DENND5A

Protein identityUniProt · HPA

UniProt accession

Q6IQ26

Gene

DENND5A

Ensembl

ENSG00000184014

Chromosome

11

Canonical length

1287 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Golgi apparatus,Vesicles

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1287 residues, UniProt reviewed canonical sequence.

>Q6IQ26|DENND5A
     1  MSGGGGGGGS APSRFADYFV ICGLDTETGL EPDELSALCQ YIQASKARDG ASPFISSTTE
    61  GENFEQTPLR RTFKSKVLAR YPENVEWNPF DQDAVGMLCM PKGLAFKTQA DPREPQFHAF
   121  IITREDGSRT FGFALTFYEE VTSKQICSAM QTLYHMHNAE YDVLHAPPAD DRDQSSMEDG
   181  EDTPVTKLQR FNSYDISRDT LYVSKCICLI TPMSFMKACR SVLEQLHQAV TSPQPPPLPL
   241  ESYIYNVLYE VPLPPPGRSL KFSGVYGPII CQRPSTNELP LFDFPVKEVF ELLGVENVFQ
   301  LFTCALLEFQ ILLYSQHYQR LMTVAETITA LMFPFQWQHV YVPILPASLL HFLDAPVPYL
   361  MGLHSNGLDD RSKLELPQEA NLCFVDIDNH FIELPEDLPQ FPNKLEFVQE VSEILMAFGI
   421  PPEGNLHCSE SASKLKRLRA SELVSDKRNG NIAGSPLHSY ELLKENETIA RLQALVKRTG
   481  VSLEKLEVRE DPSSNKDLKV QCDEEELRIY QLNIQIREVF ANRFTQMFAD YEVFVIQPSQ
   541  DKESWFTNRE QMQNFDKASF LSDQPEPYLP FLSRFLETQM FASFIDNKIM CHDDDDKDPV
   601  LRVFDSRVDK IRLLNVRTPT LRTSMYQKCT TVDEAEKAIE LRLAKIDHTA IHPHLLDMKI
   661  GQGKYEPGFF PKLQSDVLST GPASNKWTKR NAPAQWRRKD RQKQHTEHLR LDNDQREKYI
   721  QEARTMGSTI RQPKLSNLSP SVIAQTNWKF VEGLLKECRN KTKRMLVEKM GREAVELGHG
   781  EVNITGVEEN TLIASLCDLL ERIWSHGLQV KQGKSALWSH LLHYQDNRQR KLTSGSLSTS
   841  GILLDSERRK SDASSLMPPL RISLIQDMRH IQNIGEIKTD VGKARAWVRL SMEKKLLSRH
   901  LKQLLSDHEL TKKLYKRYAF LRCDDEKEQF LYHLLSFNAV DYFCFTNVFT TILIPYHILI
   961  VPSKKLGGSM FTANPWICIS GELGETQIMQ IPRNVLEMTF ECQNLGKLTT VQIGHDNSGL
  1021  YAKWLVEYVM VRNEITGHTY KFPCGRWLGK GMDDGSLERI LVGELLTSQP EVDERPCRTP
  1081  PLQQSPSVIR RLVTISPNNK PKLNTGQIQE SIGEAVNGIV KHFHKPEKER GSLTLLLCGE
  1141  CGLVSALEQA FQHGFKSPRL FKNVFIWDFL EKAQTYYETL EKNEVVPEEN WHTRARNFCR
  1201  FVTAINNTPR NIGKDGKFQM LVCLGARDHL LHHWIALLAD CPITAHMYED VALIKDHTLV
  1261  NSLIRVLQTL QEFNITLETS LVKGIDI

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DENND5A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

68 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DENND5A.

Disease | AllUniProt

Conditions DENND5A is implicated in, by any mechanism.

• Developmental and epileptic encephalopathy 49 (DEE49) MIM:617281

Disease | GeneticClinVar

32 pathogenic / likely-pathogenic of 760 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy, 49
• DENND5A-related disorder
• Bilateral frontoparietal polymicrogyria

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.38

gnomAD pLI

0.06

gnomAD missense Z

2.38

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of neuron projection development
• retrograde transport, endosome to Golgi

Molecular functions

• guanyl-nucleotide exchange factor activity
• small GTPase binding

Cellular components

• cytosol
• Golgi membrane
• trans-Golgi network

Protein domainsUniProt · Pfam · InterPro

• PLAT/LH2 domain
• cDENN domain
• RUN domain
• dDENN domain
• uDENN domain
• PLAT/LH2 domain superfamily
• RUN domain superfamily
• Tripartite DENN domain
• DENN domain, C-terminal lobe
• DENN domain-containing protein 5A/B, PLAT/LH2 domain
• DENN domain-containing protein 5A/B
• PLAT/LH2 domain
• DENN (AEX-3) domain
• RUN domain
• dDENN domain
• uDENN domain
• DENN domain-containing protein 5A, first RUN domain
• DENN domain-containing protein 5A, second RUN domain

KeywordsUniProt

• Epilepsy
• Golgi apparatus
• Guanine-nucleotide releasing factor
• Membrane
• Phosphoprotein
• Repeat

InteractionsUniProt · HPA

Protein binding partners of DENND5A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SNX1