BMP8A_MOUSE
ID BMP8A_MOUSE Reviewed; 399 AA.
AC P34821;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Bone morphogenetic protein 8A;
DE Short=BMP-8A;
DE AltName: Full=Osteogenic protein 2;
DE Short=OP-2;
DE Flags: Precursor;
GN Name=Bmp8a; Synonyms=Bmp-8, Bmp8;
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] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=1460021; DOI=10.1016/s0021-9258(19)74028-9;
RA Oezkaynak E., Schnegelsberg P.N.J., Jin D.F., Clifford G.M., Warren F.D.,
RA Drier E.A., Oppermann H.;
RT "Osteogenic protein-2. A new member of the transforming growth factor-beta
RT superfamily expressed early in embryogenesis.";
RL J. Biol. Chem. 267:25220-25227(1992).
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=8843393; DOI=10.1016/0925-4773(96)00543-6;
RA Zhao G.Q., Hogan B.L.;
RT "Evidence that mouse Bmp8a (Op2) and Bmp8b are duplicated genes that play a
RT role in spermatogenesis and placental development.";
RL Mech. Dev. 57:159-168(1996).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9463357; DOI=10.1242/dev.125.6.1103;
RA Zhao G.Q., Liaw L., Hogan B.L.;
RT "Bone morphogenetic protein 8A plays a role in the maintenance of
RT spermatogenesis and the integrity of the epididymis.";
RL Development 125:1103-1112(1998).
RN [7]
RP FUNCTION.
RX PubMed=12925636; DOI=10.2106/00004623-200308000-00017;
RA Cheng H., Jiang W., Phillips F.M., Haydon R.C., Peng Y., Zhou L., Luu H.H.,
RA An N., Breyer B., Vanichakarn P., Szatkowski J.P., Park J.Y., He T.C.;
RT "Osteogenic activity of the fourteen types of human bone morphogenetic
RT proteins (BMPs).";
RL J. Bone Joint Surg. 85:1544-1552(2003).
RN [8]
RP INDUCTION.
RX PubMed=21277400; DOI=10.1016/j.bone.2011.01.017;
RA Kosa J.P., Kis A., Bacsi K., Balla B., Nagy Z., Takacs I., Speer G.,
RA Lakatos P.;
RT "The protective role of bone morphogenetic protein-8 in the glucocorticoid-
RT induced apoptosis on bone cells.";
RL Bone 48:1052-1057(2011).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28465413; DOI=10.1126/scisignal.aal1910;
RA Wu F.J., Lin T.Y., Sung L.Y., Chang W.F., Wu P.C., Luo C.W.;
RT "BMP8A sustains spermatogenesis by activating both SMAD1/5/8 and SMAD2/3 in
RT spermatogonia.";
RL Sci. Signal. 10:0-0(2017).
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays
CC important role in various biological processes, including
CC spermatogenesis, osteogenesis, steroidogenesis as well as regulation of
CC energy balance (PubMed:9463357, PubMed:12925636, PubMed:28465413).
CC Initiates the canonical BMP signaling cascade by associating with type
CC I receptor BMPR1A and type II receptor BMPR2. Once all three components
CC are bound together in a complex at the cell surface, BMPR2
CC phosphorylates and activates BMPR1A (By similarity). In turn, BMPR1A
CC propagates signal by phosphorylating SMAD1/5/8 that travel to the
CC nucleus and act as activators and repressors of transcription of target
CC genes. In addition, activates the SMAD2/3 pathway (PubMed:28465413).
CC {ECO:0000250|UniProtKB:Q7Z5Y6, ECO:0000269|PubMed:12925636,
CC ECO:0000269|PubMed:28465413, ECO:0000269|PubMed:9463357}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P34821-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P34821-2; Sequence=VSP_046527;
CC -!- TISSUE SPECIFICITY: Expressed in testis. expressed in trophoblast cells
CC of the labyrinthine region of the placenta and in the inner root sheath
CC of hair follicles of early postnatal skin (PubMed:8843393). Expressed
CC predominantly in the neonatal mouse spermatogonia (PubMed:28465413).
CC {ECO:0000269|PubMed:28465413, ECO:0000269|PubMed:8843393}.
CC -!- DEVELOPMENTAL STAGE: Extensive expression found in 8-day embryos, fell
CC drastically in 10-day embryos and virtually absent in 17-day embryos.
CC Expressed during specific stages of spermatogenesis, with the highest
CC levels in stage 6-8 round spermatids after 3 weeks of age.
CC {ECO:0000269|PubMed:8843393}.
CC -!- INDUCTION: By dexamethasone in calvarial osteoblasts.
CC {ECO:0000269|PubMed:21277400}.
CC -!- DISRUPTION PHENOTYPE: Deletion mutant mice show normal embryonic and
CC postnatal development. Homozygous mutant females have normal fertility.
CC Males do not show germ cell defects during the initiation of
CC spermatogenesis. However, germ cell degeneration is observed in about
CC half of adult males. {ECO:0000269|PubMed:9463357}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; M97017; AAB01365.1; -; mRNA.
DR CCDS; CCDS18616.1; -. [P34821-1]
DR CCDS; CCDS57293.1; -. [P34821-2]
DR RefSeq; NP_031584.1; NM_007558.3. [P34821-1]
DR AlphaFoldDB; P34821; -.
DR SMR; P34821; -.
DR BioGRID; 198368; 1.
DR STRING; 10090.ENSMUSP00000037779; -.
DR GlyGen; P34821; 2 sites.
DR PhosphoSitePlus; P34821; -.
DR MaxQB; P34821; -.
DR PaxDb; P34821; -.
DR PRIDE; P34821; -.
DR ProteomicsDB; 273503; -. [P34821-1]
DR ProteomicsDB; 273504; -. [P34821-2]
DR DNASU; 12163; -.
DR Ensembl; ENSMUST00000040496; ENSMUSP00000037779; ENSMUSG00000032726. [P34821-2]
DR Ensembl; ENSMUST00000102641; ENSMUSP00000099701; ENSMUSG00000032726. [P34821-1]
DR GeneID; 12163; -.
DR KEGG; mmu:12163; -.
DR UCSC; uc008upg.2; mouse. [P34821-1]
DR CTD; 353500; -.
DR MGI; MGI:104515; Bmp8a.
DR VEuPathDB; HostDB:ENSMUSG00000032726; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000164770; -.
DR HOGENOM; CLU_020515_4_1_1; -.
DR InParanoid; P34821; -.
DR OMA; FRIYKMR; -.
DR PhylomeDB; P34821; -.
DR BioGRID-ORCS; 12163; 2 hits in 73 CRISPR screens.
DR PRO; PR:P34821; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P34821; protein.
DR Bgee; ENSMUSG00000032726; Expressed in decidua and 54 other tissues.
DR ExpressionAtlas; P34821; baseline and differential.
DR Genevisible; P34821; MM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0070700; F:BMP receptor binding; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0007281; P:germ cell development; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:MGI.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Chondrogenesis; Cytokine; Developmental protein;
KW Differentiation; Disulfide bond; Glycoprotein; Growth factor; Osteogenesis;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..260
FT /evidence="ECO:0000255"
FT /id="PRO_0000033884"
FT CHAIN 261..399
FT /note="Bone morphogenetic protein 8A"
FT /id="PRO_0000033885"
FT REGION 257..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 298..364
FT /evidence="ECO:0000250"
FT DISULFID 327..396
FT /evidence="ECO:0000250"
FT DISULFID 331..398
FT /evidence="ECO:0000250"
FT DISULFID 363
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VAR_SEQ 351
FT /note="V -> VSTTVACCDRWSGV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046527"
SQ SEQUENCE 399 AA; 44764 MW; B75FE32D6125E40C CRC64;
MAMRPGPLWL LGLALCALGG GHGPRPPHTC PQRRLGARER RDMQREILAV LGLPGRPRPR
AQPAAARQPA SAPLFMLDLY HAMTDDDDGG PPQAHLGRAD LVMSFVNMVE RDRTLGYQEP
HWKEFHFDLT QIPAGEAVTA AEFRIYKEPS THPLNTTLHI SMFEVVQEHS NRESDLFFLD
LQTLRSGDEG WLVLDITAAS DRWLLNHHKD LGLRLYVETA DGHSMDPGLA GLLGRQAPRS
RQPFMVTFFR ASQSPVRAPR AARPLKRRQP KKTNELPHPN KLPGIFDDGH GSRGREVCRR
HELYVSFRDL GWLDWVIAPQ GYSAYYCEGE CAFPLDSCMN ATNHAILQSL VHLMKPDVVP
KACCAPTKLS ATSVLYYDSS NNVILRKHRN MVVKACGCH
