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 27-MAR-2024, entry version 204. 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, AND INTERACTION WITH MOUSE ERFE. RX PubMed=30097509; DOI=10.1182/blood-2018-06-857995; RA Arezes J., Foy N., McHugh K., Sawant A., Quinkert D., Terraube V., RA Brinth A., Tam M., LaVallie E.R., Taylor S., Armitage A.E., Pasricha S.R., RA Cunningham O., Lambert M., Draper S.J., Jasuja R., Drakesmith H.; RT "Erythroferrone inhibits the induction of hepcidin by BMP6."; RL Blood 132:1473-1477(2018). RN [8] 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). Promotes the CC expression of HAMP, this is repressed by its interaction with ERFE CC (PubMed:30097509). {ECO:0000269|PubMed:11580864, CC ECO:0000269|PubMed:20402566, ECO:0000269|PubMed:29321139, CC ECO:0000269|PubMed:30097509}. CC -!- SUBUNIT: Interacts with ERFE; the interaction inhibits BMP-induced CC transcription of HAMP. {ECO:0000269|PubMed:30097509}. 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P22003; 4 sites, No reported glycans. DR GlyGen; P22003; 4 sites. DR iPTMnet; P22003; -. DR PhosphoSitePlus; P22003; -. DR BioMuta; BMP5; -. DR DMDM; 115075; -. DR MassIVE; P22003; -. DR PaxDb; 9606-ENSP00000359866; -. DR PeptideAtlas; P22003; -. DR ProteomicsDB; 53951; -. [P22003-1] DR ProteomicsDB; 5708; -. DR Antibodypedia; 17340; 489 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 AGR; HGNC:1072; -. 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; GYPRRTQ; -. DR OrthoDB; 2912454at2759; -. DR PhylomeDB; P22003; -. DR TreeFam; TF316134; -. DR PathwayCommons; P22003; -. DR SignaLink; P22003; -. DR SIGNOR; P22003; -. DR BioGRID-ORCS; 653; 7 hits in 1137 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 99 other cell types or tissues. DR ExpressionAtlas; P22003; baseline and differential. 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; IDA:BHF-UCL. 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:0060391; P:positive regulation of SMAD protein signal transduction; 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:0003323; P:type B pancreatic cell development; IDA:BHF-UCL. DR CDD; cd19395; TGF_beta_BMP5; 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:SF139; BONE MORPHOGENETIC PROTEIN 5; 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; P22003; HS. 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 //