ID EGFR_MACMU Reviewed; 1210 AA. AC P55245; F6YXS7; G7ML99; H9FAB2; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 22-JAN-2014, sequence version 2. DT 27-MAR-2024, entry version 176. DE RecName: Full=Epidermal growth factor receptor; DE EC=2.7.10.1; DE Flags: Precursor; GN Name=EGFR; OS Macaca mulatta (Rhesus macaque). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; OC Cercopithecidae; Cercopithecinae; Macaca. OX NCBI_TaxID=9544; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=17573; RX PubMed=17431167; DOI=10.1126/science.1139247; RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M., RA Mardis E.R., Remington K.A., Strausberg R.L., Venter J.C., Wilson R.K., RA Batzer M.A., Bustamante C.D., Eichler E.E., Hahn M.W., Hardison R.C., RA Makova K.D., Miller W., Milosavljevic A., Palermo R.E., Siepel A., RA Sikela J.M., Attaway T., Bell S., Bernard K.E., Buhay C.J., RA Chandrabose M.N., Dao M., Davis C., Delehaunty K.D., Ding Y., Dinh H.H., RA Dugan-Rocha S., Fulton L.A., Gabisi R.A., Garner T.T., Godfrey J., RA Hawes A.C., Hernandez J., Hines S., Holder M., Hume J., Jhangiani S.N., RA Joshi V., Khan Z.M., Kirkness E.F., Cree A., Fowler R.G., Lee S., RA Lewis L.R., Li Z., Liu Y.-S., Moore S.M., Muzny D., Nazareth L.V., RA Ngo D.N., Okwuonu G.O., Pai G., Parker D., Paul H.A., Pfannkoch C., RA Pohl C.S., Rogers Y.-H.C., Ruiz S.J., Sabo A., Santibanez J., RA Schneider B.W., Smith S.M., Sodergren E., Svatek A.F., Utterback T.R., RA Vattathil S., Warren W., White C.S., Chinwalla A.T., Feng Y., Halpern A.L., RA Hillier L.W., Huang X., Minx P., Nelson J.O., Pepin K.H., Qin X., RA Sutton G.G., Venter E., Walenz B.P., Wallis J.W., Worley K.C., Yang S.-P., RA Jones S.M., Marra M.A., Rocchi M., Schein J.E., Baertsch R., Clarke L., RA Csuros M., Glasscock J., Harris R.A., Havlak P., Jackson A.R., Jiang H., RA Liu Y., Messina D.N., Shen Y., Song H.X.-Z., Wylie T., Zhang L., Birney E., RA Han K., Konkel M.K., Lee J., Smit A.F.A., Ullmer B., Wang H., Xing J., RA Burhans R., Cheng Z., Karro J.E., Ma J., Raney B., She X., Cox M.J., RA Demuth J.P., Dumas L.J., Han S.-G., Hopkins J., Karimpour-Fard A., RA Kim Y.H., Pollack J.R., Vinar T., Addo-Quaye C., Degenhardt J., Denby A., RA Hubisz M.J., Indap A., Kosiol C., Lahn B.T., Lawson H.A., Marklein A., RA Nielsen R., Vallender E.J., Clark A.G., Ferguson B., Hernandez R.D., RA Hirani K., Kehrer-Sawatzki H., Kolb J., Patil S., Pu L.-L., Ren Y., RA Smith D.G., Wheeler D.A., Schenck I., Ball E.V., Chen R., Cooper D.N., RA Giardine B., Hsu F., Kent W.J., Lesk A., Nelson D.L., O'brien W.E., RA Pruefer K., Stenson P.D., Wallace J.C., Ke H., Liu X.-M., Wang P., RA Xiang A.P., Yang F., Barber G.P., Haussler D., Karolchik D., Kern A.D., RA Kuhn R.M., Smith K.E., Zwieg A.S.; RT "Evolutionary and biomedical insights from the rhesus macaque genome."; RL Science 316:222-234(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=22002653; DOI=10.1038/nbt.1992; RA Yan G., Zhang G., Fang X., Zhang Y., Li C., Ling F., Cooper D.N., Li Q., RA Li Y., van Gool A.J., Du H., Chen J., Chen R., Zhang P., Huang Z., RA Thompson J.R., Meng Y., Bai Y., Wang J., Zhuo M., Wang T., Huang Y., RA Wei L., Li J., Wang Z., Hu H., Yang P., Le L., Stenson P.D., Li B., Liu X., RA Ball E.V., An N., Huang Q., Zhang Y., Fan W., Zhang X., Li Y., Wang W., RA Katze M.G., Su B., Nielsen R., Yang H., Wang J., Wang X., Wang J.; RT "Genome sequencing and comparison of two nonhuman primate animal models, RT the cynomolgus and Chinese rhesus macaques."; RL Nat. Biotechnol. 29:1019-1023(2011). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 30-1210. RC TISSUE=Caudate nucleus; RA Pandey S., Maudhoo M.D., Guda C., Ferguson B., Fox H., Norgren R.B.; RT "De novo assembly of the rhesus macaque transcriptome from NextGen mRNA RT sequences."; RL Submitted (FEB-2012) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 893-977, TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RC TISSUE=Hypothalamus; RX PubMed=7545971; DOI=10.1159/000126769; RA Ma Y.J., Costa M.E., Ojeda S.R.; RT "Developmental expression of the genes encoding transforming growth factor RT alpha and its receptor in the hypothalamus of female rhesus macaques."; RL Neuroendocrinology 60:346-359(1994). CC -!- FUNCTION: Receptor tyrosine kinase binding ligands of the EGF family CC and activating several signaling cascades to convert extracellular cues CC into appropriate cellular responses. Known ligands include EGF, CC TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG CC and HBEGF/heparin-binding EGF. Ligand binding triggers receptor CC homo- and/or heterodimerization and autophosphorylation on key CC cytoplasmic residues. The phosphorylated receptor recruits adapter CC proteins like GRB2 which in turn activates complex downstream signaling CC cascades. Activates at least 4 major downstream signaling cascades CC including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs CC modules. May also activate the NF-kappa-B signaling cascade. Also CC directly phosphorylates other proteins like RGS16, activating its CC GTPase activity and probably coupling the EGF receptor signaling to the CC G protein-coupled receptor signaling. Also phosphorylates MUC1 and CC increases its interaction with SRC and CTNNB1/beta-catenin (By CC similarity). Positively regulates cell migration via interaction with CC CCDC88A/GIV which retains EGFR at the cell membrane following ligand CC stimulation, promoting EGFR signaling which triggers cell migration (By CC similarity). Plays a role in enhancing learning and memory performance CC (By similarity). Plays a role in mammalian pain signaling (long-lasting CC hypersensitivity) (By similarity). {ECO:0000250|UniProtKB:P00533, CC ECO:0000250|UniProtKB:Q01279}. 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 -!- ACTIVITY REGULATION: Endocytosis and inhibition of the activated EGFR CC by phosphatases like PTPRJ and PTPRK constitute immediate regulatory CC mechanisms. Upon EGF-binding phosphorylates EPS15 that regulates EGFR CC endocytosis and activity. Moreover, inducible feedback inhibitors CC including LRIG1, SOCS4, SOCS5 and ERRFI1 constitute alternative CC regulatory mechanisms for the EGFR signaling. CC -!- SUBUNIT: Binding of the ligand triggers homo- and/or heterodimerization CC of the receptor triggering its autophosphorylation. Heterodimer with CC ERBB2. Forms a complex with CCDC88A/GIV (via SH2-like regions) and CC GNAI3 which leads to enhanced EGFR signaling and triggering of cell CC migration; binding to CCDC88A requires autophosphorylation of the EGFR CC C-terminal region, and ligand stimulation is required for recruitment CC of GNAI3 to the complex. Interacts with ERRFI1; inhibits dimerization CC of the kinase domain and autophosphorylation. Part of a complex with CC ERBB2 and either PIK3C2A or PIK3C2B. Interacts with GRB2; an adapter CC protein coupling the receptor to downstream signaling pathways. CC Interacts with GAB2; involved in signaling downstream of EGFR. CC Interacts with STAT3; mediates EGFR downstream signaling in cell CC proliferation. Interacts with RIPK1; involved in NF-kappa-B activation. CC Interacts (autophosphorylated) with CBL, CBLB and CBLC; involved in CC EGFR ubiquitination and regulation; interaction with CBL is reduced in CC the presence of tensin TNS4. Interacts with SOCS5; regulates EGFR CC degradation through ELOC- and ELOB-mediated ubiquitination and CC proteasomal degradation. Interacts with PRMT5; methylates EGFR and CC enhances interaction with PTPN6. Interacts (phosphorylated) with PTPN6; CC inhibits EGFR-dependent activation of MAPK/ERK. Interacts with COPG1; CC essential for regulation of EGF-dependent nuclear transport of EGFR by CC retrograde trafficking from the Golgi to the ER. Interacts with TNK2; CC this interaction is dependent on EGF stimulation and kinase activity of CC EGFR. Interacts with PCNA; positively regulates PCNA. Interacts with CC PELP1. Interacts with MUC1. Interacts with AP2M1. Interacts with FER. CC May interact with EPS8; mediates EPS8 phosphorylation. Interacts (via CC SH2 domains) with GRB2, NCK1 and NCK2. Interacts with ATXN2. Interacts CC with GAREM1. Interacts (ubiquitinated) with ANKRD13A/B/D; the CC interaction is direct and may regulate EGFR internalization after EGF CC stimulation. Interacts with GPER1; the interaction occurs in an CC estrogen-dependent manner. Interacts (via C-terminal cytoplasmic kinase CC domain) with ZPR1 (via zinc fingers). Interacts with RNF115 and RNF126. CC Interacts with GPRC5A (via its transmembrane domain). Interacts with CC FAM83B; positively regulates EGFR inducing its autophosphorylation in CC absence of stimulation by EGF. Interacts with LAPTM4B; positively CC correlates with EGFR activation. Interacts with STX19. Interacts with CC CD44. Interacts with PGRMC1; the interaction requires PGRMC1 CC homodimerization. Interacts with PIKFYVE. Interacts with NEU3. CC Interacts with TRAF4. Interacts with the ant venom OMEGA- CC myrmeciitoxin(02)-Mg1a. {ECO:0000250|UniProtKB:P00533, CC ECO:0000250|UniProtKB:Q01279}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P00533}; CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P00533}. CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P00533}; Single- CC pass type I membrane protein {ECO:0000250|UniProtKB:P00533}. Golgi CC apparatus membrane {ECO:0000250|UniProtKB:P00533}; Single-pass type I CC membrane protein {ECO:0000250|UniProtKB:P00533}. Nucleus membrane CC {ECO:0000250|UniProtKB:P00533}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P00533}. Endosome CC {ECO:0000250|UniProtKB:P00533}. Endosome membrane CC {ECO:0000250|UniProtKB:P00533}. Nucleus {ECO:0000250|UniProtKB:P00533}. CC Note=In response to EGF, translocated from the cell membrane to the CC nucleus via Golgi and ER. Endocytosed upon activation by ligand. CC Colocalized with GPER1 in the nucleus of estrogen agonist-induced CC cancer-associated fibroblasts (CAF). {ECO:0000250|UniProtKB:P00533}. CC -!- TISSUE SPECIFICITY: Hypothalamus. {ECO:0000269|PubMed:7545971}. CC -!- DEVELOPMENTAL STAGE: Levels in the medial basal hypothalamus and CC preoptic area are elevated during neonatal life (1 week-6 months), CC decrease during juvenile development (8-18 months) and markedly CC increase during the expected time of puberty (30-36 months). CC {ECO:0000269|PubMed:7545971}. CC -!- PTM: Phosphorylated on Tyr residues in response to EGF. Phosphorylation CC at Ser-695 is partial and occurs only if Thr-693 is phosphorylated. CC Phosphorylation at Thr-678 and Thr-693 by PRKD1 inhibits EGF-induced CC MAPK8/JNK1 activation. Dephosphorylation by PTPRJ prevents endocytosis CC and stabilizes the receptor at the plasma membrane. Autophosphorylation CC at Tyr-1197 is stimulated by methylation at Arg-1199 and enhances CC interaction with PTPN6. Autophosphorylation at Tyr-1092 and/or Tyr-1110 CC recruits STAT3. Dephosphorylated by PTPN1 and PTPN2. CC {ECO:0000250|UniProtKB:P00533}. CC -!- PTM: Monoubiquitinated and polyubiquitinated upon EGF stimulation; CC which does not affect tyrosine kinase activity or signaling capacity CC but may play a role in lysosomal targeting (By similarity). CC Polyubiquitin linkage is mainly through 'Lys-63', but linkage through CC 'Lys-48', 'Lys-11' and 'Lys-29' also occurs. Deubiquitination by OTUD7B CC prevents degradation. Ubiquitinated by RNF115 and RNF126 (By CC similarity). Ubiquitinated by ZNRF1 or CBL at different lysines in CC response to EGF stimulation; leading to recruitment of the ESCRT CC machinery and subsequent degradation in the lysosomes (By similarity). CC Deubiquitinated by UCHL1 leading to the inhibition of its degradation CC (By similarity). {ECO:0000250|UniProtKB:P00533, CC ECO:0000250|UniProtKB:Q01279}. CC -!- PTM: Palmitoylated on Cys residues by ZDHHC20. Palmitoylation inhibits CC internalization after ligand binding, and increases the persistence of CC tyrosine-phosphorylated EGFR at the cell membrane. Palmitoylation CC increases the amplitude and duration of EGFR signaling. CC {ECO:0000250|UniProtKB:P00533}. CC -!- PTM: Methylated. Methylation at Arg-1199 by PRMT5 stimulates CC phosphorylation at Tyr-1197. {ECO:0000250|UniProtKB:P00533}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. EGF receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. 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; JH286850; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CM001255; EHH17303.1; -; Genomic_DNA. DR EMBL; JU327815; AFE71571.1; -; mRNA. DR EMBL; S75916; AAB33095.1; -; mRNA. DR PIR; I78540; I78540. DR RefSeq; XP_014988922.1; XM_015133436.1. DR AlphaFoldDB; P55245; -. DR BMRB; P55245; -. DR SMR; P55245; -. DR STRING; 9544.ENSMMUP00000046120; -. DR GlyCosmos; P55245; 10 sites, No reported glycans. DR PaxDb; 9544-ENSMMUP00000029471; -. DR GeneID; 613027; -. DR KEGG; mcc:613027; -. DR CTD; 1956; -. DR eggNOG; KOG1025; Eukaryota. DR HOGENOM; CLU_003384_0_1_1; -. DR InParanoid; P55245; -. DR OrthoDB; 1614410at2759; -. DR TreeFam; TF106002; -. DR Proteomes; UP000006718; Unassembled WGS sequence. DR Proteomes; UP000013456; Chromosome 3. DR GO; GO:0009925; C:basal plasma membrane; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. 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:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0048408; F:epidermal growth factor binding; IBA:GO_Central. DR GO; GO:0005006; F:epidermal growth factor receptor activity; IBA:GO_Central. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB. DR GO; GO:0071392; P:cellular response to estradiol stimulus; ISS:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007611; P:learning or memory; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IBA:GO_Central. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:1902966; P:positive regulation of protein localization to early endosome; ISS:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd00064; FU; 3. DR CDD; cd05108; PTKc_EGFR; 1. DR CDD; cd12093; TM_ErbB1; 1. DR Gene3D; 1.20.5.420; Immunoglobulin FC, subunit C; 1. DR Gene3D; 3.80.20.20; Receptor L-domain; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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:SF91; EPIDERMAL GROWTH FACTOR RECEPTOR; 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 2: Evidence at transcript level; KW ATP-binding; Cell membrane; Disulfide bond; Endoplasmic reticulum; KW Endosome; Glycoprotein; Golgi apparatus; Hydroxylation; Isopeptide bond; KW Kinase; Lipoprotein; Membrane; Methylation; Nucleotide-binding; Nucleus; KW Palmitate; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1..24 FT /evidence="ECO:0000250|UniProtKB:P00533" FT CHAIN 25..1210 FT /note="Epidermal growth factor receptor" FT /id="PRO_0000160254" FT TOPO_DOM 25..645 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 646..668 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 669..1210 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 75..300 FT /note="Approximate" FT REPEAT 390..600 FT /note="Approximate" FT DOMAIN 712..979 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 688..704 FT /note="Important for dimerization, phosphorylation and FT activation" FT /evidence="ECO:0000250" FT REGION 1097..1137 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1099..1114 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 837 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 718..726 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 745 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 790..791 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 855 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 1016 FT /note="Important for interaction with PIK3C2B" FT /evidence="ECO:0000250" FT MOD_RES 229 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 678 FT /note="Phosphothreonine; by PKC and PKD/PRKD1" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 693 FT /note="Phosphothreonine; by PKD/PRKD1" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 695 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 745 FT /note="N6-(2-hydroxyisobutyryl)lysine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 869 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 991 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 995 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 998 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1016 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1026 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1039 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1041 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1042 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1064 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1069 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1070 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1071 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1081 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1092 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1110 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1166 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1172 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1197 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P00533" FT MOD_RES 1199 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT LIPID 1049 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT LIPID 1146 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CARBOHYD 128 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 175 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 196 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 352 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 361 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 413 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 444 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 528 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 568 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT CARBOHYD 603 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT DISULFID 31..58 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 157..187 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 190..199 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 194..207 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 215..223 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 219..231 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 232..240 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 236..248 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 251..260 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 264..291 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 295..307 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 311..326 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 329..333 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 337..362 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 470..499 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 506..515 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 510..523 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 526..535 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 539..555 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 558..571 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 562..579 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 582..591 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 595..617 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 620..628 FT /evidence="ECO:0000250|UniProtKB:P00533" FT DISULFID 624..636 FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 716 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 737 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 754 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 757 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 867 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 929 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 960 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CROSSLNK 970 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P00533" FT CONFLICT 541 FT /note="V -> I (in Ref. 2; EHH17303)" FT /evidence="ECO:0000305" SQ SEQUENCE 1210 AA; 134350 MW; E114E9CEE96D64CC CRC64; MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYVL IALNTVERIP LENLQIIRGN MYYENSYALA VLSNYDANKT GLKELPMRNL QEILHGAVRF SNNPALCNVE SIQWRDIVSS EFLSNMSMDF QNHLGSCQKC DPSCPNGSCW GAGEENCQKL TKIICAQQCS GRCRGKSPSD CCHNQCAAGC TGPRESDCLV CRKFRDEATC KDTCPPLMLY NPTTYQMDVN PEGKYSFGAT CVKKCPRNYV VTDHGSCVRA CGADSYEMEE DGVRKCKKCE GPCRKVCNGI GIGEFKDTLS INATNIKHFK NCTSISGDLH ILPVAFRGDS FTHTPPLDPQ ELDILKTVKE ITGFLLIQAW PENRTDLHAF ENLEIIRGRT KQHGQFSLAV VSLNITSLGL RSLKEISDGD VIISGNKNLC YANTINWKKL FGTSSQKTKI ISNRGENSCK ATGQVCHALC SPEGCWGPEP RDCVSCQNVS RGRECVDKCN VLEGEPREFV ENSECIQCHP ECLPQVMNIT CTGRGPDNCI QCAHYIDGPH CVKTCPAGVM GENNTLVWKY ADAGHVCHLC HPNCTYGCTG PGLEGCARNG PKIPSIATGM VGALLLLLVV ALGIGLFMRR RHIVRKRTLR RLLQERELVE PLTPSGEAPN QALLRILKET EFKKIKVLGS GAFGTVYKGL WIPEGEKVKI PVAIKELREA TSPKANKEIL DEAYVMASVD NPHVCRLLGI CLTSTVQLIT QLMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA RNVLVKTPQH VKITDFGLAK LLGAEEKEYH AEGGKVPIKW MALESILHRI YTHQSDVWSY GVTVWELMTF GSKPYDGIPA SEISSILEKG ERLPQPPICT IDVYMIMVKC WMIDADSRPK FRELIIEFSK MARDPQRYLV IQGDERMHLP SPTDSNFYRA LMDEEDMDDV VDADEYLIPQ QGFFSSPSTS RTPLLSSLSA TSNNSTVACI DRNGLQSCPI KEDSFLQRYS SDPTGALTED SIDDTFLPVP EYINQSVPKR PAGSVQNPVY HNQPLNPAPS RDPHYQDPHS TAVGNPEYLN TVQPTCVNST FDSPAHWAQK GSHQISLDNP DYQQDFFPKE AKPNGIFKGS TAENAEYLRV APQSSEFIGA //