E2AK3_MOUSE
ID E2AK3_MOUSE Reviewed; 1114 AA.
AC Q9Z2B5; Q9CTK8; Q9CWT5;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Eukaryotic translation initiation factor 2-alpha kinase 3;
DE EC=2.7.11.1 {ECO:0000269|PubMed:9930704};
DE AltName: Full=PRKR-like endoplasmic reticulum kinase;
DE AltName: Full=Pancreatic eIF2-alpha kinase;
DE Flags: Precursor;
GN Name=Eif2ak3; Synonyms=Pek, Perk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS
RP OF LYS-618.
RC STRAIN=NIH Swiss; TISSUE=Fibroblast;
RX PubMed=9930704; DOI=10.1038/16729;
RA Harding H.P., Zhang Y., Ron D.;
RT "Protein translation and folding are coupled by an endoplasmic-reticulum-
RT resident kinase.";
RL Nature 397:271-274(1999).
RN [2]
RP ERRATUM OF PUBMED:9930704.
RA Harding H.P., Zhang Y., Ron D.;
RL Nature 398:90-90(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-152 AND 769-1114.
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11106749; DOI=10.1016/s1097-2765(00)00108-8;
RA Harding H.P., Novoa I., Zhang Y., Zeng H., Wek R., Schapira M., Ron D.;
RT "Regulated translation initiation controls stress-induced gene expression
RT in mammalian cells.";
RL Mol. Cell 6:1099-1108(2000).
RN [5]
RP SUBUNIT.
RX PubMed=10854322; DOI=10.1038/35014014;
RA Bertolotti A., Zhang Y., Hendershot L.M., Harding H.P., Ron D.;
RT "Dynamic interaction of BiP and ER stress transducers in the unfolded-
RT protein response.";
RL Nat. Cell Biol. 2:326-332(2000).
RN [6]
RP FUNCTION.
RX PubMed=11035797; DOI=10.1073/pnas.220247197;
RA Brewer J.W., Diehl J.A.;
RT "PERK mediates cell-cycle exit during the mammalian unfolded protein
RT response.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:12625-12630(2000).
RN [7]
RP INTERACTION WITH DNAJC3.
RX PubMed=12446838; DOI=10.1073/pnas.252341799;
RA Yan W., Frank C.L., Korth M.J., Sopher B.L., Novoa I., Ron D., Katze M.G.;
RT "Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum
RT stress-induced molecular chaperone P58IPK.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:15920-15925(2002).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, AND INTERACTION WITH MFN2.
RX PubMed=23921556; DOI=10.1038/emboj.2013.168;
RA Munoz J.P., Ivanova S., Sanchez-Wandelmer J., Martinez-Cristobal P.,
RA Noguera E., Sancho A., Diaz-Ramos A., Hernandez-Alvarez M.I., Sebastian D.,
RA Mauvezin C., Palacin M., Zorzano A.;
RT "Mfn2 modulates the UPR and mitochondrial function via repression of
RT PERK.";
RL EMBO J. 32:2348-2361(2013).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 583-701 AND 867-1078, SUBUNIT,
RP AND PHOSPHORYLATION AT THR-980.
RX PubMed=21543844; DOI=10.1107/s0907444911006445;
RA Cui W., Li J., Ron D., Sha B.;
RT "The structure of the PERK kinase domain suggests the mechanism for its
RT activation.";
RL Acta Crystallogr. D 67:423-428(2011).
CC -!- FUNCTION: Metabolic-stress sensing protein kinase that phosphorylates
CC the alpha subunit of eukaryotic translation initiation factor 2
CC (EIF2S1/eIF-2-alpha) in response to various stress conditions
CC (PubMed:9930704, PubMed:11106749, PubMed:23921556). Key activator of
CC the integrated stress response (ISR) required for adaptation to various
CC stress, such as unfolded protein response (UPR) and low amino acid
CC availability (PubMed:9930704, PubMed:11106749, PubMed:23921556).
CC EIF2S1/eIF-2-alpha phosphorylation in response to stress converts
CC EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to
CC a global attenuation of cap-dependent translation, while concomitantly
CC initiating the preferential translation of ISR-specific mRNAs, such as
CC the transcriptional activators ATF4 and QRICH1, and hence allowing
CC ATF4- and QRICH1-mediated reprogramming (PubMed:11106749,
CC PubMed:23921556). Serves as a critical effector of unfolded protein
CC response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1
CC (CCND1) (PubMed:11035797). Involved in control of mitochondrial
CC morphology and function (PubMed:23921556).
CC {ECO:0000269|PubMed:11035797, ECO:0000269|PubMed:11106749,
CC ECO:0000269|PubMed:23921556, ECO:0000269|PubMed:9930704}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:9930704};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Perturbation in protein folding in the endoplasmic
CC reticulum (ER) promotes reversible dissociation from HSPA5/BIP and
CC oligomerization, resulting in transautophosphorylation and kinase
CC activity induction. {ECO:0000269|PubMed:11106749}.
CC -!- SUBUNIT: Forms dimers with HSPA5/BIP in resting cells
CC (PubMed:21543844). Oligomerizes in ER-stressed cells (PubMed:10854322).
CC Interacts with DNAJC3 (PubMed:12446838). Interacts with MFN2
CC (PubMed:23921556). Interacts with TMEM33 (By similarity). Interacts
CC with PDIA6 (By similarity). Interacts with LACC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZJ5, ECO:0000269|PubMed:10854322,
CC ECO:0000269|PubMed:12446838, ECO:0000269|PubMed:21543844,
CC ECO:0000269|PubMed:23921556}.
CC -!- INTERACTION:
CC Q9Z2B5; Q9QXT0: Cnpy2; NbExp=7; IntAct=EBI-1226344, EBI-8321111;
CC Q9Z2B5; Q9Z2B5: Eif2ak3; NbExp=2; IntAct=EBI-1226344, EBI-1226344;
CC Q9Z2B5; Q80U63: Mfn2; NbExp=2; IntAct=EBI-1226344, EBI-8437663;
CC Q9Z2B5; P05198: EIF2S1; Xeno; NbExp=4; IntAct=EBI-1226344, EBI-1056162;
CC Q9Z2B5; P11021: HSPA5; Xeno; NbExp=2; IntAct=EBI-1226344, EBI-354921;
CC Q9Z2B5; PRO_0000037570 [P27958]; Xeno; NbExp=5; IntAct=EBI-1226344, EBI-6904269;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC I membrane protein.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: By ER stress.
CC -!- DOMAIN: The lumenal domain senses perturbations in protein folding in
CC the ER, probably through reversible interaction with HSPA5/BIP.
CC -!- PTM: Autophosphorylated. Phosphorylated at Tyr-615 following
CC endoplasmic reticulum stress, leading to activate its tyrosine-protein
CC kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate
CC its enzyme activity (By similarity). Oligomerization of the N-terminal
CC ER luminal domain by ER stress promotes PERK trans-autophosphorylation
CC of the C-terminal cytoplasmic kinase domain at multiple residues
CC including Thr-980 on the kinase activation loop. {ECO:0000250,
CC ECO:0000269|PubMed:21543844}.
CC -!- PTM: N-glycosylated.
CC -!- PTM: ADP-ribosylated by PARP16 upon ER stress, which increases kinase
CC activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. GCN2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AF076681; AAD03337.1; -; mRNA.
DR EMBL; AK010397; BAB26908.1; -; mRNA.
DR EMBL; AK003226; BAB22655.1; -; mRNA.
DR CCDS; CCDS20223.1; -.
DR PIR; T14351; T14351.
DR RefSeq; NP_001300847.1; NM_001313918.1.
DR PDB; 3QD2; X-ray; 2.81 A; B=583-1078.
DR PDB; 4YZY; X-ray; 3.20 A; A=100-399.
DR PDBsum; 3QD2; -.
DR PDBsum; 4YZY; -.
DR AlphaFoldDB; Q9Z2B5; -.
DR SMR; Q9Z2B5; -.
DR DIP; DIP-39494N; -.
DR IntAct; Q9Z2B5; 19.
DR MINT; Q9Z2B5; -.
DR STRING; 10090.ENSMUSP00000034093; -.
DR GlyGen; Q9Z2B5; 1 site.
DR iPTMnet; Q9Z2B5; -.
DR PhosphoSitePlus; Q9Z2B5; -.
DR EPD; Q9Z2B5; -.
DR MaxQB; Q9Z2B5; -.
DR PaxDb; Q9Z2B5; -.
DR PRIDE; Q9Z2B5; -.
DR ProteomicsDB; 277663; -.
DR DNASU; 13666; -.
DR GeneID; 13666; -.
DR KEGG; mmu:13666; -.
DR UCSC; uc009cgc.1; mouse.
DR CTD; 9451; -.
DR MGI; MGI:1341830; Eif2ak3.
DR eggNOG; KOG1033; Eukaryota.
DR InParanoid; Q9Z2B5; -.
DR PhylomeDB; Q9Z2B5; -.
DR Reactome; R-MMU-381042; PERK regulates gene expression.
DR BioGRID-ORCS; 13666; 3 hits in 78 CRISPR screens.
DR ChiTaRS; Eif2ak3; mouse.
DR PRO; PR:Q9Z2B5; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9Z2B5; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0071074; F:eukaryotic initiation factor eIF2 binding; IC:ParkinsonsUK-UCL.
DR GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004672; F:protein kinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0019722; P:calcium-mediated signaling; IMP:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0070417; P:cellular response to cold; ISS:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR GO; GO:0036492; P:eiF2alpha phosphorylation in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0031018; P:endocrine pancreas development; ISS:UniProtKB.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:MGI.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:MGI.
DR GO; GO:0006983; P:ER overload response; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IDA:MGI.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:MGI.
DR GO; GO:0007595; P:lactation; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
DR GO; GO:0031642; P:negative regulation of myelination; IMP:MGI.
DR GO; GO:0017148; P:negative regulation of translation; IDA:MGI.
DR GO; GO:1902010; P:negative regulation of translation in response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032055; P:negative regulation of translation in response to stress; ISO:MGI.
DR GO; GO:0001503; P:ossification; ISS:UniProtKB.
DR GO; GO:0031016; P:pancreas development; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0036499; P:PERK-mediated unfolded protein response; IMP:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903788; P:positive regulation of glutathione biosynthetic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:ParkinsonsUK-UCL.
DR GO; GO:0009967; P:positive regulation of signal transduction; IDA:MGI.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IMP:ParkinsonsUK-UCL.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:AgBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0060734; P:regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IMP:UniProtKB.
DR GO; GO:1902235; P:regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IMP:MGI.
DR GO; GO:0010998; P:regulation of translational initiation by eIF2 alpha phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0032933; P:SREBP signaling pathway; IDA:MGI.
DR GO; GO:0006412; P:translation; IDA:MGI.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR Pfam; PF00069; Pkinase; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; ATP-binding; Endoplasmic reticulum;
KW Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Signal;
KW Stress response; Transferase; Translation regulation; Transmembrane;
KW Transmembrane helix; Unfolded protein response.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..1114
FT /note="Eukaryotic translation initiation factor 2-alpha
FT kinase 3"
FT /id="PRO_0000024323"
FT TOPO_DOM 29..510
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 511..531
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 532..1114
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 589..1075
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 72..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 775..827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1087..1114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 792..809
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 935
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 595..603
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 618
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 615
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZJ5"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZJ5"
FT MOD_RES 980
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21543844"
FT MOD_RES 1092
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZJ5"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT MUTAGEN 618
FT /note="K->A: Loss of activity and autophosphorylation."
FT /evidence="ECO:0000269|PubMed:9930704"
FT CONFLICT 143..152
FT /note="VFGNKMIIPS -> GTHKTSSKEC (in Ref. 3; BAB26908)"
FT /evidence="ECO:0000305"
FT CONFLICT 826
FT /note="Missing (in Ref. 3; BAB22655)"
FT /evidence="ECO:0000305"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 195..201
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 232..244
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 252..264
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:4YZY"
FT TURN 310..313
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 314..317
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:4YZY"
FT STRAND 335..345
FT /evidence="ECO:0007829|PDB:4YZY"
FT HELIX 584..588
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 589..596
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 601..608
FT /evidence="ECO:0007829|PDB:3QD2"
FT TURN 609..611
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 614..621
FT /evidence="ECO:0007829|PDB:3QD2"
FT TURN 625..627
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 628..639
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 650..656
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 661..667
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 881..887
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 894..899
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 904..906
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 909..928
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 938..940
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 941..943
FT /evidence="ECO:0007829|PDB:3QD2"
FT STRAND 949..951
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 986..988
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 991..995
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 1002..1016
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 1022..1033
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 1039..1044
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 1046..1056
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 1060..1062
FT /evidence="ECO:0007829|PDB:3QD2"
FT HELIX 1066..1071
FT /evidence="ECO:0007829|PDB:3QD2"
SQ SEQUENCE 1114 AA; 124682 MW; 65A47D6C0DD2E046 CRC64;
MERATRPGPR ALLLLLFLLL GCAAGISAVA PARSLLAPAS ETVFGLGAAA APTSAARVPA
VATAEVTVED AEALPAAAGE PESRATEPDD DVELRPRGRS LVIISTLDGR IAALDAENDG
KKQWDLDVGS GSLVSSSLSK PEVFGNKMII PSLDGDLFQW DRDRESMEAV PFTVESLLES
SYKFGDDVVL VGGKSLITYG LSAYSGKLRY ICSALGCRRW DSDEMEEEED ILLLQRTQKT
VRAVGPRSGS EKWNFSVGHF ELRYIPDMET RAGFIESTFK PGGNKEDSKI ISDVEEQEAT
MLDTVIKVSV ADWKVMAFSR KGGRLEWEYQ FCTPIASAWL VRDGKVIPIS LFDDTSYTAS
EEALGDEEDI VEAARGATEN SVYLGMYRGQ LYLQSSVRVS EKFPTSPKAL ESVNGENAII
PLPTIKWKPL IHSPSRTPVL VGSDEFDKCL SNDKYSHEEY SNGALSILQY PYDNGYYLPY
YKRERNKRST QITVRFLDSP HYSKNIRKKD PILLLHWWKE IFGTILLCIV ATTFIVRRLF
HPQPHRQRKE SETQCQTESK YDSVSADVSD NSWNDMKYSG YVSRYLTDFE PIQCMGRGGF
GVVFEAKNKV DDCNYAIKRI RLPNRELARE KVMREVKALA KLEHPGIVRY FNAWLETPPE
KWQEEMDEIW LKDESTDWPL SSPSPMDAPS VKIRRMDPFS TKEQIEVIAP SPERSRSFSV
GISCGQTSSS ESQFSPLEFS GTDCGDNSDS ADAAYNLQDS CLTDCEDVED GTVDGNDEGH
SFELCPSEAS PYTRSREGTS SSIVFEDSGC GNASSKEEPR GNRLHDGNHY VNKLTDLKCS
SSRSSSEATT LSTSPTRPTT LSLDFTKNTV GQLQPSSPKV YLYIQMQLCR KENLKDWMNR
RCSLEDREHG VCLHIFLQIA EAVEFLHSKG LMHRDLKPSN IFFTMDDVVK VGDFGLVTAM
DQDEEEQTVL TPMPAYATHT GQVGTKLYMS PEQIHGNNYS HKVDIFSLGL ILFELLYPFS
TQMERVRILT DVRNLKFPLL FTQKYPQEHM MVQDMLSPSP TERPEATDII ENAIFENLEF
PGKTVLRQRS RSMSSSGTKH SRQPSCSYSP LPGN
