LLPS-Hos-0106
FGFR4

▼ OVERVIEW

Status: Reviewed
Protein Name: Fibroblast growth factor receptor 4
Gene Name: FGFR4, JTK2, TKF
Ensembl Gene: ENSG00000160867.14
Ensembl Protein: ENSP00000424670.1
Organism: Homo sapiens
Taxa ID: 9606
LLPS Type: Client
PDB: 5NWZ (A) More


▼ PROPERTY


——— Disorder propensity (calculated by IUPred2A)

▼ Classification

Condensates:
CondensateDescriptionTissue/CellPMIDs
Nucleolus
"...Thus, we analyzed the orthologous groups of the remaining 2316 identified proteins to the human nucleolar proteins. We detected 361 orthologues in NoPDB from the 2316 A. thaliana proteins."
N/A26980300

▼ FUNCTION

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.

▼ SEQUENCE

Protein Sequence (FASTA)
1     MRLLLALLGV  LLSVPGPPVL  SLEASEEVEL  EPCLAPSLEQ  QEQELTVALG  QPVRLCCGRA  60
61    ERGGHWYKEG  SRLAPAGRVR  GWRGRLEIAS  FLPEDAGRYL  CLARGSMIVL  QNLTLITGDS  120
121   LTSSNDDEDP  KSHRDPSNRH  SYPQQAPYWT  HPQRMEKKLH  AVPAGNTVKF  RCPAAGNPTP  180
181   TIRWLKDGQA  FHGENRIGGI  RLRHQHWSLV  MESVVPSDRG  TYTCLVENAV  GSIRYNYLLD  240
241   VLERSPHRPI  LQAGLPANTT  AVVGSDVELL  CKVYSDAQPH  IQWLKHIVIN  GSSFGADGFP  300
301   YVQVLKTADI  NSSEVEVLYL  RNVSAEDAGE  YTCLAGNSIG  LSYQSAWLTV  LPEEDPTWTA  360
361   AAPEARYTDI  ILYASGSLAL  AVLLLLAGLY  RGQALHGRHP  RPPATVQKLS  RFPLARQFSL  420
421   ESGSSGKSSS  SLVRGVRLSS  SGPALLAGLV  SLDLPLDPLW  EFPRDRLVLG  KPLGEGCFGQ  480
481   VVRAEAFGMD  PARPDQASTV  AVKMLKDNAS  DKDLADLVSE  MEVMKLIGRH  KNIINLLGVC  540
541   TQEGPLYVIV  ECAAKGNLRE  FLRARRPPGP  DLSPDGPRSS  EGPLSFPVLV  SCAYQVARGM  600
601   QYLESRKCIH  RDLAARNVLV  TEDNVMKIAD  FGLARGVHHI  DYYKKTSNGR  LPVKWMAPEA  660
661   LFDRVYTHQS  DVWSFGILLW  EIFTLGGSPY  PGIPVEELFS  LLREGHRMDR  PPHCPPELYG  720
721   LMRECWHAAP  SQRPTFKQLV  EALDKVLLAV  SEEYLDLRLT  FGPYSPSGGD  ASSTCSSSDS  780
781   VFSHDPLPLG  SSSFPFGSGV  QT  802
Nucleotide CDS Sequence (FASTA)
1     ATGCGGCTGC  TGCTGGCCCT  GTTGGGGGTC  CTGCTGAGTG  TGCCTGGGCC  TCCAGTCTTG  60
61    TCCCTGGAGG  CCTCTGAGGA  AGTGGAGCTT  GAGCCCTGCC  TGGCTCCCAG  CCTGGAGCAG  120
121   CAAGAGCAGG  AGCTGACAGT  AGCCCTTGGG  CAGCCTGTGC  GTCTGTGCTG  TGGGCGGGCT  180
181   GAGCGTGGTG  GCCACTGGTA  CAAGGAGGGC  AGTCGCCTGG  CACCTGCTGG  CCGTGTACGG  240
241   GGCTGGAGGG  GCCGCCTAGA  GATTGCCAGC  TTCCTACCTG  AGGATGCTGG  CCGCTACCTC  300
301   TGCCTGGCAC  GAGGCTCCAT  GATCGTCCTG  CAGAATCTCA  CCTTGATTAC  AGGTGACTCC  360
361   TTGACCTCCA  GCAACGATGA  TGAGGACCCC  AAGTCCCATA  GGGACCCCTC  GAATAGGCAC  420
421   AGTTACCCCC  AGCAAGCACC  CTACTGGACA  CACCCCCAGC  GCATGGAGAA  GAAACTGCAT  480
481   GCAGTACCTG  CGGGGAACAC  CGTCAAGTTC  CGCTGTCCAG  CTGCAGGCAA  CCCCACGCCC  540
541   ACCATCCGCT  GGCTTAAGGA  TGGACAGGCC  TTTCATGGGG  AGAACCGCAT  TGGAGGCATT  600
601   CGGCTGCGCC  ATCAGCACTG  GAGTCTCGTG  ATGGAGAGCG  TGGTGCCCTC  GGACCGCGGC  660
661   ACATACACCT  GCCTGGTAGA  GAACGCTGTG  GGCAGCATCC  GCTATAACTA  CCTGCTAGAT  720
721   GTGCTGGAGC  GGTCCCCGCA  CCGGCCCATC  CTGCAGGCCG  GGCTCCCGGC  CAACACCACA  780
781   GCCGTGGTGG  GCAGCGACGT  GGAGCTGCTG  TGCAAGGTGT  ACAGCGATGC  CCAGCCCCAC  840
841   ATCCAGTGGC  TGAAGCACAT  CGTCATCAAC  GGCAGCAGCT  TCGGAGCCGA  CGGTTTCCCC  900
901   TATGTGCAAG  TCCTAAAGAC  TGCAGACATC  AATAGCTCAG  AGGTGGAGGT  CCTGTACCTG  960
961   CGGAACGTGT  CAGCCGAGGA  CGCAGGCGAG  TACACCTGCC  TCGCAGGCAA  TTCCATCGGC  1020
1021  CTCTCCTACC  AGTCTGCCTG  GCTCACGGTG  CTGCCAGAGG  AGGACCCCAC  ATGGACCGCA  1080
1081  GCAGCGCCCG  AGGCCAGGTA  TACGGACATC  ATCCTGTACG  CGTCGGGCTC  CCTGGCCTTG  1140
1141  GCTGTGCTCC  TGCTGCTGGC  CGGGCTGTAT  CGAGGGCAGG  CGCTCCACGG  CCGGCACCCC  1200
1201  CGCCCGCCCG  CCACTGTGCA  GAAGCTCTCC  CGCTTCCCTC  TGGCCCGACA  GTTCTCCCTG  1260
1261  GAGTCAGGCT  CTTCCGGCAA  GTCAAGCTCA  TCCCTGGTAC  GAGGCGTGCG  TCTCTCCTCC  1320
1321  AGCGGCCCCG  CCTTGCTCGC  CGGCCTCGTG  AGTCTAGATC  TACCTCTCGA  CCCACTATGG  1380
1381  GAGTTCCCCC  GGGACAGGCT  GGTGCTTGGG  AAGCCCCTAG  GCGAGGGCTG  CTTTGGCCAG  1440
1441  GTAGTACGTG  CAGAGGCCTT  TGGCATGGAC  CCTGCCCGGC  CTGACCAAGC  CAGCACTGTG  1500
1501  GCCGTCAAGA  TGCTCAAAGA  CAACGCCTCT  GACAAGGACC  TGGCCGACCT  GGTCTCGGAG  1560
1561  ATGGAGGTGA  TGAAGCTGAT  CGGCCGACAC  AAGAACATCA  TCAACCTGCT  TGGTGTCTGC  1620
1621  ACCCAGGAAG  GGCCCCTGTA  CGTGATCGTG  GAGTGCGCCG  CCAAGGGAAA  CCTGCGGGAG  1680
1681  TTCCTGCGGG  CCCGGCGCCC  CCCAGGCCCC  GACCTCAGCC  CCGACGGTCC  TCGGAGCAGT  1740
1741  GAGGGGCCGC  TCTCCTTCCC  AGTCCTGGTC  TCCTGCGCCT  ACCAGGTGGC  CCGAGGCATG  1800
1801  CAGTATCTGG  AGTCCCGGAA  GTGTATCCAC  CGGGACCTGG  CTGCCCGCAA  TGTGCTGGTG  1860
1861  ACTGAGGACA  ATGTGATGAA  GATTGCTGAC  TTTGGGCTGG  CCCGCGGCGT  CCACCACATT  1920
1921  GACTACTATA  AGAAAACCAG  CAACGGCCGC  CTGCCTGTGA  AGTGGATGGC  GCCCGAGGCC  1980
1981  TTGTTTGACC  GGGTGTACAC  ACACCAGAGT  GACGTGTGGT  CTTTTGGGAT  CCTGCTATGG  2040
2041  GAGATCTTCA  CCCTCGGGGG  CTCCCCGTAT  CCTGGCATCC  CGGTGGAGGA  GCTGTTCTCG  2100
2101  CTGCTGCGGG  AGGGACATCG  GATGGACCGA  CCCCCACACT  GCCCCCCAGA  GCTGTACGGG  2160
2161  CTGATGCGTG  AGTGCTGGCA  CGCAGCGCCC  TCCCAGAGGC  CTACCTTCAA  GCAGCTGGTG  2220
2221  GAGGCGCTGG  ACAAGGTCCT  GCTGGCCGTC  TCTGAGGAGT  ACCTCGACCT  CCGCCTGACC  2280
2281  TTCGGACCCT  ATTCCCCCTC  TGGTGGGGAC  GCCAGCAGCA  CCTGCTCCTC  CAGCGATTCT  2340
2341  GTCTTCAGCC  ACGACCCCCT  GCCATTGGGA  TCCAGCTCCT  TCCCCTTCGG  GTCTGGGGTG  2400
2401  CAGACATGA  2409

▼ KEYWORD

ID
Family
3D-structure
Alternative splicing
ATP-binding
Cell membrane
Complete proteome
Cytoplasm
Direct protein sequencing
Disease mutation
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Immunoglobulin domain
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation

▼ GENE ONTOLOGY

ID
Classification
Description
Cellular Component
Endoplasmic reticulum
Cellular Component
Endosome
Cellular Component
Extracellular region
Cellular Component
Golgi apparatus
Cellular Component
Integral component of plasma membrane
Cellular Component
Plasma membrane
Cellular Component
Receptor complex
Cellular Component
Transport vesicle
Molecular Function
1-phosphatidylinositol-3-kinase activity
Molecular Function
ATP binding
Molecular Function
Fibroblast growth factor binding
Molecular Function
Fibroblast growth factor-activated receptor activity
Molecular Function
Heparin binding
Molecular Function
Phosphatidylinositol-4,5-bisphosphate 3-kinase activity
Molecular Function
Protein tyrosine kinase activity
Molecular Function
Ras guanyl-nucleotide exchange factor activity
Molecular Function
Transmembrane receptor protein tyrosine kinase activity
Biological Process
Cell migration
Biological Process
Cholesterol homeostasis
Biological Process
Fibroblast growth factor receptor signaling pathway
Biological Process
Glucose homeostasis
Biological Process
MAPK cascade
Biological Process
Nervous system development
Biological Process
Peptidyl-tyrosine phosphorylation
Biological Process
Phosphate ion homeostasis
Biological Process
Positive regulation of catalytic activity
Biological Process
Positive regulation of cell population proliferation
Biological Process
Positive regulation of DNA biosynthetic process
Biological Process
Positive regulation of ERK1 and ERK2 cascade
Biological Process
Positive regulation of gene expression
Biological Process
Positive regulation of protein kinase B signaling
Biological Process
Positive regulation of proteolysis
Biological Process
Protein autophosphorylation
Biological Process
Regulation of bile acid biosynthetic process
Biological Process
Regulation of extracellular matrix disassembly
Biological Process
Regulation of lipid metabolic process
Biological Process
Transmembrane receptor protein tyrosine kinase signaling pathway

▼ KEGG


▼ ORTHOLOGY

DrLLPS IDOrganismIdentityE-valueScore
LLPS-Gog-3660Gorilla gorilla99.450.01379
LLPS-Pap-2846Pan paniscus99.320.01375
LLPS-Paa-0545Papio anubis98.090.01360
LLPS-Mal-1466Mandrillus leucophaeus98.090.01362
LLPS-Man-1845Macaca nemestrina97.950.01359
LLPS-Cea-4374Cercocebus atys97.950.01360
LLPS-Maf-1118Macaca fascicularis97.680.01357
LLPS-Chs-4477Chlorocebus sabaeus97.560.01354
LLPS-Mam-4004Macaca mulatta97.540.01357
LLPS-Pat-4344Pan troglodytes96.730.01326
LLPS-Caj-2880Callithrix jacchus96.590.01339
LLPS-Loa-3703Loxodonta africana96.180.01334
LLPS-Eqc-2672Equus caballus94.950.01303
LLPS-Ict-3618Ictidomys tridecemlineatus94.820.01317
LLPS-Sus-2311Sus scrofa94.410.01313
LLPS-Cap-2177Cavia porcellus94.270.01300
LLPS-Caf-3932Canis familiaris94.130.01304
LLPS-Mup-3049Mustela putorius furo94.130.01301
LLPS-Aim-2638Ailuropoda melanoleuca93.760.01300
LLPS-Bot-0973Bos taurus93.720.01303
LLPS-Fud-1647Fukomys damarensis93.450.01297
LLPS-Mum-4140Mus musculus91.810.01286
LLPS-Mea-3933Mesocricetus auratus91.280.01272
LLPS-Ran-1171Rattus norvegicus91.020.01255
LLPS-Sah-1059Sarcophilus harrisii82.630.01139
LLPS-Mod-0002Monodelphis domestica82.560.01144
LLPS-Otg-3990Otolemur garnettii81.640.0 572
LLPS-Meg-0811Meleagris gallopavo76.131e-109 360
LLPS-Tag-2970Taeniopygia guttata74.420.0 981
LLPS-Gaga-1252Gallus gallus73.610.0 986
LLPS-Rhb-3533Rhinopithecus bieti73.420.0 835
LLPS-Scm-1809Scophthalmus maximus73.161e-157 487
LLPS-Fia-1595Ficedula albicollis72.920.0 984
LLPS-Pof-2340Poecilia formosa72.21e-157 487
LLPS-Xim-1472Xiphophorus maculatus71.886e-157 485
LLPS-Lac-2822Latimeria chalumnae69.170.0 972
LLPS-Tar-3118Takifugu rubripes67.590.0 788
LLPS-Urm-3124Ursus maritimus64.890.0 657
LLPS-Asm-2002Astyanax mexicanus64.270.0 779
LLPS-Pes-1602Pelodiscus sinensis64.10.0 865
LLPS-Poa-4051Pongo abelii63.950.0 692
LLPS-Scf-1394Scleropages formosus63.830.0 837
LLPS-Dar-1263Danio rerio63.820.0 848
LLPS-Cas-0850Carlito syrichta63.790.0 641
LLPS-Anp-2315Anas platyrhynchos63.690.0 863
LLPS-Leo-2873Lepisosteus oculatus63.650.0 857
LLPS-Orn-2722Oreochromis niloticus63.390.0 865
LLPS-Orl-2728Oryzias latipes62.410.0 854
LLPS-Icp-3239Ictalurus punctatus62.360.0 838
LLPS-Ten-0955Tetraodon nigroviridis61.950.0 841
LLPS-Xet-1326Xenopus tropicalis61.490.0 833
LLPS-Fec-1229Felis catus61.20.0 806
LLPS-Aon-3220Aotus nancymaae60.450.0 842
LLPS-Dio-1209Dipodomys ordii59.490.0 841
LLPS-Ova-0679Ovis aries59.080.0 826
LLPS-Orc-3851Oryctolagus cuniculus59.070.0 821
LLPS-Gaa-3322Gasterosteus aculeatus58.960.0 782
LLPS-Nol-3198Nomascus leucogenys58.440.0 783
LLPS-Anc-3343Anolis carolinensis58.050.0 815
LLPS-Ora-0566Ornithorhynchus anatinus56.660.0 745
LLPS-Drm-0860Drosophila melanogaster54.494e-103 341
LLPS-Myl-3022Myotis lucifugus40.233e-67 245