FGFR4

FGFR4
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	4QQ5, 4QQC, 4QQJ, 4QQT, 4QRC, 4R6V, 4TYE, 4TYG, 4TYI, 4TYJ, 4UXQ, 4XCU
Identifikatori
Aliasi	FGFR4
Vanjski ID-jevi	OMIM: 134935 MGI: 95525 HomoloGene: 20461 GeneCards: FGFR4
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	177,098,144 bp
Lokacija gena (miš)
Hrom.	Hromosom 13 (miš)
Kraj	55,316,572 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • protein kinase activity; • heparin binding; • kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • transmembrane receptor protein tyrosine kinase activity; • protein tyrosine kinase activity; • fibroblast growth factor binding; • fibroblast growth factor-activated receptor activity; • ATP binding; • phosphatidylinositol-4,5-bisphosphate 3-kinase activity; • 1-phosphatidylinositol-3-kinase activity; • Receptorska tirozin-kinaza; • transmembrane signaling receptor activity;
Ćelijska komponenta	• integral component of membrane; • endozom; • Golđijev aparat; • membrana; • cell-cell junction; • ćelijska membrana; • integral component of plasma membrane; • transport vesicle; • extracellular region; • Endoplazmatski retikulum; • citoplazma; • receptor complex;
Biološki proces	• glucose homeostasis; • Fosforilacija; • phosphate ion homeostasis; • response to bile acid; • regulation of extracellular matrix disassembly; • MAPK cascade; • regulation of bile acid biosynthetic process; • fibroblast growth factor receptor signaling pathway; • regulation of lipid metabolic process; • protein phosphorylation; • GO:1901313 positive regulation of gene expression; • positive regulation of cell population proliferation; • positive regulation of DNA biosynthetic process; • positive regulation of ERK1 and ERK2 cascade; • positive regulation of proteolysis; • protein autophosphorylation; • peptidyl-tyrosine phosphorylation; • Ćelijska migracija; • phosphatidylinositol phosphate biosynthetic process; • GO:0048554 positive regulation of catalytic activity; • phosphatidylinositol-3-phosphate biosynthetic process; • positive regulation of protein kinase B signaling; • cholesterol homeostasis; • Angiogeneza; • negative regulation of signal transduction; • Ćelijska diferencijacija; • negative regulation of apoptotic process; • transmembrane receptor protein tyrosine kinase signaling pathway; • nervous system development;
	Izvori:Amigo / QuickGO
Ortolozi
	2264
	14186
	ENSG00000160867
	ENSMUSG00000005320
	P22455
	Q03142
	NM_001291980; NM_002011; NM_022963; NM_213647; NM_001354984
	NM_008011
	NP_001278909; NP_002002; NP_075252; NP_998812; NP_001341913
	NP_032037
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Receptor 4 faktora rasta fibroblasta jest protein/enzim koji je kod ljudi kodiran genom FGFR4 sa hromosoma 5. Označava se i kao CD334 (klaster diferencjjacije 334).

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 802 aminokiseline, а molekulska težina 87.954 Da.^[5]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
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

Funkcija

Protein kodiran ovim genom član je porodice receptora faktora rasta fibroblasta, gdje je aminokiselinska sekvenca visoko konzervirana između članova i tokom evolucije. Članovi porodice FGFR međusobno se razlikuju po svojim ligandnim afinitetima i tkivnoj raspodjeli. Reprezentativni protein pune dužine sastojao bi se od vanćelijske regije, sastavljene od tri imunoglobulinu slična domena, jednog hidrofobnog segmenta koji pokriva membranu i citoplazmatskog domena tirozin-kinaze. Vanćelijski dio proteina stupa u interakciju s faktorima rasta fibroblasta, pokrećući kaskadu nizvodnih signala, što na kraju utiče na mitogenezu i diferencijaciju.

Genomska organizacija ovog gena, u poređenju sa članovima 1-3, obuhvaTa 18 egzona umjesto 19 ili 20. Iako je primijećena alternativna prerada, nema dokaza da je C-terminalna polovina domena IgIII ovog proteina varira između tri alternativna oblika, kako je naznačeno za članove 1-3. Ovaj član porodice prvenstveno veže kiseli faktor rasta fibroblasta i, iako je njegova specifična funkcija nepoznata, prekomjerno je izražen u uzorcima tumora ženskih reproduktivnih organa, što ukazuje na ulogu u tumorigenezi dojke i jajnika.^[6] U meta-analizi, uočeno je da je funkcionalni polimorfizam Gly388Arg (rs351855) FGFR4 značajno povezan sa zahvatanjem čvorova i ukupnim preživljavanjem kod pacijenata sa različitim tipovima raka.^[7]

Interakcije

Pokazano je da receptor 4 faktora rasta fibroblasta stupa u interakcije sa FGF1.^[8]^[9]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000160867 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000005320 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "UniProt, P22455" (jezik: англ.). Pristupljeno 15. 10. 2021.CS1 održavanje: nepoznati jezik (link)
^ "Entrez Gene: FGFR4 fibroblast growth factor receptor 4".
^ Frullanti, E (2011). "Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor". Eur J Cancer Prev. 20 (4): 340–347. doi:10.1097/CEJ.0b013e3283457274. PMID 21412156. S2CID 29668012.
^ Loo, B B; Darwish K K; Vainikka S S; Saarikettu J J; Vihko P P; Hermonen J J; Goldman A A; Alitalo K K; Jalkanen M M (maj 2000). "Production and characterization of the extracellular domain of recombinant human fibroblast growth factor receptor 4". Int. J. Biochem. Cell Biol. ENGLAND. 32 (5): 489–97. doi:10.1016/S1357-2725(99)00145-4. ISSN 1357-2725. PMID 10736564.
^ Kan, M; Wu X; Wang F; McKeehan W L (maj 1999). "Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase". J. Biol. Chem. UNITED STATES. 274 (22): 15947–52. doi:10.1074/jbc.274.22.15947. ISSN 0021-9258. PMID 10336501.

Dopunska literatura

Doherty P, Smith P, Walsh FS (1997). "Shared cell adhesion molecule (CAM) homology domains point to CAMs signalling via FGF receptors". Perspectives on Developmental Neurobiology. 4 (2–3): 157–68. PMID 9168198.
Warrington JA, Bailey SK, Armstrong E, et al. (1992). "A radiation hybrid map of 18 growth factor, growth factor receptor, hormone receptor, or neurotransmitter receptor genes on the distal region of the long arm of chromosome 5". Genomics. 13 (3): 803–8. doi:10.1016/0888-7543(92)90156-M. PMID 1322355.
Armstrong E, Partanen J, Cannizzaro L, et al. (1992). "Localization of the fibroblast growth factor receptor-4 gene to chromosome region 5q33-qter". Genes Chromosomes Cancer. 4 (1): 94–8. doi:10.1002/gcc.2870040116. PMID 1377018. S2CID 6377972.
Vainikka S, Partanen J, Bellosta P, et al. (1992). "Fibroblast growth factor receptor-4 shows novel features in genomic structure, ligand binding and signal transduction". EMBO J. 11 (12): 4273–80. doi:10.1002/j.1460-2075.1992.tb05526.x. PMC 557000. PMID 1385111.
Partanen J, Mäkelä TP, Eerola E, et al. (1991). "FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern". EMBO J. 10 (6): 1347–54. doi:10.1002/j.1460-2075.1991.tb07654.x. PMC 452793. PMID 1709094.
Holtrich U, Bräuninger A, Strebhardt K, Rübsamen-Waigmann H (1992). "Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family and an intracellular protein-tyrosine kinase". Proc. Natl. Acad. Sci. U.S.A. 88 (23): 10411–5. Bibcode:1991PNAS...8810411H. doi:10.1073/pnas.88.23.10411. PMC 52938. PMID 1720539.
Partanen J, Mäkelä TP, Alitalo R, et al. (1991). "Putative tyrosine kinases expressed in K-562 human leukemia cells". Proc. Natl. Acad. Sci. U.S.A. 87 (22): 8913–7. Bibcode:1990PNAS...87.8913P. doi:10.1073/pnas.87.22.8913. PMC 55070. PMID 2247464.
Vainikka S, Joukov V, Wennström S, et al. (1994). "Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1". J. Biol. Chem. 269 (28): 18320–6. doi:10.1016/S0021-9258(17)32309-8. PMID 7518429.
Wen Z, Zhong Z, Darnell JE (1995). "Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation". Cell. 82 (2): 241–50. doi:10.1016/0092-8674(95)90311-9. PMID 7543024. S2CID 6717533.
Quelle FW, Thierfelder W, Witthuhn BA, et al. (1995). "Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor". J. Biol. Chem. 270 (35): 20775–80. doi:10.1074/jbc.270.35.20775. PMID 7657660.
Ron D, Reich R, Chedid M, et al. (1993). "Fibroblast growth factor receptor 4 is a high affinity receptor for both acidic and basic fibroblast growth factor but not for keratinocyte growth factor". J. Biol. Chem. 268 (8): 5388–94. doi:10.1016/S0021-9258(18)53334-2. PMID 7680645.
Shuai K, Stark GR, Kerr IM, Darnell JE (1993). "A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma". Science. 261 (5129): 1744–6. Bibcode:1993Sci...261.1744S. doi:10.1126/science.7690989. PMID 7690989.
Jaakkola S, Salmikangas P, Nylund S, et al. (1993). "Amplification of fgfr4 gene in human breast and gynecological cancers". Int. J. Cancer. 54 (3): 378–82. doi:10.1002/ijc.2910540305. PMID 8099571. S2CID 19513080.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Reich-Slotky R, Shaoul E, Berman B, et al. (1996). "Chimeric molecules between keratinocyte growth factor and basic fibroblast growth factor define domains that confer receptor binding specificities". J. Biol. Chem. 270 (50): 29813–8. doi:10.1074/jbc.270.50.29813. PMID 8530375.
Vainikka S, Joukov V, Klint P, Alitalo K (1996). "Association of a 85-kDa serine kinase with activated fibroblast growth factor receptor-4". J. Biol. Chem. 271 (3): 1270–3. doi:10.1074/jbc.271.3.1270. PMID 8576110.
Kaptein A, Paillard V, Saunders M (1996). "Dominant negative stat3 mutant inhibits interleukin-6-induced Jak-STAT signal transduction". J. Biol. Chem. 271 (11): 5961–4. doi:10.1074/jbc.271.11.5961. PMID 8626374.
Ornitz DM, Xu J, Colvin JS, et al. (1996). "Receptor specificity of the fibroblast growth factor family". J. Biol. Chem. 271 (25): 15292–7. doi:10.1074/jbc.271.25.15292. PMID 8663044.
Agnès F, Toux MM, André C, Galibert F (1997). "Genomic organization of the extracellular coding region of the human FGFR4 and FLT4 genes: evolution of the genes encoding receptor tyrosine kinases with immunoglobulin-like domains". J. Mol. Evol. 45 (1): 43–9. Bibcode:1997JMolE..45...43A. doi:10.1007/PL00006199. PMID 9211733. S2CID 34208733.

Vanjski linkovi

FGFR4 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.

Šablon:PortalBiologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000160867 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000005320 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[UniProt-5] "UniProt, P22455" (jezik: англ.). Pristupljeno 15. 10. 2021.CS1 održavanje: nepoznati jezik (link)

[6] "Entrez Gene: FGFR4 fibroblast growth factor receptor 4".

[7] Frullanti, E (2011). "Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor". Eur J Cancer Prev. 20 (4): 340–347. doi:10.1097/CEJ.0b013e3283457274. PMID 21412156. S2CID 29668012.

[pmid10736564-8] Loo, B B; Darwish K K; Vainikka S S; Saarikettu J J; Vihko P P; Hermonen J J; Goldman A A; Alitalo K K; Jalkanen M M (maj 2000). "Production and characterization of the extracellular domain of recombinant human fibroblast growth factor receptor 4". Int. J. Biochem. Cell Biol. ENGLAND. 32 (5): 489–97. doi:10.1016/S1357-2725(99)00145-4. ISSN 1357-2725. PMID 10736564.

[pmid10336501-9] Kan, M; Wu X; Wang F; McKeehan W L (maj 1999). "Specificity for fibroblast growth factors determined by heparan sulfate in a binary complex with the receptor kinase". J. Biol. Chem. UNITED STATES. 274 (22): 15947–52. doi:10.1074/jbc.274.22.15947. ISSN 0021-9258. PMID 10336501.

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