ERBB2_CANLF
ID ERBB2_CANLF Reviewed; 1259 AA.
AC O18735;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Receptor tyrosine-protein kinase erbB-2;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-ErbB-2;
DE AltName: Full=p185erbB2;
DE AltName: CD_antigen=CD340;
DE Flags: Precursor;
GN Name=ERBB2;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RA Yokota H.;
RT "cDNA cloning of erbB-2 from canine mammary gland.";
RL Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Protein tyrosine kinase that is part of several cell surface
CC receptor complexes, but that apparently needs a coreceptor for ligand
CC binding. Essential component of a neuregulin-receptor complex, although
CC neuregulins do not interact with it alone. GP30 is a potential ligand
CC for this receptor. Regulates outgrowth and stabilization of peripheral
CC microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1
CC signaling pathway elicits the phosphorylation and thus the inhibition
CC of GSK3B at cell membrane. This prevents the phosphorylation of APC and
CC CLASP2, allowing its association with the cell membrane. In turn,
CC membrane-bound APC allows the localization of MACF1 to the cell
CC membrane, which is required for microtubule capture and stabilization
CC (By similarity). {ECO:0000250}.
CC -!- FUNCTION: In the nucleus is involved in transcriptional regulation.
CC Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter
CC and activates its transcription. Implicated in transcriptional
CC activation of CDKN1A; the function involves STAT3 and SRC. Involved in
CC the transcription of rRNA genes by RNA Pol I and enhances protein
CC synthesis and cell growth (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Homodimer. Heterodimer with EGFR, ERBB3 and ERBB4. Part of a
CC complex with EGFR and either PIK3C2A or PIK3C2B. May interact with
CC PIK3C2B when phosphorylated on Tyr-1200. Interacts with PRKCABP and
CC PLXNB1. Interacts (when phosphorylated on Tyr-1252) with MEMO1.
CC Interacts with MUC1. Interacts (when phosphorylated on Tyr-1138) with
CC GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1252) with
CC ERBIN. Interacts with SRC, KPNB1, PTK6, RANBP2, EEA1, CRM1, CLTC,
CC RPA194, MYOC and ACTB. Interacts (preferentially with the tyrosine
CC phosphorylated form) with CPNE3; this interaction occurs at the cell
CC membrane and is increased in a growth factor heregulin-dependent
CC manner. Interacts with HSP90AA1 and HSP90AB1 in an ATP-dependent
CC manner; the interaction suppresses ERBB2 kinase activity (By
CC similarity). Interacts with SORL1; this interaction regulates ERBB2
CC subcellular distribution by promoting its recycling after
CC internalization from endosomes back to the plasma membrane, hence
CC stimulates ERBB2-mediated signaling (By similarity).
CC {ECO:0000250|UniProtKB:P04626, ECO:0000250|UniProtKB:P70424}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P04626};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P04626}.
CC Early endosome {ECO:0000250|UniProtKB:P04626}. Cytoplasm, perinuclear
CC region {ECO:0000250|UniProtKB:P04626}. Nucleus
CC {ECO:0000250|UniProtKB:P04626}. Note=Translocation to the nucleus
CC requires endocytosis, probably endosomal sorting and is mediated by
CC importin beta-1/KPNB1. Also detected in endosome-to-TGN retrograde
CC vesicles. {ECO:0000250|UniProtKB:P04626}.
CC -!- PTM: Autophosphorylated. Autophosphorylation occurs in trans, i.e. one
CC subunit of the dimeric receptor phosphorylates tyrosine residues on the
CC other subunit. Ligand-binding increases phosphorylation on tyrosine
CC residues. Signaling via SEMA4C promotes phosphorylation at Tyr-1252.
CC Dephosphorylated by PTPN12. {ECO:0000250|UniProtKB:P04626}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AB008451; BAA23127.1; -; mRNA.
DR AlphaFoldDB; O18735; -.
DR SMR; O18735; -.
DR STRING; 9615.ENSCAFP00000024079; -.
DR PaxDb; O18735; -.
DR eggNOG; KOG1025; Eukaryota.
DR InParanoid; O18735; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0001042; F:RNA polymerase I core binding; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; ISS:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0032886; P:regulation of microtubule-based process; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00064; FU; 3.
DR Gene3D; 3.80.20.20; -; 2.
DR InterPro; IPR006211; Furin-like_Cys-rich_dom.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR032778; GF_recep_IV.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR000494; Rcpt_L-dom.
DR InterPro; IPR036941; Rcpt_L-dom_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt.
DR Pfam; PF00757; Furin-like; 1.
DR Pfam; PF14843; GF_recep_IV; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF01030; Recep_L_domain; 2.
DR PIRSF; PIRSF000619; TyrPK_EGF-R; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00261; FU; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57184; SSF57184; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 2: Evidence at transcript level;
KW Activator; ATP-binding; Cell membrane; Cytoplasm; Disulfide bond; Endosome;
KW Glycoprotein; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1259
FT /note="Receptor tyrosine-protein kinase erbB-2"
FT /id="PRO_0000016668"
FT TOPO_DOM 23..653
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 675..1259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 719..986
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 675..688
FT /note="Required for interaction with KPNB1 and EEA1"
FT /evidence="ECO:0000250"
FT REGION 1027..1183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1199..1201
FT /note="Interaction with PIK3C2B"
FT /evidence="ECO:0000250"
FT REGION 1203..1259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 675..688
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT ACT_SITE 844
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 725..733
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 752
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 182
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1077
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06494"
FT MOD_RES 1082
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1111
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1138
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1200
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT MOD_RES 1252
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 529
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 570
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 628
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26..53
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 162..192
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 195..204
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 199..212
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 220..227
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 224..235
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 236..244
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 240..252
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 255..264
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 268..295
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 299..311
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 315..331
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 334..338
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 342..367
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 475..504
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 511..519
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 514..527
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 530..539
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 543..559
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 562..575
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 566..583
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 586..595
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 599..622
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 625..633
FT /evidence="ECO:0000250|UniProtKB:P04626"
FT DISULFID 629..641
FT /evidence="ECO:0000250|UniProtKB:P04626"
SQ SEQUENCE 1259 AA; 137991 MW; E37364D49C4ACD46 CRC64;
MELAAWCRWG LLLALLPSGA AGTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL
ELTYLPANAS LSFLQDIQEV QGYVLIAHSQ VRQIPLQRLR IVRGTQLFED NYALAVLDNG
DPLEGGIPAP GAAQGGLREL QLRSLTEILK GGVLIQRSPQ LCHQDTILWK DVFHKNNQLA
LTLIDTNRFS ACPPCSPACK DAHCWGASSG DCQSLTRTVC AGGCARCKGP QPTDCCHEQC
AAGCTGPKHS DCLACLHFNH SGICELHCPA LVTYNTDTFE SMPNPEGRYT FGASCVTSCP
YNYLSTDVGS CTLVCPLNNQ EVTAEDGTQR CEKCSKPCAR VCYGLGMEHL REVRAVTSAN
IQEFAGCKKI FGSLAFLPES FDGDPASNTA PLQPEQLRVF EALEEITGYL YISAWPDSLP
NLSVFQNLRV IRGRVLHDGA YSLTLQGLGI SWLGLRSLRE LGSGLALIHR NARLCFVHTV
PWDQLFRNPH QALLHSANRP EEECVGEGLA CYPCAHGHCW GPGPTQCVNC SQFLRGQECV
EECRVLQGLP REYVKDRYCL PCHSECQPQN GSVTCFGSEA DQCVACAHYK DPPFCVARCP
SGVKPDLSFM PIWKFADEEG TCQPCPINCT HSCADLDEKG CPAEQRASPV TSIIAAVVGI
LLAVVVGLVL GILIKRRRQK IRKYTMRRLL QETELVEPLT PSGAMPNQAQ MRILKETELR
KVKVLGSGAF GTVYKGIWIP DGENVKIPVA IKVLRENTSP KANKEILDEA YVMAGVGSPY
VSRLLGICLT STVQLVTQLM PYGCLLDHVR EHRGRLGSQD LLNWCVQIAK GMSYLEDVRL
VHRDLAARNV LVKSPNHVKI TDFGLARLLD IDETEYHADG GKVPIKWMAL ESIPPRRFTH
QSDVWSYGVT VWELMTFGAK PYDGIPAREI PDLLEKGERL PQPPICTIDV YMIMVKCWMI
DSECRPRFRE LVAEFSRMAR DPQRFVVIQN EDLGPASPLD STFYRSLLED DDMGDLVDAE
EYLVPQQGFF CPEPTPGAGG TAHRRHRSSS TRNGGGELTL GLEPSEEEPP KSPLAPSEGA
GSDVFDGDLG MGAAKGLQSL PSQDPSPLQR YSEDPTVPLP PETDGKVAPL TCSPQPEYVN
QPEVWPQPPL ALEGPLPPSR PAGATLERPK TLSPKTLSPG KNGVVKDVFA FGSAVENPEY
LAPRGRAAPQ PHPPPAFSPA FDNLYYWDQD PSERGSPPST FEGTPTAENP EYLGLDVPV
