DENND1A
DENN domain-containing protein 1A
Also known as: DEN1A_HUMAN, FAM31A, FLJ21129, KIAA1608
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q8TEH3
- Gene
- DENND1A
- Ensembl
- ENSG00000119522
- Chromosome
- 9
- Canonical length
- 1009 aa
- Protein class
- Disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
- Subcellular location
- Vesicles,Cytosol
OverviewNCBI Gene
Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).[supplied by OMIM, Nov 2010]
Canonical amino-acid sequenceUniProt
1009 residues, UniProt reviewed canonical sequence.
>Q8TEH3|DENND1A
1 MGSRIKQNPE TTFEVYVEVA YPRTGGTLSD PEVQRQFPED YSDQEVLQTL TKFCFPFYVD
61 SLTVSQVGQN FTFVLTDIDS KQRFGFCRLS SGAKSCFCIL SYLPWFEVFY KLLNILADYT
121 TKRQENQWNE LLETLHKLPI PDPGVSVHLS VHSYFTVPDT RELPSIPENR NLTEYFVAVD
181 VNNMLHLYAS MLYERRILII CSKLSTLTAC IHGSAAMLYP MYWQHVYIPV LPPHLLDYCC
241 APMPYLIGIH LSLMEKVRNM ALDDVVILNV DTNTLETPFD DLQSLPNDVI SSLKNRLKKV
301 STTTGDGVAR AFLKAQAAFF GSYRNALKIE PEEPITFCEE AFVSHYRSGA MRQFLQNATQ
361 LQLFKQFIDG RLDLLNSGEG FSDVFEEEIN MGEYAGSDKL YHQWLSTVRK GSGAILNTVK
421 TKANPAMKTV YKFAKDHAKM GIKEVKNRLK QKDIAENGCA PTPEEQLPKT APSPLVEAKD
481 PKLREDRRPI TVHFGQVRPP RPHVVKRPKS NIAVEGRRTS VPSPEQPQPY RTLRESDSAE
541 GDEAESPEQQ VRKSTGPVPA PPDRAASIDL LEDVFSNLDM EAALQPLGQA KSLEDLRAPK
601 DLREQPGTFD YQRLDLGGSE RSRGVTVALK LTHPYNKLWS LGQDDMAIPS KPPAASPEKP
661 SALLGNSLAL PRRPQNRDSI LNPSDKEEVP TPTLGSITIP RPQGRKTPEL GIVPPPPIPR
721 PAKLQAAGAA LGDVSERLQT DRDRRAALSP GLLPGVVPQG PTELLQPLSP GPGAAGTSSD
781 ALLALLDPLS TAWSGSTLPS RPATPNVATP FTPQFSFPPA GTPTPFPQPP LNPFVPSMPA
841 APPTLPLVST PAGPFGAPPA SLGPAFASGL LLSSAGFCAP HRSQPNLSAL SMPNLFGQMP
901 MGTHTSPLQP LGPPAVAPSR IRTLPLARSS ARAAETKQGL ALRPGDPPLL PPRPPQGLEP
961 TLQPSAPQQA RDPFEDLLQK TKQDVSPSPA LAPAPDSVEQ LRKQWETFELocalizationUniProt · AlphaFold · HPA
Whether an antibody against DENND1A 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
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.52
- Highest tissue expression
- 19 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 19 nTPM
- cerebral cortex: 15 nTPM
- spleen: 13 nTPM
- amygdala: 11 nTPM
- kidney: 11 nTPM
- skeletal muscle: 11 nTPM
Single-cell type
- neutrophils: 676 nCPM
- pituicytes/fscs: 548 nCPM
- neutrophil progenitors: 537 nCPM
- monocyte progenitors: 507 nCPM
- choroid plexus epithelial cells: 502 nCPM
- monocytes: 501 nCPM
Immune cell
- classical monocyte: 20 nTPM
- basophil: 14 nTPM
- neutrophil: 13 nTPM
- intermediate monocyte: 12 nTPM
- myeloid DC: 11 nTPM
- non-classical monocyte: 9.1 nTPM
Brain region
- cerebral cortex: 38 nTPM
- basal ganglia: 37 nTPM
- amygdala: 36 nTPM
- hippocampal formation: 36 nTPM
- midbrain: 32 nTPM
- hypothalamus: 32 nTPM
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)
- 0.23
- gnomAD pLI
- 1
- gnomAD missense Z
- 1.26
- DepMap mean gene effect
- -0.05
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
- guanyl-nucleotide exchange factor activity
- phosphatidylinositol phosphate binding
- phosphatidylinositol-3-phosphate binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of DENND1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads DENND1A as an antibody target. Whether an autoantibody or antibody against DENND1A could matter depends on whether native DENND1A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
DENND1A is annotated at the cell surface, where native DENND1A is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label DENND1A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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