AGAP2 ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AGAP2provided by HGNC
Official Full Name: ArfGAP with GTPase domain, ankyrin repeat and PH domain 2provided by HGNC
Primary source: HGNC:HGNC:16921
See related: Ensembl:ENSG00000135439 MIM:605476; AllianceGenome:HGNC:16921
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: PIKE; GGAP2; CENTG1
Summary: The protein encoded by this gene belongs to the centaurin gamma-like family. It mediates anti-apoptotic effects of nerve growth factor by activating nuclear phosphoinositide 3-kinase. It is overexpressed in cancer cells, and promotes cancer cell invasion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]
Expression: Biased expression in brain (RPKM 36.4), lymph node (RPKM 4.9) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q14.1

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (57723761..57742161, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (57692114..57710515, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (58117544..58135944, complement)

Chromosome 12 - NC_000012.12 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: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PIKE-A promotes glioblastoma growth by driving PPP flux through increasing G6PD expression mediated by phosphorylation of STAT3.
Title: PIKE-A promotes glioblastoma growth by driving PPP flux through increasing G6PD expression mediated by phosphorylation of STAT3.
Exosomes derived from microRNA-199a-overexpressing mesenchymal stem cells inhibit glioma progression by down-regulating AGAP2.
Title: Exosomes derived from microRNA-199a-overexpressing mesenchymal stem cells inhibit glioma progression by down-regulating AGAP2.
chromatin immunoprecipitation studies revealed the presence of RARalpha, RXRalpha and the lysine acetyl transferase PCAF in AGAP2 promoter.
Title: SP1 and RARα regulate AGAP2 expression in cancer.
The role of AGAP2 in the pro-fibrogenic phenotype of hepatic stellate cells in response to TGFbeta.
Title: Role of AGAP2 in the profibrogenic effects induced by TGFβ in LX-2 hepatic stellate cells.
A pleckstrin homology domain in PIKE-L directly binds alpha-synuclein and antagonizes its aggregation. Accordingly, PIKE-L overexpression decreases dopaminergic cell death elicited by MPP(+), whereas PIKE-L knockdown elevates alpha-synuclein oligomerization and cell death.
Title: α-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation.
these findings support that PIKE amplification or overexpression coordinately acts with CDK4 to drive glioblastoma tumorigenesis.
Title: Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression.
Studies showed that overexpression or mutation of PIKE has been observed in a variety of tumors, promoting cancer cell growth, transformation and invasion through AKT signaling or other signaling pathways, such as focal adhesion kinase. [review]
Title: Phosphoinositide-3-Kinase Enhancers, PIKEs: Their Biological Functions and Roles in Cancer.
Mutation of Fyn phosphorylation sites on PIKE-A, depletion of Fyn, or pharmacological inhibition of Fyn blunts the association between PIKE-A and AMPK, resulting in loss of its inhibitory effect on AMPK.
Title: Fyn-phosphorylated PIKE-A binds and inhibits AMPK signaling, blocking its tumor suppressive activity.
expression of PLC-gamma1 and PIKE positively correlated with the tumor differentiation of oral squamous cell carcinoma.
Title: Reduced expression of E-cadherin and p120-catenin and elevated expression of PLC-γ1 and PIKE are associated with aggressiveness of oral squamous cell carcinoma.
PIKE reduction rescued PI3K-dependent and -independent neuronal defects in fragile X syndrome.
Title: Increased expression of the PI3K enhancer PIKE mediates deficits in synaptic plasticity and behavior in fragile X syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (34)

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
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 (AGAP2) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables GTPase activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activity	TAS Traceable Author Statement more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol 3-kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables phosphatidylinositol 3-kinase regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
involved_in activation of GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within endosomal transport	IDA Inferred from Direct Assay more info	PubMed
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	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in protein transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Flemming body	IDA Inferred from Direct Assay more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	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
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in nucleus	TAS Traceable Author Statement 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: Arf GAP with GTP-binding protein-like, ANK repeat and PH domains 2; GTP-binding and GTPase activating protein 2; centaurin, gamma 1; phosphatidylinositol 3-kinase enhancer; phosphoinositide 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.

Genomic

NG_029755.1 RefSeqGene

Range

8420..21965

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001122772.3 → NP_001116244.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform PIKE-L

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (PIKE-L). This isoform is thought to participate in the prevention of neuronal apoptosis by enhancing nuclear phosphoinositide 3-kinase activity (PMID:14528310).

Source sequence(s)

AC025165

Consensus CDS

CCDS44932.1

UniProtKB/Swiss-Prot

A8K9F7, O00578, Q548E0, Q8IWU3, Q99490

UniProtKB/TrEMBL

F8VVT9

Related

ENSP00000449241.1, ENST00000547588.6

Conserved Domains (6) summary

cd04103
Location:407 → 566

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

cd01250
Location:674 → 914

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

sd00045
Location:1058 → 1088

ANK; ANK repeat [structural motif]

cd08836
Location:932 → 1039

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

pfam06346
Location:78 → 172

Drf_FH1; Formin Homology Region 1

pfam12796
Location:1058 → 1148

Ank_2; Ankyrin repeats (3 copies)
NM_014770.4 → NP_055585.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform PIKE-A

See identical proteins and their annotated locations for NP_055585.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' terminal exon compared to variant 1. This results in a shorter isoform (PIKE-A) with a distinct N-terminus compared to isoform PIKE-L. This isoform is reported to be overexpressed in brain tumors and promote cancer cell invasion (PMID:14761976).

Source sequence(s)

AC025165, AV740795, BE280072, BI755875, D79989, DB165417

Consensus CDS

CCDS8951.1

UniProtKB/TrEMBL

B3KVD5

Related

ENSP00000257897.3, ENST00000257897.7

Conserved Domains (8) summary

cd04103
Location:71 → 230

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

smart00010
Location:69 → 236

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

cd00204
Location:702 → 791

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:338 → 558

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

pfam00169
Location:516 → 553

PH; PH domain

pfam01412
Location:577 → 691

ArfGap; Putative GTPase activating protein for Arf

pfam12796
Location:702 → 792

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:702 → 732

ANK; ANK repeat [structural motif]

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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

57723761..57742161 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005268626.3 → XP_005268683.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X2

See identical proteins and their annotated locations for XP_005268683.1

UniProtKB/TrEMBL

B3KVD5

Conserved Domains (8) summary

cd04103
Location:71 → 230

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

smart00010
Location:69 → 236

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

cd00204
Location:722 → 811

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:338 → 578

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

pfam00169
Location:509 → 573

PH; PH domain

pfam01412
Location:597 → 711

ArfGap; Putative GTPase activating protein for Arf

pfam12796
Location:722 → 812

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:722 → 752

ANK; ANK repeat [structural motif]
XM_005268625.4 → XP_005268682.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1

UniProtKB/Swiss-Prot

A8K9F7, O00578, Q548E0, Q8IWU3, Q99490

Related

ENSP00000328160.4, ENST00000328568.9

Conserved Domains (8) summary

cd04103
Location:407 → 566

Centaurin_gamma; Centaurin gamma (CENTG) GTPase

smart00010
Location:405 → 572

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

cd00204
Location:1038 → 1127

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:674 → 894

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

pfam00169
Location:852 → 889

PH; PH domain

pfam01412
Location:913 → 1027

ArfGap; Putative GTPase activating protein for Arf

pfam12796
Location:1038 → 1128

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:1038 → 1068

ANK; ANK repeat [structural motif]

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

57692114..57710515 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054371031.1 → XP_054227006.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X2
XM_054371030.1 → XP_054227005.1 arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2 isoform X1