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[uredi | uredi izvor]

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[uredi | uredi izvor]

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[uredi | uredi izvor]

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

Reference[uredi | uredi izvor]

^ ^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[uredi | uredi izvor]

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[uredi | uredi izvor]

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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p r u Proteini: Klasteri diferencijacije (također pogledati Lista ljudskih klastera diferencijacije)
1–50	CD1 a-c 1A 1B 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50
51–100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100
101–150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150
151–200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200
201–250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249
251–300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299
301–350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

p r u Enzimi
Teme	Aktivno mjesto Alosterna regulacija Difuzijski limitirani enzim EC broj Enzimska kataliza Inhibicija enzimskih reakcija Kinetika enzima Koenzim Kooperativnost Lineweaver–Burkov dijagram Michaelis–Mentenova kinetika Mjesto vezanja Spisak enzima
Tipovi	EC1 Oksidoreduktaze/spisak EC2 Transferaze/spisak EC3 Hidrolaze/spisak EC4 Lijaze/spisak EC5 Izomeraze/spisak EC6 Ligaze/spisak