FGFR4_HUMAN - dbPTM
FGFR4_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID FGFR4_HUMAN
UniProt AC P22455
Protein Name Fibroblast growth factor receptor 4
Gene Name FGFR4
Organism Homo sapiens (Human).
Sequence Length 802
Subcellular Localization Cell membrane
Single-pass type I membrane protein. Endosome. Endoplasmic reticulum. Internalized from the cell membrane to recycling endosomes, and from there back to the cell membrane.
Isoform 2: Secreted.
Isoform 3: Cytoplasm .
Protein Description Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down-regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling..
Protein Sequence MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRAERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDSLTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTPTIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLDVLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFPYVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSLESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQVVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVCTQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGMQYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEALFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYGLMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDSVFSHDPLPLGSSSFPFGSGVQT
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
112N-linked_GlycosylationGSMIVLQNLTLITGD
CCEEEEECEEEEECC		30.72UniProtKB CARBOHYD
167PhosphorylationHAVPAGNTVKFRCPA
EECCCCCEEEEECCC		24.93-
232PhosphorylationLVENAVGSIRYNYLL
EEECCCCEEEHHHHH		9.4124719451
258N-linked_GlycosylationLQAGLPANTTAVVGS
CCCCCCCCCEEEECC		35.70UniProtKB CARBOHYD
260O-linked_GlycosylationAGLPANTTAVVGSDV
CCCCCCCEEEECCCH		19.77OGP
290N-linked_GlycosylationWLKHIVINGSSFGAD
EEEEEEECCCCCCCC		33.14UniProtKB CARBOHYD
311N-linked_GlycosylationVLKTADINSSEVEVL
EEEECCCCCCCEEEE		39.78UniProtKB CARBOHYD
322N-linked_GlycosylationVEVLYLRNVSAEDAG
EEEEEEECCCHHHCC		29.51UniProtKB CARBOHYD
368PhosphorylationAAPEARYTDIILYAS
CCCCCCCCCEEECCC		18.37-
390PhosphorylationLLLLAGLYRGQALHG
HHHHHHHHHHHHHCC		16.27-
408UbiquitinationRPPATVQKLSRFPLA
CCCHHHHHHHCCCCC		44.06-
410PhosphorylationPATVQKLSRFPLARQ
CHHHHHHHCCCCCEE		38.6224719451
419PhosphorylationFPLARQFSLESGSSG
CCCCEEEEECCCCCC		23.9226657352
422PhosphorylationARQFSLESGSSGKSS
CEEEEECCCCCCCCC		49.6321406692
424PhosphorylationQFSLESGSSGKSSSS
EEEECCCCCCCCCCC		45.2430576142
425PhosphorylationFSLESGSSGKSSSSL
EEECCCCCCCCCCCE		54.4930576142
428PhosphorylationESGSSGKSSSSLVRG
CCCCCCCCCCCEECC		38.6930576142
429PhosphorylationSGSSGKSSSSLVRGV
CCCCCCCCCCEECCE		27.6823312004
430PhosphorylationGSSGKSSSSLVRGVR
CCCCCCCCCEECCEE		34.4830576142
431PhosphorylationSSGKSSSSLVRGVRL
CCCCCCCCEECCEEE		32.6024719451
439PhosphorylationLVRGVRLSSSGPALL
EECCEEECCCHHHHH		16.3421406692
440PhosphorylationVRGVRLSSSGPALLA
ECCEEECCCHHHHHH		43.8621406692
441PhosphorylationRGVRLSSSGPALLAG
CCEEECCCHHHHHHH		45.4821406692
451PhosphorylationALLAGLVSLDLPLDP
HHHHHHHCCCCCCCC		22.6221406692
471UbiquitinationRDRLVLGKPLGEGCF
CHHEECCCCCCCCCH		32.67-
519PhosphorylationKDLADLVSEMEVMKL
CHHHHHHHHHHHHHH		38.2221406692
573PhosphorylationRPPGPDLSPDGPRSS
CCCCCCCCCCCCCCC		28.4630266825
627UbiquitinationVTEDNVMKIADFGLA
ECCCCEEHHHHHHHC		30.38-
642PhosphorylationRGVHHIDYYKKTSNG
CCCEEEEEEECCCCC		19.3122322096
643PhosphorylationGVHHIDYYKKTSNGR
CCEEEEEEECCCCCC		11.4022322096
644UbiquitinationVHHIDYYKKTSNGRL
CEEEEEEECCCCCCC		43.26-
751PhosphorylationDKVLLAVSEEYLDLR
HHHHHHHCHHHHCEE		21.0728348404
754PhosphorylationLLAVSEEYLDLRLTF
HHHHCHHHHCEEEEE		11.06N.N.
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
642YPhosphorylationKinaseFGFR4P22455
GPS
643YPhosphorylationKinaseFGFR4P22455
GPS
754YPhosphorylationKinaseFGFR4P22455
PSP
-KUbiquitinationE3 ubiquitin ligaseCBLP22681
PMID:18480409
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference

Oops, there are no descriptions of PTM sites of FGFR4_HUMAN !!
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of FGFR4_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
FGFR4_HUMANFGFR4physical
10918587
ANGL4_HUMANANGPTL4physical
25640309
BLID_HUMANBLIDphysical
25640309
CASC3_HUMANCASC3physical
25640309
DIRA3_HUMANDIRAS3physical
25640309
ESIP1_HUMANEPSTI1physical
25640309
ERRFI_HUMANERRFI1physical
25640309
FA84B_HUMANFAM84Bphysical
25640309
GLCE_HUMANGLCEphysical
25640309
MTA3_HUMANMTA3physical
25640309
OSGI1_HUMANOSGIN1physical
25640309
PDLI2_HUMANPDLIM2physical
25640309
HOP2_HUMANPSMC3IPphysical
25640309
RSLAB_HUMANRASL10Bphysical
25640309
BRE1A_HUMANRNF20physical
25640309
SG3A1_HUMANSCGB3A1physical
25640309
THRSP_HUMANTHRSPphysical
25640309
NSD3_HUMANWHSC1L1physical
25640309
WIF1_HUMANWIF1physical
25640309
PTN6_HUMANPTPN6physical
28065597
PTN11_HUMANPTPN11physical
28065597
PTN12_HUMANPTPN12physical
28065597
PTPRR_HUMANPTPRRphysical
28065597
PP2BA_HUMANPPP3CAphysical
28065597
EPHA4_HUMANEPHA4physical
16365308
Drug and Disease Associations
Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D09919 Lenvatinib (USAN/INN)
D09920 Lenvatinib mesilate (JAN); Lenvatinib mesylate (USAN)
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of FGFR4_HUMAN

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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle.";
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.;
Mol. Cell 31:438-448(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-573, AND MASSSPECTROMETRY.
"Altered fibroblast growth factor receptor 4 stability promotesprostate cancer progression.";
Wang J., Yu W., Cai Y., Ren C., Ittmann M.M.;
Neoplasia 10:847-856(2008).
Cited for: CATALYTIC ACTIVITY, FUNCTION AS FGF2 RECEPTOR AND IN STIMULATION OFCELL PROLIFERATION, SUBCELLULAR LOCATION, INTERACTION WITH FGF2 ANDHIP1, PHOSPHORYLATION AT TYR-642 AND TYR-643, AND CHARACTERIZATION OFVARIANT ARG-388.
"Signal transduction by fibroblast growth factor receptor-4 (FGFR-4).Comparison with FGFR-1.";
Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G.,Alitalo K.;
J. Biol. Chem. 269:18320-18326(1994).
Cited for: FUNCTION AS FGF1 RECEPTOR AND IN ACTIVATION OF SIGNALING VIA PLCG1 ANDPIK3R1, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYR-754, ANDMUTAGENESIS OF TYR-754.

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