Molecule Information

General Information of the Molecule (ID: Mol00597)
Name
Receptor tyrosine-protein kinase erbB-3 (ERBB3) ,Homo sapiens
Synonyms
Proto-oncogene-like protein c-ErbB-3; Tyrosine kinase-type cell surface receptor HER3; HER3
    Click to Show/Hide
Molecule Type
Protein
Gene Name
ERBB3
Gene ID
2065
Location
chr12:56076799-56103505[+]
Sequence
MRANDALQVLGLLFSLARGSEVGNSQAVCPGTLNGLSVTGDAENQYQTLYKLYERCEVVM
GNLEIVLTGHNADLSFLQWIREVTGYVLVAMNEFSTLPLPNLRVVRGTQVYDGKFAIFVM
LNYNTNSSHALRQLRLTQLTEILSGGVYIEKNDKLCHMDTIDWRDIVRDRDAEIVVKDNG
RSCPPCHEVCKGRCWGPGSEDCQTLTKTICAPQCNGHCFGPNPNQCCHDECAGGCSGPQD
TDCFACRHFNDSGACVPRCPQPLVYNKLTFQLEPNPHTKYQYGGVCVASCPHNFVVDQTS
CVRACPPDKMEVDKNGLKMCEPCGGLCPKACEGTGSGSRFQTVDSSNIDGFVNCTKILGN
LDFLITGLNGDPWHKIPALDPEKLNVFRTVREITGYLNIQSWPPHMHNFSVFSNLTTIGG
RSLYNRGFSLLIMKNLNVTSLGFRSLKEISAGRIYISANRQLCYHHSLNWTKVLRGPTEE
RLDIKHNRPRRDCVAEGKVCDPLCSSGGCWGPGPGQCLSCRNYSRGGVCVTHCNFLNGEP
REFAHEAECFSCHPECQPMEGTATCNGSGSDTCAQCAHFRDGPHCVSSCPHGVLGAKGPI
YKYPDVQNECRPCHENCTQGCKGPELQDCLGQTLVLIGKTHLTMALTVIAGLVVIFMMLG
GTFLYWRGRRIQNKRAMRRYLERGESIEPLDPSEKANKVLARIFKETELRKLKVLGSGVF
GTVHKGVWIPEGESIKIPVCIKVIEDKSGRQSFQAVTDHMLAIGSLDHAHIVRLLGLCPG
SSLQLVTQYLPLGSLLDHVRQHRGALGPQLLLNWGVQIAKGMYYLEEHGMVHRNLAARNV
LLKSPSQVQVADFGVADLLPPDDKQLLYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVT
VWELMTFGAEPYAGLRLAEVPDLLEKGERLAQPQICTIDVYMVMVKCWMIDENIRPTFKE
LANEFTRMARDPPRYLVIKRESGPGIAPGPEPHGLTNKKLEEVELEPELDLDLDLEAEED
NLATTTLGSALSLPVGTLNRPRGSQSLLSPSSGYMPMNQGNLGESCQESAVSGSSERCPR
PVSLHPMPRGCLASESSEGHVTGSEAELQEKVSMCRSRSRSRSPRPRGDSAYHSQRHSLL
TPVTPLSPPGLEEEDVNGYVMPDTHLKGTPSSREGTLSSVGLSSVLGTEEEDEDEEYEYM
NRRRRHSPPHPPRPSSLEELGYEYMDVGSDLSASLGSTQSCPLHPVPIMPTAGTTPDEDY
EYMNRQRDGGGPGGDYAAMGACPASEQGYEEMRAFQGPGHQAPHVHYARLKTLRSLEATD
SAFDNPDYWHSRLFPKANAQRT
    Click to Show/Hide
3D-structure
PDB ID
5O4O
Classification
Immune system
Method
X-ray diffraction
Resolution
3.40  Å
Function
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins. Binds to neuregulin-1 (NRG1) and is activated by it; ligand-binding increases phosphorylation on tyrosine residues and promotes its association with the p85 subunit of phosphatidylinositol 3-kinase. May also be activated by CSPG5. Involved in the regulation of myeloid cell differentiation.
    Click to Show/Hide
Uniprot ID
ERBB3_HUMAN
Ensembl ID
ENSG00000065361
HGNC ID
HGNC:3431
        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
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
PI3K pathway inhibitors/MEK inhibitors
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug PI3K pathway inhibitors/MEK inhibitors
 Drug Info 
Molecule Alteration Missense mutation
p.Q809R (c.2426A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.50  Å
PDB: 6OP9
Mutant Type Structure Method: X-ray diffraction Resolution: 3.10  Å
PDB: 4RIX
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.97473
Amino acid change:
Q809R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
K
-
R
-
A
-
M
-
R
-
660
|
R
-
Y
-
L
-
E
-
R
-
G
-
E
-
S
-
I
-
E
-
670
|
P
-
L
-
D
-
P
-
S
-
E
-
K
G
A
A
N
G
K
K
680
|
V
V
L
L
A
A
R
R
I
I
F
F
K
K
E
E
T
T
E
E
690
|
L
L
R
R
K
K
L
L
K
K
V
V
L
L
G
G
S
S
G
G
700
|
V
V
F
F
G
G
T
T
V
V
H
H
K
K
G
G
V
V
W
W
710
|
I
I
P
P
E
E
G
G
E
E
S
S
I
I
K
K
I
I
P
P
720
|
V
V
C
C
I
I
K
K
V
V
I
I
E
E
D
D
K
K
S
S
730
|
G
G
R
R
Q
Q
S
S
F
F
Q
Q
A
A
V
V
T
T
D
D
740
|
H
H
M
M
L
L
A
A
I
I
G
G
S
S
L
L
D
D
H
H
750
|
A
A
H
H
I
I
V
V
R
R
L
L
L
L
G
G
L
L
C
C
760
|
P
P
G
G
S
S
S
S
L
L
Q
Q
L
L
V
V
T
T
Q
Q
770
|
Y
Y
L
L
P
P
L
L
G
G
S
S
L
L
L
L
D
D
H
H
780
|
V
V
R
R
Q
Q
H
H
R
R
G
G
A
A
L
L
G
G
P
P
790
|
Q
R
L
L
L
L
L
L
N
N
W
W
G
G
V
V
Q
Q
I
I
800
|
A
A
K
K
G
G
M
M
Y
Y
Y
Y
L
L
E
E
E
E
H
H
810
|
G
G
M
M
V
V
H
H
R
R
N
N
L
L
A
A
A
A
R
R
820
|
N
N
V
V
L
L
L
L
K
K
S
S
P
P
S
S
Q
Q
V
V
830
|
Q
Q
V
V
A
A
D
D
F
F
G
G
V
V
A
A
D
D
L
L
840
|
L
L
P
P
P
P
D
D
D
D
K
K
Q
Q
L
L
L
L
Y
Y
850
|
S
S
E
E
A
A
K
K
T
T
P
P
I
I
K
K
W
W
M
M
860
|
A
A
L
L
E
E
S
S
I
I
H
H
F
F
G
G
K
K
Y
Y
870
|
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
Y
Y
G
G
880
|
V
V
T
T
V
V
W
W
E
E
L
L
M
M
T
T
F
F
G
G
890
|
A
A
E
E
P
P
Y
Y
A
A
G
G
L
L
R
R
L
L
A
A
900
|
E
E
V
V
P
P
D
D
L
L
L
L
E
E
K
K
G
G
E
E
910
|
R
R
L
L
A
A
Q
Q
P
P
Q
Q
I
I
C
C
T
T
I
I
920
|
D
D
V
V
Y
Y
M
M
V
V
M
M
V
V
K
K
C
C
W
W
930
|
M
M
I
I
D
D
E
E
N
N
I
I
R
R
P
P
T
T
F
F
940
|
K
K
E
E
L
L
A
A
N
N
E
E
F
F
T
T
R
R
M
M
950
|
A
A
R
R
D
D
P
P
P
P
R
R
Y
Y
L
L
V
V
I
I
960
|
K
K
R
R
E
E
S
S
G
G
P
P
G
G
I
I
A
A
P
P
970
|
G
G
P
P
E
E
P
P
H
H
G
G
L
L
T
T
N
N
K
K
980
|
K
K
L
L
E
E
-
E
-
V
-
E
-
L
-
E
-
P
-
E
990
|
-
L
-
D
-
L
-
D
-
L
-
D
-
L
-
E
-
A
-
E
1000
|
-
E
-
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 DNA sequencing assay
Mechanism Description The missense mutation p.Q809R (c.2426A>G) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway
Disease Class: Solid tumour/cancer [ICD-11: 2A00-2F9Z] [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Sensitive Drug PI3K pathway inhibitors/MEK inhibitors
 Drug Info 
Molecule Alteration Missense mutation
p.Q809R (c.2426A>G)
Wild Type Structure Method: X-ray diffraction Resolution: 2.50  Å
PDB: 6OP9
Mutant Type Structure Method: X-ray diffraction Resolution: 3.10  Å
PDB: 4RIX
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.24
TM score: 0.97473
Amino acid change:
Q809R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
K
-
R
-
A
-
M
-
R
-
660
|
R
-
Y
-
L
-
E
-
R
-
G
-
E
-
S
-
I
-
E
-
670
|
P
-
L
-
D
-
P
-
S
-
E
-
K
G
A
A
N
G
K
K
680
|
V
V
L
L
A
A
R
R
I
I
F
F
K
K
E
E
T
T
E
E
690
|
L
L
R
R
K
K
L
L
K
K
V
V
L
L
G
G
S
S
G
G
700
|
V
V
F
F
G
G
T
T
V
V
H
H
K
K
G
G
V
V
W
W
710
|
I
I
P
P
E
E
G
G
E
E
S
S
I
I
K
K
I
I
P
P
720
|
V
V
C
C
I
I
K
K
V
V
I
I
E
E
D
D
K
K
S
S
730
|
G
G
R
R
Q
Q
S
S
F
F
Q
Q
A
A
V
V
T
T
D
D
740
|
H
H
M
M
L
L
A
A
I
I
G
G
S
S
L
L
D
D
H
H
750
|
A
A
H
H
I
I
V
V
R
R
L
L
L
L
G
G
L
L
C
C
760
|
P
P
G
G
S
S
S
S
L
L
Q
Q
L
L
V
V
T
T
Q
Q
770
|
Y
Y
L
L
P
P
L
L
G
G
S
S
L
L
L
L
D
D
H
H
780
|
V
V
R
R
Q
Q
H
H
R
R
G
G
A
A
L
L
G
G
P
P
790
|
Q
R
L
L
L
L
L
L
N
N
W
W
G
G
V
V
Q
Q
I
I
800
|
A
A
K
K
G
G
M
M
Y
Y
Y
Y
L
L
E
E
E
E
H
H
810
|
G
G
M
M
V
V
H
H
R
R
N
N
L
L
A
A
A
A
R
R
820
|
N
N
V
V
L
L
L
L
K
K
S
S
P
P
S
S
Q
Q
V
V
830
|
Q
Q
V
V
A
A
D
D
F
F
G
G
V
V
A
A
D
D
L
L
840
|
L
L
P
P
P
P
D
D
D
D
K
K
Q
Q
L
L
L
L
Y
Y
850
|
S
S
E
E
A
A
K
K
T
T
P
P
I
I
K
K
W
W
M
M
860
|
A
A
L
L
E
E
S
S
I
I
H
H
F
F
G
G
K
K
Y
Y
870
|
T
T
H
H
Q
Q
S
S
D
D
V
V
W
W
S
S
Y
Y
G
G
880
|
V
V
T
T
V
V
W
W
E
E
L
L
M
M
T
T
F
F
G
G
890
|
A
A
E
E
P
P
Y
Y
A
A
G
G
L
L
R
R
L
L
A
A
900
|
E
E
V
V
P
P
D
D
L
L
L
L
E
E
K
K
G
G
E
E
910
|
R
R
L
L
A
A
Q
Q
P
P
Q
Q
I
I
C
C
T
T
I
I
920
|
D
D
V
V
Y
Y
M
M
V
V
M
M
V
V
K
K
C
C
W
W
930
|
M
M
I
I
D
D
E
E
N
N
I
I
R
R
P
P
T
T
F
F
940
|
K
K
E
E
L
L
A
A
N
N
E
E
F
F
T
T
R
R
M
M
950
|
A
A
R
R
D
D
P
P
P
P
R
R
Y
Y
L
L
V
V
I
I
960
|
K
K
R
R
E
E
S
S
G
G
P
P
G
G
I
I
A
A
P
P
970
|
G
G
P
P
E
E
P
P
H
H
G
G
L
L
T
T
N
N
K
K
980
|
K
K
L
L
E
E
-
E
-
V
-
E
-
L
-
E
-
P
-
E
990
|
-
L
-
D
-
L
-
D
-
L
-
D
-
L
-
E
-
A
-
E
1000
|
-
E
-
D
Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
Experiment for
Molecule Alteration		 DNA sequencing assay
Mechanism Description The missense mutation p.Q809R (c.2426A>G) in gene ERBB3 cause the sensitivity of PI3K pathway inhibitors + MEK inhibitors by unusual activation of pro-survival pathway
References
Ref 1 Oncogenic ERBB3 mutations in human cancersCancer Cell. 2013 May 13;23(5):603-17. doi: 10.1016/j.ccr.2013.04.012.

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