GGA2 golgi associated, gamma adaptin ear containing, ARF binding protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GGA2provided by HGNC
Official Full Name: golgi associated, gamma adaptin ear containing, ARF binding protein 2provided by HGNC
Primary source: HGNC:HGNC:16064
See related: Ensembl:ENSG00000103365 MIM:606005; AllianceGenome:HGNC:16064
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: VEAR
Summary: This gene encodes a member of the Golgi-localized, gamma adaptin ear-containing, ARF-binding (GGA) family. This family includes ubiquitous coat proteins that regulate the trafficking of proteins between the trans-Golgi network and the lysosome. These proteins share an amino-terminal VHS domain which mediates sorting of the mannose 6-phosphate receptors at the trans-Golgi network. They also contain a carboxy-terminal region with homology to the ear domain of gamma-adaptins. This family member may play a significant role in cargo molecules regulation and clathrin-coated vesicle assembly. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in lymph node (RPKM 28.0), thyroid (RPKM 15.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16p12.2

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (23463542..23524359, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (23739620..23800145, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (23474863..23521815, complement)

Chromosome 16 - NC_000016.10 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 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?

Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting.
Title: Inactivation of the three GGA genes in HeLa cells partially compromises lysosomal enzyme sorting.
GGA2 and RAB13 are important specificity determinants for integrin activity-dependent traffic.
Title: GGA2 and RAB13 promote activity-dependent β1-integrin recycling.
Data suggest that overexpression of GGA2 in LUAD tumors results in the accumulation of EGFR protein and increased EGFR signaling, which helps drive tumor progression.
Title: Integrative Genomic Analyses Identifies GGA2 as a Cooperative Driver of EGFR-Mediated Lung Tumorigenesis.
Study shows that reduced expression of GGA3 resultes in accumulation of endocytosed EGFR within enlarged endosomes. GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression and promote cell growth. Finally, GGA2 was upregulated in 30.8% of human hepatocellular carcinomas and 23.3% of colorectal cancers.
Title: GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression and promote cell growth.
PI4KIIIbeta interaction with the VHS domain of GGA2 affected PI4KIIIbeta localization.
Title: Conserved role for Gga proteins in phosphatidylinositol 4-kinase localization to the trans-Golgi network.
full length alpha2B-AR associated with GGA2 but not GGA1, its third intracellular loop was found to directly interact with both GGA1 and GGA2. More interestingly, further mapping of interaction domains showed that the GGA1 hinge region and the GGA2 GAE domain bound to multiple subdomains of the loop.
Title: Regulation of α(2B)-Adrenergic Receptor Cell Surface Transport by GGA1 and GGA2.
These data indicate that clathrin is required for the function of AP-1- and GGA-coated carriers at the trans-Golgi network but may be dispensable for outward traffic en route to the plasma membrane.
Title: Clathrin terminal domain-ligand interactions regulate sorting of mannose 6-phosphate receptors mediated by AP-1 and GGA adaptors.
GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3.
Title: Analysis of Gga null mice demonstrates a non-redundant role for mammalian GGA2 during development.
GGA overexpression causes various sorting defects as measured by recycling of CD-MPR, internalization of transferrin receptor, and the subcellular localization of proteins like Tsg101, ubiquitin, and Hrs.
Title: Defects in cellular sorting and retroviral assembly induced by GGA overexpression.
GGA2 is recruited to the trans-Golgi network independently of the other Golgi-localized, gamma-ear-containing, ARF-binding proteins and is required for the efficient sorting of lysosomal enzymes
Title: Specific depletion of GGA2 causes cathepsin D missorting in HeLa cells.

Submit: New GeneRIF Correction See all GeneRIFs (15)

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

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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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Genome-wide shRNA screening identifies GGA2, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells	PubMed
Pr55(Gag)	gag	siRNA-mediated depletion of GGA2 leads to a significant increase in particle release in an HIV-1 Gag late domain-dependent manner, while GGA2 overexpression severely reduces virus particle production by impairing Gag trafficking to the membrane	PubMed
Vpr	vpr	Expression of a patient-derived HIV-1 Vpr protein reveals a significant reduction in Vpr nuclear import. Vpr F72L mutation is responsible for this decreased Vpr nuclear import and the F72L mutant is co-localized with gamma-adaptin in the Golgi apparatus	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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Markers

SHGC-60760 (e-PCR)
- UniSTS:13063

D11S2921 (e-PCR)
- UniSTS:152074

RH80401 (e-PCR)
- UniSTS:92966

D8S2279 (e-PCR)
- UniSTS:473907

D16S3347 (e-PCR)
- UniSTS:27242

D10S16 (e-PCR)
- UniSTS:155756

SHGC-33867 (e-PCR)
- UniSTS:23665

D16S3346 (e-PCR)
- UniSTS:23666

D1S1425 (e-PCR)
- UniSTS:149621

SHGC-2574 (e-PCR)
- UniSTS:90236

A004H39 (e-PCR)
- UniSTS:76938

RH93428 (e-PCR)
- UniSTS:88986

SHGC-64029 (e-PCR)
- UniSTS:33182

RH68368 (e-PCR)
- UniSTS:69833

RH75001 (e-PCR)
- UniSTS:85463

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables phosphatidylinositol binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small GTPase binding	IBA Inferred from Biological aspect of Ancestor more info
enables small GTPase binding	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Golgi to plasma membrane protein transport	IDA Inferred from Direct Assay more info	PubMed
involved_in Golgi to plasma membrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular protein transport	NAS Non-traceable Author Statement more info	PubMed
involved_in protein localization to cell surface	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to cell surface	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in clathrin-coated vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	TAS Traceable Author Statement more info
located_in endosome membrane	TAS Traceable Author Statement more info
is_active_in trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: ADP-ribosylation factor-binding protein GGA2

Names: VHS domain and ear domain of gamma-adaptin; VHS domain and ear domain-containing protein; gamma-adaptin-related protein 2; golgi-localized, gamma ear-containing, ARF-binding protein 2

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_015044.4 → NP_055859.1 ADP-ribosylation factor-binding protein GGA2

See identical proteins and their annotated locations for NP_055859.1

Status: REVIEWED

Source sequence(s)

AC008915, AF165531, DA439738

Consensus CDS

CCDS10611.1

UniProtKB/Swiss-Prot

D3DWF0, O14564, Q9NYN2, Q9UJY4, Q9UPS2

Related

ENSP00000311962.4, ENST00000309859.8

Conserved Domains (4) summary

smart00809
Location:491 → 605

Alpha_adaptinC2; Adaptin C-terminal domain

cd03567
Location:25 → 163

VHS_GGA; VHS domain family, GGA subfamily; GGA (Golgi-localized, Gamma-ear-containing, Arf-binding) comprise a subfamily of ubiquitously expressed, monomeric, motif-binding cargo/clathrin adaptor proteins. The VHS domain has a superhelical structure similar to ...

cd14239
Location:227 → 315

GAT_GGA1_GGA2; GAT domain found in ADP-ribosylation factor (Arf)-binding proteins GGA1 and GGA2

cl21478
Location:168 → 240

ATP-synt_B; ATP synthase B/B' CF(0)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

23463542..23524359 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047433801.1 → XP_047289757.1 ADP-ribosylation factor-binding protein GGA2 isoform X1
XM_047433802.1 → XP_047289758.1 ADP-ribosylation factor-binding protein GGA2 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

23739620..23800145 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054379851.1 → XP_054235826.1 ADP-ribosylation factor-binding protein GGA2 isoform X1
XM_054379852.1 → XP_054235827.1 ADP-ribosylation factor-binding protein GGA2 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_138640.1: Suppressed sequence

Description

NM_138640.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.