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   24-JAN-2024, entry version 157.
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   GlyCosmos; P34821; 2 sites, No reported glycans.
DR   GlyGen; P34821; 2 sites.
DR   PhosphoSitePlus; P34821; -.
DR   MaxQB; P34821; -.
DR   PaxDb; 10090-ENSMUSP00000037779; -.
DR   ProteomicsDB; 273503; -. [P34821-1]
DR   ProteomicsDB; 273504; -. [P34821-2]
DR   DNASU; 12163; -.
DR   Ensembl; ENSMUST00000040496.6; ENSMUSP00000037779.6; ENSMUSG00000032726.13. [P34821-2]
DR   Ensembl; ENSMUST00000102641.10; ENSMUSP00000099701.4; ENSMUSG00000032726.13. [P34821-1]
DR   GeneID; 12163; -.
DR   KEGG; mmu:12163; -.
DR   UCSC; uc008upg.2; mouse. [P34821-1]
DR   AGR; MGI:104515; -.
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; DRDIFHQ; -.
DR   OrthoDB; 2912454at2759; -.
DR   PhylomeDB; P34821; -.
DR   BioGRID-ORCS; 12163; 2 hits in 78 CRISPR screens.
DR   PRO; PR:P34821; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; P34821; Protein.
DR   Bgee; ENSMUSG00000032726; Expressed in decidua and 57 other cell types or tissues.
DR   ExpressionAtlas; P34821; baseline and differential.
DR   GO; GO:0005615; C:extracellular space; 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: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:0007283; P:spermatogenesis; IMP:MGI.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:MGI.
DR   CDD; cd19398; TGF_beta_BMP8; 1.
DR   Gene3D; 2.60.120.970; -; 1.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 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:SF119; BONE MORPHOGENETIC PROTEIN 8A-RELATED; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   SMART; SM00204; TGFB; 1.
DR   SUPFAM; SSF57501; Cystine-knot cytokines; 1.
DR   PROSITE; PS00250; TGF_BETA_1; 1.
DR   PROSITE; PS51362; TGF_BETA_2; 1.
DR   Genevisible; P34821; MM.
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
//