Molecule Information

General Information of the Molecule (ID: Mol01837)
Name
Fibroblast growth factor receptor 4 (FGFR4) ,Homo sapiens
Synonyms
Fibroblast growth factor receptor 4; FGFR-4; CD antigen CD334; JTK2; TKF
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Molecule Type
Protein
Gene Name
FGFR4
Gene ID
2264
Location
chr5:177,086,905-177,098,144[+]
Sequence
MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRA
ERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDS
LTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTP
TIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLD
VLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFP
YVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTA
AAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSL
ESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQ
VVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVC
TQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGM
QYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEA
LFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYG
LMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDS
VFSHDPLPLGSSSFPFGSGVQT
    Click to Show/Hide
3D-structure
PDB ID
5JKG
Classification
Transferase/transferase inhibitor
Method
X-ray diffraction
Resolution
2.35  Å
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.
    Click to Show/Hide
Uniprot ID
FGFR4_HUMAN
Ensembl ID
ENSG00000160867
HGNC ID
HGNC:3691
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule with Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Erdafitinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Breast cancer [ICD-11: 2C60.3] [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V550M
Wild Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 5JKG
Mutant Type Structure Method: X-ray diffraction Resolution: 3.25  Å
PDB: 5XFJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.43
TM score: 0.99507
Amino acid change:
V550M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
G
P
P
L
L
L
L
A
A
G
G
L
L
450
|
V
V
S
S
L
L
D
D
L
L
P
P
L
L
D
D
P
P
L
L
460
|
W
W
E
E
F
F
P
P
R
R
D
D
R
R
L
L
V
V
L
L
470
|
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
G
G
480
|
Q
Q
V
V
V
V
R
R
A
A
E
E
A
A
F
F
G
G
M
M
490
|
D
D
P
P
A
A
R
R
P
P
D
D
Q
Q
A
A
S
S
T
T
500
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
D
D
N
N
A
A
510
|
S
S
D
D
K
K
D
D
L
L
A
A
D
D
L
L
V
V
S
S
520
|
E
E
M
M
E
E
V
V
M
M
K
K
L
L
I
I
G
G
R
R
530
|
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
V
V
540
|
C
C
T
T
Q
Q
E
E
G
G
P
P
L
L
Y
Y
V
V
I
I
550
|
V
M
E
E
C
C
A
A
A
A
K
K
G
G
N
N
L
L
R
R
560
|
E
E
F
F
L
L
R
R
A
A
R
R
R
R
P
P
P
P
G
G
570
|
P
P
D
D
L
L
S
S
P
P
D
D
G
G
P
P
R
R
S
S
580
|
S
S
E
E
G
G
P
P
L
L
S
S
F
F
P
P
V
V
L
L
590
|
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
G
G
600
|
M
M
Q
Q
Y
Y
L
L
E
E
S
S
R
R
K
K
C
C
I
I
610
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
L
L
620
|
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
A
A
630
|
D
D
F
F
G
G
L
L
A
A
R
R
G
G
V
V
H
H
H
H
640
|
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
S
S
N
N
G
G
650
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
660
|
A
A
L
L
F
F
D
D
R
R
V
V
Y
Y
T
T
H
H
Q
Q
670
|
S
S
D
D
V
V
W
W
S
S
F
F
G
G
I
I
L
L
L
L
680
|
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
P
P
690
|
Y
Y
P
P
G
G
I
I
P
P
V
V
E
E
E
E
L
L
F
F
700
|
S
S
L
L
L
L
R
R
E
E
G
G
H
H
R
R
M
M
D
D
710
|
R
R
P
P
P
P
H
H
C
C
P
P
P
P
E
E
L
L
Y
Y
720
|
G
G
L
L
M
M
R
R
E
E
C
C
W
W
H
H
A
A
A
A
730
|
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
L
L
740
|
V
V
E
E
A
A
L
L
D
D
K
K
V
V
L
L
L
L
A
A
750
|
V
V
S
S
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.
Disease Class: Breast cancer [ICD-11: 2C60.3] [1]
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Resistant Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V550M
Wild Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 5JKG
Mutant Type Structure Method: X-ray diffraction Resolution: 3.25  Å
PDB: 5XFJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.43
TM score: 0.99507
Amino acid change:
V550M
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
G
G
P
P
L
L
L
L
A
A
G
G
L
L
450
|
V
V
S
S
L
L
D
D
L
L
P
P
L
L
D
D
P
P
L
L
460
|
W
W
E
E
F
F
P
P
R
R
D
D
R
R
L
L
V
V
L
L
470
|
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
G
G
480
|
Q
Q
V
V
V
V
R
R
A
A
E
E
A
A
F
F
G
G
M
M
490
|
D
D
P
P
A
A
R
R
P
P
D
D
Q
Q
A
A
S
S
T
T
500
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
D
D
N
N
A
A
510
|
S
S
D
D
K
K
D
D
L
L
A
A
D
D
L
L
V
V
S
S
520
|
E
E
M
M
E
E
V
V
M
M
K
K
L
L
I
I
G
G
R
R
530
|
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
V
V
540
|
C
C
T
T
Q
Q
E
E
G
G
P
P
L
L
Y
Y
V
V
I
I
550
|
V
M
E
E
C
C
A
A
A
A
K
K
G
G
N
N
L
L
R
R
560
|
E
E
F
F
L
L
R
R
A
A
R
R
R
R
P
P
P
P
G
G
570
|
P
P
D
D
L
L
S
S
P
P
D
D
G
G
P
P
R
R
S
S
580
|
S
S
E
E
G
G
P
P
L
L
S
S
F
F
P
P
V
V
L
L
590
|
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
G
G
600
|
M
M
Q
Q
Y
Y
L
L
E
E
S
S
R
R
K
K
C
C
I
I
610
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
L
L
620
|
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
A
A
630
|
D
D
F
F
G
G
L
L
A
A
R
R
G
G
V
V
H
H
H
H
640
|
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
S
S
N
N
G
G
650
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
660
|
A
A
L
L
F
F
D
D
R
R
V
V
Y
Y
T
T
H
H
Q
Q
670
|
S
S
D
D
V
V
W
W
S
S
F
F
G
G
I
I
L
L
L
L
680
|
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
P
P
690
|
Y
Y
P
P
G
G
I
I
P
P
V
V
E
E
E
E
L
L
F
F
700
|
S
S
L
L
L
L
R
R
E
E
G
G
H
H
R
R
M
M
D
D
710
|
R
R
P
P
P
P
H
H
C
C
P
P
P
P
E
E
L
L
Y
Y
720
|
G
G
L
L
M
M
R
R
E
E
C
C
W
W
H
H
A
A
A
A
730
|
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
L
L
740
|
V
V
E
E
A
A
L
L
D
D
K
K
V
V
L
L
L
L
A
A
750
|
V
V
S
S
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.
Disease Class: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1] [1]
Resistant Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
 Disease Info 
Resistant Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V550L
Wild Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 5JKG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.68  Å
PDB: 4QQJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.26
TM score: 0.94767
Amino acid change:
V550L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
440
|
-
H
-
S
-
Q
G
D
P
P
L
L
L
L
A
A
G
G
L
L
450
|
V
V
S
S
L
L
D
D
L
L
P
P
L
L
D
D
P
P
L
L
460
|
W
W
E
E
F
F
P
P
R
R
D
D
R
R
L
L
V
V
L
L
470
|
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
G
G
480
|
Q
Q
V
V
V
V
R
R
A
A
E
E
A
A
F
F
G
G
M
M
490
|
D
D
P
P
A
A
R
R
P
P
D
D
Q
Q
A
A
S
S
T
T
500
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
D
D
N
N
A
A
510
|
S
S
D
D
K
K
D
D
L
L
A
A
D
D
L
L
V
V
S
S
520
|
E
E
M
M
E
E
V
V
M
M
K
K
L
L
I
I
G
G
R
R
530
|
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
V
V
540
|
C
C
T
T
Q
Q
E
E
G
G
P
P
L
L
Y
Y
V
V
I
I
550
|
V
L
E
E
C
C
A
A
A
A
K
K
G
G
N
N
L
L
R
R
560
|
E
E
F
F
L
L
R
R
A
A
R
R
R
R
P
P
P
P
G
G
570
|
P
P
D
D
L
L
S
S
P
P
D
D
G
G
P
P
R
R
S
S
580
|
S
S
E
E
G
G
P
P
L
L
S
S
F
F
P
P
V
V
L
L
590
|
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
G
G
600
|
M
M
Q
Q
Y
Y
L
L
E
E
S
S
R
R
K
K
C
C
I
I
610
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
L
L
620
|
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
A
A
630
|
D
D
F
F
G
G
L
L
A
A
R
R
G
G
V
V
H
H
H
H
640
|
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
S
S
N
N
G
G
650
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
660
|
A
A
L
L
F
F
D
D
R
E
V
V
Y
Y
T
T
H
H
Q
Q
670
|
S
S
D
D
V
V
W
W
S
S
F
F
G
G
I
I
L
L
L
L
680
|
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
P
P
690
|
Y
Y
P
P
G
G
I
I
P
P
V
V
E
E
E
E
L
L
F
F
700
|
S
S
L
L
L
L
R
R
E
E
G
G
H
H
R
R
M
M
D
D
710
|
R
R
P
P
P
P
H
H
C
C
P
P
P
P
E
E
L
L
Y
Y
720
|
G
G
L
L
M
M
R
R
E
E
C
C
W
W
H
H
A
A
A
A
730
|
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
L
L
740
|
V
V
E
E
A
A
L
L
D
D
K
K
V
V
L
L
L
L
A
A
750
|
V
V
S
S
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.
Disease Class: Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1] [1]
Resistant Disease Intrahepatic cholangiocarcinoma [ICD-11: 2C12.1]
 Disease Info 
Resistant Drug Erdafitinib
 Drug Info 
Molecule Alteration Missense mutation
p.V550L
Wild Type Structure Method: X-ray diffraction Resolution: 2.35  Å
PDB: 5JKG
Mutant Type Structure Method: X-ray diffraction Resolution: 1.68  Å
PDB: 4QQJ
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.26
TM score: 0.94767
Amino acid change:
V550L
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
-
M
-
G
-
S
-
S
-
H
-
H
-
H
-
H
-
H
440
|
-
H
-
S
-
Q
G
D
P
P
L
L
L
L
A
A
G
G
L
L
450
|
V
V
S
S
L
L
D
D
L
L
P
P
L
L
D
D
P
P
L
L
460
|
W
W
E
E
F
F
P
P
R
R
D
D
R
R
L
L
V
V
L
L
470
|
G
G
K
K
P
P
L
L
G
G
E
E
G
G
A
A
F
F
G
G
480
|
Q
Q
V
V
V
V
R
R
A
A
E
E
A
A
F
F
G
G
M
M
490
|
D
D
P
P
A
A
R
R
P
P
D
D
Q
Q
A
A
S
S
T
T
500
|
V
V
A
A
V
V
K
K
M
M
L
L
K
K
D
D
N
N
A
A
510
|
S
S
D
D
K
K
D
D
L
L
A
A
D
D
L
L
V
V
S
S
520
|
E
E
M
M
E
E
V
V
M
M
K
K
L
L
I
I
G
G
R
R
530
|
H
H
K
K
N
N
I
I
I
I
N
N
L
L
L
L
G
G
V
V
540
|
C
C
T
T
Q
Q
E
E
G
G
P
P
L
L
Y
Y
V
V
I
I
550
|
V
L
E
E
C
C
A
A
A
A
K
K
G
G
N
N
L
L
R
R
560
|
E
E
F
F
L
L
R
R
A
A
R
R
R
R
P
P
P
P
G
G
570
|
P
P
D
D
L
L
S
S
P
P
D
D
G
G
P
P
R
R
S
S
580
|
S
S
E
E
G
G
P
P
L
L
S
S
F
F
P
P
V
V
L
L
590
|
V
V
S
S
C
C
A
A
Y
Y
Q
Q
V
V
A
A
R
R
G
G
600
|
M
M
Q
Q
Y
Y
L
L
E
E
S
S
R
R
K
K
C
C
I
I
610
|
H
H
R
R
D
D
L
L
A
A
A
A
R
R
N
N
V
V
L
L
620
|
V
V
T
T
E
E
D
D
N
N
V
V
M
M
K
K
I
I
A
A
630
|
D
D
F
F
G
G
L
L
A
A
R
R
G
G
V
V
H
H
H
H
640
|
I
I
D
D
Y
Y
Y
Y
K
K
K
K
T
T
S
S
N
N
G
G
650
|
R
R
L
L
P
P
V
V
K
K
W
W
M
M
A
A
P
P
E
E
660
|
A
A
L
L
F
F
D
D
R
E
V
V
Y
Y
T
T
H
H
Q
Q
670
|
S
S
D
D
V
V
W
W
S
S
F
F
G
G
I
I
L
L
L
L
680
|
W
W
E
E
I
I
F
F
T
T
L
L
G
G
G
G
S
S
P
P
690
|
Y
Y
P
P
G
G
I
I
P
P
V
V
E
E
E
E
L
L
F
F
700
|
S
S
L
L
L
L
R
R
E
E
G
G
H
H
R
R
M
M
D
D
710
|
R
R
P
P
P
P
H
H
C
C
P
P
P
P
E
E
L
L
Y
Y
720
|
G
G
L
L
M
M
R
R
E
E
C
C
W
W
H
H
A
A
A
A
730
|
P
P
S
S
Q
Q
R
R
P
P
T
T
F
F
K
K
Q
Q
L
L
740
|
V
V
E
E
A
A
L
L
D
D
K
K
V
V
L
L
L
L
A
A
750
|
V
V
S
S
E
E
E
E
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Mechanism Description The mutations V550L and V550E in the FGFR4 kinase domain have been demonstrated to confer clinical resistance to erdafitinib in rhabdomyosarcoma, while V550M is associated with erdafitinib resistance in breast cancer.
References
Ref 1 Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance .Br J Cancer. 2021 Mar;124(5):880-892. doi: 10.1038/s41416-020-01157-0. Epub 2020 Dec 3. 10.1038/s41416-020-01157-0

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