded by Bmp1, a mammalian gene related to
RT   Drosophila tolloid.";
RL   Development 122:3587-3595(1996).
RN   [5]
RP   FUNCTION, INTERACTION WITH POSTN, AND SUBCELLULAR LOCATION.
RX   PubMed=20181949; DOI=10.1074/jbc.m109.088864;
RA   Maruhashi T., Kii I., Saito M., Kudo A.;
RT   "Interaction between periostin and BMP-1 promotes proteolytic activation of
RT   lysyl oxidase.";
RL   J. Biol. Chem. 285:13294-13303(2010).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=24419319; DOI=10.1093/hmg/ddu013;
RA   Muir A.M., Ren Y., Butz D.H., Davis N.A., Blank R.D., Birk D.E., Lee S.J.,
RA   Rowe D., Feng J.Q., Greenspan D.S.;
RT   "Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in
RT   mice.";
RL   Hum. Mol. Genet. 23:3085-3101(2014).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=28068493; DOI=10.1177/0022034516686558;
RA   Wang J., Massoudi D., Ren Y., Muir A.M., Harris S.E., Greenspan D.S.,
RA   Feng J.Q.;
RT   "BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis.";
RL   J. Dent. Res. 96:578-585(2017).
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. Thereby participates in several developmental and
CC       physiological processes such as cartilage and bone formation, muscle
CC       growth and homeostasis, wound healing and tissue repair
CC       (PubMed:24419319, PubMed:8951074, PubMed:28068493). Roles in ECM
CC       formation include cleavage of the C-terminal propeptides from
CC       procollagens such as procollagen I, II and III or the proteolytic
CC       activation of the enzyme lysyl oxidase LOX, necessary to formation of
CC       covalent cross-links in collagen and elastic fibers (PubMed:20181949).
CC       Additional substrates include matricellular thrombospondin-1/THBS1
CC       whose cleavage leads to cell adhesion disruption and TGF-beta
CC       activation (By similarity). {ECO:0000250|UniProtKB:P13497,
CC       ECO:0000269|PubMed:20181949, ECO:0000269|PubMed:24419319,
CC       ECO:0000269|PubMed:28068493, ECO:0000269|PubMed:8951074}.
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};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC       ProRule:PRU01211};
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:0000269|PubMed:20181949}.
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network
CC       {ECO:0000269|PubMed:20181949}. Secreted, extracellular space,
CC       extracellular matrix {ECO:0000269|PubMed:20181949}. Secreted
CC       {ECO:0000250|UniProtKB:P13497}. Note=Co-localizes with POSTN in the
CC       Golgi.
CC   -!- TISSUE SPECIFICITY: At high levels in embryonic maternal deciduum and
CC       floor plate region of the neural tube. Less in developing membranous
CC       and endochondral bone, submucosa of intestine, dermis of skin and the
CC       mesenchyme of spleen and lung.
CC   -!- DISRUPTION PHENOTYPE: Deletion mice are perinatally lethal, with the
CC       most obvious gross abnormality being failure of ventral body wall
CC       closure, and persistent herniation of the gut. This phenotype likely
CC       reflects the defective and weakened nature of extracellular matrix
CC       (ECM) in these embryos (PubMed:8951074). Double knockout mice (BMP1 and
CC       TLL1) display progressive defects in teeth and bone development
CC       (PubMed:28068493, PubMed:24419319). {ECO:0000269|PubMed:24419319,
CC       ECO:0000269|PubMed:28068493, ECO:0000269|PubMed:8951074}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAA37306.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; L24755; AAA37306.1; ALT_FRAME; mRNA.
DR   EMBL; AC122268; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC066062; AAH66062.1; -; mRNA.
DR   CCDS; CCDS36972.1; -.
DR   PIR; I49540; I49540.
DR   RefSeq; NP_033885.2; NM_009755.3.
DR   RefSeq; XP_006518523.1; XM_006518460.3.
DR   AlphaFoldDB; P98063; -.
DR   SMR; P98063; -.
DR   BioGRID; 198360; 6.
DR   IntAct; P98063; 2.
DR   STRING; 10090.ENSMUSP00000022693; -.
DR   MEROPS; M12.005; -.
DR   GlyCosmos; P98063; 5 sites, No reported glycans.
DR   GlyGen; P98063; 5 sites.
DR   iPTMnet; P98063; -.
DR   PhosphoSitePlus; P98063; -.
DR   CPTAC; non-CPTAC-3562; -.
DR   PaxDb; 10090-ENSMUSP00000022693; -.
DR   PeptideAtlas; P98063; -.
DR   ProteomicsDB; 273748; -.
DR   Pumba; P98063; -.
DR   Antibodypedia; 2912; 351 antibodies from 36 providers.
DR   DNASU; 12153; -.
DR   Ensembl; ENSMUST00000022693.9; ENSMUSP00000022693.8; ENSMUSG00000022098.11.
DR   GeneID; 12153; -.
DR   KEGG; mmu:12153; -.
DR   UCSC; uc007uoc.2; mouse.
DR   AGR; MGI:88176; -.
DR   CTD; 649; -.
DR   MGI; MGI:88176; Bmp1.
DR   VEuPathDB; HostDB:ENSMUSG00000022098; -.
DR   eggNOG; KOG3714; Eukaryota.
DR   GeneTree; ENSGT00940000157176; -.
DR   HOGENOM; CLU_005140_0_0_1; -.
DR   InParanoid; P98063; -.
DR   OMA; RTVQTIN; -.
DR   OrthoDB; 2873870at2759; -.
DR   PhylomeDB; P98063; -.
DR   TreeFam; TF314351; -.
DR   BRENDA; 3.4.24.19; 3474.
DR   Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR   Reactome; R-MMU-2214320; Anchoring fibril formation.
DR   Reactome; R-MMU-2243919; Crosslinking of collagen fibrils.
DR   Reactome; R-MMU-8963896; HDL assembly.
DR   BioGRID-ORCS; 12153; 2 hits in 82 CRISPR screens.
DR   ChiTaRS; Bmp1; mouse.
DR   PRO; PR:P98063; -.
DR   Proteomes; UP000000589; Chromosome 14.
DR   RNAct; P98063; Protein.
DR   Bgee; ENSMUSG00000022098; Expressed in gastrula and 259 other cell types or tissues.
DR   ExpressionAtlas; P98063; baseline and differential.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0031982; C:vesicle; ISO:MGI.
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; ISO:MGI.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IDA:MGI.
DR   GO; GO:0008233; F:peptidase activity; ISO:MGI.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
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; ISO:MGI.
DR   GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR   GO; GO:0006508; P:proteolysis; ISO:MGI.
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; 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; PTHR24251:SF42; BONE MORPHOGENETIC PROTEIN 1; 1.
DR   PANTHER; PTHR24251; OVOCHYMASE-RELATED; 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; SSF57196; EGF/Laminin; 2.
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.
DR   Genevisible; P98063; MM.
PE   1: Evidence at protein level;
KW   Calcium; Chondrogenesis; Cleavage on pair of basic residues; Cytokine;
KW   Developmental protein; Differentiation; Disulfide bond; EGF-like domain;
KW   Extracellular matrix; Glycoprotein; Golgi apparatus; Growth factor;
KW   Hydrolase; Metal-binding; Metalloprotease; Methylation; Osteogenesis;
KW   Protease; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   PROPEP          26..125
FT                   /evidence="ECO:0000250|UniProtKB:P13497"
FT                   /id="PRO_0000028891"
FT   CHAIN           126..991
FT                   /note="Bone morphogenetic protein 1"
FT                   /id="PRO_0000028892"
FT   DOMAIN          126..325
FT                   /note="Peptidase M12A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DOMAIN          327..439
FT                   /note="CUB 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   DOMAIN          440..551
FT                   /note="CUB 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   DOMAIN          552..593
FT                   /note="EGF-like 1; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          596..707
FT                   /note="CUB 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   DOMAIN          708..748
FT                   /note="EGF-like 2; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          752..864
FT                   /note="CUB 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   DOMAIN          865..981
FT                   /note="CUB 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT   REGION          86..131
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        86..112
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        219
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   BINDING         218
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   BINDING         222
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   BINDING         228
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   MOD_RES         939
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WVM6"
FT   MOD_RES         942
FT                   /note="Omega-N-methylarginine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WVM6"
FT   CARBOHYD        96
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        147
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        368
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        604
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        168..324
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DISULFID        188..210
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DISULFID        190..191
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01211"
FT   DISULFID        327..353
FT                   /evidence="ECO:0000250"
FT   DISULFID        380..402
FT                   /evidence="ECO:0000250"
FT   DISULFID        440..466
FT                   /evidence="ECO:0000250"
FT   DISULFID        493..515
FT                   /evidence="ECO:0000250"
FT   DISULFID        556..568
FT                   /evidence="ECO:0000250"
FT   DISULFID        564..577
FT                   /evidence="ECO:0000250"
FT   DISULFID        579..592
FT                   /evidence="ECO:0000250"
FT   DISULFID        596..622
FT                   /evidence="ECO:0000250"
FT   DISULFID        649..671
FT                   /evidence="ECO:0000250"
FT   DISULFID        712..723
FT                   /evidence="ECO:0000250"
FT   DISULFID        719..732
FT                   /evidence="ECO:0000250"
FT   DISULFID        734..747
FT                   /evidence="ECO:0000250"
FT   DISULFID        752..778
FT                   /evidence="ECO:0000250"
FT   DISULFID        805..827
FT                   /evidence="ECO:0000250"
FT   DISULFID        865..895
FT                   /evidence="ECO:0000250"
FT   DISULFID        922..944
FT                   /evidence="ECO:0000250"
FT   CONFLICT        395..397
FT                   /note="APL -> VWV (in Ref. 1; AAA37306)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        519
FT                   /note="K -> N (in Ref. 1; AAA37306)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   991 AA;  111666 MW;  F838441CF1DA9F1A CRC64;
     MPGVARPPLP LLSLPLLLLL LLLPRAGRPL DLADYTYDLG EEDAPELLNY KDPCKAAAFL
     GDIALDEEDL RAFQVQQAAV LRQQTARRPS IKAAGNSSAL GGQGTSGQPQ RESRGRWRGR
     PRSRRAATSR PERVWPDGVI PFVIGGNFTG SQRAVFRQAM RHWEKHTCVT FLERTDEDSY
     IVFTYRPCGC CSYVGRRGGG PQAISIGKNC DKFGIVVHEL GHVIGFWHEH TRPDRDRHVS
     IVRENIQPGQ EYNFLKMEVQ EVESLGETYD FDSIMHYARN TFSRGIFLDT IVPKYEVNGV
     KPSIGQRTRL SKGDIAQARK LYKCPACGET LQDSTGNFSS PEYPNGYSAH MHCVWRISVT
     PGEKIILNFT SMDLYRSRLC WYDYVEVRDG FWRKAPLRGR FCGGKLPEPI VSTDSRLWVE
     FRSSSNWVGK GFFAVYEAIC GGDVKKDNGH IQSPNYPDDY RPSKVCIWRI QVSEGFHVGL
     TFQSFEIERH DSCAYDYLEV RDGHSESSNL IGRYCGYEKP DDIKSTSSRL WLKFVSDGSI
     NKAGFAVNFF KEVDECSRPN RGGCEQRCLN TLGSYKCSCD PGYELAPDKR RCEAACGGFL
     TKLNGSITSP GWPKEYPPNK NCIWQLVAPT QYRISLQFDF FETEGNDVCK YDFVEVRSGL
     TADSKLHGKF CGSEKPEVIT SQYNNMRVEF KSDNTVSKKG FKAHFFSDKD ECSKDNGGCQ
     QDCVNTFGSY ECQCRSGFVL HDNKHDCKEA GCEHKVTSTS GTITSPNWPD KYPSKKECTW
     AISSTPGHRV KLTFVEMDIE SQPECAYDHL EVFDGRDAKA PVLGRFCGSK KPEPVLATGN
     RMFLRFYSDN SVQRKGFQAS HSTECGGQVR ADVKTKDLYS HAQFGDNNYP GGVDCEWVIV
     AEEGYGVELV FQTFEVEEET DCGYDYIELF DGYDSTAPRL GRYCGSGPPE EVYSAGDSVL
     VKFHSDDTIS KKGFHLRYTS TKFQDTLHSR K
//