ERBB2_RAT
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 03-AUG-2022, entry version 207.
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). {ECO:0000250|UniProtKB:P04626,
CC 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-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};
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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 GlyGen; P06494; 6 sites.
DR iPTMnet; P06494; -.
DR PhosphoSitePlus; P06494; -.
DR PaxDb; P06494; -.
DR UCSC; RGD:2561; rat.
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-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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043219; C:lateral loop; IDA:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005902; C:microvillus; IDA:RGD.
DR GO; GO:0043209; C:myelin sheath; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA: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:0043235; C:receptor complex; ISO:RGD.
DR GO; GO:0044214; C:spanning component of plasma membrane; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0060724; F:coreceptor activity involved in epidermal growth factor receptor signaling pathway; 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:0008022; F:protein C-terminus binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
DR GO; GO:0030296; F:protein tyrosine kinase activator 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:0001042; F:RNA polymerase I core binding; ISS:UniProtKB.
DR GO; GO:0030297; F:transmembrane receptor protein tyrosine kinase activator activity; 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:0007417; P:central nervous system development; TAS:RGD.
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: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:0007528; P:neuromuscular junction development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0048709; P:oligodendrocyte differentiation; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD.
DR GO; GO:0007422; P:peripheral nervous system development; IMP:RGD.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:RGD.
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:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:RGD.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; 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: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:0046777; P:protein autophosphorylation; IDA:RGD.
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: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 Gene3D; 3.80.20.20; -; 2.
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; 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; 4.
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 1: Evidence at protein level;
KW 3D-structure; Activator; ATP-binding; Cell membrane; Cytoplasm;
KW Disulfide bond; DNA-binding; Endosome; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Proto-oncogene; Receptor;
KW Reference proteome; Signal; Transcription; Transcription regulation;
KW Transferase; Transmembrane; Transmembrane helix; 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 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
