BMP5_HUMAN
ID BMP5_HUMAN Reviewed; 454 AA.
AC P22003; B4E0Y4; Q9H547; Q9NTM5;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Bone morphogenetic protein 5;
DE Short=BMP-5;
DE Flags: Precursor;
GN Name=BMP5;
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] (ISOFORM 1).
RC TISSUE=Bone;
RX PubMed=2263636; DOI=10.1073/pnas.87.24.9843;
RA Celeste A.J., Iannazzi J.A., Taylor R.C., Hewick R.M., Rosen V., Wang E.A.,
RA Wozney J.M.;
RT "Identification of transforming growth factor beta family members present
RT in bone-inductive protein purified from bovine bone.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9843-9847(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, and Spleen;
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 FUNCTION.
RX PubMed=11580864; DOI=10.1186/1471-2202-2-12;
RA Beck H.N., Drahushuk K., Jacoby D.B., Higgins D., Lein P.J.;
RT "Bone morphogenetic protein-5 (BMP-5) promotes dendritic growth in cultured
RT sympathetic neurons.";
RL BMC Neurosci. 2:12-12(2001).
RN [6]
RP FUNCTION.
RX PubMed=20402566; DOI=10.3109/08977191003752296;
RA Snelling S.J., Hulley P.A., Loughlin J.;
RT "BMP5 activates multiple signaling pathways and promotes chondrogenic
RT differentiation in the ATDC5 growth plate model.";
RL Growth Factors 28:268-279(2010).
RN [7]
RP FUNCTION.
RX PubMed=29321139; DOI=10.1523/jneurosci.1540-17.2018;
RA Jovanovic V.M., Salti A., Tilleman H., Zega K., Jukic M.M., Zou H.,
RA Friedel R.H., Prakash N., Blaess S., Edenhofer F., Brodski C.;
RT "BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In
RT Vivo and in Human Induced Pluripotent and Neural Stem Cells.";
RL J. Neurosci. 38:1662-1676(2018).
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays
CC essential roles in many developmental processes, including cartilage
CC and bone formation or neurogenesis (PubMed:11580864, PubMed:29321139).
CC Initiates the canonical BMP signaling cascade by associating with type
CC I receptor BMPR1A and type II receptor BMPR2 (PubMed:11580864). In
CC turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel
CC to the nucleus and act as activators and repressors of transcription of
CC target genes (PubMed:29321139, PubMed:11580864). Can also signal
CC through non-canonical pathway such as MAPK p38 signaling cascade to
CC promote chondrogenic differentiation (PubMed:20402566).
CC {ECO:0000269|PubMed:11580864, ECO:0000269|PubMed:20402566,
CC ECO:0000269|PubMed:29321139}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250}.
CC -!- INTERACTION:
CC P22003; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-11710063, EBI-16439278;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P22003-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22003-2; Sequence=VSP_056841;
CC -!- TISSUE SPECIFICITY: Expressed in the lung and liver.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 5 entry;
CC URL="https://en.wikipedia.org/wiki/Bone_morphogenetic_protein_5";
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DR EMBL; M60314; AAA36736.1; -; mRNA.
DR EMBL; AK303576; BAG64596.1; -; mRNA.
DR EMBL; AL133386; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137178; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027958; AAH27958.1; -; mRNA.
DR CCDS; CCDS4958.1; -. [P22003-1]
DR PIR; A39263; BMHU5.
DR RefSeq; NP_001316683.1; NM_001329754.1. [P22003-2]
DR RefSeq; NP_066551.1; NM_021073.3. [P22003-1]
DR AlphaFoldDB; P22003; -.
DR SMR; P22003; -.
DR BioGRID; 107121; 7.
DR IntAct; P22003; 5.
DR STRING; 9606.ENSP00000359866; -.
DR GlyGen; P22003; 4 sites.
DR iPTMnet; P22003; -.
DR PhosphoSitePlus; P22003; -.
DR BioMuta; BMP5; -.
DR DMDM; 115075; -.
DR MassIVE; P22003; -.
DR PaxDb; P22003; -.
DR PeptideAtlas; P22003; -.
DR PRIDE; P22003; -.
DR ProteomicsDB; 53951; -. [P22003-1]
DR ProteomicsDB; 5708; -.
DR Antibodypedia; 17340; 469 antibodies from 35 providers.
DR DNASU; 653; -.
DR Ensembl; ENST00000370830.4; ENSP00000359866.3; ENSG00000112175.8. [P22003-1]
DR GeneID; 653; -.
DR KEGG; hsa:653; -.
DR MANE-Select; ENST00000370830.4; ENSP00000359866.3; NM_021073.4; NP_066551.1.
DR UCSC; uc003pcq.4; human. [P22003-1]
DR CTD; 653; -.
DR DisGeNET; 653; -.
DR GeneCards; BMP5; -.
DR HGNC; HGNC:1072; BMP5.
DR HPA; ENSG00000112175; Tissue enriched (placenta).
DR MIM; 112265; gene.
DR neXtProt; NX_P22003; -.
DR OpenTargets; ENSG00000112175; -.
DR PharmGKB; PA25382; -.
DR VEuPathDB; HostDB:ENSG00000112175; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000158644; -.
DR HOGENOM; CLU_020515_4_1_1; -.
DR InParanoid; P22003; -.
DR OMA; HQESSRM; -.
DR PhylomeDB; P22003; -.
DR TreeFam; TF316134; -.
DR PathwayCommons; P22003; -.
DR SignaLink; P22003; -.
DR SIGNOR; P22003; -.
DR BioGRID-ORCS; 653; 7 hits in 1059 CRISPR screens.
DR ChiTaRS; BMP5; human.
DR GeneWiki; Bone_morphogenetic_protein_5; -.
DR GenomeRNAi; 653; -.
DR Pharos; P22003; Tbio.
DR PRO; PR:P22003; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P22003; protein.
DR Bgee; ENSG00000112175; Expressed in calcaneal tendon and 98 other tissues.
DR ExpressionAtlas; P22003; baseline and differential.
DR Genevisible; P22003; HS.
DR GO; GO:0005615; C:extracellular space; ISS:BHF-UCL.
DR GO; GO:0031982; C:vesicle; ISS:BHF-UCL.
DR GO; GO:0070700; F:BMP receptor binding; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:1905069; P:allantois development; ISS:BHF-UCL.
DR GO; GO:0097065; P:anterior head development; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IBA:GO_Central.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISS:BHF-UCL.
DR GO; GO:0060411; P:cardiac septum morphogenesis; ISS:BHF-UCL.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0060710; P:chorio-allantoic fusion; ISS:BHF-UCL.
DR GO; GO:0043583; P:ear development; IEA:Ensembl.
DR GO; GO:0003272; P:endocardial cushion formation; ISS:BHF-UCL.
DR GO; GO:0061384; P:heart trabecula morphogenesis; ISS:BHF-UCL.
DR GO; GO:0030902; P:hindbrain development; ISS:BHF-UCL.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; NAS:BHF-UCL.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; NAS:BHF-UCL.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0071676; P:negative regulation of mononuclear cell migration; NAS:BHF-UCL.
DR GO; GO:0010894; P:negative regulation of steroid biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0021502; P:neural fold elevation formation; ISS:BHF-UCL.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl.
DR GO; GO:0003344; P:pericardium morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060037; P:pharyngeal system development; ISS:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:1900006; P:positive regulation of dendrite development; IDA:BHF-UCL.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0001501; P:skeletal system development; NAS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0003323; P:type B pancreatic cell development; IDA:BHF-UCL.
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 1: Evidence at protein level;
KW Alternative splicing; Chondrogenesis; Cleavage on pair of basic residues;
KW Cytokine; Developmental protein; Differentiation; Disulfide bond;
KW Glycoprotein; Growth factor; Osteogenesis; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT PROPEP 31..316
FT /evidence="ECO:0000255"
FT /id="PRO_0000033866"
FT CHAIN 317..454
FT /note="Bone morphogenetic protein 5"
FT /id="PRO_0000033867"
FT REGION 318..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..343
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 353..419
FT /evidence="ECO:0000250"
FT DISULFID 382..451
FT /evidence="ECO:0000250"
FT DISULFID 386..453
FT /evidence="ECO:0000250"
FT DISULFID 418
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT VAR_SEQ 369..405
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056841"
FT VARIANT 2
FT /note="H -> Y (in dbSNP:rs9475437)"
FT /id="VAR_047054"
FT VARIANT 121
FT /note="N -> S (in dbSNP:rs35124644)"
FT /id="VAR_061896"
SQ SEQUENCE 454 AA; 51737 MW; 631277413CCC22EE CRC64;
MHLTVFLLKG IVGFLWSCWV LVGYAKGGLG DNHVHSSFIY RRLRNHERRE IQREILSILG
LPHRPRPFSP GKQASSAPLF MLDLYNAMTN EENPEESEYS VRASLAEETR GARKGYPASP
NGYPRRIQLS RTTPLTTQSP PLASLHDTNF LNDADMVMSF VNLVERDKDF SHQRRHYKEF
RFDLTQIPHG EAVTAAEFRI YKDRSNNRFE NETIKISIYQ IIKEYTNRDA DLFLLDTRKA
QALDVGWLVF DITVTSNHWV INPQNNLGLQ LCAETGDGRS INVKSAGLVG RQGPQSKQPF
MVAFFKASEV LLRSVRAANK RKNQNRNKSS SHQDSSRMSS VGDYNTSEQK QACKKHELYV
SFRDLGWQDW IIAPEGYAAF YCDGECSFPL NAHMNATNHA IVQTLVHLMF PDHVPKPCCA
PTKLNAISVL YFDDSSNVIL KKYRNMVVRS CGCH
