Protein Description

Gene Symbol ERBB3
Entrez ID 2065
Uniprot ID P21860
Description erb-b2 receptor tyrosine kinase 3
Chromosomal Location chr12: 56,079,857-56,103,505
Ontology GO ID GO Term Definition Evidence

BP

GO:0000165

MAPK cascade

An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain two additional tiers: the upstream MAP4K and the downstream MAP Kinase-activated kinase (MAPKAPK). The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.

TAS

BP

GO:0003197

endocardial cushion development

The progression of a cardiac cushion over time, from its initial formation to the mature structure. The endocardial cushion is a specialized region of mesenchymal cells that will give rise to the heart septa and valves.

IEA

BP

GO:0007162

negative regulation of cell adhesion

Any process that stops, prevents, or reduces the frequency, rate or extent of cell adhesion.

IDA

BP

GO:0007165

signal transduction

The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.

IDA

BP

GO:0007169

transmembrane receptor protein tyrosine kinase signaling pathway

A series of molecular signals initiated by the binding of an extracellular ligand to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with regulation of a downstream cellular process, e.g. transcription.

ISS

BP

GO:0007422

peripheral nervous system development

The process whose specific outcome is the progression of the peripheral nervous system over time, from its formation to the mature structure. The peripheral nervous system is one of the two major divisions of the nervous system. Nerves in the PNS connect the central nervous system (CNS) with sensory organs, other organs, muscles, blood vessels and glands.

ISS

BP

GO:0007507

heart development

The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood.

ISS

BP

GO:0009968

negative regulation of signal transduction

Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction.

IDA

BP

GO:0010628

positive regulation of gene expression

Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA (for protein-coding genes) and the translation of that mRNA into protein. Protein maturation is included when required to form an active form of a product from an inactive precursor form.

IEA

BP

GO:0014037

Schwann cell differentiation

The process in which a relatively unspecialized cell acquires the specialized features of a Schwann cell. Schwann cells are found in the peripheral nervous system, where they insulate neurons and axons, and regulate the environment in which neurons function.

ISS

BP

GO:0014065

phosphatidylinositol 3-kinase signaling

A series of reactions within the signal-receiving cell, mediated by the intracellular phosphatidylinositol 3-kinase (PI3K). Many cell surface receptor linked signaling pathways signal through PI3K to regulate numerous cellular functions.

IDA

BP

GO:0014066

regulation of phosphatidylinositol 3-kinase signaling

Any process that modulates the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.

TAS

BP

GO:0014068

positive regulation of phosphatidylinositol 3-kinase signaling

Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the phosphatidylinositol 3-kinase cascade.

TAS

BP

GO:0018108

peptidyl-tyrosine phosphorylation

The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine.

IEA

BP

GO:0021545

cranial nerve development

The process whose specific outcome is the progression of the cranial nerves over time, from its formation to the mature structure. The cranial nerves are composed of twelve pairs of nerves that emanate from the nervous tissue of the hindbrain. These nerves are sensory, motor, or mixed in nature, and provide the motor and general sensory innervation of the head, neck and viscera. They mediate vision, hearing, olfaction and taste and carry the parasympathetic innervation of the autonomic ganglia that control visceral functions.

ISS

BP

GO:0038128

ERBB2 signaling pathway

A series of molecular signals initiated by binding of a ligand to a member of the ERBB family of receptors on the surface of a cell, where the signal is transmitted by ERBB2. The pathway ends with regulation of a downstream cellular process, e.g. transcription. ERBB2 receptors are themselves unable to bind to ligands, but act as a signal-amplifying tyrosine kinase within a heterodimeric pair.

TAS

BP

GO:0042060

wound healing

The series of events that restore integrity to a damaged tissue, following an injury.

NAS

BP

GO:0042127

regulation of cell proliferation

Any process that modulates the frequency, rate or extent of cell proliferation.

IDA

BP

GO:0043524

negative regulation of neuron apoptotic process

Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons.

ISS

BP

GO:0043547

positive regulation of GTPase activity

Any process that activates or increases the activity of a GTPase.

IEA

BP

GO:0046854

phosphatidylinositol phosphorylation

The process of introducing one or more phosphate groups into a phosphatidylinositol, any glycerophosphoinositol having one phosphatidyl group esterified to one of the hydroxy groups of inositol.

IEA

BP

GO:0048015

phosphatidylinositol-mediated signaling

A series of molecular signals in which a cell uses a phosphatidylinositol-mediated signaling to convert a signal into a response. Phosphatidylinositols include phosphatidylinositol (PtdIns) and its phosphorylated derivatives.

TAS

BP

GO:0051048

negative regulation of secretion

Any process that stops, prevents, or reduces the frequency, rate or extent of the controlled release of a substance from a cell or a tissue.

IDA

BP

GO:0051402

neuron apoptotic process

Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system.

IMP

BP

GO:0055025

positive regulation of cardiac muscle tissue development

Any process that activates, maintains or increases the frequency, rate or extent of cardiac muscle tissue development.

IEA

BP

GO:0061098

positive regulation of protein tyrosine kinase activity

Any process that increases the rate, frequency, or extent of protein tyrosine kinase activity.

IMP

BP

GO:0070886

positive regulation of calcineurin-NFAT signaling cascade

Any process that activates or increases the frequency, rate or extent of signaling via the calcineurin-NFAT signaling cascade.

IEA

BP

GO:0097192

extrinsic apoptotic signaling pathway in absence of ligand

A series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with withdrawal of a ligand from a cell surface receptor, and ends when the execution phase of apoptosis is triggered.

IMP

BP

GO:2000145

regulation of cell motility

Any process that modulates the frequency, rate or extent of cell motility.

TAS

CC

GO:0005615

extracellular space

That part of a multicellular organism outside the cells proper, usually taken to be outside the plasma membranes, and occupied by fluid.

IDA

CC

GO:0005622

intracellular

The living contents of a cell; the matter contained within (but not including) the plasma membrane, usually taken to exclude large vacuoles and masses of secretory or ingested material. In eukaryotes it includes the nucleus and cytoplasm.

IEA

CC

GO:0005886

plasma membrane

The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

TAS

CC

GO:0005887

integral component of plasma membrane

The component of the plasma membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.

TAS

CC

GO:0016323

basolateral plasma membrane

The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis.

IDA

CC

GO:0016324

apical plasma membrane

The region of the plasma membrane located at the apical end of the cell.

IEA

CC

GO:0016328

lateral plasma membrane

The portion of the plasma membrane at the lateral side of the cell. In epithelial cells, lateral plasma membranes are on the sides of cells which lie at the interface of adjacent cells.

IEA

CC

GO:0043235

receptor complex

Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.

IDA|ISS

MF

GO:0004713

protein tyrosine kinase activity

Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

TAS

MF

GO:0004888

transmembrane signaling receptor activity

Combining with an extracellular or intracellular signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity or state as part of signal transduction.

ISS

MF

GO:0005088

Ras guanyl-nucleotide exchange factor activity

Stimulates the exchange of guanyl nucleotides associated with a GTPase of the Ras superfamily. Under normal cellular physiological conditions, the concentration of GTP is higher than that of GDP, favoring the replacement of GDP by GTP in association with the GTPase.

TAS

MF

GO:0005515

protein binding

Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).

IPI

MF

GO:0005524

ATP binding

Interacting selectively and non-covalently with ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.

IEA

MF

GO:0019838

growth factor binding

Interacting selectively and non-covalently with any growth factor, proteins or polypeptides that stimulate a cell or organism to grow or proliferate.

IPI|ISS

MF

GO:0030296

protein tyrosine kinase activator activity

Increases the activity of a protein tyrosine kinase, an enzyme which phosphorylates a tyrosyl phenolic group on a protein.

IDA

MF

GO:0038132

neuregulin binding

Interacting selectively and non-covalently with a neuregulin, a member of the EGF family of growth factors.

IDA

MF

GO:0042803

protein homodimerization activity

Interacting selectively and non-covalently with an identical protein to form a homodimer.

NAS

MF

GO:0046934

phosphatidylinositol-4,5-bisphosphate 3-kinase activity

Catalysis of the reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + ATP = a 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate + ADP + 2 H(+).

TAS

MF

GO:0046982

protein heterodimerization activity

Interacting selectively and non-covalently with a nonidentical protein to form a heterodimer.

IDA|IPI

Domain ID Description

IPR000494

Receptor L-domain

IPR000719

Protein kinase domain

IPR001245

Serine-threonine/tyrosine-protein kinase, catalytic domain

IPR006211

Furin-like cysteine-rich domain

IPR006212

Furin-like repeat

IPR009030

Growth factor receptor cysteine-rich domain

IPR011009

Protein kinase-like domain

IPR016245

Tyrosine protein kinase, EGF/ERB/XmrK receptor

IPR032675

Leucine-rich repeat domain, L domain-like

IPR032778

Growth factor receptor domain 4

Pathway ID Pathway Term Pathway Source

hsa01521

EGFR tyrosine kinase inhibitor resistance

KEGG

hsa04012

ErbB signaling pathway

KEGG

hsa04020

Calcium signaling pathway

KEGG

hsa04144

Endocytosis

KEGG

hsa05205

Proteoglycans in cancer

KEGG

hsa05206

MicroRNAs in cancer

KEGG

WP1591

Heart Development

WikiPathways

WP2261

Signaling Pathways in Glioblastoma

WikiPathways

WP2864

Apoptosis-related network due to altered Notch3 in ovarian cancer

WikiPathways

WP673

ErbB Signaling Pathway

WikiPathways

h_ErbB3Pathway

Neuroregulin receptor degredation protein-1 Controls ErbB3 receptor recycling

BioCarta

h_her2Pathway

Role of ERBB2 in Signal Transduction and Oncology

BioCarta

UMLS CUI UMLS Term

C0011854

Diabetes Mellitus, Insulin-Dependent

C0016978

Gallbladder Neoplasm

C0024121

Lung Neoplasms

C0028754

Obesity

C0033578

Prostatic Neoplasms

C0242656

Disease Progression

C1458155

Mammary Neoplasms

Tissue Cell Type

adrenal gland

glandular cells

appendix

glandular cells

bronchus

respiratory epithelial cells

caudate

neuronal cells

cerebellum

Purkinje cells

cerebral cortex

neuronal cells

cervix, uterine

glandular cells

colon

glandular cells

colon

peripheral nerve/ganglion

duodenum

glandular cells

epididymis

glandular cells

esophagus

squamous epithelial cells

gallbladder

glandular cells

heart muscle

myocytes

kidney

cells in tubules

lymph node

non-germinal center cells

nasopharynx

respiratory epithelial cells

pancreas

exocrine glandular cells

pancreas

islets of Langerhans

parathyroid gland

glandular cells

placenta

decidual cells

prostate

glandular cells

rectum

glandular cells

seminal vesicle

glandular cells

skin

fibroblasts

skin

keratinocytes

small intestine

glandular cells

soft tissue

fibroblasts

soft tissue

peripheral nerve

stomach

glandular cells

testis

cells in seminiferous ducts

testis

Leydig cells

Database Name

GWASdb

Pubmed ID Author Year Title

22617121

Ouandaogo et al.

2012

Differences in transcriptomic profiles of human cumulus cells isolated from oocytes at GV, MI and MII stages after in vivo andin vitro oocyte maturation

Gene Symbol Entrez ID Uniprot ID Score

HRAS

3265

P01112

0.00

ITGB4

3691

P16144

0.00

KRAS

3845

P01116

0.00

PIK3CD

5293

O00329

0.00

PIK3CG

5294

P48736

0.00

PLCG2

5336

P16885

0.00

MAP2K1

5604

Q02750

0.00

SH3GL1

6455

Q99961

0.00

SH3GL3

6457

Q99963

0.00

TRAF6

7189

Q9Y4K3

0.00

WWP1

11059

Q9H0M0

0.00

SHC2

25759

P98077

0.00

SH3GLB1

51100

Q9Y371

0.00

SH3GLB2

56904

Q9NR46

0.00

SMURF1

57154

Q9HCE7

0.00

SMURF2

64750

Q9HAU4

0.00

ITCH

83737

Q96J02

0.00

FLNA

2316

P21333

0.55

SOS1

6654

Q07889

0.55

ANXA2

302

P07355

0.63

B2M

567

P61769

0.63

CANX

821

P27824

0.63

SLC31A1

1317

O15431

0.63

EIF1AX

1964

P47813

0.63

HLA-A

3105

P16189

0.63

HLA-A

3105

P30443

0.63

HLA-A

3105

P30512

0.63

HLA-B

3106

P30481

0.63

HLA-B

3106

P30483

0.63

HLA-DPA1

3113

P20036

0.63

HNRNPA2B1

3181

P22626

0.63

HNRNPAB

3182

Q99729

0.63

HNRNPH2

3188

P55795

0.63

DNAJA1

3301

P31689

0.63

HSPA5

3309

P11021

0.63

MDM2

4193

Q00987

0.63

ROR1

4919

Q01973

0.63

PIK3CB

5291

P42338

0.63

PON2

5445

Q15165

0.63

MASP1

5648

P48740

0.63

S100A10

6281

P60903

0.63

SSR1

6745

P43307

0.63

TUFM

7284

P49411

0.63

RAE1

8480

P78406

0.63

AIFM1

9131

O95831

0.63

AP1M2

10053

Q9Y6Q5

0.63

LRPPRC

10128

P42704

0.63

RASA4

10156

O43374

0.63

CDC37

11140

Q16543

0.63

PHLDA1

22822

Q8WV24

0.63

MRPS27

23107

Q92552

0.63

MRPS28

28957

Q9Y2Q9

0.63

MRPS18B

28973

Q9Y676

0.63

UQCR10

29796

Q9UDW1

0.63

MRPS17

51373

Q9Y2R5

0.63

MRPS23

51649

Q9Y3D9

0.63

DNAJB11

51726

Q9UBS4

0.63

YBEY

54059

P58557

0.63

PTCD3

55037

Q96EY7

0.63

MRPS22

56945

P82650

0.63

ODF2L

57489

Q9ULJ1

0.63

MRPS14

63931

O60783

0.63

PDF

64146

Q9HBH1

0.63

MRPS25

64432

P82663

0.63

MRPS26

64949

Q9BYN8

0.63

MRPS34

65993

P82930

0.63

FLYWCH1

84256

Q4VC44

0.63

B3GLCT

145173

Q6Y288

0.63

ACTBL2

345651

Q562R1

0.63

TUBB8

347688

Q3ZCM7

0.63

POTEKP

440915

Q9BYX7

0.63

NEDD4

4734

P46934

0.65

PTPN11

5781

Q06124

0.70

EGR1

1958

P18146

0.72

RPN1

6184

P04843

0.72

ZNF207

7756

O43670

0.72

HDAC6

10013

Q9UBN7

0.72

HSP90AB1

3326

P08238

0.73

CSK

1445

P41240

0.75

EGF

1950

P01133

0.75

PIK3CA

5290

P42336

0.82

TUBA4A

7277

P68366

0.82

MUC1

4582

P15941

0.83

ERBB3

2065

P21860

0.84

GRB2

2885

P62993

0.89

PIK3R2

5296

O00459

0.89

RNF41

10193

Q9H4P4

0.89

EGFR

1956

P00533

0.90

NRG1

3084

Q02297

0.90

ERBB2

2064

P04626

0.97

PIK3R1

5295

P27986

0.97

CBL

867

P22681

0.00

CBLB

868

Q13191

0.00

ARHGEF7

8874

Q14155

0.00

EPN2

22905

O95208

0.00

EPN1

29924

Q9Y6I3

0.00

CDK5

1020

Q00535

0.52

PTK2B

2185

Q14289

0.52

SRPK2

6733

P78362

0.52

PTK2

5747

Q05397

0.62

ABL1

25

P00519

0.63

ABL2

27

P42684

0.63

AGTR2

186

P50052

0.63

AKT1

207

P31749

0.63

CHN2

1124

P52757

0.63

CRK

1398

P46108

0.63

CRKL

1399

P46109

0.63

DAB1

1600

O75553

0.63

FER

2241

P16591

0.63

FGFR1

2260

P11362

0.63

HCK

3055

P08631

0.63

ITK

3702

Q08881

0.63

JAK2

3717

O60674

0.63

JAK3

3718

P52333

0.63

SH2D1A

4068

O60880

0.63

NCK1

4690

P16333

0.63

PLCG1

5335

P19174

0.63

RASA1

5921

P20936

0.63

SRC

6714

P12931

0.63

SYK

6850

P43405

0.63

TXK

7294

P42681

0.63

VAV1

7409

P15498

0.63

VAV2

7410

P52735

0.63

ZAP70

7535

P43403

0.63

BCAR3

8412

O75815

0.63

NCK2

8440

O43639

0.63

RIN1

9610

Q13671

0.63

SH2B3

10019

Q9UQQ2

0.63

VAV3

10451

Q9UKW4

0.63

TNS2

23371

Q63HR2

0.63

LRIG1

26018

Q96JA1

0.63

DAPP1

27071

Q9UN19

0.63

SHC3

53358

Q92529

0.63

TNS3

64759

Q68CZ2

0.63

TNS4

84951

Q8IZW8

0.63

IL6ST

3572

P40189

0.73

PTGES3

10728

Q15185

0.75

ERBB4

2066

Q15303

0.78

HSP90AA1

3320

P07900

0.82

PIK3R3

8503

Q92569

0.82

CD82

3732

P27701

0.83

PTK6

5753

Q13882

0.86

RGS4

5999

P49798

0.86

NRG2

9542

O14511

0.86

GRB7

2886

Q14451

0.90

PA2G4

5036

Q9UQ80

0.90

SHC1

6464

P29353

0.90