EKS-HOS-00305

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00305

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/EGFR	494.5	3.0E-148	444	701	258

Status

Reviewed

Ensembl Protein

ENSP00000404047

UniProt Accession

P04626; B2RZG3; B4DHN3; Q14256; Q6LDV1; Q9UMK4;

Protein Name

Receptor tyrosine-protein kinase erbB-2

Protein Synonyms/Alias

Metastatic lymph node gene 19 protein; MLN 19; Proto-oncogene Neu; Proto-oncogene c-ErbB-2; Tyrosine kinase-type cell surface receptor HER2; p185erbB2;

Gene Name

ERBB2

Gene Synonyms/Alias

ERBB2; HER2, MLN19, NEU, NGL;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000141736	ENSP00000463002	ENST00000580074
ENSG00000141736	ENSP00000385185	ENST00000406381
ENSG00000141736	ENSP00000463719	ENST00000578709
ENSG00000141736	ENSP00000463427	ENST00000578373
ENSG00000141736	ENSP00000443562	ENST00000540147
ENSG00000141736	ENSP00000464252	ENST00000582818
ENSG00000141736	ENSP00000463714	ENST00000584450
ENSG00000141736	ENSP00000269571	ENST00000269571
ENSG00000141736	ENSP00000446466	ENST00000541774
ENSG00000141736	ENSP00000462270	ENST00000584099
ENSG00000141736	ENSP00000464420	ENST00000578502
ENSG00000141736	ENSP00000462024	ENST00000582648
ENSG00000141736	ENSP00000462808	ENST00000578199
ENSG00000141736	ENSP00000446382	ENST00000540042
ENSG00000141736	ENSP00000404047	ENST00000445658
ENSG00000141736	ENSP00000462438	ENST00000584601

Organism

Homo sapiens

Functional Description

Protein tyrosine kinase that is part of several cellsurface 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. In the nucleus is involved in transcriptionalregulation. 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.

Protein Length

979

Protein Sequence
(FASTA)

MELAALCRWG LLLALLPPGA ASTQDNYLST DVGSCTLVCP LHNQEVTAED GTQRCEKCSK 60

PCARVCYGLG MEHLREVRAV TSANIQEFAG CKKIFGSLAF LPESFDGDPA SNTAPLQPEQ 120

LQVFETLEEI TGYLYISAWP DSLPDLSVFQ NLQVIRGRIL HNGAYSLTLQ GLGISWLGLR 180

SLRELGSGLA LIHHNTHLCF VHTVPWDQLF RNPHQALLHT ANRPEDECVG EGLACHQLCA 240

RGHCWGPGPT QCVNCSQFLR GQECVEECRV LQGLPREYVN ARHCLPCHPE CQPQNGSVTC 300

FGPEADQCVA CAHYKDPPFC VARCPSGVKP DLSYMPIWKF PDEEGACQPC PINCTHSCVD 360

LDDKGCPAEQ RASPLTSIIS AVVGILLVVV LGVVFGILIK RRQQKIRKYT MRRLLQETEL 420

VEPLTPSGAM PNQAQMRILK ETELRKVKVL GSGAFGTVYK GIWIPDGENV KIPVAIKVLR 480

ENTSPKANKE ILDEAYVMAG VGSPYVSRLL GICLTSTVQL VTQLMPYGCL LDHVRENRGR 540

LGSQDLLNWC MQIAKGMSYL EDVRLVHRDL AARNVLVKSP NHVKITDFGL ARLLDIDETE 600

YHADGGKVPI KWMALESILR RRFTHQSDVW SYGVTVWELM TFGAKPYDGI PAREIPDLLE 660

KGERLPQPPI CTIDVYMIMV KCWMIDSECR PRFRELVSEF SRMARDPQRF VVIQNEDLGP 720

ASPLDSTFYR SLLEDDDMGD LVDAEEYLVP QQGFFCPDPA PGAGGMVHHR HRSSSTRSGG 780

GDLTLGLEPS EEEAPRSPLA PSEGAGSDVF DGDLGMGAAK GLQSLPTHDP SPLQRYSEDP 840

TVPLPSETDG YVAPLTCSPQ PEYVNQPDVR PQPPSPREGP LPAARPAGAT LERPKTLSPG 900

KNGVVKDVFA FGGAVENPEY LTPQGGAAPQ PHPPPAFSPA FDNLYYWDQD PPERGAPPST 960

FKGTPTAENP EYLGLDVPV 979

Nucleotide Sequence
(FASTA)

ATGGAGCTGG CGGCCTTGTG CCGCTGGGGG CTCCTCCTCG CCCTCTTGCC CCCCGGAGCC 60

GCGAGCACCC AAGACAACTA CCTTTCTACG GACGTGGGAT CCTGCACCCT CGTCTGCCCC 120

CTGCACAACC AAGAGGTGAC AGCAGAGGAT GGAACACAGC GGTGTGAGAA GTGCAGCAAG 180

CCCTGTGCCC GAGTGTGCTA TGGTCTGGGC ATGGAGCACT TGCGAGAGGT GAGGGCAGTT 240

ACCAGTGCCA ATATCCAGGA GTTTGCTGGC TGCAAGAAGA TCTTTGGGAG CCTGGCATTT 300

CTGCCGGAGA GCTTTGATGG GGACCCAGCC TCCAACACTG CCCCGCTCCA GCCAGAGCAG 360

CTCCAAGTGT TTGAGACTCT GGAAGAGATC ACAGGTTACC TATACATCTC AGCATGGCCG 420

GACAGCCTGC CTGACCTCAG CGTCTTCCAG AACCTGCAAG TAATCCGGGG ACGAATTCTG 480

CACAATGGCG CCTACTCGCT GACCCTGCAA GGGCTGGGCA TCAGCTGGCT GGGGCTGCGC 540

TCACTGAGGG AACTGGGCAG TGGACTGGCC CTCATCCACC ATAACACCCA CCTCTGCTTC 600

GTGCACACGG TGCCCTGGGA CCAGCTCTTT CGGAACCCGC ACCAAGCTCT GCTCCACACT 660

GCCAACCGGC CAGAGGACGA GTGTGTGGGC GAGGGCCTGG CCTGCCACCA GCTGTGCGCC 720

CGAGGGCACT GCTGGGGTCC AGGGCCCACC CAGTGTGTCA ACTGCAGCCA GTTCCTTCGG 780

GGCCAGGAGT GCGTGGAGGA ATGCCGAGTA CTGCAGGGGC TCCCCAGGGA GTATGTGAAT 840

GCCAGGCACT GTTTGCCGTG CCACCCTGAG TGTCAGCCCC AGAATGGCTC AGTGACCTGT 900

TTTGGACCGG AGGCTGACCA GTGTGTGGCC TGTGCCCACT ATAAGGACCC TCCCTTCTGC 960

GTGGCCCGCT GCCCCAGCGG TGTGAAACCT GACCTCTCCT ACATGCCCAT CTGGAAGTTT 1020

CCAGATGAGG AGGGCGCATG CCAGCCTTGC CCCATCAACT GCACCCACTC CTGTGTGGAC 1080

CTGGATGACA AGGGCTGCCC CGCCGAGCAG AGAGCCAGCC CTCTGACGTC CATCATCTCT 1140

GCGGTGGTTG GCATTCTGCT GGTCGTGGTC TTGGGGGTGG TCTTTGGGAT CCTCATCAAG 1200

CGACGGCAGC AGAAGATCCG GAAGTACACG ATGCGGAGAC TGCTGCAGGA AACGGAGCTG 1260

GTGGAGCCGC TGACACCTAG CGGAGCGATG CCCAACCAGG CGCAGATGCG GATCCTGAAA 1320

GAGACGGAGC TGAGGAAGGT GAAGGTGCTT GGATCTGGCG CTTTTGGCAC AGTCTACAAG 1380

GGCATCTGGA TCCCTGATGG GGAGAATGTG AAAATTCCAG TGGCCATCAA AGTGTTGAGG 1440

GAAAACACAT CCCCCAAAGC CAACAAAGAA ATCTTAGACG AAGCATACGT GATGGCTGGT 1500

GTGGGCTCCC CATATGTCTC CCGCCTTCTG GGCATCTGCC TGACATCCAC GGTGCAGCTG 1560

GTGACACAGC TTATGCCCTA TGGCTGCCTC TTAGACCATG TCCGGGAAAA CCGCGGACGC 1620

CTGGGCTCCC AGGACCTGCT GAACTGGTGT ATGCAGATTG CCAAGGGGAT GAGCTACCTG 1680

GAGGATGTGC GGCTCGTACA CAGGGACTTG GCCGCTCGGA ACGTGCTGGT CAAGAGTCCC 1740

AACCATGTCA AAATTACAGA CTTCGGGCTG GCTCGGCTGC TGGACATTGA CGAGACAGAG 1800

TACCATGCAG ATGGGGGCAA GGTGCCCATC AAGTGGATGG CGCTGGAGTC CATTCTCCGC 1860

CGGCGGTTCA CCCACCAGAG TGATGTGTGG AGTTATGGTG TGACTGTGTG GGAGCTGATG 1920

ACTTTTGGGG CCAAACCTTA CGATGGGATC CCAGCCCGGG AGATCCCTGA CCTGCTGGAA 1980

AAGGGGGAGC GGCTGCCCCA GCCCCCCATC TGCACCATTG ATGTCTACAT GATCATGGTC 2040

AAATGTTGGA TGATTGACTC TGAATGTCGG CCAAGATTCC GGGAGTTGGT GTCTGAATTC 2100

TCCCGCATGG CCAGGGACCC CCAGCGCTTT GTGGTCATCC AGAATGAGGA CTTGGGCCCA 2160

GCCAGTCCCT TGGACAGCAC CTTCTACCGC TCACTGCTGG AGGACGATGA CATGGGGGAC 2220

CTGGTGGATG CTGAGGAGTA TCTGGTACCC CAGCAGGGCT TCTTCTGTCC AGACCCTGCC 2280

CCGGGCGCTG GGGGCATGGT CCACCACAGG CACCGCAGCT CATCTACCAG GAGTGGCGGT 2340

GGGGACCTGA CACTAGGGCT GGAGCCCTCT GAAGAGGAGG CCCCCAGGTC TCCACTGGCA 2400

CCCTCCGAAG GGGCTGGCTC CGATGTATTT GATGGTGACC TGGGAATGGG GGCAGCCAAG 2460

GGGCTGCAAA GCCTCCCCAC ACATGACCCC AGCCCTCTAC AGCGGTACAG TGAGGACCCC 2520

ACAGTACCCC TGCCCTCTGA GACTGATGGC TACGTTGCCC CCCTGACCTG CAGCCCCCAG 2580

CCTGAATATG TGAACCAGCC AGATGTTCGG CCCCAGCCCC CTTCGCCCCG AGAGGGCCCT 2640

CTGCCTGCTG CCCGACCTGC TGGTGCCACT CTGGAAAGGC CCAAGACTCT CTCCCCAGGG 2700

AAGAATGGGG TCGTCAAAGA CGTTTTTGCC TTTGGGGGTG CCGTGGAGAA CCCCGAGTAC 2760

TTGACACCCC AGGGAGGAGC TGCCCCTCAG CCCCACCCTC CTCCTGCCTT CAGCCCAGCC 2820

TTCGACAACC TCTATTACTG GGACCAGGAC CCACCAGAGC GGGGGGCTCC ACCCAGCACC 2880

TTCAAAGGGA CACCTACGGC AGAGAACCCA GAGTACCTGG GTCTGGACGT GCCAGTGTGA 2940

Domain Profile

S: 1     lkklkvlGsGafGtvykGiwipegenvkipvaikvleektgkkankelldealvlasldh  60

         l+k+kvlGsGafGtvykGiwip+genvkipvaikvl+e+t++kanke+ldea+v+a + +

Q: 444   LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS  503

         69**********************************************************

S: 61    anlvrllglclsstlqlvtqllplGclldyvrehkdklGsqellnwcvqiakGmsyleek  120

         ++++rllg+cl+st+qlvtql+p+Gclld+vre++++lGsq+llnwc+qiakGmsyle+

Q: 504   PYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDV  563

         ************************************************************

S: 121   rlvhrdlaarnvlvkspnhvkitdfGlaklleadekelkaeggkvpikwlalesilkrky  180

         rlvhrdlaarnvlvkspnhvkitdfGla+ll+ de+e++a+ggkvpikw+alesil+r++

Q: 564   RLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRF  623

         ************************************************************

S: 181   thqsdvwsyGvtvwelltfGakpydgipakeipdllekGerlaqppictidvymvlvkcw  240

         thqsdvwsyGvtvwel+tfGakpydgipa+eipdllekGerl+qppictidvym++vkcw

Q: 624   THQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW  683

         ************************************************************

S: 241   midaesrpkfkelaeefs  258

         mid+e+rp+f+el++efs

Q: 684   MIDSECRPRFRELVSEFS  701

         ****************96

Domain Sequence
(FASTA)

LRKVKVLGSG AFGTVYKGIW IPDGENVKIP VAIKVLRENT SPKANKEILD EAYVMAGVGS 60

PYVSRLLGIC LTSTVQLVTQ LMPYGCLLDH VRENRGRLGS QDLLNWCMQI AKGMSYLEDV 120

RLVHRDLAAR NVLVKSPNHV KITDFGLARL LDIDETEYHA DGGKVPIKWM ALESILRRRF 180

THQSDVWSYG VTVWELMTFG AKPYDGIPAR EIPDLLEKGE RLPQPPICTI DVYMIMVKCW 240

MIDSECRPRF RELVSEFS 258

Keyword

3D-structure; Activator; Alternative initiation; Alternative splicing; ATP-binding; Cell membrane; Chromosomal rearrangement; Complete proteome; Cytoplasm; Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Receptor; Reference proteome; Signal; Transcription; Transcription regulation; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Xenopus tropicalis"; ?>

Gene Ontology

GO:0016324	; C:apical plasma membrane
GO:0009925	; C:basal plasma membrane
GO:0016323	; C:basolateral plasma membrane
GO:0010008	; C:endosome membrane
GO:0016021	; C:integral to membrane
GO:0043219	; C:lateral loop
GO:0045121	; C:membrane raft
GO:0005902	; C:microvillus
GO:0005634	; C:nucleus
GO:0048471	; C:perinuclear region of cytoplasm
GO:0045211	; C:postsynaptic membrane
GO:0043235	; C:receptor complex
GO:0005524	; F:ATP binding
GO:0005006	; F:epidermal growth factor-activated receptor activity
GO:0043125	; F:ErbB-3 class receptor binding
GO:0046982	; F:protein heterodimerization activity
GO:0004716	; F:receptor signaling protein tyrosine kinase activity
GO:0001042	; F:RNA polymerase I core binding
GO:0007411	; P:axon guidance
GO:0008283	; P:cell proliferation
GO:0060209	; P:estrus
GO:0010001	; P:glial cell differentiation
GO:0007507	; P:heart development
GO:0001889	; P:liver development
GO:0030879	; P:mammary gland development
GO:0060056	; P:mammary gland involution
GO:0008045	; P:motor neuron axon guidance
GO:0042552	; P:myelination
GO:0043066	; P:negative regulation of apoptotic process
GO:0033088	; P:negative regulation of immature T cell proliferation in thymus
GO:0007528	; P:neuromuscular junction development
GO:0007422	; P:peripheral nervous system development
GO:0014065	; P:phosphatidylinositol 3-kinase cascade
GO:0045785	; P:positive regulation of cell adhesion
GO:0030307	; P:positive regulation of cell growth
GO:0050679	; P:positive regulation of epithelial cell proliferation
GO:0043406	; P:positive regulation of MAP kinase activity
GO:0043410	; P:positive regulation of MAPK cascade
GO:0014068	; P:positive regulation of phosphatidylinositol 3-kinase cascade
GO:0046579	; P:positive regulation of Ras protein signal transduction
GO:0032321	; P:positive regulation of Rho GTPase activity
GO:0045943	; P:positive regulation of transcription from RNA polymerase I promoter
GO:0045945	; P:positive regulation of transcription from RNA polymerase III promoter
GO:0045727	; P:positive regulation of translation
GO:0046777	; P:protein autophosphorylation
GO:0045765	; P:regulation of angiogenesis
GO:0070372	; P:regulation of ERK1 and ERK2 cascade
GO:0032886	; P:regulation of microtubule-based process
GO:0048678	; P:response to axon injury
GO:0042493	; P:response to drug
GO:0032570	; P:response to progesterone stimulus
GO:0048485	; P:sympathetic nervous system development
GO:0043586	; P:tongue development
GO:0006351	; P:transcription, DNA-dependent
GO:0042060	; P:wound healing

KEGG

hsa:2064

;

InterPros

IPR021157	; Cyt_c1_TM_anchor_C.
IPR000494	; EGF_rcpt_L.
IPR006211	; Furin-like_Cys-rich_dom.
IPR006212	; Furin_repeat.
IPR009030	; Growth_fac_rcpt.
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.

Pfam

PF00757	; Furin-like; 1.
PF07714	; Pkinase_Tyr; 1.
PF01030	; Recep_L_domain; 2.

SMARTs

SM00261	; FU; 3.
SM00219	; TyrKc; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013