ID PDPK1_RAT Reviewed; 559 AA. AC O55173; G3V9W3; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2012, sequence version 2. DT 24-JAN-2024, entry version 182. DE RecName: Full=3-phosphoinositide-dependent protein kinase 1; DE EC=2.7.11.1; DE AltName: Full=Protein kinase B kinase; DE Short=PkB kinase; GN Name=Pdpk1; Synonyms=Pdk1; 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=Brain; RX PubMed=9445477; DOI=10.1126/science.279.5351.710; RA Stephens L.R., Anderson K.E., Stokoe D., Erdjument-Bromage H., RA Painter G.F., Holmes A.B., Gaffney P.R.J., Reese C.B., McCormick F., RA Tempst P., Coadwell W.J., Hawkins P.T.; RT "Protein kinase B kinases that mediate phosphatidylinositol 3,4,5- RT trisphosphate-dependent activation of protein kinase B."; RL Science 279:710-714(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15632090; DOI=10.1101/gr.2889405; RA Florea L., Di Francesco V., Miller J., Turner R., Yao A., Harris M., RA Walenz B., Mobarry C., Merkulov G.V., Charlab R., Dew I., Deng Z., RA Istrail S., Li P., Sutton G.; RT "Gene and alternative splicing annotation with AIR."; RL Genome Res. 15:54-66(2005). RN [4] RP FUNCTION IN PHOSPHORYLATION OF PRKCD AND PRKCZ, AUTOPHOSPHORYLATION, AND RP INTERACTION WITH PRKCD AND PRKCZ. RX PubMed=11781095; DOI=10.1021/bi010719z; RA Hodgkinson C.P., Sale G.J.; RT "Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by RT a C-terminal PRK2 fragment."; RL Biochemistry 41:561-569(2002). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY RP 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). CC -!- FUNCTION: Serine/threonine kinase which acts as a master kinase, CC phosphorylating and activating a subgroup of the AGC family of protein CC kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, CC PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal CC protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent CC protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and CC glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated CC kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central CC role in the transduction of signals from insulin by providing the CC activating phosphorylation to PKB/AKT1, thus propagating the signal to CC downstream targets controlling cell proliferation and survival, as well CC as glucose and amino acid uptake and storage. Negatively regulates the CC TGF-beta-induced signaling by: modulating the association of SMAD3 and CC SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and CC SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the CC translocation of SMAD7 from the nucleus to the cytoplasm in response to CC TGF-beta. Activates PPARG transcriptional activity and promotes CC adipocyte differentiation. Activates the NF-kappa-B pathway via CC phosphorylation of IKKB. The tyrosine phosphorylated form is crucial CC for the regulation of focal adhesions by angiotensin II. Controls CC proliferation, survival, and growth of developing pancreatic cells. CC Participates in the regulation of Ca(2+) entry and Ca(2+)-activated CC K(+) channels of mast cells. Essential for the motility of vascular CC endothelial cells (ECs) and is involved in the regulation of their CC chemotaxis. Plays a critical role in cardiac homeostasis by serving as CC a dual effector for cell survival and beta-adrenergic response. Plays CC an important role during thymocyte development by regulating the CC expression of key nutrient receptors on the surface of pre-T cells and CC mediating Notch-induced cell growth and proliferative responses. CC Provides negative feedback inhibition to toll-like receptor-mediated CC NF-kappa-B activation in macrophages (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:11781095}. 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 -!- 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: Homodimerization regulates its activity by CC maintaining the kinase in an autoinhibitory conformation. NPRL2 down- CC regulates its activity by interfering with tyrosine phosphorylation at CC the Tyr-9, Tyr-376 and Tyr-379 residues. The 14-3-3 protein YWHAQ acts CC as a negative regulator by association with the residues surrounding CC the Ser-244 residue. STRAP positively regulates its activity by CC enhancing its autophosphorylation and by stimulating its dissociation CC from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its CC activity by stimulating its dissociation from YWHAQ. Activated by CC phosphorylation on Tyr-9, Tyr-376 and Tyr-379 by INSR in response to CC insulin (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Homodimer in its autoinhibited state. Active as monomer. CC Interacts with NPRL2, PPARG, PAK1, PTK2B, GRB14, PKN1 (via C-terminus), CC STRAP and IKKB. The Tyr-9 phosphorylated form interacts with SRC, RASA1 CC and CRK (via their SH2 domains). Interacts with SGK3 in a CC phosphorylation-dependent manner. The tyrosine-phosphorylated form CC interacts with PTPN6. The Ser-244 phosphorylated form interacts with CC YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH CC domain) with SMAD3, SMAD4 and SMAD7 (By similarity). Interacts with CC PKN2; the interaction stimulates PDPK1 autophosphorylation, its CC PI(3,4,5)P3-dependent kinase activity toward 'Ser-473' of AKT1 but also CC activates its kinase activity toward PRKCD and PRKCZ. {ECO:0000250, CC ECO:0000269|PubMed:11781095}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. CC Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. CC Cell junction, focal adhesion {ECO:0000250}. Note=Tyrosine CC phosphorylation seems to occur only at the cell membrane. Translocates CC to the cell membrane following insulin stimulation by a mechanism that CC involves binding to GRB14 and INSR. SRC and HSP90 promote its CC localization to the cell membrane. Its nuclear localization is CC dependent on its association with PTPN6 and its phosphorylation at Ser- CC 396. Restricted to the nucleus in neuronal cells while in non-neuronal CC cells it is found in the cytoplasm. The Ser-244 phosphorylated form is CC distributed along the perinuclear region in neuronal cells while in CC non-neuronal cells it is found in both the nucleus and the cytoplasm. CC IGF1 transiently increases phosphorylation at Ser-244 of neuronal CC PDPK1, resulting in its translocation to other cellular compartments. CC The tyrosine-phosphorylated form colocalizes with PTK2B in focal CC adhesions after angiotensin II stimulation (By similarity). CC {ECO:0000250}. CC -!- DOMAIN: The PH domain plays a pivotal role in the localization and CC nuclear import of PDPK1 and is also essential for its homodimerization. CC {ECO:0000250}. CC -!- DOMAIN: The PIF-pocket is a small lobe in the catalytic domain required CC by the enzyme for the binding to the hydrophobic motif of its CC substrates. It is an allosteric regulatory site that can accommodate CC small compounds acting as allosteric inhibitors. CC {ECO:0000250|UniProtKB:O15530}. CC -!- PTM: Phosphorylation on Ser-244 in the activation loop is required for CC full activity. PDPK1 itself can autophosphorylate Ser-244, leading to CC its own activation. Autophosphorylation is inhibited by the apoptotic CC C-terminus cleavage product of PKN2. Tyr-9 phosphorylation is critical CC for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90- CC mediated protection of PDPK1 degradation. Angiotensin II stimulates the CC tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a CC calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-376 and CC Tyr-379 by INSR in response to insulin. Palmitate negatively regulates CC autophosphorylation at Ser-244 and palmitate-induced phosphorylation at CC Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to CC phosphorylate PKB/AKT1. Phosphorylation at Thr-357 by MELK partially CC inhibits kinase activity, the inhibition is cooperatively enhanced by CC phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity). CC {ECO:0000250}. CC -!- PTM: Monoubiquitinated in the kinase domain, deubiquitinated by USP4. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. PDPK1 subfamily. {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; Y15748; CAA75758.1; -; mRNA. DR EMBL; CH473948; EDM03805.1; -; Genomic_DNA. DR RefSeq; NP_112343.1; NM_031081.1. DR AlphaFoldDB; O55173; -. DR SMR; O55173; -. DR CORUM; O55173; -. DR STRING; 10116.ENSRNOP00000061683; -. DR iPTMnet; O55173; -. DR PhosphoSitePlus; O55173; -. DR jPOST; O55173; -. DR PaxDb; 10116-ENSRNOP00000061683; -. DR Ensembl; ENSRNOT00000067660.2; ENSRNOP00000061683.1; ENSRNOG00000006136.6. DR Ensembl; ENSRNOT00055045426; ENSRNOP00055037224; ENSRNOG00055026228. DR Ensembl; ENSRNOT00060016542; ENSRNOP00060012928; ENSRNOG00060009727. DR Ensembl; ENSRNOT00065016490; ENSRNOP00065012535; ENSRNOG00065010212. DR GeneID; 81745; -. DR KEGG; rno:81745; -. DR UCSC; RGD:620307; rat. DR AGR; RGD:620307; -. DR CTD; 5170; -. DR RGD; 620307; Pdpk1. DR eggNOG; KOG0592; Eukaryota. DR GeneTree; ENSGT00940000155267; -. DR HOGENOM; CLU_000288_63_9_1; -. DR InParanoid; O55173; -. DR OrthoDB; 208777at2759; -. DR TreeFam; TF105423; -. DR BRENDA; 2.7.11.1; 5301. DR Reactome; R-RNO-114604; GPVI-mediated activation cascade. DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling. DR Reactome; R-RNO-165158; Activation of AKT2. DR Reactome; R-RNO-202424; Downstream TCR signaling. DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-RNO-2871837; FCERI mediated NF-kB activation. DR Reactome; R-RNO-354192; Integrin signaling. DR Reactome; R-RNO-389357; CD28 dependent PI3K/Akt signaling. DR Reactome; R-RNO-392451; G beta:gamma signalling through PI3Kgamma. DR Reactome; R-RNO-5218920; VEGFR2 mediated vascular permeability. DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-RNO-5625740; RHO GTPases activate PKNs. DR Reactome; R-RNO-6804757; Regulation of TP53 Degradation. DR Reactome; R-RNO-9634635; Estrogen-stimulated signaling through PRKCZ. DR PRO; PR:O55173; -. DR Proteomes; UP000002494; Chromosome 10. DR Proteomes; UP000234681; Chromosome 10. DR Bgee; ENSRNOG00000006136; Expressed in testis and 19 other cell types or tissues. DR GO; GO:0042995; C:cell projection; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD. DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0043204; C:perikaryon; IDA:RGD. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0014069; C:postsynaptic density; ISO:RGD. DR GO; GO:0004676; F:3-phosphoinositide-dependent protein kinase activity; IDA:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005158; F:insulin receptor binding; IDA:RGD. DR GO; GO:0016004; F:phospholipase activator activity; ISO:RGD. DR GO; GO:0043274; F:phospholipase binding; ISO:RGD. DR GO; GO:0019901; F:protein kinase binding; IDA:RGD. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD. DR GO; GO:0016477; P:cell migration; ISO:RGD. DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IEP:RGD. DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISO:RGD. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:RGD. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD. DR GO; GO:0048041; P:focal adhesion assembly; IMP:RGD. DR GO; GO:0006972; P:hyperosmotic response; ISO:RGD. DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD. DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:RGD. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:RGD. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD. DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISO:RGD. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD. DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISO:RGD. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:RGD. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:RGD. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; ISO:RGD. DR GO; GO:0010594; P:regulation of endothelial cell migration; ISO:RGD. DR GO; GO:0043304; P:regulation of mast cell degranulation; ISO:RGD. DR GO; GO:0003323; P:type B pancreatic cell development; ISO:RGD. DR CDD; cd01262; PH_PDK1; 1. DR CDD; cd05581; STKc_PDK1; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR033931; PDK1-typ_PH. DR InterPro; IPR039046; PDPK1. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24356:SF163; 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1-RELATED; 1. DR PANTHER; PTHR24356; SERINE/THREONINE-PROTEIN KINASE; 1. DR Pfam; PF14593; PH_3; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF50729; PH domain-like; 1. 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; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; O55173; RN. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cell junction; Cell membrane; Cytoplasm; Kinase; KW Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase; Ubl conjugation. FT CHAIN 1..559 FT /note="3-phosphoinositide-dependent protein kinase 1" FT /id="PRO_0000086502" FT DOMAIN 85..345 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 462..553 FT /note="PH" FT REGION 25..83 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 116..160 FT /note="PIF-pocket" FT /evidence="ECO:0000250|UniProtKB:O15530" FT COMPBIAS 25..69 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 208 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 95..97 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 114 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 163..165 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 169 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 212 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT BINDING 226 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 9 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 25 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 244 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 307 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0" FT MOD_RES 357 FT /note="Phosphothreonine; by MELK" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 376 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 379 FT /note="Phosphotyrosine; by SRC and INSR" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 396 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 397 FT /note="Phosphoserine; by MAP3K5" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 401 FT /note="Phosphoserine; by MAP3K5" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 413 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 504 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0" FT MOD_RES 516 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:O15530" FT MOD_RES 532 FT /note="Phosphoserine; by PKC/PRKCQ" FT /evidence="ECO:0000250|UniProtKB:Q9Z2A0" FT CONFLICT 401 FT /note="S -> C (in Ref. 1; CAA75758)" FT /evidence="ECO:0000305" SQ SEQUENCE 559 AA; 63593 MW; 4D06A17F769B800F CRC64; MARTTSQLYD AVPIQSSVVL CSCPSPSMVR SQTEPSSSPG IPSGVSRQGS TMDGTTAEAR PSTNPLQQHP AQLPPQPRKK RPEDFKFGKI LGEGSFSTVV LARELATSRE YAIKILEKRH IIKENKVPYV TRERDVMSRL DHPFFVKLYF TFQDDEKLYF GLSYAKNGEL LKYIRKIGSF DETCTRFYTA EIVSALEYLH GKGIIHRDLK PENILLNEDM HIQITDFGTA KVLSPDSKQA RANSFVGTAQ YVSPELLTEK SACKSSDLWA LGCIIYQLVA GLPPFRAGNE YLIFQKIIKL EYDFPEKFFP KARDLVEKLL VLDATKRLGC EEMEGYGPLK AHPFFESITW ENLHQQTPPK LTAYLPAMSE DDEDCYGNYD NLLSQFGCMQ VSSSSSSHSL SAVDASLPQR SGSNIEQYIH DLDTNSFELD LQFSEDEKRL LLEKQAGGNP WHQFVENNLI LKMGPVDKRK GLFARRRQLL LTEGPHLYYV DPVNKVLKGE IPWSQELRPE AKNFKTFFVH TPNRTYYLMD PSGNAHKWCR KIQEVWRQQY QSSPDAAVQ //