ID FGFR4_HUMAN Reviewed; 802 AA. AC P22455; O43785; Q14309; Q71TW8; Q8TDA0; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 25-NOV-2008, entry version 103. DE RecName: Full=Fibroblast growth factor receptor 4; DE Short=FGFR-4; DE EC=2.7.10.1; DE AltName: CD_antigen=CD334; DE Flags: Precursor; GN Name=FGFR4; Synonyms=JTK2, TKF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX MEDLINE=91224085; PubMed=1709094; RA Partanen J.M., Maekelae T.P., Eerola E., Korhonen J., Hirvonen H., RA Claesson-Welsh L., Alitalo K.; RT "FGFR-4, a novel acidic fibroblast growth factor receptor with a RT distinct expression pattern."; RL EMBO J. 10:1347-1354(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Mammary gland; RX MEDLINE=93194827; PubMed=7680645; RA Ron D., Reich R., Chedid M., Lengel C., Cohen O.E., Chan A.M., RA Neufeld G., Miki T., Tronick S.R.; RT "Fibroblast growth factor receptor 4 is a high affinity receptor for RT both acidic and basic fibroblast growth factor but not for RT keratinocyte growth factor."; RL J. Biol. Chem. 268:5388-5394(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-136, TISSUE RP SPECIFICITY, AND SUBCELLULAR LOCATION. RC TISSUE=Intestine; RX MEDLINE=20133241; PubMed=10631118; DOI=10.1006/bbrc.1999.2010; RA Takaishi S., Sawada M., Morita Y., Seno H., Fukuzawa H., Chiba T.; RT "Identification of a novel alternative splicing of human FGF receptor RT 4: soluble-form splice variant expressed in human gastrointestinal RT epithelial cells."; RL Biochem. Biophys. Res. Commun. 267:658-662(2000). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=98119018; PubMed=9457674; DOI=10.1007/s003359900703; RA Kostrzewa M., Muller U.; RT "Genomic structure and complete sequence of the human FGFR4 gene."; RL Mamm. Genome 9:131-135(1998). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-136. RA Lind D.L., Cox D.R.; RT "Sequence variation in fibroblast growth factor receptors 3 and 4."; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-10; LEU-136 AND RP ARG-388. RG NIEHS SNPs program; RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-136. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 609-676. RC TISSUE=Blood; RX MEDLINE=91062389; PubMed=2247464; RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.; RT "Putative tyrosine kinases expressed in K-562 human leukemia cells."; RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990). RN [10] RP PROTEIN SEQUENCE OF 22-38. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [11] RP VARIANTS [LARGE SCALE ANALYSIS] ILE-10; LEU-136; ALA-179; SER-426; RP ASN-516; MET-550; THR-712 AND ASN-772. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Receptor for acidic fibroblast growth factor. Does not CC bind to basic fibroblast growth factor. Binds FGF19. CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a CC [protein]-L-tyrosine phosphate. CC -!- SUBUNIT: Interacts with KLB (By similarity). CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. Note=Isoform 2 may be secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P22455-1; Sequence=Displayed; CC Name=2; Synonyms=Soluble-form; CC IsoId=P22455-2; Sequence=VSP_035108; CC -!- TISSUE SPECIFICITY: Expressed in gastrointestinal epithelial CC cells, pancreas, and gastric and pancreatic cancer cell lines. CC -!- PTM: Glycosylated (By similarity). Phosphorylated on tyrosine CC residue (By similarity). Phosphorylation requires the presence of CC a functional (phosphorylated) FGFR1 and not necessarily by means CC of FGFR heterodimerization (By similarity). CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Fibroblast growth factor receptor subfamily. CC -!- SIMILARITY: Contains 3 Ig-like C2-type (immunoglobulin-like) CC domains. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- WEB RESOURCE: Name=NIEHS SNPs; CC URL="http://egp.gs.washington.edu/data/fgfr4/"; 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; X57205; CAA40490.1; -; mRNA. DR EMBL; L03840; AAB59389.1; -; mRNA. DR EMBL; AF202063; AAF27432.1; -; mRNA. DR EMBL; Y13901; CAA74200.1; -; Genomic_DNA. DR EMBL; AF487555; AAM13666.1; -; Genomic_DNA. DR EMBL; EF571596; ABQ01235.1; -; Genomic_DNA. DR EMBL; CH471195; EAW85036.1; -; Genomic_DNA. DR EMBL; BC011847; AAH11847.1; -; mRNA. DR EMBL; M59373; AAA63208.1; -; mRNA. DR PIR; S15345; TVHUF4. DR RefSeq; NP_002002.3; -. DR RefSeq; NP_075252.2; -. DR RefSeq; NP_998812.1; -. DR UniGene; Hs.165950; -. DR PDB; 1QCT; Model; -; B/E=36-353. DR PDBsum; 1QCT; -. DR SMR; P22455; 144-352, 453-747. DR DIP; DIP:5149N; -. DR PhosphoSite; P22455; -. DR Ensembl; ENSG00000160867; Homo sapiens. DR GeneID; 2264; -. DR KEGG; hsa:2264; -. DR H-InvDB; HIX0005452; -. DR HGNC; HGNC:3691; FGFR4. DR HPA; CAB005196; -. DR MIM; 134935; gene. DR PharmGKB; PA28130; -. DR HOVERGEN; P22455; -. DR Reactome; REACT_9470; Signaling by FGFR. DR DrugBank; DB00039; Palifermin. DR LinkHub; P22455; -. DR NextBio; 9195; -. DR ArrayExpress; P22455; -. DR CleanEx; HS_FGFR4; -. DR GermOnline; ENSG00000160867; Homo sapiens. DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0005007; F:fibroblast growth factor receptor activity; TAS:ProtInc. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling...; TAS:ProtInc. DR GO; GO:0006468; P:protein amino acid phosphorylation; IEA:InterPro. DR InterPro; IPR016248; Fibroblast_GF_rcpt. DR InterPro; IPR013151; Ig. DR InterPro; IPR007110; Ig-like. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR013098; Ig_I-set. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR000719; Prot_kinase_core. DR InterPro; IPR017441; Protein_kinase_ATP_bd_CS. DR InterPro; IPR001245; Tyr_pkinase. DR InterPro; IPR008266; Tyr_pkinase_AS. DR Gene3D; G3DSA:2.60.40.10; Ig-like_fold; 3. DR Pfam; PF07679; I-set; 1. DR Pfam; PF00047; ig; 2. DR Pfam; PF07714; Pkinase_Tyr; 1. DR PIRSF; PIRSF000628; FGFR; 1. DR PRINTS; PR00109; TYRKINASE. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00408; IGc2; 3. DR SMART; SM00219; TyrKc; 1. DR PROSITE; PS50835; IG_LIKE; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; KW Direct protein sequencing; Glycoprotein; Immunoglobulin domain; KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; KW Receptor; Repeat; Signal; Transferase; Transmembrane; KW Tyrosine-protein kinase. FT SIGNAL 1 21 FT CHAIN 22 802 Fibroblast growth factor receptor 4. FT /FTId=PRO_0000016787. FT TOPO_DOM 22 369 Extracellular (Potential). FT TRANSMEM 370 390 Potential. FT TOPO_DOM 391 802 Cytoplasmic (Potential). FT DOMAIN 22 118 Ig-like C2-type 1. FT DOMAIN 152 240 Ig-like C2-type 2. FT DOMAIN 249 349 Ig-like C2-type 3. FT DOMAIN 467 755 Protein kinase. FT NP_BIND 473 481 ATP (By similarity). FT ACT_SITE 612 612 Proton acceptor (By similarity). FT BINDING 503 503 ATP (By similarity). FT MOD_RES 643 643 Phosphotyrosine; by autocatalysis (By FT similarity). FT CARBOHYD 112 112 N-linked (GlcNAc...) (Potential). FT CARBOHYD 258 258 N-linked (GlcNAc...) (Potential). FT CARBOHYD 290 290 N-linked (GlcNAc...) (Potential). FT CARBOHYD 311 311 N-linked (GlcNAc...) (Potential). FT CARBOHYD 322 322 N-linked (GlcNAc...) (Potential). FT DISULFID 57 101 Potential. FT DISULFID 172 224 Potential. FT DISULFID 271 333 Potential. FT VAR_SEQ 353 416 EEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQ FT ALHGRHPRPPATVQKLSRFPLAR -> GTGRIPHLTCDSLT FT PAGRTKSPTL (in isoform 2). FT /FTId=VSP_035108. FT VARIANT 10 10 V -> I (in dbSNP:rs1966265). FT /FTId=VAR_029185. FT VARIANT 136 136 P -> L. FT /FTId=VAR_042211. FT VARIANT 179 179 T -> A. FT /FTId=VAR_042212. FT VARIANT 388 388 G -> R (in dbSNP:rs351855). FT /FTId=VAR_014797. FT VARIANT 426 426 G -> S. FT /FTId=VAR_046102. FT VARIANT 516 516 D -> N. FT /FTId=VAR_042213. FT VARIANT 550 550 V -> M (in breast pleomorphic lobular FT sample; somatic mutation). FT /FTId=VAR_046103. FT VARIANT 712 712 P -> T (in a lung adenocarcinoma sample; FT somatic mutation). FT /FTId=VAR_046104. FT VARIANT 772 772 S -> N (in a lung neuroendocrine FT carcinoma sample; somatic mutation). FT /FTId=VAR_046105. FT CONFLICT 121 121 L -> S (in Ref. 3; AAF27432). FT CONFLICT 194 194 E -> G (in Ref. 3; AAF27432). FT CONFLICT 297 297 D -> V (in Ref. 1; CAA40490). FT STRAND 45 47 FT STRAND 65 67 FT STRAND 75 81 FT HELIX 93 95 FT STRAND 100 102 FT STRAND 114 116 FT STRAND 160 163 FT STRAND 168 171 FT TURN 176 178 FT TURN 180 183 FT STRAND 189 191 FT TURN 192 194 FT STRAND 199 205 FT STRAND 208 213 FT HELIX 216 218 FT STRAND 220 227 FT STRAND 229 242 FT STRAND 256 260 FT STRAND 263 265 FT STRAND 267 271 FT STRAND 273 275 FT STRAND 277 285 FT STRAND 295 298 FT STRAND 301 304 FT STRAND 312 322 FT HELIX 325 327 FT STRAND 331 336 FT STRAND 342 349 SQ SEQUENCE 802 AA; 87954 MW; B22B259831BB889F CRC64; MRLLLALLGV LLSVPGPPVL SLEASEEVEL EPCLAPSLEQ QEQELTVALG QPVRLCCGRA ERGGHWYKEG SRLAPAGRVR GWRGRLEIAS FLPEDAGRYL CLARGSMIVL QNLTLITGDS LTSSNDDEDP KSHRDPSNRH SYPQQAPYWT HPQRMEKKLH AVPAGNTVKF RCPAAGNPTP TIRWLKDGQA FHGENRIGGI RLRHQHWSLV MESVVPSDRG TYTCLVENAV GSIRYNYLLD VLERSPHRPI LQAGLPANTT AVVGSDVELL CKVYSDAQPH IQWLKHIVIN GSSFGADGFP YVQVLKTADI NSSEVEVLYL RNVSAEDAGE YTCLAGNSIG LSYQSAWLTV LPEEDPTWTA AAPEARYTDI ILYASGSLAL AVLLLLAGLY RGQALHGRHP RPPATVQKLS RFPLARQFSL ESGSSGKSSS SLVRGVRLSS SGPALLAGLV SLDLPLDPLW EFPRDRLVLG KPLGEGCFGQ VVRAEAFGMD PARPDQASTV AVKMLKDNAS DKDLADLVSE MEVMKLIGRH KNIINLLGVC TQEGPLYVIV ECAAKGNLRE FLRARRPPGP DLSPDGPRSS EGPLSFPVLV SCAYQVARGM QYLESRKCIH RDLAARNVLV TEDNVMKIAD FGLARGVHHI DYYKKTSNGR LPVKWMAPEA LFDRVYTHQS DVWSFGILLW EIFTLGGSPY PGIPVEELFS LLREGHRMDR PPHCPPELYG LMRECWHAAP SQRPTFKQLV EALDKVLLAV SEEYLDLRLT FGPYSPSGGD ASSTCSSSDS VFSHDPLPLG SSSFPFGSGV QT //