RAB4A RAB4A, member RAS oncogene family [Homo sapiens (human)] - Gene

Summary

Official Symbol: RAB4Aprovided by HGNC
Official Full Name: RAB4A, member RAS oncogene familyprovided by HGNC
Primary source: HGNC:HGNC:9781
See related: Ensembl:ENSG00000168118 MIM:179511; AllianceGenome:HGNC:9781
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: RAB4; HRES1; HRES-1; HRES-1/RAB4
Summary: This gene is a member of the largest group in the Ras superfamily of small GTPases, which regulate membrane trafficking. The encoded protein is associated with early endosomes and is involved in their sorting and recycling. The protein also plays a role in regulating the recycling of receptors from endosomes to the plasma membrane. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2012]
Expression: Ubiquitous expression in prostate (RPKM 22.3), heart (RPKM 17.5) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 1q42.13

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (229271111..229305894)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (228649787..228684556)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (229406858..229441641)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Receptor-mediated internalization promotes increased endosome size and number in a RAB4- and RAB5-dependent manner.
Title: Receptor-mediated internalization promotes increased endosome size and number in a RAB4- and RAB5-dependent manner.
RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.
Title: RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.
Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.
Title: Agonist-activated glucagon receptors are deubiquitinated at early endosomes by two distinct deubiquitinases to facilitate Rab4a-dependent recycling.
Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation.
Title: Complex Rab4-Mediated Regulation of Endosomal Size and EGFR Activation.
-type prostaglandin D synthase regulates the trafficking of the PGD2 DP1 receptor by interacting with the GTPase Rab4
Title: L-type prostaglandin D synthase regulates the trafficking of the PGD(2) DP1 receptor by interacting with the GTPase Rab4.
These findings bring attention to the effects of C-terminal carboxylmethylation on RAB GTPases and provide a rationale for targeting ICMT in the treatment of metastatic cancer
Title: Isoprenylcysteine carboxylmethyltransferase function is essential for RAB4A-mediated integrin β3 recycling, cell migration and cancer metastasis.
The results contradict the model of feedback activation of Rab5 and instead indicate that Rbpt5 is recruited by both Rabex5 recognizing ubiquitylated cargo and by Rab4 to activate Rab5 in a feed-forward manner.
Title: Rabaptin5 is recruited to endosomes by Rab4 and Rabex5 to regulate endosome maturation.
Rab4 expression is up-regulated by laminar shear stress, which contributed to improved vascular endothelial cell autophagy and function.
Title: Laminar Shear Stress Promotes Vascular Endothelial Cell Autophagy Through Upregulation with Rab4.
Together the findings indicate that Arl1 links Rab4-dependent formation of endosomal sorting domains with downstream assembly of adaptor protein complexes that constitute the endosomal sorting machinery.
Title: Rab4 orchestrates a small GTPase cascade for recruitment of adaptor proteins to early endosomes.
HRES-1/Rab4 regulates autophagy through promoting the formation of LC3(+) autophagosomes and the preservation of mitochondria.
Title: HRES-1/Rab4 promotes the formation of LC3(+) autophagosomes and the accumulation of mitochondria during autophagy.

Submit: New GeneRIF Correction See all GeneRIFs (34)

Phenotypes

Go to the top of the page Help

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9. EBI GWAS Catalog EBI GWAS CatalogPubMed
Linkage and association of successful aging to the 6q25 region in large Amish kindreds. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Expression of HRES-1/Rab4 is induced by HIV-1 Tat, which in turn down-regulates expression of CD4 and susceptibility to re-infection by HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

SHGC-12949 (e-PCR)
- UniSTS:7941

D1S2524 (e-PCR)
- UniSTS:36909

G20320 (e-PCR)
- UniSTS:17966

A005L42 (e-PCR)
- UniSTS:17967

RH45658 (e-PCR)
- UniSTS:82749

A003A03 (e-PCR)
- UniSTS:17223

RH70076 (e-PCR)
- UniSTS:21881

STS-X16660 (e-PCR)
- UniSTS:15231

RAB4A_1449 (e-PCR)
- UniSTS:277646

RAB4A_v481 (e-PCR)
- UniSTS:277646

SPHAR__5294 (e-PCR)
- UniSTS:464559

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein activity	IEA Inferred from Electronic Annotation more info
enables GDP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	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 protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Rab protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in antigen processing and presentation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of endocytosis	IBA Inferred from Biological aspect of Ancestor more info
involved_in vesicle-mediated transport	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cytoplasmic vesicle membrane	TAS Traceable Author Statement more info
located_in early endosome membrane	TAS Traceable Author Statement more info
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in insulin-responsive compartment	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic recycling endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in recycling endosome membrane	IEA Inferred from Electronic Annotation more info
located_in vesicle	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: ras-related protein Rab-4A

Names: HTLV-1 related endogenous sequence

NP_001258927.1

EC 3.6.5.2

NP_004569.2

EC 3.6.5.2

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_001271998.2 → NP_001258927.1 ras-related protein Rab-4A isoform 2

See identical proteins and their annotated locations for NP_001258927.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences in the coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

AY585832, BC004309, BI546021, BX354553

Consensus CDS

CCDS73046.1

UniProtKB/TrEMBL

A0A087WYT5

Related

ENSP00000482077.1, ENST00000618010.4

Conserved Domains (1) summary

cl38936
Location:5 → 69

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
NM_004578.4 → NP_004569.2 ras-related protein Rab-4A isoform 1

See identical proteins and their annotated locations for NP_004569.2

Status: REVIEWED

Description

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

Source sequence(s)

AL162595, AY585832, BC004309, BI546021

Consensus CDS

CCDS31050.1

UniProtKB/Swiss-Prot

P20338, Q5T7P7, Q9BQ44

UniProtKB/TrEMBL

Q53GC2

Related

ENSP00000355651.4, ENST00000366690.5

Conserved Domains (1) summary

cd04113
Location:14 → 174

Rab4; Rab GTPase family 4 (Rab4)

RNA

NR_073545.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AY585832, BC002438, BC004309, BI828974, HY142709