GGA3 golgi associated, gamma adaptin ear containing, ARF binding protein 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GGA3provided by HGNC
Official Full Name: golgi associated, gamma adaptin ear containing, ARF binding protein 3provided by HGNC
Primary source: HGNC:HGNC:17079
See related: Ensembl:ENSG00000125447 MIM:606006; AllianceGenome:HGNC:17079
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
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. Multiple alternatively spliced transcript variants have been identified in this gene. [provided by RefSeq, Feb 2010]
Expression: Ubiquitous expression in spleen (RPKM 11.9), lymph node (RPKM 11.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q25.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (75236599..75262363, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (76128675..76154454, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (73232694..73258444, complement)

Chromosome 17 - NC_000017.11 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?

Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
Title: Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
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.
GGA3 interacts with L-type prostaglandin D synthase and regulates the recycling and signaling of the DP1 receptor for prostaglandin D2 in a Rab4-dependent mechanism.
Title: GGA3 interacts with L-type prostaglandin D synthase and regulates the recycling and signaling of the DP1 receptor for prostaglandin D(2) in a Rab4-dependent mechanism.
SNPs: rs6414624 in EVC and rs78338345 in GGA3 are novel susceptibility loci for type 2 diabetes mellitus in Japanese individuals.
Title: Two novel susceptibility loci for type 2 diabetes mellitus identified by longitudinal exome-wide association studies in a Japanese population.
In the absence of GGA3, integrins are increasingly retained inside the cell, traffic toward the perinuclear lysosomal compartment and their degradation is enhanced.
Title: Regulation of Cell Migration and β1 Integrin Trafficking by the Endosomal Adaptor GGA3.
This work identifies GGA3 as a key player in a novel DXXLL-mediated endosomal sorting machinery that targets TrkA to the plasma membrane, where it prolongs the activation of Akt signaling and survival responses.
Title: GGA3 mediates TrkA endocytic recycling to promote sustained Akt phosphorylation and cell survival.
role of GGA3 in the cell surface export of alpha2B-adrenergic receptor
Title: GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export.
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.
GGA3 is involved in the cellular processes relevant for Alzheimer's disease pathogenesis.
Title: Elucidation of the BACE1 regulating factor GGA3 in Alzheimer's disease.
Subcellular fractionation of Alzheimer's disease cortex with low levels of Golgi-localized GGA proteins shows an alteration of beta-secretase distribution and extensive co-localization with amyloid beta precursor protein APP.
Title: Decreased expression of GGA3 protein in Alzheimer's disease frontal cortex and increased co-distribution of BACE with the amyloid precursor protein.

Submit: New GeneRIF Correction See all GeneRIFs (24)

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
Pr55(Gag)	gag	siRNA-mediated depletion of GGA3 leads to a significant increase in particle release in an HIV-1 Gag late domain-dependent manner, while GGA3 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

RH25373 (e-PCR)
- UniSTS:91953

RH98808 (e-PCR)
- UniSTS:85087

NoName (e-PCR)
- UniSTS:146574

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 protein-containing complex binding	IDA Inferred from Direct Assay 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	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Golgi to plasma membrane protein transport	IMP Inferred from Mutant Phenotype 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 negative regulation of amyloid-beta formation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in protein destabilization	IDA Inferred from Direct Assay 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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein targeting to lysosome	IPI Inferred from Physical Interaction more info	PubMed
involved_in regulation of protein stability	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 early endosome membrane	TAS Traceable Author Statement more info
located_in endosome membrane	TAS Traceable Author Statement more info
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in recycling 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 GGA3

Names: Golgi-localized, gamma ear-containing, ARF-binding protein 3

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_001172703.3 → NP_001166174.1 ADP-ribosylation factor-binding protein GGA3 isoform 1

See identical proteins and their annotated locations for NP_001166174.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) contains an alternate 5' terminal exon, and it thus differs in its 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant long. The encoded isoform (1) is shorter at the N-terminus, compared to isoform long. Both variants 1 and 3 encode isoform 1.

Source sequence(s)

AF190864, AK301895, AK302278, CB240770, HY030361

Consensus CDS

CCDS54164.1

UniProtKB/TrEMBL

J3KSS7

Related

ENSP00000462081.1, ENST00000582717.5

Conserved Domains (3) summary

smart00809
Location:529 → 643

Alpha_adaptinC2; Adaptin C-terminal domain

cd14240
Location:141 → 227

GAT_GGA3; GAT domain found in ADP-ribosylation factor-binding protein GGA3

cl02544
Location:1 → 74

VHS_ENTH_ANTH; VHS, ENTH and ANTH domain superfamily; composed of proteins containing a VHS, ENTH or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal ...
NM_001172704.3 → NP_001166175.1 ADP-ribosylation factor-binding protein GGA3 isoform 2

See identical proteins and their annotated locations for NP_001166175.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains alternate 5' exon structure and it thus differs in its 5' UTR and initiates translation at a downstream in-frame start codon, and it also contains an alternate 3' terminal exon that results in an alternate 3' coding region, compared to variant long. The encoded isoform (2) is shorter at the N-terminus and has a distinct C-terminus, compared to isoform long.

Source sequence(s)

AF190864, AK301895, AK302278, CB240770, HY030361

Consensus CDS

CCDS58597.1

UniProtKB/TrEMBL

J3KSS7

Related

ENSP00000463288.1, ENST00000578348.5

Conserved Domains (3) summary

smart00809
Location:479 → 568

Alpha_adaptinC2; Adaptin C-terminal domain

cd14240
Location:91 → 177

GAT_GGA3; GAT domain found in ADP-ribosylation factor-binding protein GGA3

cl02544
Location:1 → 24

VHS_ENTH_ANTH; VHS, ENTH and ANTH domain superfamily; composed of proteins containing a VHS, ENTH or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal ...
NM_001291641.2 → NP_001278570.1 ADP-ribosylation factor-binding protein GGA3 isoform 1

See identical proteins and their annotated locations for NP_001278570.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an additional exon in the 5' region, and it thus differs in its 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant long. The encoded isoform (1) is shorter at the N-terminus, compared to isoform long. Both variants 1 and 3 encode isoform 1.

Source sequence(s)

AF190864, AK291685, AL833603, BC070044, CB240770, DA312660

Consensus CDS

CCDS54164.1

UniProtKB/TrEMBL

J3KSS7

Conserved Domains (3) summary

smart00809
Location:529 → 643

Alpha_adaptinC2; Adaptin C-terminal domain

cd14240
Location:141 → 227

GAT_GGA3; GAT domain found in ADP-ribosylation factor-binding protein GGA3

cl02544
Location:1 → 74

VHS_ENTH_ANTH; VHS, ENTH and ANTH domain superfamily; composed of proteins containing a VHS, ENTH or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal ...
NM_001291642.2 → NP_001278571.1 ADP-ribosylation factor-binding protein GGA3 isoform 3

See identical proteins and their annotated locations for NP_001278571.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains alternate 5' exon structure, and it thus differs in its 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant long. The encoded isoform (3) is shorter at the N-terminus, compared to isoform long.

Source sequence(s)

AF190864, AK291685, AK296843, CB240770, DA312660

UniProtKB/TrEMBL

A8K6M0, B7Z456

Conserved Domains (3) summary

smart00809
Location:479 → 593

Alpha_adaptinC2; Adaptin C-terminal domain

cd14240
Location:91 → 177

GAT_GGA3; GAT domain found in ADP-ribosylation factor-binding protein GGA3

cl02544
Location:1 → 24

VHS_ENTH_ANTH; VHS, ENTH and ANTH domain superfamily; composed of proteins containing a VHS, ENTH or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal ...
NM_014001.5 → NP_054720.1 ADP-ribosylation factor-binding protein GGA3 isoform short

See identical proteins and their annotated locations for NP_054720.1

Status: REVIEWED

Description

Transcript Variant: This variant (short) lacks an alternate in-frame exon in the 5' coding region, compared to variant long, resulting in an isoform (short) that is shorter than isoform long.

Source sequence(s)

AF190864, AK291685, BC070044, CB240770, DA312660

Consensus CDS

CCDS11716.1

UniProtKB/TrEMBL

A8K6M0

Related

ENSP00000446421.2, ENST00000538886.5

Conserved Domains (3) summary

smart00809
Location:568 → 682

Alpha_adaptinC2; Adaptin C-terminal domain

cd14240
Location:180 → 266

GAT_GGA3; GAT domain found in ADP-ribosylation factor-binding protein GGA3

cl02544
Location:8 → 113

VHS_ENTH_ANTH; VHS, ENTH and ANTH domain superfamily; composed of proteins containing a VHS, ENTH or ANTH domain. The VHS domain is present in Vps27 (Vacuolar Protein Sorting), Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and STAM (Signal ...
NM_138619.4 → NP_619525.1 ADP-ribosylation factor-binding protein GGA3 isoform long

See identical proteins and their annotated locations for NP_619525.1

Status: REVIEWED

Description

Transcript Variant: This variant (long) encodes the longest isoform (long).

Source sequence(s)

AF190864, AF219138, AK291685, BC070044, CB240770, DA312660

Consensus CDS

CCDS11717.1

UniProtKB/Swiss-Prot

B7Z7E2, B7Z7M9, J3KRN0, Q15017, Q6IS16, Q9NZ52, Q9UJY3

UniProtKB/TrEMBL

A8K6I6

Related

ENSP00000438085.3, ENST00000537686.6

Conserved Domains (3) summary

smart00809
Location:601 → 715

Alpha_adaptinC2; Adaptin C-terminal domain

cd03567
Location:8 → 146

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 ...

cd14240
Location:213 → 299

GAT_GGA3; GAT domain found in ADP-ribosylation factor-binding protein GGA3