FGF16_HUMAN
ID FGF16_HUMAN Reviewed; 207 AA.
AC O43320;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Fibroblast growth factor 16;
DE Short=FGF-16;
GN Name=FGF16;
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].
RC TISSUE=Heart;
RX PubMed=9473496; DOI=10.1006/bbrc.1998.8073;
RA Miyake A., Konishi M., Martin F.H., Hernday N.A., Ozaki K., Yamamoto S.,
RA Mikami T., Arakawa T., Itoh N.;
RT "Structure and expression of a novel member, FGF-16, on the fibroblast
RT growth factor family.";
RL Biochem. Biophys. Res. Commun. 243:148-152(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [3]
RP INTERACTION WITH FGFR2 AND FGFR3, AND FUNCTION IN STIMULATION OF CELL
RP PROLIFERATION.
RX PubMed=16597617; DOI=10.1074/jbc.m601252200;
RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.;
RT "Receptor specificity of the fibroblast growth factor family. The complete
RT mammalian FGF family.";
RL J. Biol. Chem. 281:15694-15700(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [5]
RP REVIEW.
RX PubMed=20094046; DOI=10.1038/nrc2780;
RA Turner N., Grose R.;
RT "Fibroblast growth factor signalling: from development to cancer.";
RL Nat. Rev. Cancer 10:116-129(2010).
RN [6]
RP INVOLVEMENT IN MF4.
RX PubMed=23709756; DOI=10.1136/jmedgenet-2013-101659;
RA Jamsheer A., Zemojtel T., Kolanczyk M., Stricker S., Hecht J., Krawitz P.,
RA Doelken S.C., Glazar R., Socha M., Mundlos S.;
RT "Whole exome sequencing identifies FGF16 nonsense mutations as the cause of
RT X-linked recessive metacarpal 4/5 fusion.";
RL J. Med. Genet. 50:579-584(2013).
RN [7]
RP INVOLVEMENT IN MF4, AND VARIANT MF4 LEU-68.
RX PubMed=25333065; DOI=10.1002/mgg3.81;
RA Laurell T., Nilsson D., Hofmeister W., Lindstrand A., Ahituv N.,
RA Vandermeer J., Amilon A., Anneren G., Arner M., Pettersson M., Jaentti N.,
RA Rosberg H.E., Cattini P.A., Nordenskjoeld A., Maekitie O.,
RA Grigelioniene G., Nordgren A.;
RT "Identification of three novel FGF16 mutations in X-linked recessive fusion
RT of the fourth and fifth metacarpals and possible correlation with heart
RT disease.";
RL Mol. Genet. Genomic Med. 2:402-411(2014).
CC -!- FUNCTION: Plays an important role in the regulation of embryonic
CC development, cell proliferation and cell differentiation, and is
CC required for normal cardiomyocyte proliferation and heart development.
CC {ECO:0000269|PubMed:16597617}.
CC -!- SUBUNIT: Interacts with FGFR1 and FGFR2. {ECO:0000269|PubMed:16597617}.
CC -!- INTERACTION:
CC O43320; Q92989: CLP1; NbExp=3; IntAct=EBI-11479104, EBI-2559831;
CC O43320; Q92997: DVL3; NbExp=3; IntAct=EBI-11479104, EBI-739789;
CC O43320; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-11479104, EBI-10961706;
CC O43320; Q0VD86: INCA1; NbExp=3; IntAct=EBI-11479104, EBI-6509505;
CC O43320; Q15323: KRT31; NbExp=3; IntAct=EBI-11479104, EBI-948001;
CC O43320; P23508: MCC; NbExp=3; IntAct=EBI-11479104, EBI-307531;
CC O43320; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-11479104, EBI-79165;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:O54769}.
CC -!- DISEASE: Metacarpal 4-5 fusion (MF4) [MIM:309630]: A rare congenital
CC malformation of the hand characterized by the partial or complete
CC fusion of the fourth and fifth metacarpals. The anomaly occurs as an
CC isolated trait or part of a syndrome. {ECO:0000269|PubMed:23709756,
CC ECO:0000269|PubMed:25333065}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family.
CC {ECO:0000305}.
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DR EMBL; AB009391; BAA24956.1; -; mRNA.
DR EMBL; BX682239; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS75996.1; -.
DR PIR; JC5941; JC5941.
DR RefSeq; NP_003859.1; NM_003868.2.
DR AlphaFoldDB; O43320; -.
DR SMR; O43320; -.
DR BioGRID; 114350; 14.
DR IntAct; O43320; 8.
DR STRING; 9606.ENSP00000399324; -.
DR GlyGen; O43320; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O43320; -.
DR PhosphoSitePlus; O43320; -.
DR BioMuta; FGF16; -.
DR MassIVE; O43320; -.
DR PaxDb; O43320; -.
DR PRIDE; O43320; -.
DR Antibodypedia; 72310; 247 antibodies from 27 providers.
DR DNASU; 8823; -.
DR Ensembl; ENST00000439435.3; ENSP00000399324.2; ENSG00000196468.8.
DR GeneID; 8823; -.
DR KEGG; hsa:8823; -.
DR MANE-Select; ENST00000439435.3; ENSP00000399324.2; NM_003868.3; NP_003859.1.
DR UCSC; uc033ejs.2; human.
DR CTD; 8823; -.
DR DisGeNET; 8823; -.
DR GeneCards; FGF16; -.
DR HGNC; HGNC:3672; FGF16.
DR HPA; ENSG00000196468; Tissue enhanced (choroid).
DR MalaCards; FGF16; -.
DR MIM; 300827; gene.
DR MIM; 309630; phenotype.
DR neXtProt; NX_O43320; -.
DR OpenTargets; ENSG00000196468; -.
DR Orphanet; 2498; Syndactyly type 8.
DR PharmGKB; PA28111; -.
DR VEuPathDB; HostDB:ENSG00000196468; -.
DR eggNOG; KOG3885; Eukaryota.
DR GeneTree; ENSGT00940000160087; -.
DR HOGENOM; CLU_081609_0_0_1; -.
DR InParanoid; O43320; -.
DR OMA; NRTKKHQ; -.
DR OrthoDB; 1097566at2759; -.
DR PhylomeDB; O43320; -.
DR PathwayCommons; O43320; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3.
DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation.
DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation.
DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation.
DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2.
DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer.
DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2.
DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3.
DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4.
DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2.
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling.
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling.
DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3.
DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling.
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4.
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease.
DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR SignaLink; O43320; -.
DR BioGRID-ORCS; 8823; 11 hits in 228 CRISPR screens.
DR GenomeRNAi; 8823; -.
DR Pharos; O43320; Tbio.
DR PRO; PR:O43320; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; O43320; protein.
DR Bgee; ENSG00000196468; Expressed in hindlimb stylopod and 44 other tissues.
DR Genevisible; O43320; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:2000546; P:positive regulation of endothelial cell chemotaxis to fibroblast growth factor; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central.
DR GO; GO:0009266; P:response to temperature stimulus; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00058; FGF; 1.
DR InterPro; IPR028285; FGF16.
DR InterPro; IPR002209; Fibroblast_GF_fam.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR11486; PTHR11486; 1.
DR PANTHER; PTHR11486:SF27; PTHR11486:SF27; 1.
DR Pfam; PF00167; FGF; 1.
DR PRINTS; PR00263; HBGFFGF.
DR SMART; SM00442; FGF; 1.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00247; HBGF_FGF; 1.
PE 1: Evidence at protein level;
KW Disease variant; Glycoprotein; Growth factor; Phosphoprotein;
KW Reference proteome; Secreted.
FT CHAIN 1..207
FT /note="Fibroblast growth factor 16"
FT /id="PRO_0000147613"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 68
FT /note="R -> L (in MF4)"
FT /evidence="ECO:0000269|PubMed:25333065"
FT /id="VAR_072396"
SQ SEQUENCE 207 AA; 23759 MW; D8AD160BDABDB5F8 CRC64;
MAEVGGVFAS LDWDLHGFSS SLGNVPLADS PGFLNERLGQ IEGKLQRGSP TDFAHLKGIL
RRRQLYCRTG FHLEIFPNGT VHGTRHDHSR FGILEFISLA VGLISIRGVD SGLYLGMNER
GELYGSKKLT RECVFREQFE ENWYNTYAST LYKHSDSERQ YYVALNKDGS PREGYRTKRH
QKFTHFLPRP VDPSKLPSMS RDLFHYR
