Agap2 ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Agap2provided by MGI
Official Full Name: ArfGAP with GTPase domain, ankyrin repeat and PH domain 2provided by MGI
Primary source: MGI:MGI:3580016
See related: Ensembl:ENSMUSG00000025422 AllianceGenome:MGI:3580016
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: PIKE; AGAP-2; Centg1; cnt-g1; mKIAA0167
Summary: The protein encoded by this gene is a member of the centaurin GTPase family. This gene product regulates the activity of multiple kinases, including PI3K. Reduced expression of this gene results in multiple defects, including neural deficiencies, while increased expression of this gene has been observed in some tumors. Alternative splicing results in multiple protein isoforms. [provided by RefSeq, Jul 2014]
Expression: Biased expression in frontal lobe adult (RPKM 84.2), cortex adult (RPKM 70.9) and 8 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 D3; 10 74.5 cM

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (126911154..126929039)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (127075269..127093170)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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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?

Dopamine and DOPAC were not changed in 3-mo-old mice but were decreased at 8 mo in the striatum of PIKE-KO mice compared with wild-type mice. DA and DOPAC in hippocampus and substantia nigra were significantly decreased in 3-mo-old and 8-mo-old PIKE-KO mice as compared with wild-type mice. More severe motor defects in PIKE-KO and Fyn-KO mice than in wild-type mice exposed to alpha synuclein and MPTP.
Title: α-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation.
Depletion of PIKE-A in C2C12 myotubes diminished the inhibitory activities of TNF-alpha on mitochondrial respiration and lipid oxidation, whereas PIKE-A overexpression exacerbated these cellular responses.
Title: Tumor Necrosis Factor-α Promotes Phosphoinositide 3-Kinase Enhancer A and AMP-Activated Protein Kinase Interaction to Suppress Lipid Oxidation in Skeletal Muscle.
PIKE plays pivotal roles to advance oligodendroglia development and myelinogenesis through Akt/mTOR activation.
Title: PIKE is essential for oligodendroglia development and CNS myelination.
Results demonstrate that the integrity of PIKE signaling is essential for protecting the neurons from excitotoxicity-stimulated damage both in vitro and in vivo.
Title: Essential role of PIKE GTPases in neuronal protection against excitotoxic insults.
Fyn regulates the activity of the adipogenic transcription factor signal transducer and activator of transcription 5a (STAT5a) through enhancing its interaction with the GTPase phosphoinositide 3-kinase enhancer A (PIKE-A).
Title: Fyn regulates adipogenesis by promoting PIKE-A/STAT5a interaction.
PIKE is a critical factor in controlling synaptic AMPA receptor insertion.
Title: PIKE-mediated PI3-kinase activity is required for AMPA receptor surface expression.
data established the critical role of PIKE in regulating neuronal survival and development by substantiating the PI3K/Akt pathway.
Title: Phosphoinositide 3-kinase enhancer regulates neuronal dendritogenesis and survival in neocortex.
PIKE-A is required for prolactin-mediated STAT5a activation in mammary gland development.
Title: PIKE-A is required for prolactin-mediated STAT5a activation in mammary gland development.
PIKE knockout mice show augmented lipid oxidation, which is accompanied by enhanced AMPK phosphorylation in muscle and adipose tissue and is implicated in obesity and diabetes development.
Title: Deficiency of phosphoinositide 3-kinase enhancer protects mice from diet-induced obesity and insulin resistance.
PIKE-L acts as a downstream survival effector for netrin-1 through UNC5B in the nervous system
Title: Netrin-1 mediates neuronal survival through PIKE-L interaction with the dependence receptor UNC5B.

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Variation

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Alleles

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

Endonuclease-mediated (2)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables GTP binding	ISO Inferred from Sequence Orthology more info
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activator activity	ISO Inferred from Sequence Orthology more info
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	ISO Inferred from Sequence Orthology more info
enables ionotropic glutamate receptor binding	IEA Inferred from Electronic Annotation more info
enables ionotropic glutamate receptor binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol 3-kinase regulator activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activator activity	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within actin cytoskeleton organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of cell surface receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to glycine	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glycine	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within endosomal transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of epithelial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mammary gland alveolus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of mammary gland epithelial cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of mammary gland epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of epithelial cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in phosphatidylinositol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of mammary gland epithelial cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of mammary gland epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of protein kinase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to cell surface	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein localization to cell surface	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of receptor signaling pathway via JAK-STAT	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Flemming body	IEA Inferred from Electronic Annotation more info
located_in Flemming body	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
located_in endosome	ISO Inferred from Sequence Orthology more info
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IEP Inferred from Expression Pattern more info	PubMed
is_active_in membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in postsynapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynapse	IEP Inferred from Expression Pattern more info	PubMed

General protein information

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Preferred Names: arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2

Names: centaurin, gamma 1; phosphatidylinositol 3-kinase enhancer

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_001033263.5 → NP_001028435.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform 1

See identical proteins and their annotated locations for NP_001028435.1

Status: REVIEWED

Description

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

Source sequence(s)

AA189612, AC131760, AK147446

Consensus CDS

CCDS24228.1

UniProtKB/Swiss-Prot

Q3UHD9, Q5DU45

Related

ENSMUSP00000043466.7, ENSMUST00000039259.7

Conserved Domains (8) summary

cd04103
Location:401 → 560

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

smart00010
Location:399 → 566

small_GTPase; Small GTPase of the Ras superfamily; ill-defined subfamily

cd00204
Location:1077 → 1141

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd01250
Location:668 → 908

PH_AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain

pfam00169
Location:839 → 903

PH; PH domain

pfam01412
Location:927 → 1041

ArfGap; Putative GTPase activating protein for Arf

pfam13857
Location:1072 → 1125

Ank_5; Ankyrin repeats (many copies)

sd00045
Location:1084 → 1115

ANK; ANK repeat [structural motif]
NM_001301014.1 → NP_001287943.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform 2

See identical proteins and their annotated locations for NP_001287943.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AA189612, AC131760, AK147446

Consensus CDS

CCDS88097.1

UniProtKB/Swiss-Prot

Q3UHD9

Related

ENSMUSP00000151946.2, ENSMUST00000217941.2

Conserved Domains (8) summary

cd04103
Location:401 → 560

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

smart00010
Location:399 → 566

small_GTPase; Small GTPase of the Ras superfamily; ill-defined subfamily

cd00204
Location:1057 → 1121

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

cd01250
Location:668 → 888

PH_AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain

pfam00169
Location:846 → 883

PH; PH domain

pfam01412
Location:907 → 1021

ArfGap; Putative GTPase activating protein for Arf

pfam13857
Location:1052 → 1105

Ank_5; Ankyrin repeats (many copies)

sd00045
Location:1064 → 1095

ANK; ANK repeat [structural motif]

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_000076.7 Reference GRCm39 C57BL/6J

Range

126911154..126929039

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006513561.5 → XP_006513624.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X3

See identical proteins and their annotated locations for XP_006513624.1

Conserved Domains (4) summary

cd04103
Location:71 → 230

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

cd01250
Location:338 → 578

PH_AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain

cd08836
Location:596 → 703

ArfGap_AGAP; ArfGAP with GTPase domain, ANK repeat and PH domains

pfam04592
Location:806 → 858

SelP_N; Selenoprotein P, N terminal region
XM_006513563.4 → XP_006513626.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X5

See identical proteins and their annotated locations for XP_006513626.1

UniProtKB/TrEMBL

A0A5F8MPB7

Related

ENSMUSP00000158894.2, ENSMUST00000239120.2

Conserved Domains (5) summary

cd04103
Location:71 → 230

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

cd01250
Location:338 → 558

PH_AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain

sd00045
Location:734 → 765

ANK; ANK repeat [structural motif]

cd08836
Location:576 → 683

ArfGap_AGAP; ArfGAP with GTPase domain, ANK repeat and PH domains

pfam12796
Location:739 → 791

Ank_2; Ankyrin repeats (3 copies)
XM_006513558.5 → XP_006513621.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1

See identical proteins and their annotated locations for XP_006513621.1

Conserved Domains (5) summary

cd04103
Location:401 → 560

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

PHA03247
Location:52 → 320

PHA03247; large tegument protein UL36; Provisional

cd01250
Location:668 → 908

PH_AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain

cd08836
Location:926 → 1033

ArfGap_AGAP; ArfGAP with GTPase domain, ANK repeat and PH domains

pfam04592
Location:1136 → 1188

SelP_N; Selenoprotein P, N terminal region
XM_006513559.5 → XP_006513622.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X2

See identical proteins and their annotated locations for XP_006513622.1

Conserved Domains (5) summary

cd04103
Location:401 → 560

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

PHA03247
Location:52 → 320

PHA03247; large tegument protein UL36; Provisional

cd01250
Location:668 → 888

PH_AGAP; Arf-GAP with GTPase, ANK repeat and PH domain-containing protein Pleckstrin homology (PH) domain

cd08836
Location:906 → 1013

ArfGap_AGAP; ArfGAP with GTPase domain, ANK repeat and PH domains

pfam04592
Location:1116 → 1168

SelP_N; Selenoprotein P, N terminal region
XM_006513562.5 → XP_006513625.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X4

See identical proteins and their annotated locations for XP_006513625.1

Conserved Domains (3) summary

cd04103
Location:401 → 560

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

PHA03247
Location:52 → 320

PHA03247; large tegument protein UL36; Provisional

cl17171
Location:668 → 739

PH-like; Pleckstrin homology-like domain