BMP8A_HUMAN
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 03-AUG-2022, entry version 137.
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; 66.
DR IntAct; Q7Z5Y6; 1.
DR MINT; Q7Z5Y6; -.
DR STRING; 9606.ENSP00000327440; -.
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; Q7Z5Y6; -.
DR PeptideAtlas; Q7Z5Y6; -.
DR PRIDE; Q7Z5Y6; -.
DR ProteomicsDB; 69359; -.
DR Antibodypedia; 31907; 179 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 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; KVPNDNY; -.
DR OrthoDB; 1063560at2759; -.
DR PhylomeDB; Q7Z5Y6; -.
DR TreeFam; TF316134; -.
DR PathwayCommons; Q7Z5Y6; -.
DR SignaLink; Q7Z5Y6; -.
DR BioGRID-ORCS; 353500; 20 hits in 1062 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 104 other tissues.
DR Genevisible; Q7Z5Y6; HS.
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: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 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 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 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
