Molecule Information

General Information of the Molecule (ID: Mol00065)
Name
Receptor tyrosine-protein kinase erbB-2 (ERBB2) ,Homo sapiens
Molecule Type
Protein
Gene Name
ERBB2
Gene ID
2064
Location
chr17:39687914-39730426[+]
Sequence
MELAALCRWGLLLALLPPGAASTQVCTGTDMKLRLPASPETHLDMLRHLYQGCQVVQGNL
ELTYLPTNASLSFLQDIQEVQGYVLIAHNQVRQVPLQRLRIVRGTQLFEDNYALAVLDNG
DPLNNTTPVTGASPGGLRELQLRSLTEILKGGVLIQRNPQLCYQDTILWKDIFHKNNQLA
LTLIDTNRSRACHPCSPMCKGSRCWGESSEDCQSLTRTVCAGGCARCKGPLPTDCCHEQC
AAGCTGPKHSDCLACLHFNHSGICELHCPALVTYNTDTFESMPNPEGRYTFGASCVTACP
YNYLSTDVGSCTLVCPLHNQEVTAEDGTQRCEKCSKPCARVCYGLGMEHLREVRAVTSAN
IQEFAGCKKIFGSLAFLPESFDGDPASNTAPLQPEQLQVFETLEEITGYLYISAWPDSLP
DLSVFQNLQVIRGRILHNGAYSLTLQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHTV
PWDQLFRNPHQALLHTANRPEDECVGEGLACHQLCARGHCWGPGPTQCVNCSQFLRGQEC
VEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHYKDPPFCVARC
PSGVKPDLSYMPIWKFPDEEGACQPCPINCTHSCVDLDDKGCPAEQRASPLTSIISAVVG
ILLVVVLGVVFGILIKRRQQKIRKYTMRRLLQETELVEPLTPSGAMPNQAQMRILKETEL
RKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSP
YVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR
LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT
HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM
IDSECRPRFRELVSEFSRMARDPQRFVVIQNEDLGPASPLDSTFYRSLLEDDDMGDLVDA
EEYLVPQQGFFCPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEG
AGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCSPQPEYV
NQPDVRPQPPSPREGPLPAARPAGATLERPKTLSPGKNGVVKDVFAFGGAVENPEYLTPQ
GGAAPQPHPPPAFSPAFDNLYYWDQDPPERGAPPSTFKGTPTAENPEYLGLDVPV
    Click to Show/Hide
3D-structure
PDB ID
7MN5
Classification
Signaling protein
Method
Electron microscopy
Resolution
2.93  Å
Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.
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Uniprot ID
ERBB2_HUMAN
Ensembl ID
ENSG00000141736
HGNC ID
HGNC:3430
        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
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
1 drug(s) in total
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Neratinib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Disease Class: HER2 negative breast cancer [ICD-11: 2C60.11] [1]
Sensitive Disease HER2 negative breast cancer [ICD-11: 2C60.11]
 Disease Info 
Sensitive Drug Neratinib
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
Wild Type Structure Method: X-ray diffraction Resolution: 3.09  Å
PDB: 3WLW
Mutant Type Structure Method: Electron microscopy Resolution: 3.09  Å
PDB: 7MN6
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.33
TM score: 0.96205
Amino acid change:
S310F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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840
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890
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920
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960
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970
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990
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1000
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D
-
S
-
T
-
F
-
Y
-
R
-
S
-
L
-
L
1010
|
-
E
-
D
-
D
-
D
-
M
-
G
-
D
-
L
-
V
-
D
1020
|
-
A
-
E
-
E
-
Y
-
L
-
V
-
P
-
Q
-
Q
-
G
1030
|
-
G
-
G
-
S
-
L
-
E
-
V
-
L
-
F
-
Q
-
G
1040
|
-
P
-
S
-
S
-
P
-
S
-
G
-
S
-
S
-
M
-
K
1050
|
-
I
-
E
-
E
-
G
-
K
-
L
-
V
-
I
-
W
-
I
1060
|
-
N
-
G
-
D
-
K
-
G
-
Y
-
N
-
G
-
L
-
A
1070
|
-
E
-
V
-
G
-
K
-
K
-
F
-
E
-
K
-
D
-
T
1080
|
-
G
-
I
-
K
-
V
-
T
-
V
-
E
-
H
-
P
-
D
1090
|
-
K
-
L
-
E
-
E
-
K
-
F
-
P
-
Q
-
V
-
A
1100
|
-
A
-
T
-
G
-
D
-
G
-
P
-
D
-
I
-
I
-
F
1110
|
-
W
-
A
-
H
-
D
-
R
-
F
-
G
-
G
-
Y
-
A
1120
|
-
Q
-
S
-
G
-
L
-
L
-
A
-
E
-
I
-
T
-
P
1130
|
-
D
-
K
-
A
-
F
-
Q
-
D
-
K
-
L
-
Y
-
P
1140
|
-
F
-
T
-
W
-
D
-
A
-
V
-
R
-
Y
-
N
-
G
1150
|
-
K
-
L
-
I
-
A
-
Y
-
P
-
I
-
A
-
V
-
E
1160
|
-
A
-
L
-
S
-
L
-
I
-
Y
-
N
-
K
-
D
-
L
1170
|
-
L
-
P
-
N
-
P
-
P
-
K
-
T
-
W
-
E
-
E
1180
|
-
I
-
P
-
A
-
L
-
D
-
K
-
E
-
L
-
K
-
A
1190
|
-
K
-
G
-
K
-
S
-
A
-
L
-
M
-
F
-
N
-
L
1200
|
-
Q
-
E
-
P
-
Y
-
F
-
T
-
W
-
P
-
L
-
I
1210
|
-
A
-
A
-
D
-
G
-
G
-
Y
-
A
-
F
-
K
-
Y
1220
|
-
E
-
N
-
G
-
K
-
Y
-
D
-
I
-
K
-
D
-
V
1230
|
-
G
-
V
-
D
-
N
-
A
-
G
-
A
-
K
-
A
-
G
1240
|
-
L
-
T
-
F
-
L
-
V
-
D
-
L
-
I
-
K
-
N
1250
|
-
K
-
H
-
M
-
N
-
A
-
D
-
T
-
D
-
Y
-
S
1260
|
-
I
-
A
-
E
-
A
-
A
-
F
-
N
-
K
-
G
-
E
1270
|
-
T
-
A
-
M
-
T
-
I
-
N
-
G
-
P
-
W
-
A
1280
|
-
W
-
S
-
N
-
I
-
D
-
T
-
S
-
K
-
V
-
N
1290
|
-
Y
-
G
-
V
-
T
-
V
-
L
-
P
-
T
-
F
-
K
1300
|
-
G
-
Q
-
P
-
S
-
K
-
P
-
F
-
V
-
G
-
V
1310
|
-
L
-
S
-
A
-
G
-
I
-
N
-
A
-
A
-
S
-
P
1320
|
-
N
-
K
-
E
-
L
-
A
-
K
-
E
-
F
-
L
-
E
1330
|
-
N
-
Y
-
L
-
L
-
T
-
D
-
E
-
G
-
L
-
E
1340
|
-
A
-
V
-
N
-
K
-
D
-
K
-
P
-
L
-
G
-
A
1350
|
-
V
-
A
-
L
-
K
-
S
-
Y
-
E
-
E
-
E
-
L
1360
|
-
A
-
K
-
D
-
P
-
R
-
I
-
A
-
A
-
T
-
M
1370
|
-
E
-
N
-
A
-
Q
-
K
-
G
-
E
-
I
-
M
-
P
1380
|
-
N
-
I
-
P
-
Q
-
M
-
S
-
A
-
F
-
W
-
Y
1390
|
-
A
-
V
-
R
-
T
-
A
-
V
-
I
-
N
-
A
-
A
1400
|
-
S
-
G
-
R
-
Q
-
T
-
V
-
D
-
E
-
A
-
L
1410
|
-
K
-
D
-
A
-
Q
-
T
-
N
-
S
-
S
-
S
-
S
1420
|
-
G
-
P
-
S
-
S
-
P
-
S
-
A
-
W
-
S
-
H
1430
|
-
P
-
Q
-
F
-
E
-
K
-
G
-
G
-
G
-
S
-
G
1440
|
-
G
-
G
-
S
-
G
-
G
-
S
-
S
-
A
-
W
-
S
1450
|
-
H
-
P
-
Q
-
F
-
E
-
K
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Selumetinib
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [ICD-11: 2C94.0] [2]
Resistant Disease Bladder cancer [ICD-11: 2C94.0]
 Disease Info 
Resistant Drug Selumetinib
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
Wild Type Structure Method: X-ray diffraction Resolution: 3.09  Å
PDB: 3WLW
Mutant Type Structure Method: Electron microscopy Resolution: 3.09  Å
PDB: 7MN6
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.33
TM score: 0.96205
Amino acid change:
S310F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
T
M
Q
E
V
L
C
A
T
A
G
L
T
C
D
R
M
W
10
|
K
G
L
L
R
L
L
L
P
A
A
L
S
L
P
P
E
P
T
G
20
|
H
A
L
A
D
S
M
T
L
Q
R
V
H
C
L
T
Y
G
Q
T
30
|
G
D
C
M
Q
K
V
L
V
R
Q
L
G
P
N
A
L
S
E
P
40
|
L
E
T
T
Y
H
L
L
P
D
T
M
N
L
A
R
S
H
L
L
50
|
S
Y
F
Q
L
G
Q
C
D
Q
I
V
Q
V
E
Q
V
G
Q
N
60
|
G
L
Y
E
V
L
L
T
I
Y
A
L
H
P
N
T
Q
N
V
A
70
|
R
S
Q
L
V
S
P
F
L
L
Q
Q
R
D
L
I
R
Q
I
E
80
|
V
V
R
Q
G
G
T
Y
Q
V
L
L
F
I
E
A
D
H
N
N
90
|
Y
Q
A
V
L
R
A
Q
V
V
L
P
D
L
N
Q
G
R
D
L
100
|
P
R
L
I
N
V
N
R
T
G
T
T
P
Q
V
L
T
F
G
E
110
|
A
D
S
N
P
Y
G
A
G
L
L
A
R
V
E
L
L
D
Q
N
120
|
L
G
R
D
S
P
L
L
T
N
E
N
I
T
L
T
K
P
G
V
130
|
G
T
V
G
L
A
I
S
Q
P
R
G
N
G
P
L
Q
R
L
E
140
|
C
L
Y
Q
Q
L
D
R
T
S
I
L
L
T
W
E
K
I
D
L
150
|
I
K
F
G
H
G
K
V
N
L
N
I
Q
Q
L
R
A
N
L
P
160
|
T
Q
L
L
I
C
D
Y
T
Q
N
D
R
T
S
I
R
L
A
W
170
|
C
K
H
D
P
I
C
F
S
H
P
K
M
N
C
N
K
Q
G
L
180
|
S
A
R
L
C
T
W
L
G
I
E
D
S
T
S
N
E
R
D
S
190
|
C
R
Q
A
S
C
L
H
T
P
R
C
T
S
V
P
C
M
A
C
200
|
G
K
G
G
C
S
A
R
R
C
C
W
K
G
G
E
P
S
L
S
210
|
P
E
T
D
D
C
C
Q
C
S
H
L
E
T
Q
R
C
T
A
V
220
|
A
C
G
A
C
G
T
G
G
C
P
A
K
R
H
C
S
K
D
G
230
|
C
P
L
L
A
P
C
T
L
D
H
C
F
C
N
H
H
E
S
Q
240
|
G
C
I
A
C
A
E
G
L
C
H
T
C
G
P
P
A
K
L
H
250
|
V
S
T
D
Y
C
N
L
T
A
D
C
T
L
F
H
E
F
S
N
260
|
M
H
P
S
N
G
P
I
E
C
G
E
R
L
Y
H
T
C
F
P
270
|
G
A
A
L
S
V
C
T
V
Y
T
N
A
T
C
D
P
T
Y
F
280
|
N
E
Y
S
L
M
S
P
T
N
D
P
V
E
G
G
S
R
C
Y
290
|
T
T
L
F
V
G
C
A
P
S
L
C
H
V
N
T
Q
A
E
C
300
|
V
P
T
Y
A
N
E
Y
D
L
G
S
T
T
Q
D
R
V
C
G
310
|
E
F
K
C
C
T
S
L
K
V
P
C
C
P
A
L
R
H
V
N
320
|
C
Q
Y
E
G
V
L
T
G
A
M
E
E
D
H
G
L
T
R
Q
330
|
E
R
V
C
R
E
A
K
V
C
T
S
S
K
A
P
N
C
I
A
340
|
Q
R
E
V
F
C
A
Y
G
G
C
L
K
G
K
M
I
E
F
H
350
|
G
L
S
R
L
E
A
V
F
R
L
A
P
V
E
T
S
S
F
A
360
|
D
N
G
I
D
Q
P
E
A
F
S
A
N
G
T
C
A
K
P
K
370
|
L
I
Q
F
P
G
E
S
Q
L
L
A
Q
F
V
L
F
P
E
E
380
|
T
S
L
F
E
D
E
G
I
D
T
P
G
A
Y
S
L
N
Y
T
390
|
I
A
S
P
A
L
W
Q
P
P
D
E
S
Q
L
L
P
Q
D
V
400
|
L
F
S
E
V
T
F
L
Q
E
N
E
L
I
Q
T
V
G
I
Y
410
|
R
L
G
Y
R
I
I
S
L
A
H
W
N
P
G
D
A
S
Y
L
420
|
S
P
L
D
T
L
L
S
Q
V
G
F
L
Q
G
N
I
L
S
Q
430
|
W
V
L
I
G
R
L
G
R
R
S
I
L
L
R
H
E
N
L
G
440
|
G
A
S
Y
G
S
L
L
A
T
L
L
I
Q
H
G
H
L
N
G
450
|
T
I
H
S
L
W
C
L
F
G
V
L
H
R
T
S
V
L
P
R
460
|
W
E
D
L
Q
G
L
S
F
G
R
L
N
A
P
L
H
I
Q
H
470
|
A
H
L
N
L
T
H
H
T
L
A
C
N
F
R
V
P
H
E
T
480
|
D
V
E
P
C
W
V
D
G
Q
E
L
G
F
L
R
A
N
C
P
490
|
H
H
Q
Q
L
A
C
L
A
L
R
H
G
T
H
A
C
N
W
R
500
|
G
P
P
E
G
D
P
E
T
C
Q
V
C
G
V
E
N
G
C
L
510
|
S
A
Q
C
F
H
L
Q
R
L
G
C
Q
A
E
R
C
G
V
H
520
|
E
C
E
W
C
G
R
P
V
G
L
P
Q
T
G
Q
L
C
P
V
530
|
R
N
E
C
Y
S
V
Q
N
F
A
L
R
R
H
G
C
Q
L
E
540
|
P
C
C
V
H
E
P
E
E
C
C
R
Q
V
P
L
Q
Q
N
G
550
|
G
L
S
P
V
R
T
E
C
Y
F
V
G
N
P
A
E
R
A
H
560
|
D
C
Q
L
C
P
V
C
A
H
-
P
-
E
-
C
-
Q
-
P
570
|
-
Q
-
N
-
G
-
S
-
V
-
T
-
C
-
F
-
G
-
P
580
|
-
E
-
A
-
D
-
Q
-
C
-
V
-
A
-
C
-
A
-
H
590
|
-
Y
-
K
-
D
-
P
-
P
-
F
-
C
-
V
-
A
-
R
600
|
-
C
-
P
-
S
-
G
-
V
-
K
-
P
-
D
-
L
-
S
610
|
-
Y
-
M
-
P
-
I
-
W
-
K
-
F
-
P
-
D
-
E
620
|
-
E
-
G
-
A
-
C
-
Q
-
P
-
C
-
P
-
I
-
N
630
|
-
C
-
T
-
H
-
S
-
C
-
V
-
D
-
L
-
D
-
D
640
|
-
K
-
G
-
C
-
P
-
A
-
E
-
Q
-
R
-
A
-
S
650
|
-
P
-
L
-
T
-
S
-
I
-
I
-
S
-
A
-
V
-
V
660
|
-
G
-
I
-
L
-
L
-
V
-
V
-
V
-
L
-
G
-
V
670
|
-
V
-
F
-
G
-
I
-
L
-
I
-
K
-
R
-
R
-
Q
680
|
-
Q
-
K
-
I
-
R
-
K
-
Y
-
T
-
M
-
R
-
R
690
|
-
L
-
L
-
Q
-
E
-
T
-
E
-
L
-
V
-
E
-
P
700
|
-
L
-
T
-
P
-
S
-
G
-
A
-
M
-
P
-
N
-
Q
710
|
-
A
-
Q
-
M
-
R
-
I
-
L
-
K
-
E
-
T
-
E
720
|
-
L
-
R
-
K
-
V
-
K
-
V
-
L
-
G
-
S
-
G
730
|
-
A
-
F
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Y
-
K
-
G
-
I
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740
|
-
I
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P
-
D
-
G
-
E
-
N
-
V
-
K
-
I
-
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750
|
-
V
-
A
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I
-
K
-
V
-
L
-
R
-
E
-
N
-
T
760
|
-
S
-
P
-
K
-
A
-
N
-
K
-
E
-
I
-
L
-
D
770
|
-
E
-
A
-
Y
-
V
-
M
-
A
-
G
-
V
-
D
-
S
780
|
-
P
-
Y
-
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-
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L
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I
-
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790
|
-
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-
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-
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800
|
-
L
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M
-
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-
Y
-
G
-
C
-
L
-
L
-
D
-
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810
|
-
V
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R
-
E
-
N
-
R
-
G
-
R
-
L
-
G
-
S
820
|
-
Q
-
D
-
L
-
L
-
N
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W
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C
-
M
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-
I
830
|
-
A
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K
-
G
-
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-
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-
Y
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-
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840
|
-
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L
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-
H
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-
D
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-
A
-
A
-
R
850
|
-
N
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P
-
N
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H
-
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860
|
-
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I
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870
|
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E
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Y
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880
|
-
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G
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890
|
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900
|
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910
|
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920
|
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A
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930
|
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940
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950
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960
|
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970
|
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980
|
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I
990
|
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-
A
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-
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1000
|
-
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-
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1010
|
-
E
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D
-
D
-
D
-
M
-
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D
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-
D
1020
|
-
A
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E
-
E
-
Y
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Q
-
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1030
|
-
G
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G
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1040
|
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1050
|
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E
-
E
-
G
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-
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-
I
1060
|
-
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D
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-
G
-
Y
-
N
-
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L
-
A
1070
|
-
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-
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E
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1080
|
-
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I
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-
D
1090
|
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-
A
1100
|
-
A
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I
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1110
|
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-
A
1120
|
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1130
|
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1140
|
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1150
|
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A
-
Y
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-
I
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A
-
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-
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1160
|
-
A
-
L
-
S
-
L
-
I
-
Y
-
N
-
K
-
D
-
L
1170
|
-
L
-
P
-
N
-
P
-
P
-
K
-
T
-
W
-
E
-
E
1180
|
-
I
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P
-
A
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D
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E
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-
A
1190
|
-
K
-
G
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K
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-
A
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-
M
-
F
-
N
-
L
1200
|
-
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-
Y
-
F
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T
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-
I
1210
|
-
A
-
A
-
D
-
G
-
G
-
Y
-
A
-
F
-
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-
Y
1220
|
-
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-
N
-
G
-
K
-
Y
-
D
-
I
-
K
-
D
-
V
1230
|
-
G
-
V
-
D
-
N
-
A
-
G
-
A
-
K
-
A
-
G
1240
|
-
L
-
T
-
F
-
L
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V
-
D
-
L
-
I
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-
N
1250
|
-
K
-
H
-
M
-
N
-
A
-
D
-
T
-
D
-
Y
-
S
1260
|
-
I
-
A
-
E
-
A
-
A
-
F
-
N
-
K
-
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-
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1270
|
-
T
-
A
-
M
-
T
-
I
-
N
-
G
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P
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W
-
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1280
|
-
W
-
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-
N
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I
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D
-
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S
-
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-
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-
N
1290
|
-
Y
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G
-
V
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P
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F
-
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1300
|
-
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-
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-
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1310
|
-
L
-
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-
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-
G
-
I
-
N
-
A
-
A
-
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-
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1320
|
-
N
-
K
-
E
-
L
-
A
-
K
-
E
-
F
-
L
-
E
1330
|
-
N
-
Y
-
L
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L
-
T
-
D
-
E
-
G
-
L
-
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1340
|
-
A
-
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-
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-
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-
A
1350
|
-
V
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A
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E
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1360
|
-
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D
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R
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A
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1370
|
-
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N
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1380
|
-
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A
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F
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W
-
Y
1390
|
-
A
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V
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R
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T
-
A
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V
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I
-
N
-
A
-
A
1400
|
-
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G
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D
-
E
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A
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L
1410
|
-
K
-
D
-
A
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Q
-
T
-
N
-
S
-
S
-
S
-
S
1420
|
-
G
-
P
-
S
-
S
-
P
-
S
-
A
-
W
-
S
-
H
1430
|
-
P
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Q
-
F
-
E
-
K
-
G
-
G
-
G
-
S
-
G
1440
|
-
G
-
G
-
S
-
G
-
G
-
S
-
S
-
A
-
W
-
S
1450
|
-
H
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P
-
Q
-
F
-
E
-
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
J82 cells Bladder Homo sapiens (Human) CVCL_0359
RT4 cells Bladder Homo sapiens (Human) CVCL_0036
T24 cells Bladder Homo sapiens (Human) CVCL_0554
SW780 cells Bladder Homo sapiens (Human) CVCL_1728
HT1376 cells Bladder Homo sapiens (Human) CVCL_1292
RT112 cells Bladder Homo sapiens (Human) CVCL_1670
TCCSuP cells Bladder Homo sapiens (Human) CVCL_1738
UM-UC3 cells Urinary bladder Homo sapiens (Human) CVCL_1783
WH cells Bladder Homo sapiens (Human) CVCL_0C39
VM-CUBIII cells Urinary bladder Homo sapiens (Human) CVCL_9830
VM-CUBII cells Urinary bladder Homo sapiens (Human) CVCL_9829
VM-CUBI cells Obturator lymph node Homo sapiens (Human) CVCL_1786
UM-UC-14 cells Kidney Homo sapiens (Human) CVCL_2747
TSU-PR1 cells Urinary bladder Homo sapiens (Human) CVCL_4014
SW1710 cells Bladder Homo sapiens (Human) CVCL_1721
SD cells Bladder Homo sapiens (Human) CVCL_W902
KU-19 cells Blood Bos taurus (Bovine) CVCL_VN09
JO'N cells Urinary bladder Homo sapiens (Human) CVCL_M891
JMSU-1 cells Ascites Homo sapiens (Human) CVCL_2081
HT1197 cells Urinary bladder Homo sapiens (Human) CVCL_1291
DSH1 cells Urinary bladder Homo sapiens (Human) CVCL_1182
CAL-29 cells Urinary bladder Homo sapiens (Human) CVCL_1808
BFTC-905 cells Urinary bladder Homo sapiens (Human) CVCL_1083
BC-3C cells Urinary bladder Homo sapiens (Human) CVCL_1958
97-7 cells Bladder Homo sapiens (Human) CVCL_8625
97-24 cells Bladder Homo sapiens (Human) CVCL_8621
97-18 cells Bladder Homo sapiens (Human) CVCL_8619
97-1 cells Bladder Homo sapiens (Human) CVCL_8616
96-1 cells Bladder Homo sapiens (Human) CVCL_8609
94-10 cells Bladder Homo sapiens (Human) CVCL_8608
647V cells Urinary bladder Homo sapiens (Human) CVCL_1049
253J cells Lymph node Homo sapiens (Human) CVCL_7935/CVCL_7938
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
ERBB2 TKIs
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [3]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug ERBB2 TKIs
 Drug Info 
Molecule Alteration Missense mutation
p.S310F (c.929C>T)
Wild Type Structure Method: X-ray diffraction Resolution: 3.09  Å
PDB: 3WLW
Mutant Type Structure Method: Electron microscopy Resolution: 3.09  Å
PDB: 7MN6
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.33
TM score: 0.96205
Amino acid change:
S310F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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T
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A
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10
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L
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L
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A
A
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L
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P
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P
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20
|
H
A
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A
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T
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H
C
L
T
Y
G
Q
T
30
|
G
D
C
M
Q
K
V
L
V
R
Q
L
G
P
N
A
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S
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40
|
L
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T
T
Y
H
L
L
P
D
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M
N
L
A
R
S
H
L
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50
|
S
Y
F
Q
L
G
Q
C
D
Q
I
V
Q
V
E
Q
V
G
Q
N
60
|
G
L
Y
E
V
L
L
T
I
Y
A
L
H
P
N
T
Q
N
V
A
70
|
R
S
Q
L
V
S
P
F
L
L
Q
Q
R
D
L
I
R
Q
I
E
80
|
V
V
R
Q
G
G
T
Y
Q
V
L
L
F
I
E
A
D
H
N
N
90
|
Y
Q
A
V
L
R
A
Q
V
V
L
P
D
L
N
Q
G
R
D
L
100
|
P
R
L
I
N
V
N
R
T
G
T
T
P
Q
V
L
T
F
G
E
110
|
A
D
S
N
P
Y
G
A
G
L
L
A
R
V
E
L
L
D
Q
N
120
|
L
G
R
D
S
P
L
L
T
N
E
N
I
T
L
T
K
P
G
V
130
|
G
T
V
G
L
A
I
S
Q
P
R
G
N
G
P
L
Q
R
L
E
140
|
C
L
Y
Q
Q
L
D
R
T
S
I
L
L
T
W
E
K
I
D
L
150
|
I
K
F
G
H
G
K
V
N
L
N
I
Q
Q
L
R
A
N
L
P
160
|
T
Q
L
L
I
C
D
Y
T
Q
N
D
R
T
S
I
R
L
A
W
170
|
C
K
H
D
P
I
C
F
S
H
P
K
M
N
C
N
K
Q
G
L
180
|
S
A
R
L
C
T
W
L
G
I
E
D
S
T
S
N
E
R
D
S
190
|
C
R
Q
A
S
C
L
H
T
P
R
C
T
S
V
P
C
M
A
C
200
|
G
K
G
G
C
S
A
R
R
C
C
W
K
G
G
E
P
S
L
S
210
|
P
E
T
D
D
C
C
Q
C
S
H
L
E
T
Q
R
C
T
A
V
220
|
A
C
G
A
C
G
T
G
G
C
P
A
K
R
H
C
S
K
D
G
230
|
C
P
L
L
A
P
C
T
L
D
H
C
F
C
N
H
H
E
S
Q
240
|
G
C
I
A
C
A
E
G
L
C
H
T
C
G
P
P
A
K
L
H
250
|
V
S
T
D
Y
C
N
L
T
A
D
C
T
L
F
H
E
F
S
N
260
|
M
H
P
S
N
G
P
I
E
C
G
E
R
L
Y
H
T
C
F
P
270
|
G
A
A
L
S
V
C
T
V
Y
T
N
A
T
C
D
P
T
Y
F
280
|
N
E
Y
S
L
M
S
P
T
N
D
P
V
E
G
G
S
R
C
Y
290
|
T
T
L
F
V
G
C
A
P
S
L
C
H
V
N
T
Q
A
E
C
300
|
V
P
T
Y
A
N
E
Y
D
L
G
S
T
T
Q
D
R
V
C
G
310
|
E
F
K
C
C
T
S
L
K
V
P
C
C
P
A
L
R
H
V
N
320
|
C
Q
Y
E
G
V
L
T
G
A
M
E
E
D
H
G
L
T
R
Q
330
|
E
R
V
C
R
E
A
K
V
C
T
S
S
K
A
P
N
C
I
A
340
|
Q
R
E
V
F
C
A
Y
G
G
C
L
K
G
K
M
I
E
F
H
350
|
G
L
S
R
L
E
A
V
F
R
L
A
P
V
E
T
S
S
F
A
360
|
D
N
G
I
D
Q
P
E
A
F
S
A
N
G
T
C
A
K
P
K
370
|
L
I
Q
F
P
G
E
S
Q
L
L
A
Q
F
V
L
F
P
E
E
380
|
T
S
L
F
E
D
E
G
I
D
T
P
G
A
Y
S
L
N
Y
T
390
|
I
A
S
P
A
L
W
Q
P
P
D
E
S
Q
L
L
P
Q
D
V
400
|
L
F
S
E
V
T
F
L
Q
E
N
E
L
I
Q
T
V
G
I
Y
410
|
R
L
G
Y
R
I
I
S
L
A
H
W
N
P
G
D
A
S
Y
L
420
|
S
P
L
D
T
L
L
S
Q
V
G
F
L
Q
G
N
I
L
S
Q
430
|
W
V
L
I
G
R
L
G
R
R
S
I
L
L
R
H
E
N
L
G
440
|
G
A
S
Y
G
S
L
L
A
T
L
L
I
Q
H
G
H
L
N
G
450
|
T
I
H
S
L
W
C
L
F
G
V
L
H
R
T
S
V
L
P
R
460
|
W
E
D
L
Q
G
L
S
F
G
R
L
N
A
P
L
H
I
Q
H
470
|
A
H
L
N
L
T
H
H
T
L
A
C
N
F
R
V
P
H
E
T
480
|
D
V
E
P
C
W
V
D
G
Q
E
L
G
F
L
R
A
N
C
P
490
|
H
H
Q
Q
L
A
C
L
A
L
R
H
G
T
H
A
C
N
W
R
500
|
G
P
P
E
G
D
P
E
T
C
Q
V
C
G
V
E
N
G
C
L
510
|
S
A
Q
C
F
H
L
Q
R
L
G
C
Q
A
E
R
C
G
V
H
520
|
E
C
E
W
C
G
R
P
V
G
L
P
Q
T
G
Q
L
C
P
V
530
|
R
N
E
C
Y
S
V
Q
N
F
A
L
R
R
H
G
C
Q
L
E
540
|
P
C
C
V
H
E
P
E
E
C
C
R
Q
V
P
L
Q
Q
N
G
550
|
G
L
S
P
V
R
T
E
C
Y
F
V
G
N
P
A
E
R
A
H
560
|
D
C
Q
L
C
P
V
C
A
H
-
P
-
E
-
C
-
Q
-
P
570
|
-
Q
-
N
-
G
-
S
-
V
-
T
-
C
-
F
-
G
-
P
580
|
-
E
-
A
-
D
-
Q
-
C
-
V
-
A
-
C
-
A
-
H
590
|
-
Y
-
K
-
D
-
P
-
P
-
F
-
C
-
V
-
A
-
R
600
|
-
C
-
P
-
S
-
G
-
V
-
K
-
P
-
D
-
L
-
S
610
|
-
Y
-
M
-
P
-
I
-
W
-
K
-
F
-
P
-
D
-
E
620
|
-
E
-
G
-
A
-
C
-
Q
-
P
-
C
-
P
-
I
-
N
630
|
-
C
-
T
-
H
-
S
-
C
-
V
-
D
-
L
-
D
-
D
640
|
-
K
-
G
-
C
-
P
-
A
-
E
-
Q
-
R
-
A
-
S
650
|
-
P
-
L
-
T
-
S
-
I
-
I
-
S
-
A
-
V
-
V
660
|
-
G
-
I
-
L
-
L
-
V
-
V
-
V
-
L
-
G
-
V
670
|
-
V
-
F
-
G
-
I
-
L
-
I
-
K
-
R
-
R
-
Q
680
|
-
Q
-
K
-
I
-
R
-
K
-
Y
-
T
-
M
-
R
-
R
690
|
-
L
-
L
-
Q
-
E
-
T
-
E
-
L
-
V
-
E
-
P
700
|
-
L
-
T
-
P
-
S
-
G
-
A
-
M
-
P
-
N
-
Q
710
|
-
A
-
Q
-
M
-
R
-
I
-
L
-
K
-
E
-
T
-
E
720
|
-
L
-
R
-
K
-
V
-
K
-
V
-
L
-
G
-
S
-
G
730
|
-
A
-
F
-
G
-
T
-
V
-
Y
-
K
-
G
-
I
-
W
740
|
-
I
-
P
-
D
-
G
-
E
-
N
-
V
-
K
-
I
-
P
750
|
-
V
-
A
-
I
-
K
-
V
-
L
-
R
-
E
-
N
-
T
760
|
-
S
-
P
-
K
-
A
-
N
-
K
-
E
-
I
-
L
-
D
770
|
-
E
-
A
-
Y
-
V
-
M
-
A
-
G
-
V
-
D
-
S
780
|
-
P
-
Y
-
V
-
S
-
R
-
L
-
L
-
G
-
I
-
C
790
|
-
L
-
T
-
S
-
T
-
V
-
Q
-
L
-
V
-
T
-
Q
800
|
-
L
-
M
-
P
-
Y
-
G
-
C
-
L
-
L
-
D
-
H
810
|
-
V
-
R
-
E
-
N
-
R
-
G
-
R
-
L
-
G
-
S
820
|
-
Q
-
D
-
L
-
L
-
N
-
W
-
C
-
M
-
Q
-
I
830
|
-
A
-
K
-
G
-
M
-
S
-
Y
-
L
-
E
-
D
-
V
840
|
-
R
-
L
-
V
-
H
-
R
-
D
-
L
-
A
-
A
-
R
850
|
-
N
-
V
-
L
-
V
-
K
-
S
-
P
-
N
-
H
-
V
860
|
-
K
-
I
-
T
-
D
-
F
-
G
-
L
-
A
-
R
-
L
870
|
-
L
-
D
-
I
-
D
-
E
-
T
-
E
-
Y
-
H
-
A
880
|
-
D
-
G
-
G
-
K
-
V
-
P
-
I
-
K
-
W
-
M
890
|
-
A
-
L
-
E
-
S
-
I
-
L
-
R
-
R
-
R
-
F
900
|
-
T
-
H
-
Q
-
S
-
D
-
V
-
W
-
S
-
Y
-
G
910
|
-
V
-
T
-
V
-
W
-
E
-
L
-
M
-
T
-
F
-
G
920
|
-
A
-
K
-
P
-
Y
-
D
-
G
-
I
-
P
-
A
-
R
930
|
-
E
-
I
-
P
-
D
-
L
-
L
-
E
-
K
-
G
-
E
940
|
-
R
-
L
-
P
-
Q
-
P
-
P
-
I
-
C
-
T
-
I
950
|
-
D
-
V
-
Y
-
M
-
I
-
M
-
V
-
K
-
C
-
W
960
|
-
M
-
I
-
D
-
S
-
E
-
C
-
R
-
P
-
R
-
F
970
|
-
R
-
E
-
L
-
V
-
S
-
E
-
F
-
S
-
R
-
M
980
|
-
A
-
R
-
D
-
P
-
Q
-
R
-
F
-
V
-
V
-
I
990
|
-
Q
-
N
-
E
-
D
-
L
-
G
-
P
-
A
-
S
-
P
1000
|
-
L
-
D
-
S
-
T
-
F
-
Y
-
R
-
S
-
L
-
L
1010
|
-
E
-
D
-
D
-
D
-
M
-
G
-
D
-
L
-
V
-
D
1020
|
-
A
-
E
-
E
-
Y
-
L
-
V
-
P
-
Q
-
Q
-
G
1030
|
-
G
-
G
-
S
-
L
-
E
-
V
-
L
-
F
-
Q
-
G
1040
|
-
P
-
S
-
S
-
P
-
S
-
G
-
S
-
S
-
M
-
K
1050
|
-
I
-
E
-
E
-
G
-
K
-
L
-
V
-
I
-
W
-
I
1060
|
-
N
-
G
-
D
-
K
-
G
-
Y
-
N
-
G
-
L
-
A
1070
|
-
E
-
V
-
G
-
K
-
K
-
F
-
E
-
K
-
D
-
T
1080
|
-
G
-
I
-
K
-
V
-
T
-
V
-
E
-
H
-
P
-
D
1090
|
-
K
-
L
-
E
-
E
-
K
-
F
-
P
-
Q
-
V
-
A
1100
|
-
A
-
T
-
G
-
D
-
G
-
P
-
D
-
I
-
I
-
F
1110
|
-
W
-
A
-
H
-
D
-
R
-
F
-
G
-
G
-
Y
-
A
1120
|
-
Q
-
S
-
G
-
L
-
L
-
A
-
E
-
I
-
T
-
P
1130
|
-
D
-
K
-
A
-
F
-
Q
-
D
-
K
-
L
-
Y
-
P
1140
|
-
F
-
T
-
W
-
D
-
A
-
V
-
R
-
Y
-
N
-
G
1150
|
-
K
-
L
-
I
-
A
-
Y
-
P
-
I
-
A
-
V
-
E
1160
|
-
A
-
L
-
S
-
L
-
I
-
Y
-
N
-
K
-
D
-
L
1170
|
-
L
-
P
-
N
-
P
-
P
-
K
-
T
-
W
-
E
-
E
1180
|
-
I
-
P
-
A
-
L
-
D
-
K
-
E
-
L
-
K
-
A
1190
|
-
K
-
G
-
K
-
S
-
A
-
L
-
M
-
F
-
N
-
L
1200
|
-
Q
-
E
-
P
-
Y
-
F
-
T
-
W
-
P
-
L
-
I
1210
|
-
A
-
A
-
D
-
G
-
G
-
Y
-
A
-
F
-
K
-
Y
1220
|
-
E
-
N
-
G
-
K
-
Y
-
D
-
I
-
K
-
D
-
V
1230
|
-
G
-
V
-
D
-
N
-
A
-
G
-
A
-
K
-
A
-
G
1240
|
-
L
-
T
-
F
-
L
-
V
-
D
-
L
-
I
-
K
-
N
1250
|
-
K
-
H
-
M
-
N
-
A
-
D
-
T
-
D
-
Y
-
S
1260
|
-
I
-
A
-
E
-
A
-
A
-
F
-
N
-
K
-
G
-
E
1270
|
-
T
-
A
-
M
-
T
-
I
-
N
-
G
-
P
-
W
-
A
1280
|
-
W
-
S
-
N
-
I
-
D
-
T
-
S
-
K
-
V
-
N
1290
|
-
Y
-
G
-
V
-
T
-
V
-
L
-
P
-
T
-
F
-
K
1300
|
-
G
-
Q
-
P
-
S
-
K
-
P
-
F
-
V
-
G
-
V
1310
|
-
L
-
S
-
A
-
G
-
I
-
N
-
A
-
A
-
S
-
P
1320
|
-
N
-
K
-
E
-
L
-
A
-
K
-
E
-
F
-
L
-
E
1330
|
-
N
-
Y
-
L
-
L
-
T
-
D
-
E
-
G
-
L
-
E
1340
|
-
A
-
V
-
N
-
K
-
D
-
K
-
P
-
L
-
G
-
A
1350
|
-
V
-
A
-
L
-
K
-
S
-
Y
-
E
-
E
-
E
-
L
1360
|
-
A
-
K
-
D
-
P
-
R
-
I
-
A
-
A
-
T
-
M
1370
|
-
E
-
N
-
A
-
Q
-
K
-
G
-
E
-
I
-
M
-
P
1380
|
-
N
-
I
-
P
-
Q
-
M
-
S
-
A
-
F
-
W
-
Y
1390
|
-
A
-
V
-
R
-
T
-
A
-
V
-
I
-
N
-
A
-
A
1400
|
-
S
-
G
-
R
-
Q
-
T
-
V
-
D
-
E
-
A
-
L
1410
|
-
K
-
D
-
A
-
Q
-
T
-
N
-
S
-
S
-
S
-
S
1420
|
-
G
-
P
-
S
-
S
-
P
-
S
-
A
-
W
-
S
-
H
1430
|
-
P
-
Q
-
F
-
E
-
K
-
G
-
G
-
G
-
S
-
G
1440
|
-
G
-
G
-
S
-
G
-
G
-
S
-
S
-
A
-
W
-
S
1450
|
-
H
-
P
-
Q
-
F
-
E
-
K
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
Experiment for
Drug Resistance		 WST-1 assay
Mechanism Description The missense mutation p.S310F (c.929C>T) in gene ERBB2 cause the sensitivity of ERBB2 TKIs by aberration of the drug's therapeutic target
References
Ref 1 HER kinase inhibition in patients with HER2- and HER3-mutant cancersNature. 2018 Feb 8;554(7691):189-194. doi: 10.1038/nature25475. Epub 2018 Jan 31.
Ref 2 Impact of ERBB2 mutations on in vitro sensitivity of bladder cancer to lapatinibCancer Biol Ther. 2014 Sep;15(9):1239-47. doi: 10.4161/cbt.29687. Epub 2014 Jul 14.
Ref 3 Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14476-81. doi: 10.1073/pnas.1203201109. Epub 2012 Aug 20.

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