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

Gene ID: 23258, updated on 5-Mar-2024

Summary

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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
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Genomic context

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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_000011.10Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:9116861-9117362 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:9117363-9117862 Neighboring gene keratin 8 pseudogene 41 Neighboring gene uncharacterized LOC105376542 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:9142475-9143138 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4401 Neighboring gene Sharpr-MPRA regulatory region 9656 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:9190693-9191892 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:9250779-9251379 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr11:9251982-9252582 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:9273812-9274511 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3121 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4403 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3122 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3123 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4405 Neighboring gene MPRA-validated peak1192 silencer Neighboring gene tRNA-Leu (CAA) 5-1 Neighboring gene transmembrane protein 41B Neighboring gene proline rich 13 pseudogene 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Novel loss-of-function variant in DENND5A impedes melanosomal cargo transport and predisposes to familial cutaneous melanoma. Yang M, et al. Genet Med, 2022 Jan. PMID 34906508, Free PMC Article
  2. Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A. Han C, et al. Am J Hum Genet, 2016 Dec 1. PMID 27866705, Free PMC Article
  3. Mapping the interactions between a RUN domain from DENND5/Rab6IP1 and sorting nexin 1. Fernandes H, et al. PLoS One, 2012. PMID 22558185, Free PMC Article
  4. Structural basis for recruitment of Rab6-interacting protein 1 to Golgi via a RUN domain. Recacha R, et al. Structure, 2009 Jan 14. PMID 19141279
  5. Two-hybrid system screen with the small GTP-binding protein Rab6. Identification of a novel mouse GDP dissociation inhibitor isoform and two other potential partners of Rab6. Janoueix-Lerosey I, et al. J Biol Chem, 1995 Jun 16. PMID 7782346

See all (25) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
Submit: New GeneRIF Correction

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
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ22354, FLJ33829, FLJ43455, KIAA1091

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

  1. NG_053019.1 RefSeqGene

    Range
    4986..131511
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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

  1. 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

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

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    9138825..9265350 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    9223596..9350195 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6IQ26.2 GenPept UniProtKB/Swiss-Prot:Q6IQ26

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