ID PASK_HUMAN Reviewed; 1323 AA. AC Q96RG2; G5E9F1; Q05BE4; Q68DY3; Q6GSJ5; Q86XH6; Q99763; Q9UFR7; DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 02-SEP-2026, entry version 222. DE RecName: Full=PAS domain-containing serine/threonine-protein kinase; DE Short=PAS-kinase; DE Short=PASKIN; DE Short=hPASK; DE EC=2.7.11.1; GN Name=PASK; Synonyms=KIAA0135; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT THR-1161 AND RP THR-1165, MUTAGENESIS OF LYS-1028; THR-1161 AND THR-1165, AND VARIANT RP CYS-1266. RC TISSUE=Cervix carcinoma; RX PubMed=11459942; DOI=10.1073/pnas.161284798; RA Rutter J., Michnoff C.H., Harper S.M., Gardner K.H., McKnight S.L.; RT "PAS kinase: an evolutionarily conserved PAS domain-regulated RT serine/threonine kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 98:8991-8996(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS MET-694 RP AND CYS-1266. RC TISSUE=Bone marrow; RX PubMed=8590280; DOI=10.1093/dnares/2.4.167; RA Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. IV. The RT coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 2:167-174(1995). RN [3] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP ILE-250. RC TISSUE=Eye, Lymph, and Testis; 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 866-1323 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9110174; DOI=10.1101/gr.7.4.353; RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.; RT "Large-scale concatenation cDNA sequencing."; RL Genome Res. 7:353-358(1997). RN [9] RP FUNCTION IN PHOSPHORYLATION OF GYS1. RX PubMed=16275910; DOI=10.1073/pnas.0508481102; RA Wilson W.A., Skurat A.V., Probst B., de Paoli-Roach A., Roach P.J., RA Rutter J.; RT "Control of mammalian glycogen synthase by PAS kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 102:16596-16601(2005). RN [10] RP FUNCTION IN PHOSPHORYLATION OF PDX1. RX PubMed=17052199; DOI=10.1042/bst0340791; RA An R., da Silva Xavier G., Hao H.X., Semplici F., Rutter J., Rutter G.A.; RT "Regulation by Per-Arnt-Sim (PAS) kinase of pancreatic duodenal homeobox-1 RT nuclear import in pancreatic beta-cells."; RL Biochem. Soc. Trans. 34:791-793(2006). RN [11] RP FUNCTION IN PHOSPHORYLATION OF EEF1A1, AUTOPHOSPHORYLATION, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF THR-1161 AND THR-1165. RX PubMed=17595531; DOI=10.1159/000104169; RA Eckhardt K., Troger J., Reissmann J., Katschinski D.M., Wagner K.F., RA Stengel P., Paasch U., Hunziker P., Borter E., Barth S., Schlafli P., RA Spielmann P., Stiehl D.P., Camenisch G., Wenger R.H.; RT "Male germ cell expression of the PAS domain kinase PASKIN and its novel RT target eukaryotic translation elongation factor eEF1A1."; RL Cell. Physiol. Biochem. 20:227-240(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP FUNCTION. RX PubMed=21181396; DOI=10.1007/s00125-010-2010-7; RA da Silva Xavier G., Farhan H., Kim H., Caxaria S., Johnson P., Hughes S., RA Bugliani M., Marselli L., Marchetti P., Birzele F., Sun G., Scharfmann R., RA Rutter J., Siniakowicz K., Weir G., Parker H., Reimann F., Gribble F.M., RA Rutter G.A.; RT "Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in RT human islets in type 2 diabetes and regulates glucagon secretion."; RL Diabetologia 54:819-827(2011). RN [15] RP FUNCTION IN PHOSPHORYLATION OF RPS6, ACTIVITY REGULATION, DOMAIN PROTEIN RP KINASE, AUTOPHOSPHORYLATION, AND LIPID-BINDING. RX PubMed=21418524; DOI=10.1111/j.1742-4658.2011.08100.x; RA Schlafli P., Troger J., Eckhardt K., Borter E., Spielmann P., Wenger R.H.; RT "Substrate preference and phosphatidylinositol monophosphate inhibition of RT the catalytic domain of the Per-Arnt-Sim domain kinase PASKIN."; RL FEBS J. 278:1757-1768(2011). RN [16] RP REVIEW ON FUNCTION. RX PubMed=19189049; DOI=10.1007/s00018-009-8699-0; RA Schlafli P., Borter E., Spielmann P., Wenger R.H.; RT "The PAS-domain kinase PASKIN: a new sensor in energy homeostasis."; RL Cell. Mol. Life Sci. 66:876-883(2009). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582 AND SER-939, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP STRUCTURE BY NMR OF 131-237. RX PubMed=12377121; DOI=10.1016/s0969-2126(02)00857-2; RA Amezcua C.A., Harper S.M., Rutter J., Gardner K.H.; RT "Structure and interactions of PAS kinase N-terminal PAS domain: model for RT intramolecular kinase regulation."; RL Structure 10:1349-1361(2002). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 977-1300 IN COMPLEX WITH ADP, RP AUTOPHOSPHORYLATION, FUNCTION, AND MUTAGENESIS OF LYS-1028; ARG-1058; RP ALA-1151; TYR-1152 AND THR-1161. RX PubMed=20943661; DOI=10.1074/jbc.m110.157594; RA Kikani C.K., Antonysamy S.A., Bonanno J.B., Romero R., Zhang F.F., RA Russell M., Gheyi T., Iizuka M., Emtage S., Sauder J.M., Turk B.E., RA Burley S.K., Rutter J.; RT "Structural bases of PAS domain-regulated kinase (PASK) activation in the RT absence of activation loop phosphorylation."; RL J. Biol. Chem. 285:41034-41043(2010). RN [21] RP VARIANTS [LARGE SCALE ANALYSIS] LYS-11; ILE-250; ARG-426; ALA-512; SER-514; RP ARG-684; ASP-725; LYS-796; GLN-844; HIS-937; MET-1210; CYS-1266 AND RP SER-1301. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Serine/threonine-protein kinase involved in energy CC homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 CC and RPS6. Probably plays a role under changing environmental conditions CC (oxygen, glucose, nutrition), rather than under standard conditions. CC Acts as a sensor involved in energy homeostasis: regulates glycogen CC synthase synthesis by mediating phosphorylation of GYS1, leading to CC GYS1 inactivation. May be involved in glucose-stimulated insulin CC production in pancreas and regulation of glucagon secretion by glucose CC in alpha cells; however such data require additional evidence. May play CC a role in regulation of protein translation by phosphorylating EEF1A1, CC leading to increase translation efficiency. May also participate in CC respiratory regulation. {ECO:0000269|PubMed:16275910, CC ECO:0000269|PubMed:17052199, ECO:0000269|PubMed:17595531, CC ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21181396, CC ECO:0000269|PubMed:21418524}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC -!- ACTIVITY REGULATION: Protein kinase activity is inhibited by the first CC PAS domain: binding of an unidentified ligand desinhibits the protein CC kinase activity. May be activated by autophosphorylation on Thr-1161 CC and Thr-1165 (PubMed:11459942). The activating role of CC autophosphorylation at Thr-1161 is unclear: according to a report, CC autophosphorylation at Thr-1161 does not play a major role in CC activation (PubMed:20943661). Autophosphorylation is enhanced upon CC phosphatidylinositol monophosphate (phosphatidylinositol 4-phosphate) CC binding and inhibited upon phosphatidylinositol bi- and tri-phosphate CC binding. In contrast, phosphorylation of target proteins is inhibited CC upon all phosphatidylinositol-binding (phosphatidylinositol CC mono- bi- and tri-phosphate). {ECO:0000269|PubMed:11459942, CC ECO:0000269|PubMed:20943661, ECO:0000269|PubMed:21418524}. CC -!- INTERACTION: CC Q96RG2; P16220: CREB1; NbExp=2; IntAct=EBI-1042651, EBI-711855; CC Q96RG2; P02545: LMNA; NbExp=2; IntAct=EBI-1042651, EBI-351935; CC Q96RG2; Q93100: PHKB; NbExp=2; IntAct=EBI-1042651, EBI-740559; CC Q96RG2; P62753: RPS6; NbExp=3; IntAct=EBI-1042651, EBI-356625; CC Q96RG2; P07293: CACNA1S; Xeno; NbExp=2; IntAct=EBI-1042651, EBI-8613624; CC Q96RG2; P02542: DES; Xeno; NbExp=2; IntAct=EBI-1042651, EBI-8614455; CC Q96RG2; Q28115: GFAP; Xeno; NbExp=2; IntAct=EBI-1042651, EBI-907866; CC Q96RG2; P02646: TNNI3; Xeno; NbExp=2; IntAct=EBI-1042651, EBI-8614386; CC Q96RG2; P20152: Vim; Xeno; NbExp=2; IntAct=EBI-1042651, EBI-299269; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17595531}. Nucleus CC {ECO:0000269|PubMed:17595531}. Note=Localizes in the nucleus of testis CC germ cells and in the midpiece of sperm tails. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96RG2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96RG2-2; Sequence=VSP_009302; CC Name=3; CC IsoId=Q96RG2-4; Sequence=VSP_045543, VSP_045544; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with slightly higher CC expression in brain, prostate and testis. Reduced expression was found CC in placenta. Present in germ cells of testis and in the midpiece of CC sperm tails (at protein level). CC -!- DOMAIN: The protein kinase domain mediates binding to CC phosphatidylinositol. {ECO:0000269|PubMed:21418524}. CC -!- PTM: Autophosphorylated on Thr-1161 and Thr-1165. Autophosphorylation CC is activated by phospholipids. {ECO:0000269|PubMed:11459942}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA09484.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF387103; AAK69752.1; -; mRNA. DR EMBL; D50925; BAA09484.2; ALT_INIT; mRNA. DR EMBL; CR749231; CAH18087.1; -; mRNA. DR EMBL; AC005237; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471063; EAW71238.1; -; Genomic_DNA. DR EMBL; BC043495; AAH43495.1; -; mRNA. DR EMBL; BC050565; AAH50565.1; -; mRNA. DR EMBL; BC063585; AAH63585.1; -; mRNA. DR EMBL; U79240; AAB50198.1; -; mRNA. DR CCDS; CCDS2545.1; -. [Q96RG2-1] DR CCDS; CCDS58758.1; -. [Q96RG2-4] DR CCDS; CCDS58759.1; -. [Q96RG2-2] DR PIR; T17211; T17211. DR RefSeq; NP_001239048.1; NM_001252119.2. [Q96RG2-2] DR RefSeq; NP_001239049.1; NM_001252120.2. [Q96RG2-1] DR RefSeq; NP_001239051.1; NM_001252122.2. DR RefSeq; NP_001239053.1; NM_001252124.2. [Q96RG2-4] DR RefSeq; NP_055963.2; NM_015148.4. [Q96RG2-1] DR PDB; 1LL8; NMR; -; A=131-237. DR PDB; 3DLS; X-ray; 2.30 A; A/B/C/D/E/F=977-1300. DR AlphaFoldDB; Q96RG2; -. DR BMRB; Q96RG2; -. DR SMR; Q96RG2; -. DR BioGRID; 116790; 172. DR FunCoup; Q96RG2; 3778. DR IntAct; Q96RG2; 140. DR MINT; Q96RG2; -. DR NDEx; IQUERY-CP-PASK; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000351475; -. DR BindingDB; Q96RG2; -. DR ChEMBL; CHEMBL6054; -. DR MoonDB; Q96RG2; Predicted. DR GlyGen; Q96RG2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96RG2; -. DR PhosphoSitePlus; Q96RG2; -. DR BioMuta; PASK; -. DR DMDM; 116242701; -. DR jPOST; Q96RG2; -. DR MassIVE; Q96RG2; -. DR PaxDb; 9606-ENSP00000351475; -. DR PeptideAtlas; Q96RG2; -. DR ProteomicsDB; 33919; -. DR ProteomicsDB; 77959; -. [Q96RG2-1] DR ProteomicsDB; 77960; -. [Q96RG2-2] DR Pumba; Q96RG2; -. DR Antibodypedia; 20301; 212 antibodies from 29 providers. DR DNASU; 23178; -. DR Ensembl; ENST00000234040.9; ENSP00000234040.5; ENSG00000115687.15. [Q96RG2-1] DR Ensembl; ENST00000358649.8; ENSP00000351475.4; ENSG00000115687.15. [Q96RG2-2] DR Ensembl; ENST00000403638.7; ENSP00000384438.3; ENSG00000115687.15. [Q96RG2-4] DR Ensembl; ENST00000405260.5; ENSP00000384016.1; ENSG00000115687.15. [Q96RG2-1] DR Ensembl; ENST00000544142.5; ENSP00000441374.2; ENSG00000115687.15. [Q96RG2-1] DR Ensembl; ENST00000872362.1; ENSP00000542421.1; ENSG00000115687.15. [Q96RG2-1] DR Ensembl; ENST00000930256.1; ENSP00000600315.1; ENSG00000115687.15. [Q96RG2-2] DR Ensembl; ENST00000930258.1; ENSP00000600317.1; ENSG00000115687.15. [Q96RG2-2] DR Ensembl; ENST00000930267.1; ENSP00000600326.1; ENSG00000115687.15. [Q96RG2-1] DR Ensembl; ENST00000930268.1; ENSP00000600327.1; ENSG00000115687.15. [Q96RG2-1] DR Ensembl; ENST00000930269.1; ENSP00000600328.1; ENSG00000115687.15. [Q96RG2-1] DR GeneID; 23178; -. DR KEGG; hsa:23178; -. DR MANE-Select; ENST00000234040.9; ENSP00000234040.5; NM_015148.4; NP_055963.2. DR UCSC; uc002wao.2; human. [Q96RG2-1] DR AGR; HGNC:17270; -. DR ClinPGx; PA32953; -. DR CTD; 23178; -. DR DisGeNET; 23178; -. DR GeneCards; PASK; -. DR HGNC; HGNC:17270; PASK. DR HPA; ENSG00000115687; Tissue enhanced (lymphoid). DR MalaCards; PASK; -. DR MIM; 607505; gene. DR OpenTargets; ENSG00000115687; -. DR VEuPathDB; HostDB:ENSG00000115687; -. DR eggNOG; KOG0583; Eukaryota. DR eggNOG; KOG1152; Eukaryota. DR GeneTree; ENSGT00940000159035; -. DR HOGENOM; CLU_006086_0_0_1; -. DR InParanoid; Q96RG2; -. DR OMA; AFIDHHP; -. DR OrthoDB; 10252171at2759; -. DR PAN-GO; Q96RG2; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q96RG2; -. DR PathwayCommons; Q96RG2; -. DR SignaLink; Q96RG2; -. DR SIGNOR; Q96RG2; -. DR Agora; ENSG00000115687; -. DR BioGRID-ORCS; 23178; 13 hits in 1186 CRISPR screens. DR ChiTaRS; PASK; human. DR EvolutionaryTrace; Q96RG2; -. DR GeneWiki; PASK; -. DR GenomeRNAi; 23178; -. DR Pharos; Q96RG2; Tchem. DR PRO; PR:Q96RG2; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q96RG2; protein. DR Bgee; ENSG00000115687; Expressed in right uterine tube and 125 other cell types or tissues. DR ExpressionAtlas; Q96RG2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; IDA:UniProtKB. DR GO; GO:0045727; P:positive regulation of translation; TAS:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0070092; P:regulation of glucagon secretion; ISS:UniProtKB. DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; ISS:UniProtKB. DR CDD; cd00130; PAS; 2. DR CDD; cd14004; STKc_PASK; 1. DR FunFam; 3.30.450.20:FF:000059; PAS domain containing serine/threonine kinase; 1. DR FunFam; 1.10.510.10:FF:000351; PAS domain-containing serine/threonine-protein kinase; 1. DR FunFam; 3.30.200.20:FF:000346; PAS domain-containing serine/threonine-protein kinase; 1. DR Gene3D; 3.30.450.20; PAS domain; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR NCBIfam; TIGR00229; sensory_box; 1. DR PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1. DR PANTHER; PTHR24346:SF51; PAS DOMAIN-CONTAINING SERINE_THREONINE-PROTEIN KINASE; 1. DR Pfam; PF13426; PAS_9; 2. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00091; PAS; 2. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 1. DR PROSITE; PS50112; PAS; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PDBsum; 1LL8; -. DR PDBsum; 3DLS; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; KW Kinase; Lipid-binding; Nucleotide-binding; Nucleus; Phosphoprotein; KW Proteomics identification; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1..1323 FT /note="PAS domain-containing serine/threonine-protein FT kinase" FT /id="PRO_0000086480" FT DOMAIN 119..190 FT /note="PAS 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 335..402 FT /note="PAS 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 999..1251 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 20..47 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 837..857 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1298..1323 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 31..43 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 1128 FT /note="Proton acceptor" FT BINDING 1005..1013 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 1028 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 1082..1089 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT BINDING 1146 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8CEE6" FT MOD_RES 34 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q8CEE6" FT MOD_RES 582 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 939 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1161 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11459942" FT MOD_RES 1165 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11459942" FT VAR_SEQ 1111 FT /note="Q -> QVRAGQSR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:8590280" FT /id="VSP_009302" FT VAR_SEQ 1112..1143 FT /note="LVSAVGYLRLKDIIHRDIKDENIVIAEDFTIK -> VRAGQSRVSVNAGLGA FT WVRWLQRSVIHTRFSL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045543" FT VAR_SEQ 1144..1323 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045544" FT VARIANT 11 FT /note="E -> K (in a metastatic melanoma sample; somatic FT mutation; dbSNP:rs1277219458)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040986" FT VARIANT 250 FT /note="V -> I (in dbSNP:rs1470414)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17344846" FT /id="VAR_028293" FT VARIANT 426 FT /note="Q -> R (in dbSNP:rs35187712)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040987" FT VARIANT 512 FT /note="T -> A (in dbSNP:rs56033464)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040988" FT VARIANT 514 FT /note="L -> S (in dbSNP:rs2240543)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_028294" FT VARIANT 684 FT /note="P -> R (in dbSNP:rs56372985)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040989" FT VARIANT 694 FT /note="V -> M (in dbSNP:rs6727226)" FT /evidence="ECO:0000269|PubMed:8590280" FT /id="VAR_028295" FT VARIANT 725 FT /note="G -> D (in dbSNP:rs2005771)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_028296" FT VARIANT 796 FT /note="E -> K (in dbSNP:rs35129131)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040990" FT VARIANT 844 FT /note="P -> Q (in dbSNP:rs36082918)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040991" FT VARIANT 937 FT /note="R -> H (in dbSNP:rs56139954)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040992" FT VARIANT 1210 FT /note="V -> M (in dbSNP:rs10167000)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_028297" FT VARIANT 1266 FT /note="F -> C (in dbSNP:rs1131293)" FT /evidence="ECO:0000269|PubMed:11459942, FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:8590280" FT /id="VAR_028298" FT VARIANT 1301 FT /note="P -> S" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_040993" FT MUTAGEN 1028 FT /note="K->R: Loss of autophosphorylating activity." FT /evidence="ECO:0000269|PubMed:11459942, FT ECO:0000269|PubMed:20943661" FT MUTAGEN 1058 FT /note="R->A: Induces lower protein kinase activity." FT /evidence="ECO:0000269|PubMed:20943661" FT MUTAGEN 1058 FT /note="R->K: Does not affect protein kinase activity." FT /evidence="ECO:0000269|PubMed:20943661" FT MUTAGEN 1151 FT /note="A->K: Induces lower protein kinase activity and FT ability to autophosphorylate." FT /evidence="ECO:0000269|PubMed:20943661" FT MUTAGEN 1152 FT /note="Y->F: Induces lower protein kinase activity." FT /evidence="ECO:0000269|PubMed:20943661" FT MUTAGEN 1161 FT /note="T->A: Loss of catalytic activity (PubMed:11459942). FT According to another report, does not affect the protein FT kinase activity (PubMed:20943661). Does not affect protein FT translation." FT /evidence="ECO:0000269|PubMed:11459942, FT ECO:0000269|PubMed:17595531, ECO:0000269|PubMed:20943661" FT MUTAGEN 1165 FT /note="T->A: Loss of catalytic activity. Does not affect FT protein translation." FT /evidence="ECO:0000269|PubMed:11459942, FT ECO:0000269|PubMed:17595531" FT CONFLICT 205 FT /note="S -> T (in Ref. 2; BAA09484)" FT /evidence="ECO:0000305" FT CONFLICT 407 FT /note="S -> C (in Ref. 4; CAH18087)" FT /evidence="ECO:0000305" FT CONFLICT 623 FT /note="S -> R (in Ref. 2; BAA09484)" FT /evidence="ECO:0000305" FT CONFLICT 741 FT /note="W -> R (in Ref. 4; CAH18087)" FT /evidence="ECO:0000305" FT CONFLICT 850 FT /note="T -> M (in Ref. 2; BAA09484)" FT /evidence="ECO:0000305" FT CONFLICT 899 FT /note="Y -> H (in Ref. 1; AAK69752)" FT /evidence="ECO:0000305" FT CONFLICT 1048 FT /note="K -> E (in Ref. 4; CAH18087)" FT /evidence="ECO:0000305" FT CONFLICT 1062 FT /note="A -> S (in Ref. 7; AAH50565)" FT /evidence="ECO:0000305" FT CONFLICT 1129 FT /note="I -> F (in Ref. 8; AAB50198)" FT /evidence="ECO:0000305" FT STRAND 133..141 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 144..147 FT /evidence="ECO:0007829|PDB:1LL8" FT HELIX 151..155 FT /evidence="ECO:0007829|PDB:1LL8" FT TURN 159..164 FT /evidence="ECO:0007829|PDB:1LL8" FT HELIX 167..170 FT /evidence="ECO:0007829|PDB:1LL8" FT TURN 174..176 FT /evidence="ECO:0007829|PDB:1LL8" FT HELIX 177..181 FT /evidence="ECO:0007829|PDB:1LL8" FT TURN 182..184 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 188..191 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 193..195 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 198..203 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 211..214 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 217..219 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:1LL8" FT STRAND 227..234 FT /evidence="ECO:0007829|PDB:1LL8" FT HELIX 987..991 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 994..998 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 999..1004 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1006..1010 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1012..1018 FT /evidence="ECO:0007829|PDB:3DLS" FT TURN 1019..1022 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1023..1032 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1039..1043 FT /evidence="ECO:0007829|PDB:3DLS" FT TURN 1044..1046 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1047..1050 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1051..1056 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1067..1072 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1074..1082 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1090..1095 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1102..1121 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1131..1133 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1134..1136 FT /evidence="ECO:0007829|PDB:3DLS" FT STRAND 1142..1144 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1166..1168 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1171..1174 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1182..1198 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1206..1209 FT /evidence="ECO:0007829|PDB:3DLS" FT TURN 1210..1212 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1222..1231 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1236..1238 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1242..1247 FT /evidence="ECO:0007829|PDB:3DLS" FT TURN 1249..1252 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1257..1259 FT /evidence="ECO:0007829|PDB:3DLS" FT HELIX 1262..1265 FT /evidence="ECO:0007829|PDB:3DLS" SQ SEQUENCE 1323 AA; 142929 MW; F8A3633CC6F6C8CD CRC64; MEDGGLTAFE EDQRCLSQSL PLPVSAEGPA AQTTAEPSRS FSSAHRHLSR RNGLSRLCQS RTALSEDRWS SYCLSSLAAQ NICTSKLHCP AAPEHTDPSE PRGSVSCCSL LRGLSSGWSS PLLPAPVCNP NKAIFTVDAK TTEILVANDK ACGLLGYSSQ DLIGQKLTQF FLRSDSDVVE ALSEEHMEAD GHAAVVFGTV VDIISRSGEK IPVSVWMKRM RQERRLCCVV VLEPVERVST WVAFQSDGTV TSCDSLFAHL HGYVSGEDVA GQHITDLIPS VQLPPSGQHI PKNLKIQRSV GRARDGTTFP LSLKLKSQPS SEEATTGEAA PVSGYRASVW VFCTISGLIT LLPDGTIHGI NHSFALTLFG YGKTELLGKN ITFLIPGFYS YMDLAYNSSL QLPDLASCLD VGNESGCGER TLDPWQGQDP AEGGQDPRIN VVLAGGHVVP RDEIRKLMES QDIFTGTQTE LIAGGQLLSC LSPQPAPGVD NVPEGSLPVH GEQALPKDQQ ITALGREEPV AIESPGQDLL GESRSEPVDV KPFASCEDSE APVPAEDGGS DAGMCGLCQK AQLERMGVSG PSGSDLWAGA AVAKPQAKGQ LAGGSLLMHC PCYGSEWGLW WRSQDLAPSP SGMAGLSFGT PTLDEPWLGV ENDREELQTC LIKEQLSQLS LAGALDVPHA ELVPTECQAV TAPVSSCDLG GRDLCGGCTG SSSACYALAT DLPGGLEAVE AQEVDVNSFS WNLKELFFSD QTDQTSSNCS CATSELRETP SSLAVGSDPD VGSLQEQGSC VLDDRELLLL TGTCVDLGQG RRFRESCVGH DPTEPLEVCL VSSEHYAASD RESPGHVPST LDAGPEDTCP SAEEPRLNVQ VTSTPVIVMR GAAGLQREIQ EGAYSGSCYH RDGLRLSIQF EVRRVELQGP TPLFCCWLVK DLLHSQRDSA ARTRLFLASL PGSTHSTAAE LTGPSLVEVL RARPWFEEPP KAVELEGLAA CEGEYSQKYS TMSPLGSGAF GFVWTAVDKE KNKEVVVKFI KKEKVLEDCW IEDPKLGKVT LEIAILSRVE HANIIKVLDI FENQGFFQLV MEKHGSGLDL FAFIDRHPRL DEPLASYIFR QLVSAVGYLR LKDIIHRDIK DENIVIAEDF TIKLIDFGSA AYLERGKLFY TFCGTIEYCA PEVLMGNPYR GPELEMWSLG VTLYTLVFEE NPFCELEETV EAAIHPPYLV SKELMSLVSG LLQPVPERRT TLEKLVTDPW VTQPVNLADY TWEEVFRVNK PESGVLSAAS LEMGNRSLSD VAQAQELCGG PVPGEAPNGQ GCLHPGDPRL LTS //