ID ERBB2_RAT Reviewed; 1257 AA. AC P06494; Q6P732; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 3. DT 27-MAR-2024, entry version 215. DE RecName: Full=Receptor tyrosine-protein kinase erbB-2; DE EC=2.7.10.1; DE AltName: Full=Epidermal growth factor receptor-related protein; DE AltName: Full=Proto-oncogene Neu; DE AltName: Full=Proto-oncogene c-ErbB-2; DE AltName: Full=p185erbB2; DE AltName: Full=p185neu; DE AltName: CD_antigen=CD340; DE Flags: Precursor; GN Name=Erbb2; Synonyms=Neu; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Neuroblastoma; RX PubMed=3945311; DOI=10.1038/319226a0; RA Bargmann C.I., Hung M.-C., Weinberg R.A.; RT "The neu oncogene encodes an epidermal growth factor receptor-related RT protein."; RL Nature 319:226-230(1986). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 634-699. RX PubMed=1682063; DOI=10.1093/carcin/12.10.1975; RA Masui T., Mann A.M., Macatee T.L., Garland E.M., Okamura T., Smith R.A., RA Cohen S.M.; RT "Direct DNA sequencing of the rat neu oncogene transmembrane domain reveals RT no mutation in urinary bladder carcinomas induced by N-butyl-N-(4- RT hydroxybutyl)nitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide or RT N-methyl-N-nitrosourea."; RL Carcinogenesis 12:1975-1978(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 852-905. RC TISSUE=Sciatic nerve; RX PubMed=2025425; DOI=10.1016/0896-6273(91)90167-x; RA Lai C., Lemke G.; RT "An extended family of protein-tyrosine kinase genes differentially RT expressed in the vertebrate nervous system."; RL Neuron 6:691-704(1991). RN [5] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=7945309; DOI=10.1006/bbrc.1994.2368; RA Xie Y., Hung M.C.; RT "Nuclear localization of p185neu tyrosine kinase and its association with RT transcriptional transactivation."; RL Biochem. Biophys. Res. Commun. 203:1589-1598(1994). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1056; SER-1080 AND SER-1085, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [7] RP STRUCTURE BY NMR OF 650-668. RX PubMed=1346763; DOI=10.1002/j.1460-2075.1992.tb05025.x; RA Gullick W.J., Bottomley A.C., Lofts F.J., Doak D.G., Mulvey D., Newman R., RA Crumpton M.J., Sternberg M.J.E., Campbell I.D.; RT "Three dimensional structure of the transmembrane region of the proto- RT oncogenic and oncogenic forms of the neu protein."; RL EMBO J. 11:43-48(1992). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 23-631 IN COMPLEX WITH THE RP ANTIBODY HERCEPTIN, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-68; ASN-188 RP AND ASN-260. RX PubMed=12610629; DOI=10.1038/nature01392; RA Cho H.-S., Mason K., Ramyar K.X., Stanley A.M., Gabelli S.B., RA Denney D.W. Jr., Leahy D.J.; RT "Structure of the extracellular region of HER2 alone and in complex with RT the Herceptin Fab."; RL Nature 421:756-760(2003). 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). 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 manner CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P04626}. 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-1198. Interacts with PRKCABP and CC PLXNB1. Interacts (when phosphorylated on Tyr-1250) with MEMO1. CC Interacts with MUC1. Interacts (when phosphorylated on Tyr-1141) with CC GRB7 (via SH2 domain). Interacts (when phosphorylated on Tyr-1250) with CC ERBIN Interacts with SRC, KPNB1, RANBP2, EEA1, CRM1, CLTC, PTK6, CC RPA194, MYOC and ACTB. Interacts with HSP90AA1 and HSP90AB1; the CC interaction suppresses ERBB2 kinase activity (By similarity). Interacts CC with SORL1; this interaction regulates ERBB2 subcellular distribution CC by promoting its recycling after internalization from endosomes back to CC the plasma membrane, hence stimulates ERBB2-mediated signaling (By CC similarity). Interacts with SH3BGRL (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 Cell projection, ruffle 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. Internalized from the cell membrane in response to EGF CC stimulation. {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-1250. 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}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH61863.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA27059.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X03362; CAA27059.1; ALT_INIT; mRNA. DR EMBL; BC061863; AAH61863.1; ALT_INIT; mRNA. DR PIR; A24562; TVRTNU. DR PDB; 1IIJ; NMR; -; A=647-681. DR PDB; 1N8Y; X-ray; 2.40 A; C=23-631. DR PDBsum; 1IIJ; -. DR PDBsum; 1N8Y; -. DR AlphaFoldDB; P06494; -. DR SMR; P06494; -. DR STRING; 10116.ENSRNOP00000040591; -. DR BindingDB; P06494; -. DR ChEMBL; CHEMBL3848; -. DR GlyCosmos; P06494; 6 sites, No reported glycans. DR GlyGen; P06494; 6 sites. DR iPTMnet; P06494; -. DR PhosphoSitePlus; P06494; -. DR PaxDb; 10116-ENSRNOP00000040591; -. DR UCSC; RGD:2561; rat. DR AGR; RGD:2561; -. DR RGD; 2561; Erbb2. DR eggNOG; KOG1025; Eukaryota. DR InParanoid; P06494; -. DR PhylomeDB; P06494; -. DR BRENDA; 2.7.10.1; 5301. DR Reactome; R-RNO-1227986; Signaling by ERBB2. DR Reactome; R-RNO-1250196; SHC1 events in ERBB2 signaling. DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling. DR Reactome; R-RNO-1306955; GRB7 events in ERBB2 signaling. DR Reactome; R-RNO-1358803; Downregulation of ERBB2:ERBB3 signaling. DR Reactome; R-RNO-1963640; GRB2 events in ERBB2 signaling. DR Reactome; R-RNO-1963642; PI3K events in ERBB2 signaling. DR Reactome; R-RNO-416572; Sema4D induced cell migration and growth-cone collapse. DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade. DR Reactome; R-RNO-6785631; ERBB2 Regulates Cell Motility. DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-RNO-8847993; ERBB2 Activates PTK6 Signaling. DR Reactome; R-RNO-8863795; Downregulation of ERBB2 signaling. DR Reactome; R-RNO-9652282; Drug-mediated inhibition of ERBB2 signaling. DR EvolutionaryTrace; P06494; -. DR PRO; PR:P06494; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD. DR GO; GO:0009925; C:basal plasma membrane; IDA:RGD. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0010008; C:endosome membrane; ISO:RGD. DR GO; GO:0038143; C:ERBB3:ERBB2 complex; ISO:RGD. DR GO; GO:0043219; C:lateral loop; IDA:RGD. DR GO; GO:0005902; C:microvillus; IDA:RGD. DR GO; GO:0043209; C:myelin sheath; ISO:RGD. DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD. DR GO; GO:0042734; C:presynaptic membrane; ISO:RGD. DR GO; GO:0043235; C:receptor complex; ISO:RGD. DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0002116; C:semaphorin receptor complex; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0015026; F:coreceptor activity; ISO:RGD. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0043125; F:ErbB-3 class receptor binding; ISO:RGD. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:RGD. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:RGD. DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD. DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD. DR GO; GO:0001042; F:RNA polymerase I core binding; ISS:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD. DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISO:RGD. DR GO; GO:0004888; F:transmembrane signaling receptor activity; ISO:RGD. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD. 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:0038134; P:ERBB2-EGFR signaling pathway; ISO:RGD. DR GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; ISO:RGD. DR GO; GO:0038135; P:ERBB2-ERBB4 signaling pathway; IDA:MGI. DR GO; GO:0044849; P:estrous cycle; IMP:RGD. DR GO; GO:0010001; P:glial cell differentiation; IGI:RGD. DR GO; GO:0007507; P:heart development; ISO:RGD. DR GO; GO:0033080; P:immature T cell proliferation in thymus; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB. DR GO; GO:0001889; P:liver development; IEP:RGD. DR GO; GO:0060056; P:mammary gland involution; IEP:RGD. DR GO; GO:0008045; P:motor neuron axon guidance; ISO:RGD. DR GO; GO:0042552; P:myelination; ISO:RGD. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD. DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISO:RGD. DR GO; GO:0007399; P:nervous system development; ISO:RGD. DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central. DR GO; GO:0007528; P:neuromuscular junction development; ISO:RGD. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:RGD. DR GO; GO:0048709; P:oligodendrocyte differentiation; ISO:RGD. DR GO; GO:0007422; P:peripheral nervous system development; IMP:RGD. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045785; P:positive regulation of cell adhesion; ISO:RGD. DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:RGD. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:RGD. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD. DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:UniProtKB. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:RGD. DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISO:RGD. 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:0045595; P:regulation of cell differentiation; TAS:RGD. DR GO; GO:0042127; P:regulation of cell population proliferation; TAS:RGD. 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:0048678; P:response to axon injury; IDA:RGD. DR GO; GO:0032570; P:response to progesterone; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0014044; P:Schwann cell development; ISO:RGD. DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISO:RGD. DR GO; GO:0007165; P:signal transduction; ISO:RGD. DR GO; GO:0007519; P:skeletal muscle tissue development; IEP:RGD. DR GO; GO:0048485; P:sympathetic nervous system development; IMP:RGD. DR GO; GO:0043586; P:tongue development; IEP:RGD. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISO:RGD. DR GO; GO:0042060; P:wound healing; ISO:RGD. DR CDD; cd00064; FU; 3. DR CDD; cd05109; PTKc_HER2; 1. DR CDD; cd12094; TM_ErbB2; 1. DR Gene3D; 1.20.5.100; Cytochrome c1, transmembrane anchor, C-terminal; 1. DR Gene3D; 4.10.1140.10; membrane-bound form of the juxtamembrane domain of the epidermal growth factor receptor like domain; 1. DR Gene3D; 3.80.20.20; Receptor L-domain; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID50066; -. 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; IPR049328; TM_ErbB1. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016245; Tyr_kinase_EGF/ERB/XmrK_rcpt. DR PANTHER; PTHR24416:SF137; RECEPTOR TYROSINE-PROTEIN KINASE ERBB-2; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. 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 Pfam; PF21314; TM_ErbB1; 1. DR PIRSF; PIRSF000619; TyrPK_EGF-R; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00261; FU; 4. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 2. DR SUPFAM; SSF52058; L domain-like; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; ATP-binding; Cell membrane; Cell projection; KW Cytoplasm; Disulfide bond; DNA-binding; Endosome; Glycoprotein; Kinase; KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; KW 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..1257 FT /note="Receptor tyrosine-protein kinase erbB-2" FT /id="PRO_0000016671" FT TOPO_DOM 23..654 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 655..677 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 678..1257 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 722..989 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 678..691 FT /note="Required for interaction with KPNB1 and EEA1" FT /evidence="ECO:0000250" FT REGION 1029..1181 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1197..1199 FT /note="Interaction with PIK3C2B" FT /evidence="ECO:0000250" FT REGION 1200..1257 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 678..691 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250" FT COMPBIAS 1222..1244 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 847 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 728..736 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 755 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 879 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P04626" FT MOD_RES 1056 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 1080 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 1085 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 1109 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P04626" FT MOD_RES 1114 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P04626" FT MOD_RES 1141 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P04626" FT MOD_RES 1168 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P04626" FT MOD_RES 1198 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P04626" FT MOD_RES 1250 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P04626" FT CARBOHYD 68 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007744|PDB:1N8Y" FT CARBOHYD 188 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0007744|PDB:1N8Y" FT CARBOHYD 260 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12610629, FT ECO:0007744|PDB:1N8Y" FT CARBOHYD 532 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 573 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 631 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 26..53 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 163..193 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 196..205 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 200..213 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 221..228 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 225..236 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 237..245 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 241..253 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 256..265 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 269..296 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 300..312 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 316..332 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 335..339 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 343..368 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 476..506 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 513..522 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 517..530 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 533..542 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 546..562 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 565..578 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 569..586 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 589..598 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 602..625 FT /evidence="ECO:0007744|PDB:1N8Y" FT DISULFID 628..636 FT /evidence="ECO:0000250|UniProtKB:P04626" FT DISULFID 632..644 FT /evidence="ECO:0000250|UniProtKB:P04626" FT VARIANT 661 FT /note="V -> E (in oncogenic NEU)" FT CONFLICT 145 FT /note="S -> G (in Ref. 2; AAH61863)" FT /evidence="ECO:0000305" FT CONFLICT 505..509 FT /note="LCVSS -> CGLE (in Ref. 2; AAH61863)" FT /evidence="ECO:0000305" FT STRAND 25..27 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 39..50 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 54..63 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 72..74 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 84..88 FT /evidence="ECO:0007829|PDB:1N8Y" FT TURN 109..111 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 112..117 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 153..158 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 170..173 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 183..185 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 201..203 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 205..209 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 228..232 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 233..235 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 241..243 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 245..249 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 252..261 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 264..268 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 272..274 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 290..292 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 295..299 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 310..315 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 320..324 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 330..334 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 349..351 FT /evidence="ECO:0007829|PDB:1N8Y" FT TURN 359..361 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 362..365 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 369..377 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 379..383 FT /evidence="ECO:0007829|PDB:1N8Y" FT TURN 386..389 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 395..401 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 406..409 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 411..414 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 424..426 FT /evidence="ECO:0007829|PDB:1N8Y" FT TURN 439..441 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 442..448 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 464..470 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 483..486 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 494..499 FT /evidence="ECO:0007829|PDB:1N8Y" FT TURN 507..510 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 518..520 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 522..526 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 530..538 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 541..544 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 547..553 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 558..561 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 573..575 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 577..582 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 583..585 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 586..594 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 597..601 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 604..606 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 615..619 FT /evidence="ECO:0007829|PDB:1N8Y" FT STRAND 623..627 FT /evidence="ECO:0007829|PDB:1N8Y" FT HELIX 650..669 FT /evidence="ECO:0007829|PDB:1IIJ" FT HELIX 670..674 FT /evidence="ECO:0007829|PDB:1IIJ" FT HELIX 675..679 FT /evidence="ECO:0007829|PDB:1IIJ" SQ SEQUENCE 1257 AA; 138832 MW; 6129264583011402 CRC64; MELAAWCRWG FLLALLPPGI AGTQVCTGTD MKLRLPASPE THLDMLRHLY QGCQVVQGNL ELTYVPANAS LSFLQDIQEV QGYMLIAHNQ VKRVPLQRLR IVRGTQLFED KYALAVLDNR DPQDNVAAST PGRTPEGLRE LQLRSLTEIL KGGVLIRGNP QLCYQDMVLW KDVFRKNNQL APVDIDTNRS RACPPCAPAC KDNHCWGESP EDCQILTGTI CTSGCARCKG RLPTDCCHEQ CAAGCTGPKH SDCLACLHFN HSGICELHCP ALVTYNTDTF ESMHNPEGRY TFGASCVTTC PYNYLSTEVG SCTLVCPPNN QEVTAEDGTQ RCEKCSKPCA RVCYGLGMEH LRGARAITSD NVQEFDGCKK IFGSLAFLPE SFDGDPSSGI APLRPEQLQV FETLEEITGY LYISAWPDSL RDLSVFQNLR IIRGRILHDG AYSLTLQGLG IHSLGLRSLR ELGSGLALIH RNAHLCFVHT VPWDQLFRNP HQALLHSGNR PEEDLCVSSG LVCNSLCAHG HCWGPGPTQC VNCSHFLRGQ ECVEECRVWK GLPREYVSDK RCLPCHPECQ PQNSSETCFG SEADQCAACA HYKDSSSCVA RCPSGVKPDL SYMPIWKYPD EEGICQPCPI NCTHSCVDLD ERGCPAEQRA SPVTFIIATV VGVLLFLILV VVVGILIKRR RQKIRKYTMR RLLQETELVE PLTPSGAMPN QAQMRILKET ELRKVKVLGS GAFGTVYKGI WIPDGENVKI PVAIKVLREN TSPKANKEIL DEAYVMAGVG SPYVSRLLGI CLTSTVQLVT QLMPYGCLLD HVREHRGRLG SQDLLNWCVQ IAKGMSYLED VRLVHRDLAA RNVLVKSPNH VKITDFGLAR LLDIDETEYH ADGGKVPIKW MALESILRRR FTHQSDVWSY GVTVWELMTF GAKPYDGIPA REIPDLLEKG ERLPQPPICT IDVYMIMVKC WMIDSECRPR FRELVSEFSR MARDPQRFVV IQNEDLGPSS PMDSTFYRSL LEDDDMGDLV DAEEYLVPQQ GFFSPDPTPG TGSTAHRRHR SSSTRSGGGE LTLGLEPSEE GPPRSPLAPS EGAGSDVFDG DLAMGVTKGL QSLSPHDLSP LQRYSEDPTL PLPPETDGYV APLACSPQPE YVNQSEVQPQ PPLTPEGPLP PVRPAGATLE RPKTLSPGKN GVVKDVFAFG GAVENPEYLV PREGTASPPH PSPAFSPAFD NLYYWDQNSS EQGPPPSNFE GTPTAENPEY LGLDVPV //