P70424 (ERBB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Receptor tyrosine-protein kinase erbB-2
EC=2.7.10.1

Alternative name(s):
Proto-oncogene Neu
Proto-oncogene c-ErbB-2
p185erbB2
CD_antigen=CD340

Gene names

Name:	Erbb2
Synonyms:	Kiaa3023, Neu

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1256 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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 By similarity. Ref.4 In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth By similarity. Ref.4
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1197. Interacts with PRKCABP and PLXNB1. Interacts (when phosphorylated on Tyr-1249) with MEMO1. Interacts with MUC1. Interacts (when phosphorylated on Tyr-1140) with GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1249) with ERBB2IP. Interacts with KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, RPA94 and ACTB By similarity. Interacts with SRC. Ref.4 Ref.5
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasm › perinuclear region By similarity. Nucleus By similarity.
Tissue specificity	Expressed predominantly in uterine epithelial cells. In the muscle, expression localizes to the synaptic sites of muscle fibers.
Developmental stage	On days 1-4 of pregnancy, ERBB2 is detected primarily in epithelial cells, the day 1 uterus showing the highest accumulation. On day 5, the epithelium and the decidualizing stromal cells around the implanting blastocyst exhibit accumulation of this receptor. On days 6-8, the expression persists in the epithelium at both the implantation and interimplantation sites in addition to modest levels in the secondary decidual zone. On days 7 and 8, accumulation is also prominent in the trophoblastic giant cells.
Post-translational modification	Autophosphorylated. Ligand-binding increases phosphorylation on tyrosine residues. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Signaling via SEMA4C promotes phosphorylation at Tyr-1249 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence BAC98297.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Domain	Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Activator Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	heart development Inferred from mutant phenotype PubMed 12072561PubMed 9362461. Source: MGI motor neuron axon guidance Inferred from mutant phenotype PubMed 10655525. Source: MGI myelination Inferred from mutant phenotype PubMed 10704452. Source: MGI negative regulation of immature T cell proliferation in thymus Inferred from mutant phenotype PubMed 16230479. Source: MGI neuromuscular junction development Inferred from mutant phenotype PubMed 10655525. Source: MGI peripheral nervous system development Inferred from mutant phenotype PubMed 9362461. Source: MGI phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara positive regulation of MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of Rho GTPase activity Inferred from mutant phenotype PubMed 22019888. Source: BHF-UCL positive regulation of cell adhesion Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of epithelial cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of protein phosphorylation Inferred from mutant phenotype PubMed 22019888. Source: BHF-UCL positive regulation of transcription from RNA polymerase I promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase III promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of translation Inferred from sequence or structural similarity. Source: UniProtKB regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB regulation of microtubule-based process Inferred from sequence or structural similarity. Source: UniProtKB signal transduction by phosphorylation Inferred from electronic annotation. Source: GOC transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from direct assay PubMed 15306553. Source: MGI basolateral plasma membrane Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay PubMed 15306553. Source: MGI endosome membrane Inferred from electronic annotation. Source: Compara integral to membrane Non-traceable author statement PubMed 15609325. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell receptor complex Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW RNA polymerase I core binding Inferred from sequence or structural similarity. Source: UniProtKB receptor signaling protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro transmembrane receptor protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Erbb3	Q61526	2	EBI-2945468,EBI-931878
Stat3	P42227	4	EBI-2945468,EBI-602878

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 1256	1234	Receptor tyrosine-protein kinase erbB-2		PRO_0000042181
Regions
	Topological domain	23 – 653	631	Extracellular Potential
	Transmembrane	654 – 674	21	Helical; Potential
	Topological domain	675 – 1256	582	Cytoplasmic Potential
	Domain	721 – 988	268	Protein kinase
	Nucleotide binding	727 – 735	9	ATP By similarity
	Region	677 – 690	14	Nuclear localization signal By similarity
	Region	677 – 690	14	Required for interaction with KPNB1 and EEA1 By similarity
	Region	1196 – 1198	3	Interaction with PIK3C2B By similarity
	Compositional bias	193 – 269	77	Cys-rich
	Compositional bias	1117 – 1163	47	Pro-rich
Sites
	Active site	846	1	Proton acceptor By similarity
	Binding site	754	1	ATP By similarity
Amino acid modifications
	Modified residue	1055	1	Phosphoserine By similarity
	Modified residue	1108	1	Phosphoserine By similarity
	Modified residue	1140	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	1197	1	Phosphotyrosine Potential
	Modified residue	1249	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	68	1	N-linked (GlcNAc...) Potential
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	188	1	N-linked (GlcNAc...) Potential
	Glycosylation	260	1	N-linked (GlcNAc...) Potential
	Glycosylation	531	1	N-linked (GlcNAc...) Potential
	Glycosylation	572	1	N-linked (GlcNAc...) Potential
	Glycosylation	630	1	N-linked (GlcNAc...) Potential
	Disulfide bond	26 ↔ 53		By similarity
	Disulfide bond	163 ↔ 193		By similarity
	Disulfide bond	196 ↔ 205		By similarity
	Disulfide bond	200 ↔ 213		By similarity
	Disulfide bond	221 ↔ 228		By similarity
	Disulfide bond	225 ↔ 236		By similarity
	Disulfide bond	237 ↔ 245		By similarity
	Disulfide bond	241 ↔ 253		By similarity
	Disulfide bond	256 ↔ 265		By similarity
	Disulfide bond	269 ↔ 296		By similarity
	Disulfide bond	300 ↔ 312		By similarity
	Disulfide bond	316 ↔ 332		By similarity
	Disulfide bond	335 ↔ 339		By similarity
	Disulfide bond	343 ↔ 368		By similarity
	Disulfide bond	476 ↔ 505		By similarity
	Disulfide bond	512 ↔ 521		By similarity
	Disulfide bond	516 ↔ 529		By similarity
	Disulfide bond	532 ↔ 541		By similarity
	Disulfide bond	545 ↔ 561		By similarity
	Disulfide bond	564 ↔ 577		By similarity
	Disulfide bond	568 ↔ 585		By similarity
	Disulfide bond	588 ↔ 597		By similarity
	Disulfide bond	601 ↔ 624		By similarity
	Disulfide bond	627 ↔ 635		By similarity
	Disulfide bond	631 ↔ 643		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P70424 [UniParc]. Last modified September 27, 2005. Version 3. Checksum: 6040978428B93A28	FASTA	1,256	138,579
	10 20 30 40 50 60 MELAAWCRWG FLLALLSPGA AGTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL 70 80 90 100 110 120 ELTYLPANAS LSFLQDIQEV QGYMLIAHNR VKHVPLQRLR IVRGTQLFED KYALAVLDNR 130 140 150 160 170 180 DPLDNVTTAA PGRTPEGLRE LQLRSLTEIL KGGVLIRGNP QLCYQDMVLW KDVLRKNNQL 190 200 210 220 230 240 APVDMDTNRS RACPPCAPTC KDNHCWGESP EDCQILTGTI CTSGCARCKG RLPTDCCHEQ 250 260 270 280 290 300 CAAGCTGPKH SDCLACLHFN HSGICELHCP ALITYNTDTF ESMLNPEGRY TFGASCVTTC 310 320 330 340 350 360 PYNYLSTEVG SCTLVCPPNN QEVTAEDGTQ RCEKCSKPCA GVCYGLGMEH LRGARAITSD 370 380 390 400 410 420 NIQEFAGCKK IFGSLAFLPE SFDGNPSSGV APLKPEHLQV FETLEEITGY LYISAWPESF 430 440 450 460 470 480 QDLSVFQNLR VIRGRILHDG AYSLTLQGLG IHSLGLRSLR ELGSGLALIH RNTHLCFVNT 490 500 510 520 530 540 VPWDQLFRNP HQALLHSGNR PEEACGLEGL VCNSLCARGH CWGPGPTQCV NCSQFLRGQE 550 560 570 580 590 600 CVEECRVWKG LPREYVRGKH CLPCHPECQP QNSSETCYGS EADQCEACAH YKDSSSCVAR 610 620 630 640 650 660 CPSGVKPDLS YMPIWKYPDE EGICQPCPIN CTHSCVDLDE RGCPAEQRAS PVTFIIATVV 670 680 690 700 710 720 GVLLFLIIVV VIGILIKRRR QKIRKYTMRR LLQETELVEP LTPSGAVPNQ AQMRILKETE 730 740 750 760 770 780 LRKLKVLGSG AFGTVYKGIW IPDGENVKIP VAIKVLRENT SPKANKEILD EAYVMAGVGS 790 800 810 820 830 840 PYVSRLLGIC LTSTVQLVTQ LMPYGCLLDH VREHRGRLGS QDLLNWCVQI AKGMSYLEEV 850 860 870 880 890 900 RLVHRDLAAR NVLVKSPNHV KITDFGLARL LDIDETEYHA DGGKVPIKWM ALESILRRRF 910 920 930 940 950 960 THQSDVWSYG VTVWELMTFG AKPYDGIPAR EIPDLLEKGE RLPQPPICTI DVYMIMVKCW 970 980 990 1000 1010 1020 MIDSECRPRF RELVSEFSRM ARDPQRFVVI QNEDLGPSSP MDSTFYRSLL EDDDMGELVD 1030 1040 1050 1060 1070 1080 AEEYLVPQQG FFSPDPALGT GSTAHRRHRS SSARSGGGEL TLGLEPSEEE PPRSPLAPSE 1090 1100 1110 1120 1130 1140 GAGSDVFDGD LAVGVTKGLQ SLSPHDLSPL QRYSEDPTLP LPPETDGYVA PLACSPQPEY 1150 1160 1170 1180 1190 1200 VNQPEVRPQS PLTPEGPPPP IRPAGATLER PKTLSPGKNG VVKDVFAFGG AVENPEYLAP 1210 1220 1230 1240 1250 RAGTASQPHP SPAFSPAFDN LYYWDQNSSE QGPPPSTFEG TPTAENPEYL GLDVPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of mouse homologues of KIAA gene: III. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H. DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Embryonic tail.
[2]	"Differential expression of the erbB2 gene in the periimplantation mouse uterus: potential mediator of signaling by epidermal growth factor-like growth factors." Lim J., Dey S.K., Das S.K. Endocrinology 138:1328-1337(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 786-934. Strain: CD-1. Tissue: Uterus.
[3]	"Synapse-associated expression of an acetylcholine receptor-inducing protein, ARIA/heregulin, and its putative receptors, ErbB2 and ErbB3, in developing mammalian muscle." Moscoso L.M., Chu G.C., Gautam M., Noakes P.G., Merlie J.P., Sanes J.R. Dev. Biol. 172:158-169(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1012-1107.
[4]	"Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor." Muthuswamy S.K., Muller W.J. Oncogene 11:271-279(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SRC.
[5]	"The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins." Jaulin-Bastard F., Saito H., Le Bivic A., Ollendorff V., Marchetto S., Birnbaum D., Borg J.-P. J. Biol. Chem. 276:15256-15263(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRKCABP.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK129487 mRNA. Translation: BAC98297.1. Different initiation. U71126 mRNA. Translation: AAB17380.1. L47239 mRNA. Translation: AAA93532.1.
IPI	IPI00626433.
RefSeq	NP_001003817.1. NM_001003817.1.
UniGene	Mm.290822.
3D structure databases
ProteinModelPortal	P70424.
SMR	P70424. Positions 23-630, 678-1026.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70424. 4 interactions.
MINT	MINT-138121.
PTM databases
PhosphoSite	P70424.
Proteomic databases
PaxDb	P70424.
PRIDE	P70424.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000058295; ENSMUSP00000053897; ENSMUSG00000062312.
GeneID	13866.
KEGG	mmu:13866.
UCSC	uc007lgi.1. mouse.
Organism-specific databases
CTD	2064.
MGI	MGI:95410. Erbb2.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00600000084253.
HOGENOM	HOG000230982.
HOVERGEN	HBG000490.
InParanoid	P70424.
KO	K05083.
OMA	GGCARCK.
OrthoDB	EOG461434.
Gene expression databases
ArrayExpress	P70424.
Bgee	P70424.
Genevestigator	P70424.
GermOnline	ENSMUSG00000062312. Mus musculus.
Family and domain databases
Gene3D	3.80.20.20. 2 hits.
InterPro	IPR000494. EGF_rcpt_L. IPR006211. Furin-like_Cys-rich_dom. IPR006212. Furin_repeat. IPR009030. Growth_fac_rcpt_N_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016245. Tyr_kinase_EGF/ERB/XmrK_rcpt. [Graphical view]
Pfam	PF00757. Furin-like. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF01030. Recep_L_domain. 2 hits. [Graphical view]
PIRSF	PIRSF000619. TyrPK_EGF-R. 1 hit.
PRINTS	PR00109. TYRKINASE.
SMART	SM00261. FU. 4 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF57184. Grow_fac_recept. 2 hits. SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	284764.
SOURCE	Search...

Entry information

Entry name

ERBB2_MOUSE

Accession

Primary (citable) accession number: P70424
Secondary accession number(s): Q61525, Q6ZPE0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	September 27, 2005
Last modified:	May 29, 2013
This is version 141 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program