BMP1_MOUSE
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 03-AUG-2022, entry version 184.
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;
CC Evidence={ECO:0000255|PROSITE-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 GlyGen; P98063; 5 sites.
DR iPTMnet; P98063; -.
DR PhosphoSitePlus; P98063; -.
DR CPTAC; non-CPTAC-3562; -.
DR PaxDb; P98063; -.
DR PeptideAtlas; P98063; -.
DR PRIDE; P98063; -.
DR ProteomicsDB; 273748; -.
DR Antibodypedia; 2912; 309 antibodies from 36 providers.
DR DNASU; 12153; -.
DR Ensembl; ENSMUST00000022693; ENSMUSP00000022693; ENSMUSG00000022098.
DR GeneID; 12153; -.
DR KEGG; mmu:12153; -.
DR UCSC; uc007uoc.2; mouse.
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; 170905at2759; -.
DR PhylomeDB; P98063; -.
DR TreeFam; TF314351; -.
DR BRENDA; 3.4.24.19; 3474.
DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix.
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 77 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 256 other tissues.
DR ExpressionAtlas; P98063; baseline and differential.
DR Genevisible; P98063; MM.
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; 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; 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 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 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
