ID   BMP8A_HUMAN             Reviewed;         402 AA.
AC   Q7Z5Y6; Q5T3A5;
DT   21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 2.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=Bone morphogenetic protein 8A;
DE            Short=BMP-8A;
DE   Flags: Precursor;
GN   Name=BMP8A;
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], AND VARIANT HIS-293.
RA   Onishi M., Yasunaga T., Tanaka H., Nishimune Y., Nozaki M.;
RT   "Evolution of testis specific Scot-t genes encoding succinyl-CoA:3-oxoacid
RT   CoA-transferase, functional retroposons generated from somatic tissue-type
RT   paralog.";
RL   Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   FUNCTION.
RX   PubMed=22579288; DOI=10.1016/j.cell.2012.02.066;
RA   Whittle A.J., Carobbio S., Martins L., Slawik M., Hondares E.,
RA   Vazquez M.J., Morgan D., Csikasz R.I., Gallego R., Rodriguez-Cuenca S.,
RA   Dale M., Virtue S., Villarroya F., Cannon B., Rahmouni K., Lopez M.,
RA   Vidal-Puig A.;
RT   "BMP8B increases brown adipose tissue thermogenesis through both central
RT   and peripheral actions.";
RL   Cell 149:871-885(2012).
RN   [4]
RP   FUNCTION.
RX   PubMed=31940275; DOI=10.1530/rep-19-0305;
RA   Wu F.J., Wang Y.W., Luo C.W.;
RT   "Human BMP8A suppresses luteinization of rat granulosa cells via the
RT   SMAD1/5/8 pathway.";
RL   Reproduction 159:315-324(2020).
CC   -!- FUNCTION: Induces cartilage and bone formation. May be the
CC       osteoinductive factor responsible for the phenomenon of epithelial
CC       osteogenesis. Plays a role in calcium regulation and bone homeostasis
CC       (By similarity). Signaling protein involved in regulation of
CC       thermogenesis and energy balance. Proposed to increase the peripheral
CC       response of brown adipose tissue (BAT) to adrenergic stimulation while
CC       acting centrally in the hypothalamus to increase sympathetic output to
CC       BAT. {ECO:0000250, ECO:0000269|PubMed:22579288}.
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:22579288, PubMed:31940275). Initiates the
CC       canonical BMP signaling cascade by associating with type I receptor
CC       BMPR1A and type II receptor BMPR2 (PubMed:31940275). Once all three
CC       components are bound together in a complex at the cell surface, BMPR2
CC       phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal
CC       by phosphorylating SMAD1/5/8 that travel to the nucleus and act as
CC       activators and repressors of transcription of target genes. In
CC       addition, activates the SMAD2/3 pathway (PubMed:31940275).
CC       {ECO:0000269|PubMed:22579288, ECO:0000269|PubMed:31940275}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC   -!- CAUTION: Experiments with human recombinant protein (in mouse system by
CC       intracerebroventricular treatment) are reported for BMP8B but the
CC       protein is corresponding to BMP8A according sequence data provided by
CC       the supplier; related experiments with Bmp8b-/- mice show similar
CC       results. {ECO:0000305|PubMed:22579288}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 8A entry;
CC       URL="https://en.wikipedia.org/wiki/Bone_morphogenetic_protein_8A";
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DR   EMBL; AY303954; AAP74559.1; -; mRNA.
DR   EMBL; AL365277; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS437.1; -.
DR   RefSeq; NP_861525.2; NM_181809.3.
DR   AlphaFoldDB; Q7Z5Y6; -.
DR   SMR; Q7Z5Y6; -.
DR   BioGRID; 131696; 67.
DR   IntAct; Q7Z5Y6; 1.
DR   MINT; Q7Z5Y6; -.
DR   STRING; 9606.ENSP00000327440; -.
DR   GlyCosmos; Q7Z5Y6; 2 sites, No reported glycans.
DR   GlyGen; Q7Z5Y6; 2 sites.
DR   iPTMnet; Q7Z5Y6; -.
DR   PhosphoSitePlus; Q7Z5Y6; -.
DR   BioMuta; BMP8A; -.
DR   DMDM; 90111975; -.
DR   jPOST; Q7Z5Y6; -.
DR   MassIVE; Q7Z5Y6; -.
DR   PaxDb; 9606-ENSP00000327440; -.
DR   PeptideAtlas; Q7Z5Y6; -.
DR   ProteomicsDB; 69359; -.
DR   Antibodypedia; 31907; 202 antibodies from 25 providers.
DR   DNASU; 353500; -.
DR   Ensembl; ENST00000331593.6; ENSP00000327440.5; ENSG00000183682.8.
DR   GeneID; 353500; -.
DR   KEGG; hsa:353500; -.
DR   MANE-Select; ENST00000331593.6; ENSP00000327440.5; NM_181809.4; NP_861525.2.
DR   UCSC; uc001cdi.4; human.
DR   AGR; HGNC:21650; -.
DR   CTD; 353500; -.
DR   DisGeNET; 353500; -.
DR   GeneCards; BMP8A; -.
DR   HGNC; HGNC:21650; BMP8A.
DR   HPA; ENSG00000183682; Tissue enriched (thyroid).
DR   neXtProt; NX_Q7Z5Y6; -.
DR   OpenTargets; ENSG00000183682; -.
DR   PharmGKB; PA134894231; -.
DR   VEuPathDB; HostDB:ENSG00000183682; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   GeneTree; ENSGT00940000155272; -.
DR   HOGENOM; CLU_020515_4_1_1; -.
DR   InParanoid; Q7Z5Y6; -.
DR   OMA; QPFMVGF; -.
DR   OrthoDB; 2912454at2759; -.
DR   PhylomeDB; Q7Z5Y6; -.
DR   TreeFam; TF316134; -.
DR   PathwayCommons; Q7Z5Y6; -.
DR   SignaLink; Q7Z5Y6; -.
DR   BioGRID-ORCS; 353500; 21 hits in 1140 CRISPR screens.
DR   ChiTaRS; BMP8A; human.
DR   GeneWiki; Bone_morphogenetic_protein_8A; -.
DR   GenomeRNAi; 353500; -.
DR   Pharos; Q7Z5Y6; Tbio.
DR   PRO; PR:Q7Z5Y6; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q7Z5Y6; Protein.
DR   Bgee; ENSG00000183682; Expressed in right lobe of thyroid gland and 106 other cell types or tissues.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0002024; P:diet induced thermogenesis; IDA:UniProtKB.
DR   GO; GO:0097009; P:energy homeostasis; IDA:UniProtKB.
DR   GO; GO:0046676; P:negative regulation of insulin secretion; IDA:UniProtKB.
DR   GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
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   PRINTS; PR00669; INHIBINA.
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; Q7Z5Y6; HS.
PE   2: Evidence at transcript level;
KW   Chondrogenesis; Cytokine; Developmental protein; Differentiation;
KW   Disulfide bond; Glycoprotein; Growth factor; Osteogenesis;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000255"
FT   PROPEP          20..263
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000227896"
FT   CHAIN           264..402
FT                   /note="Bone morphogenetic protein 8A"
FT                   /id="PRO_0000227897"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        301..367
FT                   /evidence="ECO:0000250"
FT   DISULFID        330..399
FT                   /evidence="ECO:0000250"
FT   DISULFID        334..401
FT                   /evidence="ECO:0000250"
FT   DISULFID        366
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250"
FT   VARIANT         84
FT                   /note="M -> V (in dbSNP:rs4660269)"
FT                   /id="VAR_059859"
FT   VARIANT         293
FT                   /note="R -> H (in dbSNP:rs6525)"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="VAR_052571"
SQ   SEQUENCE   402 AA;  44798 MW;  F50E2C06D261E31E CRC64;
     MAARPGPLWL LGLTLCALGG GGPGLRPPPG CPQRRLGARE RRDVQREILA VLGLPGRPRP
     RAPPAASRLP ASAPLFMLDL YHAMAGDDDE DGAPAEQRLG RADLVMSFVN MVERDRALGH
     QEPHWKEFRF DLTQIPAGEA VTAAEFRIYK VPSIHLLNRT LHVSMFQVVQ EQSNRESDLF
     FLDLQTLRAG DEGWLVLDVT AASDCWLLKR HKDLGLRLYV ETEDGHSVDP GLAGLLGQRA
     PRSQQPFVVT FFRASPSPIR TPRAVRPLRR RQPKKSNELP QANRLPGIFD DVRGSHGRQV
     CRRHELYVSF QDLGWLDWVI APQGYSAYYC EGECSFPLDS CMNATNHAIL QSLVHLMKPN
     AVPKACCAPT KLSATSVLYY DSSNNVILRK HRNMVVKACG CH
//