Gak cyclin G associated kinase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Gakprovided by MGI
Official Full Name: cyclin G associated kinaseprovided by MGI
Primary source: MGI:MGI:2442153
See related: Ensembl:ENSMUSG00000062234 AllianceGenome:MGI:2442153
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: D130045N16Rik
Summary: Predicted to enable clathrin binding activity and cyclin binding activity. Acts upstream of or within several processes, including epithelial cell differentiation; establishment of skin barrier; and intrahepatic bile duct development. Predicted to be located in Golgi apparatus and clathrin-coated vesicle. Predicted to be active in cytoplasm; intracellular membrane-bounded organelle; and vesicle. Is expressed in several structures, including central nervous system; liver; and retina. Orthologous to human GAK (cyclin G associated kinase). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Ubiquitous expression in colon adult (RPKM 34.6), large intestine adult (RPKM 29.7) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 F; 5 53.2 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (108716973..108777643, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (108569107..108629777, complement)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inhibiting calpain 1 and 2 in cyclin G associated kinase-knockout mice mitigates podocyte injury.
Title: Inhibiting calpain 1 and 2 in cyclin G associated kinase-knockout mice mitigates podocyte injury.
PTEN-like domains of GAK and auxilin are not essential for Hsc70-dependent chaperoning and uncoating of clathrin, but depending on the tissue, these domains appear to increase the efficiency of these co-chaperones.
Title: The clathrin-binding and J-domains of GAK support the uncoating and chaperoning of clathrin by Hsc70 in the brain.
GAK knockout causes senescence and centrosome duplication in MEF cells.
Title: Disruption of clathrin-mediated trafficking causes centrosome overduplication and senescence.
These results suggest that inhibition of GAK by gefitinib may cause pulmonary alveolar dysfunction.
Title: Neonatal lethality in knockout mice expressing the kinase-dead form of the gefitinib target GAK is caused by pulmonary dysfunction.
GAK deletion blocks development and causes lethality in adult animals by disrupting clathrin-mediated endocytosis
Title: Essential role of cyclin-G-associated kinase (Auxilin-2) in developing and mature mice.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D5Mit338 (e-PCR), detects polymorphism
- UniSTS:130484

RH131491 (e-PCR)
- UniSTS:214774

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables clathrin binding	IBA Inferred from Biological aspect of Ancestor more info
enables cyclin binding	ISO Inferred from Sequence Orthology more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within Golgi organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Golgi organization	ISO Inferred from Sequence Orthology more info
involved_in Golgi organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in Golgi to lysosome transport	ISO Inferred from Sequence Orthology more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in clathrin coat assembly	ISO Inferred from Sequence Orthology more info
involved_in clathrin coat disassembly	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within clathrin coat disassembly	IGI Inferred from Genetic Interaction more info	PubMed
involved_in clathrin coat disassembly	ISO Inferred from Sequence Orthology more info
involved_in clathrin-dependent endocytosis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within clathrin-dependent endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in clathrin-dependent endocytosis	ISO Inferred from Sequence Orthology more info
involved_in clathrin-dependent endocytosis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within endoplasmic reticulum organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within epidermal cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within epithelial cell development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within establishment of skin barrier	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within forebrain morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular transport	ISO Inferred from Sequence Orthology more info
involved_in intracellular transport	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within intrahepatic bile duct development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within keratinocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of neuron projection development	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of neural precursor cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within neuroepithelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of neural precursor cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to Golgi apparatus	ISO Inferred from Sequence Orthology more info
involved_in protein localization to plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in receptor-mediated endocytosis	ISO Inferred from Sequence Orthology more info
involved_in regulation of clathrin coat assembly	ISO Inferred from Sequence Orthology more info
involved_in regulation of clathrin coat assembly	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within stem cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in clathrin-coated vesicle	ISO Inferred from Sequence Orthology more info
located_in clathrin-coated vesicle	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in focal adhesion	IEA Inferred from Electronic Annotation more info
is_active_in intracellular membrane-bounded organelle	IBA Inferred from Biological aspect of Ancestor more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in vesicle	IBA Inferred from Biological aspect of Ancestor more info
located_in vesicle	ISO Inferred from Sequence Orthology more info
located_in vesicle	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: cyclin-G-associated kinase

Names: dnaJ homolog subfamily C member 26

NP_001268980.1

EC 2.7.11.1

NP_001268981.1

EC 2.7.11.1

NP_001346851.1

EC 2.7.11.1

NP_001346852.1

EC 2.7.11.1

NP_001346853.1

EC 2.7.11.1

NP_705797.1

EC 2.7.11.1

XP_006534968.1

EC 2.7.11.1

XP_036020971.1

EC 2.7.11.1

XP_036020972.1

EC 2.7.11.1

XP_036020973.1

EC 2.7.11.1

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.

mRNA and Protein(s)

NM_001282051.1 → NP_001268980.1 cyclin-G-associated kinase isoform 2

See identical proteins and their annotated locations for NP_001268980.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in its 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1. Variants 2 and 6 both encode the same isoform (2).

Source sequence(s)

AC133896, AI466057, AK166682, BC065109, BY312464

UniProtKB/TrEMBL

Q3UDE5

Conserved Domains (4) summary

cd06257
Location:1092 → 1137

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

pfam10409
Location:407 → 545

PTEN_C2; C2 domain of PTEN tumor-suppressor protein

cl21453
Location:1 → 159

PKc_like; Protein Kinases, catalytic domain

cl26464
Location:552 → 1008

Atrophin-1; Atrophin-1 family
NM_001282052.1 → NP_001268981.1 cyclin-G-associated kinase isoform 3

Status: VALIDATED

Description

Transcript Variant: This variant (3) differs in its 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AC133896, AI466057, AK166682, BC062975, BY312464

UniProtKB/TrEMBL

Q3UDE5

Conserved Domains (3) summary

cd06257
Location:1041 → 1086

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

pfam10409
Location:356 → 494

PTEN_C2; C2 domain of PTEN tumour-suppressor protein

cl21453
Location:1 → 108

PKc_like; Protein Kinases, catalytic domain
NM_001359922.1 → NP_001346851.1 cyclin-G-associated kinase isoform 4

Status: VALIDATED

Source sequence(s)

AC133896, AC161813

UniProtKB/TrEMBL

Q3UDE5

Conserved Domains (5) summary

cd06257
Location:1043 → 1088

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

pfam10409
Location:407 → 545

PTEN_C2; C2 domain of PTEN tumor-suppressor protein

cl21453
Location:1 → 159

PKc_like; Protein Kinases, catalytic domain

cl26464
Location:777 → 930

Atrophin-1; Atrophin-1 family

cl28033
Location:631 → 964

Herpes_ICP4_C; Herpesvirus ICP4-like protein C-terminal region
NM_001359923.1 → NP_001346852.1 cyclin-G-associated kinase isoform 5

Status: VALIDATED

Source sequence(s)

AC161813, AK051394

UniProtKB/TrEMBL

Q3UDE5

Related

ENSMUST00000137872.8

Conserved Domains (2) summary

pfam10409
Location:407 → 545

PTEN_C2; C2 domain of PTEN tumor-suppressor protein

cl21453
Location:1 → 159

PKc_like; Protein Kinases, catalytic domain
NM_001359924.1 → NP_001346853.1 cyclin-G-associated kinase isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (6), as well as variant 2, encodes isoform 2.

Source sequence(s)

AC133896, AC161813, AK150112

UniProtKB/TrEMBL

Q3UDE5

Conserved Domains (4) summary

cd06257
Location:1092 → 1137

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

pfam10409
Location:407 → 545

PTEN_C2; C2 domain of PTEN tumor-suppressor protein

cl21453
Location:1 → 159

PKc_like; Protein Kinases, catalytic domain

cl26464
Location:552 → 1008

Atrophin-1; Atrophin-1 family
NM_153569.2 → NP_705797.1 cyclin-G-associated kinase isoform 1

See identical proteins and their annotated locations for NP_705797.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC133896, AI466057, AK166682, BY312464

Consensus CDS

CCDS19513.1

UniProtKB/Swiss-Prot

Q6P1I8, Q6P9S5, Q8BM74, Q8K0Q4, Q99KY4

UniProtKB/TrEMBL

A0A0R4J0F6, Q3UIZ0

Related

ENSMUSP00000036705.9, ENSMUST00000046603.15

Conserved Domains (4) summary

cd06257
Location:1253 → 1298

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

smart00220
Location:41 → 311

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14036
Location:39 → 320

STKc_GAK; Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase

pfam10409
Location:568 → 706

PTEN_C2; C2 domain of PTEN tumour-suppressor protein

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000071.7 Reference GRCm39 C57BL/6J

Range

108716973..108777643 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006534905.4 → XP_006534968.1 cyclin-G-associated kinase isoform X1

UniProtKB/Swiss-Prot

Q6P1I8, Q6P9S5, Q8BM74, Q8K0Q4, Q99KY4

UniProtKB/TrEMBL

Q3UIZ0

Conserved Domains (5) summary

cd06257
Location:1204 → 1249

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

PHA03247
Location:938 → 1091

PHA03247; large tegument protein UL36; Provisional

cd14036
Location:39 → 320

STKc_GAK; Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase

cd14564
Location:398 → 560

PTP_GAK; protein tyrosine phosphatase-like domain of cyclin-G-associated kinase

pfam10409
Location:568 → 706

PTEN_C2; C2 domain of PTEN tumor-suppressor protein
XM_036165079.1 → XP_036020972.1 cyclin-G-associated kinase isoform X2

Conserved Domains (3) summary

cd06257
Location:774 → 819

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

PHA03247
Location:234 → 690

PHA03247; large tegument protein UL36; Provisional

pfam10409
Location:89 → 227

PTEN_C2; C2 domain of PTEN tumor-suppressor protein
XM_036165078.1 → XP_036020971.1 cyclin-G-associated kinase isoform X2

Conserved Domains (3) summary

cd06257
Location:774 → 819

DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

PHA03247
Location:234 → 690

PHA03247; large tegument protein UL36; Provisional

pfam10409
Location:89 → 227

PTEN_C2; C2 domain of PTEN tumor-suppressor protein
XM_036165080.1 → XP_036020973.1 cyclin-G-associated kinase isoform X3

Conserved Domains (3) summary

cd14036
Location:39 → 320

STKc_GAK; Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase

cd14564
Location:398 → 560

PTP_GAK; protein tyrosine phosphatase-like domain of cyclin-G-associated kinase

pfam10409
Location:568 → 683

PTEN_C2; C2 domain of PTEN tumor-suppressor protein