DENND5A DENN domain containing 5A [Homo sapiens (human)] - Gene

Summary

Official Symbol: DENND5Aprovided by HGNC
Official Full Name: DENN domain containing 5Aprovided by HGNC
Primary source: HGNC:HGNC:19344
See related: Ensembl:ENSG00000184014 MIM:617278; AllianceGenome:HGNC:19344
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: DEE49; EIEE49; RAB6IP1
Summary: This gene encodes a DENN-domain-containing protein that functions as a RAB-activating guanine nucleotide exchange factor (GEF). This protein catalyzes the conversion of GDP to GTP and thereby converts inactive GDP-bound Rab proteins into their active GTP-bound form. The encoded protein is recruited by RAB6 onto Golgi membranes and is therefore referred to as RAB6-interacting protein 1. This protein binds with RAB39 as well. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Mutations in this gene are associated with early infantile epileptic encephalopathy-49. [provided by RefSeq, Feb 2017]
Expression: Ubiquitous expression in brain (RPKM 36.4), heart (RPKM 21.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.4

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (9138825..9265350, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (9223596..9350195, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (9160372..9286897, complement)

Chromosome 11 - NC_000011.10 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
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?

Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma.
Title: Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma.
identification of an epileptic encephalopathy additionally featuring cerebral calcifications and coarse facial features caused by recessive loss-of-function mutations in DENND5A
Title: Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A.
A RUN Domain from DENND5/Rab6IP1 binds sorting Nexin 1 and is involved in the trafficking of vesicles at the level of Golgi.
Title: Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1.
crystal structure of Rab6a(GTP) in complex with a 378-residue internal fragment of the effector Rab6IP1 was solved at 3.2 angstroms resolution. This Rab6IP1 region encompasses an all alpha-helical RUN domain followed in tandem by a PLAT domain
Title: Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain.

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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

Associated conditions

Description	Tests
Developmental and epileptic encephalopathy, 49 MedGen: C4310635 OMIM: 617281 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-148440 (e-PCR)
- UniSTS:176394

G59833 (e-PCR)
- UniSTS:136982

D11S4704 (e-PCR)
- UniSTS:70688

WI-14657 (e-PCR)
- UniSTS:78141

D11S4413 (e-PCR)
- UniSTS:44181

D11S4422 (e-PCR)
- UniSTS:44720

D11S2377 (e-PCR)
- UniSTS:1201

RH18241 (e-PCR)
- UniSTS:60854

SHGC-146144 (e-PCR)
- UniSTS:175038

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement 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

Process	Evidence Code	Pubs
involved_in negative regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in retrograde transport, endosome to Golgi	IBA Inferred from Biological aspect of Ancestor more info
involved_in retrograde transport, endosome to Golgi	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
part_of retromer complex	IDA Inferred from Direct Assay more info	PubMed
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: DENN domain-containing protein 5A

Names: DENN/MADD domain containing 5A; RAB6 interacting protein 1; rab6-interacting protein 1

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_053019.1 RefSeqGene

Range

4986..131511

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001243254.2 → NP_001230183.1 DENN domain-containing protein 5A isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate donor splice site at the penultimate coding exon compared to variant 1. This results in a frame-shift, and a shorter isoform (2) with a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC055845, AK295881, AL117448, DN999250

Consensus CDS

CCDS58119.1

UniProtKB/TrEMBL

A0A7P0T9Z2

Related

ENSP00000435866.1, ENST00000530044.5

Conserved Domains (5) summary

smart00801
Location:513 → 588

dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins

smart00593
Location:884 → 947

RUN; domain involved in Ras-like GTPase signaling

smart00800
Location:12 → 138

uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

cd01757
Location:954 → 1062

PLAT_RAB6IP1; PLAT/LH2 domain present in RAB6 interacting protein 1 (Rab6IP1)_like family. PLAT/LH2 domains consists of an eight stranded beta-barrel. In RabIP1 this domain may participate in lipid-mediated modulation of Rab6IP1's function via it's generally proposed ...

pfam02141
Location:202 → 390

DENN; DENN (AEX-3) domain
NM_001348749.2 → NP_001335678.1 DENN domain-containing protein 5A isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame exon in the 5' coding region, compared to variant 1, and encodes a shorter isoform (3), compared to isoform 1.

Source sequence(s)

AC055845, AC079296, AP006259

Consensus CDS

CCDS91437.1

UniProtKB/TrEMBL

A0A7P0T9Z2, A0A7P0Z4N9

Related

ENSP00000506456.1, ENST00000681203.1

Conserved Domains (5) summary

smart00801
Location:489 → 564

dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins

smart00800
Location:12 → 114

uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

cd01757
Location:930 → 1038

PLAT_RAB6IP1; PLAT/LH2 domain present in RAB6 interacting protein 1 (Rab6IP1)_like family. PLAT/LH2 domains consists of an eight stranded beta-barrel. In RabIP1 this domain may participate in lipid-mediated modulation of Rab6IP1's function via it's generally proposed ...

pfam02141
Location:178 → 366

DENN; DENN (AEX-3) domain

cl02689
Location:771 → 918

RUN; RUN domain
NM_001348750.2 → NP_001335679.1 DENN domain-containing protein 5A isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an additional alternate exon in its 5' end which results in the use of a downstream in-frame start codon, compared to variant 1, and encodes a shorter isoform (4), compared to isoform 1.

Source sequence(s)

AC055845, AC079296, AP006259

UniProtKB/TrEMBL

B4DYK4

Related

ENSP00000505621.1, ENST00000680554.1

Conserved Domains (5) summary

smart00801
Location:417 → 492

dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins

smart00800
Location:1 → 42

uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

cd01757
Location:858 → 966

PLAT_RAB6IP1; PLAT/LH2 domain present in RAB6 interacting protein 1 (Rab6IP1)_like family. PLAT/LH2 domains consists of an eight stranded beta-barrel. In RabIP1 this domain may participate in lipid-mediated modulation of Rab6IP1's function via it's generally proposed ...

pfam02141
Location:106 → 294

DENN; DENN (AEX-3) domain

cl02689
Location:699 → 846

RUN; RUN domain
NM_015213.4 → NP_056028.2 DENN domain-containing protein 5A isoform 1

See identical proteins and their annotated locations for NP_056028.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AB029014, AC055845, AL117448, DN999250

Consensus CDS

CCDS31423.1

UniProtKB/Swiss-Prot

B4DJ15, E9PS91, Q6IQ26, Q96GN3, Q9H6U7, Q9UFV0, Q9UPR1

UniProtKB/TrEMBL

A0A7P0T9Z2

Related

ENSP00000328524.3, ENST00000328194.8

Conserved Domains (5) summary

smart00801
Location:513 → 588

dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins

smart00800
Location:12 → 138

uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

cd01757
Location:954 → 1062

PLAT_RAB6IP1; PLAT/LH2 domain present in RAB6 interacting protein 1 (Rab6IP1)_like family. PLAT/LH2 domains consists of an eight stranded beta-barrel. In RabIP1 this domain may participate in lipid-mediated modulation of Rab6IP1's function via it's generally proposed ...

pfam02141
Location:202 → 390

DENN; DENN (AEX-3) domain

cl02689
Location:795 → 942

RUN; RUN domain

RNA

NR_145966.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC055845, AC079296, AP006259

Related

ENST00000530780.2