PASK_HUMAN
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 03-AUG-2022, entry version 203.
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 evidences. May
CC play a role in regulation of protein translation by phosphorylating
CC EEF1A1, leading to increase translation efficiency. May also
CC participate in 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=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: 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};
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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_001252119.1. [Q96RG2-2]
DR RefSeq; NP_001239049.1; NM_001252120.1. [Q96RG2-1]
DR RefSeq; NP_001239051.1; NM_001252122.1.
DR RefSeq; NP_001239053.1; NM_001252124.1. [Q96RG2-4]
DR RefSeq; NP_055963.2; NM_015148.3. [Q96RG2-1]
DR RefSeq; XP_011509130.1; XM_011510828.1. [Q96RG2-2]
DR RefSeq; XP_011509131.1; XM_011510829.1. [Q96RG2-2]
DR RefSeq; XP_011509132.1; XM_011510830.1. [Q96RG2-2]
DR RefSeq; XP_016859124.1; XM_017003635.1. [Q96RG2-1]
DR RefSeq; XP_016859125.1; XM_017003636.1. [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 PDBsum; 1LL8; -.
DR PDBsum; 3DLS; -.
DR AlphaFoldDB; Q96RG2; -.
DR BMRB; Q96RG2; -.
DR SMR; Q96RG2; -.
DR BioGRID; 116790; 154.
DR IntAct; Q96RG2; 78.
DR MINT; Q96RG2; -.
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 EPD; Q96RG2; -.
DR jPOST; Q96RG2; -.
DR MassIVE; Q96RG2; -.
DR MaxQB; Q96RG2; -.
DR PaxDb; Q96RG2; -.
DR PeptideAtlas; Q96RG2; -.
DR PRIDE; Q96RG2; -.
DR ProteomicsDB; 33919; -.
DR ProteomicsDB; 77959; -. [Q96RG2-1]
DR ProteomicsDB; 77960; -. [Q96RG2-2]
DR Antibodypedia; 20301; 220 antibodies from 29 providers.
DR DNASU; 23178; -.
DR Ensembl; ENST00000234040.9; ENSP00000234040.5; ENSG00000115687.14. [Q96RG2-1]
DR Ensembl; ENST00000358649.8; ENSP00000351475.4; ENSG00000115687.14. [Q96RG2-2]
DR Ensembl; ENST00000403638.7; ENSP00000384438.3; ENSG00000115687.14. [Q96RG2-4]
DR Ensembl; ENST00000405260.5; ENSP00000384016.1; ENSG00000115687.14. [Q96RG2-1]
DR Ensembl; ENST00000544142.5; ENSP00000441374.2; ENSG00000115687.14. [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 CTD; 23178; -.
DR DisGeNET; 23178; -.
DR GeneCards; PASK; -.
DR HGNC; HGNC:17270; PASK.
DR HPA; ENSG00000115687; Tissue enhanced (lymphoid).
DR MIM; 607505; gene.
DR neXtProt; NX_Q96RG2; -.
DR OpenTargets; ENSG00000115687; -.
DR PharmGKB; PA32953; -.
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; NPDLYFS; -.
DR OrthoDB; 297397at2759; -.
DR PhylomeDB; Q96RG2; -.
DR TreeFam; TF323242; -.
DR PathwayCommons; Q96RG2; -.
DR SignaLink; Q96RG2; -.
DR SIGNOR; Q96RG2; -.
DR BioGRID-ORCS; 23178; 13 hits in 1113 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 123 other tissues.
DR ExpressionAtlas; Q96RG2; baseline and differential.
DR Genevisible; Q96RG2; HS.
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:UniProtKB-KW.
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 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 Pfam; PF13426; PAS_9; 2.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00091; PAS; 2.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR TIGRFAMs; TIGR00229; sensory_box; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Kinase; Lipid-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; 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 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..161
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
