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Protein

PAS domain-containing serine/threonine-protein kinase

Gene

PASK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in alpha cells; however such data require additional evidences. May play a role in regulation of protein translation by phosphorylating EEF1A1, leading to increase translation efficiency. May also participate to respiratory regulation.6 Publications

Caution

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Protein kinase activity is inhibited by the first PAS domain: binding of an unidentified ligand desinhibits the protein kinase activity. May be activated by autophosphorylation on Thr-1161 and Thr-1165 (PubMed:11459942). The activating role of autophosphorylation at Thr-1161 is unclear: according to a report, autophosphorylation at Thr-1161 does not play a major role in activation (PubMed:20943661). Autophosphorylation is enhanced upon phosphatidylinositol monophosphate (phosphatidylinositol 4-phosphate) binding and inhibited upon phosphatidylinositol bi- and tri-phosphate binding. In contrast, phosphorylation of target proteins is inhibited upon all phosphatidylinositol-binding (phosphatidylinositol mono- bi- and tri-phosphate).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei1028ATP1
Active sitei1128Proton acceptor1
Binding sitei1146ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1005 – 1013ATP9
Nucleotide bindingi1082 – 1089ATP8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • phosphatidylinositol binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • negative regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of translation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of energy homeostasis Source: UniProtKB
  • regulation of glucagon secretion Source: UniProtKB
  • regulation of respiratory gaseous exchange Source: UniProtKB

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ96RG2
SIGNORiQ96RG2

Names & Taxonomyi

Protein namesi
Recommended name:
PAS domain-containing serine/threonine-protein kinase (EC:2.7.11.1)
Short name:
PAS-kinase
Short name:
PASKIN
Short name:
hPASK
Gene namesi
Name:PASK
Synonyms:KIAA0135
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115687.13
HGNCiHGNC:17270 PASK
MIMi607505 gene
neXtProtiNX_Q96RG2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1028K → R: Loss of autophosphorylating activity. 2 Publications1
Mutagenesisi1058R → A: Induces lower protein kinase activity. 1 Publication1
Mutagenesisi1058R → K: Does not affect protein kinase activity. 1 Publication1
Mutagenesisi1151A → K: Induces lower protein kinase activity and ability to autophosphorylate. 1 Publication1
Mutagenesisi1152Y → F: Induces lower protein kinase activity. 1 Publication1
Mutagenesisi1161T → A: Loss of catalytic activity (PubMed:11459942). According to another report, does not affect the protein kinase activity (PubMed:20943661). Does not affect protein translation. 3 Publications1
Mutagenesisi1165T → A: Loss of catalytic activity. Does not affect protein translation. 2 Publications1

Organism-specific databases

DisGeNETi23178
OpenTargetsiENSG00000115687
PharmGKBiPA32953

Chemistry databases

ChEMBLiCHEMBL6054
GuidetoPHARMACOLOGYi2139

Polymorphism and mutation databases

BioMutaiPASK
DMDMi116242701

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000864801 – 1323PAS domain-containing serine/threonine-protein kinaseAdd BLAST1323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei19PhosphoserineBy similarity1
Modified residuei34PhosphothreonineBy similarity1
Modified residuei582PhosphoserineCombined sources1
Modified residuei939PhosphoserineCombined sources1
Modified residuei1161Phosphothreonine; by autocatalysis1 Publication1
Modified residuei1165Phosphothreonine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated on Thr-1161 and Thr-1165. Autophosphorylation is activated by phospholipids.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96RG2
MaxQBiQ96RG2
PaxDbiQ96RG2
PeptideAtlasiQ96RG2
PRIDEiQ96RG2

PTM databases

iPTMnetiQ96RG2
PhosphoSitePlusiQ96RG2

Expressioni

Tissue specificityi

Ubiquitously expressed, with slightly higher expression in brain, prostate and testis. Reduced expression was found in placenta. Present in germ cells of testis and in the midpiece of sperm tails (at protein level).

Gene expression databases

BgeeiENSG00000115687
CleanExiHS_PASK
ExpressionAtlasiQ96RG2 baseline and differential
GenevisibleiQ96RG2 HS

Organism-specific databases

HPAiHPA016450
HPA021079

Interactioni

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi11679068 interactors.
IntActiQ96RG2 63 interactors.
MINTiQ96RG2
STRINGi9606.ENSP00000234040

Chemistry databases

BindingDBiQ96RG2

Structurei

Secondary structure

11323
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi133 – 138Combined sources6
Turni139 – 141Combined sources3
Beta strandi143 – 147Combined sources5
Helixi151 – 155Combined sources5
Turni159 – 161Combined sources3
Helixi167 – 170Combined sources4
Turni174 – 176Combined sources3
Helixi177 – 181Combined sources5
Beta strandi188 – 191Combined sources4
Beta strandi198 – 203Combined sources6
Beta strandi211 – 214Combined sources4
Beta strandi221 – 234Combined sources14
Helixi987 – 991Combined sources5
Helixi994 – 998Combined sources5
Beta strandi999 – 1004Combined sources6
Beta strandi1006 – 1010Combined sources5
Beta strandi1012 – 1018Combined sources7
Turni1019 – 1022Combined sources4
Beta strandi1023 – 1032Combined sources10
Beta strandi1039 – 1043Combined sources5
Turni1044 – 1046Combined sources3
Beta strandi1047 – 1050Combined sources4
Helixi1051 – 1056Combined sources6
Beta strandi1067 – 1072Combined sources6
Beta strandi1074 – 1082Combined sources9
Helixi1090 – 1095Combined sources6
Helixi1102 – 1121Combined sources20
Helixi1131 – 1133Combined sources3
Beta strandi1134 – 1136Combined sources3
Beta strandi1142 – 1144Combined sources3
Helixi1166 – 1168Combined sources3
Helixi1171 – 1174Combined sources4
Helixi1182 – 1198Combined sources17
Helixi1206 – 1209Combined sources4
Turni1210 – 1212Combined sources3
Helixi1222 – 1231Combined sources10
Helixi1236 – 1238Combined sources3
Helixi1242 – 1247Combined sources6
Turni1249 – 1252Combined sources4
Helixi1257 – 1259Combined sources3
Helixi1262 – 1265Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LL8NMR-A131-237[»]
3DLSX-ray2.30A/B/C/D/E/F977-1300[»]
ProteinModelPortaliQ96RG2
SMRiQ96RG2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96RG2

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini119 – 190PAS 1PROSITE-ProRule annotationAdd BLAST72
Domaini335 – 402PAS 2PROSITE-ProRule annotationAdd BLAST68
Domaini999 – 1251Protein kinasePROSITE-ProRule annotationAdd BLAST253

Domaini

The protein kinase domain mediates binding to phosphatidylinositol.1 Publication

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1152 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000119045
HOGENOMiHOG000115456
HOVERGENiHBG047936
InParanoidiQ96RG2
KOiK08801
OMAiWSSYCLS
OrthoDBiEOG091G07RY
PhylomeDBiQ96RG2
TreeFamiTF323242

Family and domain databases

CDDicd00130 PAS, 2 hits
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000014 PAS
IPR035965 PAS-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF13426 PAS_9, 2 hits
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00091 PAS, 2 hits
SM00220 S_TKc, 1 hit
SUPFAMiSSF55785 SSF55785, 1 hit
SSF56112 SSF56112, 1 hit
TIGRFAMsiTIGR00229 sensory_box, 1 hit
PROSITEiView protein in PROSITE
PS50112 PAS, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96RG2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEDGGLTAFE EDQRCLSQSL PLPVSAEGPA AQTTAEPSRS FSSAHRHLSR
60 70 80 90 100
RNGLSRLCQS RTALSEDRWS SYCLSSLAAQ NICTSKLHCP AAPEHTDPSE
110 120 130 140 150
PRGSVSCCSL LRGLSSGWSS PLLPAPVCNP NKAIFTVDAK TTEILVANDK
160 170 180 190 200
ACGLLGYSSQ DLIGQKLTQF FLRSDSDVVE ALSEEHMEAD GHAAVVFGTV
210 220 230 240 250
VDIISRSGEK IPVSVWMKRM RQERRLCCVV VLEPVERVST WVAFQSDGTV
260 270 280 290 300
TSCDSLFAHL HGYVSGEDVA GQHITDLIPS VQLPPSGQHI PKNLKIQRSV
310 320 330 340 350
GRARDGTTFP LSLKLKSQPS SEEATTGEAA PVSGYRASVW VFCTISGLIT
360 370 380 390 400
LLPDGTIHGI NHSFALTLFG YGKTELLGKN ITFLIPGFYS YMDLAYNSSL
410 420 430 440 450
QLPDLASCLD VGNESGCGER TLDPWQGQDP AEGGQDPRIN VVLAGGHVVP
460 470 480 490 500
RDEIRKLMES QDIFTGTQTE LIAGGQLLSC LSPQPAPGVD NVPEGSLPVH
510 520 530 540 550
GEQALPKDQQ ITALGREEPV AIESPGQDLL GESRSEPVDV KPFASCEDSE
560 570 580 590 600
APVPAEDGGS DAGMCGLCQK AQLERMGVSG PSGSDLWAGA AVAKPQAKGQ
610 620 630 640 650
LAGGSLLMHC PCYGSEWGLW WRSQDLAPSP SGMAGLSFGT PTLDEPWLGV
660 670 680 690 700
ENDREELQTC LIKEQLSQLS LAGALDVPHA ELVPTECQAV TAPVSSCDLG
710 720 730 740 750
GRDLCGGCTG SSSACYALAT DLPGGLEAVE AQEVDVNSFS WNLKELFFSD
760 770 780 790 800
QTDQTSSNCS CATSELRETP SSLAVGSDPD VGSLQEQGSC VLDDRELLLL
810 820 830 840 850
TGTCVDLGQG RRFRESCVGH DPTEPLEVCL VSSEHYAASD RESPGHVPST
860 870 880 890 900
LDAGPEDTCP SAEEPRLNVQ VTSTPVIVMR GAAGLQREIQ EGAYSGSCYH
910 920 930 940 950
RDGLRLSIQF EVRRVELQGP TPLFCCWLVK DLLHSQRDSA ARTRLFLASL
960 970 980 990 1000
PGSTHSTAAE LTGPSLVEVL RARPWFEEPP KAVELEGLAA CEGEYSQKYS
1010 1020 1030 1040 1050
TMSPLGSGAF GFVWTAVDKE KNKEVVVKFI KKEKVLEDCW IEDPKLGKVT
1060 1070 1080 1090 1100
LEIAILSRVE HANIIKVLDI FENQGFFQLV MEKHGSGLDL FAFIDRHPRL
1110 1120 1130 1140 1150
DEPLASYIFR QLVSAVGYLR LKDIIHRDIK DENIVIAEDF TIKLIDFGSA
1160 1170 1180 1190 1200
AYLERGKLFY TFCGTIEYCA PEVLMGNPYR GPELEMWSLG VTLYTLVFEE
1210 1220 1230 1240 1250
NPFCELEETV EAAIHPPYLV SKELMSLVSG LLQPVPERRT TLEKLVTDPW
1260 1270 1280 1290 1300
VTQPVNLADY TWEEVFRVNK PESGVLSAAS LEMGNRSLSD VAQAQELCGG
1310 1320
PVPGEAPNGQ GCLHPGDPRL LTS
Length:1,323
Mass (Da):142,929
Last modified:October 17, 2006 - v3
Checksum:iF8A3633CC6F6C8CD
GO
Isoform 2 (identifier: Q96RG2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1111-1111: Q → QVRAGQSR

Note: No experimental confirmation available.
Show »
Length:1,330
Mass (Da):143,684
Checksum:i8177593F181C6914
GO
Isoform 3 (identifier: Q96RG2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1112-1143: LVSAVGYLRLKDIIHRDIKDENIVIAEDFTIK → VRAGQSRVSVNAGLGAWVRWLQRSVIHTRFSL
     1144-1323: Missing.

Note: No experimental confirmation available.
Show »
Length:1,143
Mass (Da):123,048
Checksum:i535BFCA305C18419
GO

Sequence cautioni

The sequence BAA09484 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti205S → T in BAA09484 (PubMed:8590280).Curated1
Sequence conflicti407S → C in CAH18087 (PubMed:17974005).Curated1
Sequence conflicti623S → R in BAA09484 (PubMed:8590280).Curated1
Sequence conflicti741W → R in CAH18087 (PubMed:17974005).Curated1
Sequence conflicti850T → M in BAA09484 (PubMed:8590280).Curated1
Sequence conflicti899Y → H in AAK69752 (PubMed:11459942).Curated1
Sequence conflicti1048K → E in CAH18087 (PubMed:17974005).Curated1
Sequence conflicti1062A → S in AAH50565 (PubMed:15489334).Curated1
Sequence conflicti1129I → F in AAB50198 (PubMed:9110174).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04098611E → K in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_028293250V → I2 PublicationsCorresponds to variant dbSNP:rs1470414Ensembl.1
Natural variantiVAR_040987426Q → R1 PublicationCorresponds to variant dbSNP:rs35187712Ensembl.1
Natural variantiVAR_040988512T → A1 PublicationCorresponds to variant dbSNP:rs56033464Ensembl.1
Natural variantiVAR_028294514L → S1 PublicationCorresponds to variant dbSNP:rs2240543Ensembl.1
Natural variantiVAR_040989684P → R1 PublicationCorresponds to variant dbSNP:rs56372985Ensembl.1
Natural variantiVAR_028295694V → M1 PublicationCorresponds to variant dbSNP:rs6727226Ensembl.1
Natural variantiVAR_028296725G → D1 PublicationCorresponds to variant dbSNP:rs2005771Ensembl.1
Natural variantiVAR_040990796E → K1 PublicationCorresponds to variant dbSNP:rs35129131Ensembl.1
Natural variantiVAR_040991844P → Q1 PublicationCorresponds to variant dbSNP:rs36082918Ensembl.1
Natural variantiVAR_040992937R → H1 PublicationCorresponds to variant dbSNP:rs56139954Ensembl.1
Natural variantiVAR_0282971210V → M1 PublicationCorresponds to variant dbSNP:rs10167000Ensembl.1
Natural variantiVAR_0282981266F → C3 PublicationsCorresponds to variant dbSNP:rs1131293Ensembl.1
Natural variantiVAR_0409931301P → S1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0093021111Q → QVRAGQSR in isoform 2. 1 Publication1
Alternative sequenceiVSP_0455431112 – 1143LVSAV…DFTIK → VRAGQSRVSVNAGLGAWVRW LQRSVIHTRFSL in isoform 3. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_0455441144 – 1323Missing in isoform 3. 1 PublicationAdd BLAST180

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF387103 mRNA Translation: AAK69752.1
D50925 mRNA Translation: BAA09484.2 Different initiation.
CR749231 mRNA Translation: CAH18087.1
AC005237 Genomic DNA No translation available.
CH471063 Genomic DNA Translation: EAW71238.1
BC043495 mRNA Translation: AAH43495.1
BC050565 mRNA Translation: AAH50565.1
BC063585 mRNA Translation: AAH63585.1
U79240 mRNA Translation: AAB50198.1
CCDSiCCDS2545.1 [Q96RG2-1]
CCDS58758.1 [Q96RG2-4]
CCDS58759.1 [Q96RG2-2]
PIRiT17211
RefSeqiNP_001239048.1, NM_001252119.1 [Q96RG2-2]
NP_001239049.1, NM_001252120.1 [Q96RG2-1]
NP_001239051.1, NM_001252122.1
NP_001239053.1, NM_001252124.1 [Q96RG2-4]
NP_055963.2, NM_015148.3 [Q96RG2-1]
XP_011509130.1, XM_011510828.1 [Q96RG2-2]
XP_011509131.1, XM_011510829.1 [Q96RG2-2]
XP_011509132.1, XM_011510830.1 [Q96RG2-2]
XP_016859124.1, XM_017003635.1 [Q96RG2-1]
XP_016859125.1, XM_017003636.1 [Q96RG2-1]
UniGeneiHs.397891

Genome annotation databases

EnsembliENST00000234040; ENSP00000234040; ENSG00000115687 [Q96RG2-1]
ENST00000358649; ENSP00000351475; ENSG00000115687 [Q96RG2-2]
ENST00000403638; ENSP00000384438; ENSG00000115687 [Q96RG2-4]
ENST00000405260; ENSP00000384016; ENSG00000115687 [Q96RG2-1]
ENST00000544142; ENSP00000441374; ENSG00000115687 [Q96RG2-1]
GeneIDi23178
KEGGihsa:23178
UCSCiuc002wao.2 human [Q96RG2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPASK_HUMAN
AccessioniPrimary (citable) accession number: Q96RG2
Secondary accession number(s): G5E9F1
, Q05BE4, Q68DY3, Q6GSJ5, Q86XH6, Q99763, Q9UFR7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: October 17, 2006
Last modified: March 28, 2018
This is version 175 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome