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PASK PAS domain containing serine/threonine kinase [ Homo sapiens (human) ]

Gene ID: 23178, updated on 3-Apr-2024

Summary

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Official Symbol
PASKprovided by HGNC
Official Full Name
PAS domain containing serine/threonine kinaseprovided by HGNC
Primary source
HGNC:HGNC:17270
See related
Ensembl:ENSG00000115687 MIM:607505; AllianceGenome:HGNC:17270
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
STK37; PASKIN
Summary
This gene encodes a member of the serine/threonine kinase family that contains two PAS domains. Expression of this gene is regulated by glucose, and the encoded protein plays a role in the regulation of insulin gene expression. Downregulation of this gene may play a role in type 2 diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
Expression
Broad expression in testis (RPKM 7.9), lymph node (RPKM 6.8) and 21 other tissues See more
Orthologs
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Genomic context

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Location:
2q37.3
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (241106099..241150347, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (241605207..241649447, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (242045514..242089637, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985787 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:241949545-241950150 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:241950151-241950754 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:241957354-241957854 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:241957855-241958355 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_57691 Neighboring gene SNED1 antisense RNA 1 Neighboring gene sushi, nidogen and EGF like domains 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:241973517-241974460 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:241974461-241975402 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:241975403-241976346 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17412 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17413 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12526 Neighboring gene mitochondrial transcription termination factor 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242012857-242013373 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242040949-242041488 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242041489-242042028 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17414 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17415 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_57723 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_57727 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_57732 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17416 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12527 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17417 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242079269-242079769 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17418 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12528 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12529 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12530 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17419 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12531 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242097726-242098226 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:242106157-242106656 Neighboring gene uncharacterized LOC105373971 Neighboring gene protein phosphatase 1 regulatory subunit 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242125644-242126166 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242127362-242128046 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:242128047-242128730 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242129664-242130164 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242130165-242130665 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242152515-242153074 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242155713-242156244 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12532 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17420 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_57796 Neighboring gene anoctamin 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:242163435-242164395 Neighboring gene uncharacterized LOC105376810 Neighboring gene high density lipoprotein binding protein

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Bibliography

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Related articles in PubMed

  1. Activation of PASK by mTORC1 is required for the onset of the terminal differentiation program. Kikani CK, et al. Proc Natl Acad Sci U S A, 2019 May 21. PMID 31072927, Free PMC Article
  2. The role of PAS kinase in PASsing the glucose signal. Grose JH, et al. Sensors (Basel), 2010. PMID 22219681, Free PMC Article
  3. Per-arnt-sim (PAS) domain kinase (PASK) as a regulator of glucagon secretion. MacDonald PE, et al. Diabetologia, 2011 Apr. PMID 21327866
  4. Structure and interactions of PAS kinase N-terminal PAS domain: model for intramolecular kinase regulation. Amezcua CA, et al. Structure, 2002 Oct. PMID 12377121
  5. PAS kinase: an evolutionarily conserved PAS domain-regulated serine/threonine kinase. Rutter J, et al. Proc Natl Acad Sci U S A, 2001 Jul 31. PMID 11459942, Free PMC Article

See all (57) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MTORC1-PASK signaling is required for the rise of myogenin-positive committed myoblasts.
    Title: Activation of PASK by mTORC1 is required for the onset of the terminal differentiation program.
  2. we show that the nuclear PASK associates with the mammalian H3K4 MLL2 methyltransferase complex and enhances H3K4 di- and tri-methylation. We also show that PASK is a histone kinase that phosphorylates H3 at T3, T6, S10 and T11.
    Title: The metabolic sensor PASK is a histone 3 kinase that also regulates H3K4 methylation by associating with H3K4 MLL2 methyltransferase complex.
  3. we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose toward respiration and away from lipid biogenesis
    Title: The Regulation of Cbf1 by PAS Kinase Is a Pivotal Control Point for Lipogenesis vs. Respiration in Saccharomyces cerevisiae.
  4. PASK phosphorylates and inactivates GSK3beta, thereby preventing PDX-1 serine phosphorylation and alleviating GSK3beta-mediated PDX-1 protein degradation in pancreatic beta-cells.
    Title: Per-Arnt-Sim kinase regulates pancreatic duodenal homeobox-1 protein stability via phosphorylation of glycogen synthase kinase 3β in pancreatic β-cells.
  5. Mutations that affect PAS domain cause a severe protein trafficking defect and change the interactions with Kv11.1 channels.
    Title: Trafficking defects in PAS domain mutant Kv11.1 channels: roles of reduced domain stability and altered domain-domain interactions.
  6. The role of PAS kinase in PASsing the glucose signal.
    Title: The role of PAS kinase in PASsing the glucose signal.
  7. Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) has a role in insulin hypersecretion
    Title: Human mutation within Per-Arnt-Sim (PAS) domain-containing protein kinase (PASK) causes basal insulin hypersecretion.
  8. PASK is involved in the regulation of glucagon secretion by glucose and may be a useful target for the treatment of type 2 diabetes.
    Title: Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion.
  9. Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation.
    Title: Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation.
  10. Results suggest that elevated glucose concentrations rapidly increase Per-Arnt-Sim kinase activity in pancreatic islet beta cells, followed by up-regulation by glucose of preproinsulin and pancreatic duodenum homeobox 1 gene expression.
    Title: Involvement of Per-Arnt-Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose.
Submit: New GeneRIF Correction See all GeneRIFs (12)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study in Han Chinese identifies three novel loci for human height.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0135, DKFZp434O051, DKFZp686P2031

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables phosphatidylinositol binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in energy homeostasis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of glycogen biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of glycogen biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of translation TAS
Traceable Author Statement
more info
 PubMed 
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of glucagon secretion ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of respiratory gaseous exchange ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
PAS domain-containing serine/threonine-protein kinase
Names
per-arnt-sim (PAS) domain kinase
NP_001239048.1
NP_001239049.1
NP_001239051.1
NP_001239053.1
NP_055963.2
XP_011509136.2
XP_047299691.1
XP_047299692.1
XP_054197046.1
XP_054197047.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_052850.1 RefSeqGene

    Range
    5876..49249
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001252119.2 → NP_001239048.1  PAS domain-containing serine/threonine-protein kinase isoform 1

    See identical proteins and their annotated locations for NP_001239048.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1).
    Source sequence(s)
    BC063585, D50925, DA104684
    Consensus CDS
    CCDS58759.1
    UniProtKB/TrEMBL
    B7Z7R6
    Related
    ENSP00000351475.4, ENST00000358649.8
    Conserved Domains (3) summary
    smart00091
    Location:344 → 401
    PAS; PAS domain
    cd00130
    Location:133 → 232
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    cd14004
    Location:998 → 1258
    STKc_PASK; Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase

  2. NM_001252120.2 → NP_001239049.1  PAS domain-containing serine/threonine-protein kinase isoform 2

    See identical proteins and their annotated locations for NP_001239049.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate splice site in the 3' coding region, but maintains the reading frame, compared to variant 1. Variants 2 and 3 encode the same isoform (2), which is shorter than isoform 1.
    Source sequence(s)
    AC005237, BC063585
    Consensus CDS
    CCDS2545.1
    UniProtKB/Swiss-Prot
    G5E9F1, Q05BE4, Q68DY3, Q6GSJ5, Q86XH6, Q96RG2, Q99763, Q9UFR7
    UniProtKB/TrEMBL
    B7Z7R6
    Related
    ENSP00000441374.2, ENST00000544142.5
    Conserved Domains (5) summary
    smart00091
    Location:344 → 401
    PAS; PAS domain
    smart00220
    Location:999 → 1251
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00130
    Location:133 → 232
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    cd14004
    Location:998 → 1251
    STKc_PASK; Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase
    pfam13426
    Location:133 → 232
    PAS_9; PAS domain

  3. NM_001252122.2 → NP_001239051.1  PAS domain-containing serine/threonine-protein kinase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses two alternate splice sites in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AK302417, BC063585, DA104684
    UniProtKB/TrEMBL
    B7Z7R6
    Conserved Domains (5) summary
    smart00091
    Location:309 → 366
    PAS; PAS domain
    smart00220
    Location:964 → 1216
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00130
    Location:133 → 232
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    cd14004
    Location:963 → 1216
    STKc_PASK; Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase
    pfam13426
    Location:133 → 232
    PAS_9; PAS domain

  4. NM_001252124.2 → NP_001239053.1  PAS domain-containing serine/threonine-protein kinase isoform 4

    See identical proteins and their annotated locations for NP_001239053.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks a splice site in the 3' coding region, which results in a frameshift and alternate 3' UTR compared to variant 1. The encoded isoform (4) is shorter and has a distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AC005237, AL117400, BC050565, BC063585, DA104684
    Consensus CDS
    CCDS58758.1
    UniProtKB/TrEMBL
    B7Z7R6
    Related
    ENSP00000384438.3, ENST00000403638.7
    Conserved Domains (4) summary
    smart00091
    Location:344 → 401
    PAS; PAS domain
    cd00130
    Location:133 → 232
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    pfam13426
    Location:133 → 232
    PAS_9; PAS domain
    cl21453
    Location:998 → 1115
    PKc_like; Protein Kinases, catalytic domain

  5. NM_015148.4 → NP_055963.2  PAS domain-containing serine/threonine-protein kinase isoform 2

    See identical proteins and their annotated locations for NP_055963.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, but maintains the reading frame, compared to variant 1. Variants 2 and 3 encode the same isoform (2), which is shorter than isoform 1.
    Source sequence(s)
    BC063585, DA104684
    Consensus CDS
    CCDS2545.1
    UniProtKB/Swiss-Prot
    G5E9F1, Q05BE4, Q68DY3, Q6GSJ5, Q86XH6, Q96RG2, Q99763, Q9UFR7
    UniProtKB/TrEMBL
    B7Z7R6
    Related
    ENSP00000234040.5, ENST00000234040.9
    Conserved Domains (5) summary
    smart00091
    Location:344 → 401
    PAS; PAS domain
    smart00220
    Location:999 → 1251
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00130
    Location:133 → 232
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    cd14004
    Location:998 → 1251
    STKc_PASK; Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase
    pfam13426
    Location:133 → 232
    PAS_9; PAS domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    241106099..241150347 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047443736.1 → XP_047299692.1  PAS domain-containing serine/threonine-protein kinase isoform X2

  2. XM_047443735.1 → XP_047299691.1  PAS domain-containing serine/threonine-protein kinase isoform X1

  3. XM_011510834.2 → XP_011509136.2  PAS domain-containing serine/threonine-protein kinase isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    241605207..241649447 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341072.1 → XP_054197047.1  PAS domain-containing serine/threonine-protein kinase isoform X2

  2. XM_054341071.1 → XP_054197046.1  PAS domain-containing serine/threonine-protein kinase isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q96RG2.3 GenPept UniProtKB/Swiss-Prot:Q96RG2

Gene LinkOut

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