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DENND1B DENN domain containing 1B [ Homo sapiens (human) ]

Gene ID: 163486, updated on 3-Apr-2024

Summary

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Official Symbol
DENND1Bprovided by HGNC
Official Full Name
DENN domain containing 1Bprovided by HGNC
Primary source
HGNC:HGNC:28404
See related
Ensembl:ENSG00000213047 MIM:613292; AllianceGenome:HGNC:28404
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FAM31B; C1ORF18; C1orf218
Summary
Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1B, 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]
Expression
Ubiquitous expression in colon (RPKM 1.5), thyroid (RPKM 1.4) and 25 other tissues See more
Orthologs
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Genomic context

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See DENND1B in Genome Data Viewer
Location:
1q31.3
Exon count:
29
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (197504748..197782150, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (196766532..197041541, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (197473878..197744610, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904477 Neighboring gene crumbs cell polarity complex component 1 Neighboring gene mitochondrial ribosomal protein S21 pseudogene 3 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:197541395-197542594 Neighboring gene MPRA-validated peak643 silencer Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 32 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1661 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1662 Neighboring gene Sharpr-MPRA regulatory region 12429 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2276 Neighboring gene RPL24 pseudogene 5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197757007-197757507 Neighboring gene family with sequence similarity 204 member B, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197769368-197770108 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:197771590-197772329 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:197779872-197780608 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:197782608-197783566 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr1:197783567-197784524 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:197859970-197860527 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1663 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1664 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197887073-197887799 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:197890605-197891127 Neighboring gene chromosome 1 open reading frame 53 Neighboring gene LIM homeobox 9

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. Variation at DENND1B and Asthma on the Island of Tristan da Cunha. Duffy DL, et al. Twin Res Hum Genet, 2019 Oct. PMID 31608842
  2. Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children. Fiuza BSD, et al. Mol Immunol, 2017 Oct. PMID 28668455
  3. DENND1B gene variants associate with elevated exhaled nitric oxide in healthy high-risk neonates. Chawes BL, et al. Pediatr Pulmonol, 2015 Feb. PMID 24347560
  4. Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors. Kulasekaran G, et al. J Biol Chem, 2015 Jul 17. PMID 26055712, Free PMC Article
  5. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. Wu X, et al. Proc Natl Acad Sci U S A, 2011 Nov 15. PMID 22065758, Free PMC Article

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Variation at DENND1B and Asthma on the Island of Tristan da Cunha.
    Title: Variation at DENND1B and Asthma on the Island of Tristan da Cunha.
  2. polymorphisms in the DENND1B are significantly associated with development of asthma and atopy and these polymorphisms can influence DENND1B expression and consequently, asthma.
    Title: Polymorphisms in DENND1B gene are associated with asthma and atopy phenotypes in Brazilian children.
  3. Study reveals a previously unrecognized mechanism by which DENND1B regulates surface TCR dynamics to fine-tune TH2 cell signaling and effector functions. Dennd1b-/- TH2 cells exhibit delayed TCR downmodulation following TCR activation that is associated with enhanced TCR signaling and greater transcriptional activation and secretion of TH2-associated cytokines.
    Title: Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease.
  4. Increased fraction of exhaled nitric oxide in healthy newborns seems strongly influenced by genetics including father's atopy and child's variants in the DENND1B locus at chromosome 1q31.3.
    Title: DENND1B gene variants associate with elevated exhaled nitric oxide in healthy high-risk neonates.
  5. The guanine nucleotide exchange factor activity of connecdenn 1 and 2 are autoinhibited, and this is regulated by Akt activation downstream of insulin stimulation.
    Title: Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors.
  6. Data indicate that folliculin-CT is structurally similar to the DENN domain of DENND1B.
    Title: Crystal structure of folliculin reveals a hidDENN function in genetically inherited renal cancer.
  7. analysis of DENND1B-S complexed with its substrate Rab35
    Title: Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.
  8. Observational study of gene-disease association. (HuGE Navigator)
    Title: Analyses of shared genetic factors between asthma and obesity in children.
  9. We have identified a locus containing DENND1B on chromosome 1q31.3 that is associated with susceptibility to asthma.
    Title: Variants of DENND1B associated with asthma in children.
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

EBI GWAS Catalog

Description
Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling.
EBI GWAS Catalog
Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
EBI GWAS Catalog
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
EBI GWAS Catalog
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog
Variants of DENND1B associated with asthma in children.
EBI GWAS Catalog

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

  • FLJ20054, FLJ21179, FLJ33888, MGC27044, MGC103810, DKFZp547O0715

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables guanyl-nucleotide exchange factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables phosphatidylinositol phosphate binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables small GTPase binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in T cell receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in T cell receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in endocytic recycling IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in endocytic recycling ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in endocytosis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of T-helper 2 cell cytokine production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein transport IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in clathrin-coated vesicle IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in intracellular membrane-bounded organelle IBA
Inferred from Biological aspect of Ancestor
more info
  
is_active_in nuclear speck IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nuclear speck IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
DENN domain-containing protein 1B
Names
DENN/MADD domain containing 1B
connecdenn 2
family with sequence similarity 31, member B

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.

mRNA and Protein(s)

  1. NM_001195215.2 → NP_001182144.1  DENN domain-containing protein 1B isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
    Source sequence(s)
    AI692985, AK093982, AL139136, BC074735, BK006960, BP220095, DA495773
    Consensus CDS
    CCDS72997.1
    UniProtKB/Swiss-Prot
    B5MD89, D3PFD5, Q5T3B8, Q5T3B9, Q5T3C1, Q5TAI8, Q6B0I8, Q6P3S1, Q8NDT1, Q8TBE6, Q9H774, Q9NXU2
    Related
    ENSP00000479816.1, ENST00000620048.6
    Conserved Domains (3) summary
    smart00801
    Location:323 → 388
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:94 → 291
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:9 → 89
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  2. NM_001195216.2 → NP_001182145.1  DENN domain-containing protein 1B isoform 4

    See identical proteins and their annotated locations for NP_001182145.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR, compared to variant 3. The resulting isoform (4) has a distinct C-terminus and is shorter than isoform 3.
    Source sequence(s)
    BC063456, DA495773
    UniProtKB/Swiss-Prot
    Q6P3S1
    Related
    ENST00000468589.5

  3. NM_001300858.2 → NP_001287787.1  DENN domain-containing protein 1B isoform 5

    See identical proteins and their annotated locations for NP_001287787.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (5) contains multiple differences at the 5' and 3' ends, compared to variant 3, including initiation of translation at an alternate start codon. The resulting isoform (5) has distinct N- and C-termini and is shorter than isoform 3.
    Source sequence(s)
    AL139136, BC022561, BC063877, DA495773
    Consensus CDS
    CCDS72996.1
    UniProtKB/Swiss-Prot
    Q6P3S1
    Related
    ENSP00000235453.4, ENST00000235453.8
    Conserved Domains (3) summary
    smart00801
    Location:293 → 358
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:84 → 261
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:11 → 79
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  4. NM_144977.5 → NP_659414.2  DENN domain-containing protein 1B isoform 2

    See identical proteins and their annotated locations for NP_659414.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 3. The resulting isoform (2) has a distinct C-terminus and is shorter than isoform 3.
    Source sequence(s)
    AL139136, BC063877, DA495773
    Consensus CDS
    CCDS41452.2
    UniProtKB/Swiss-Prot
    Q6P3S1
    Related
    ENSP00000356366.3, ENST00000367396.7
    Conserved Domains (3) summary
    smart00801
    Location:323 → 388
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:94 → 291
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:9 → 89
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

RNA

  1. NR_125340.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (6) lacks three alternate internal exons, compared to variant 3. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 3, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AI692985, AK091207, AK093982, AL139136, BC074735, BK006960, DA495773

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_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    197504748..197782150 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011509248.3 → XP_011507550.1  DENN domain-containing protein 1B isoform X2

    Conserved Domains (3) summary
    smart00801
    Location:336 → 401
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:107 → 304
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:22 → 102
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  2. XM_047447711.1 → XP_047303667.1  DENN domain-containing protein 1B isoform X7

  3. XM_005244931.3 → XP_005244988.1  DENN domain-containing protein 1B isoform X5

    See identical proteins and their annotated locations for XP_005244988.1

    Conserved Domains (3) summary
    smart00801
    Location:303 → 368
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:94 → 271
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:9 → 89
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  4. XM_024453626.2 → XP_024309394.1  DENN domain-containing protein 1B isoform X7

    Conserved Domains (2) summary
    smart00801
    Location:122 → 187
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:1 → 90
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN

  5. XM_011509249.3 → XP_011507551.1  DENN domain-containing protein 1B isoform X4

    See identical proteins and their annotated locations for XP_011507551.1

    Conserved Domains (3) summary
    smart00801
    Location:313 → 378
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:84 → 281
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:11 → 79
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  6. XM_011509247.2 → XP_011507549.1  DENN domain-containing protein 1B isoform X3

    Conserved Domains (3) summary
    smart00801
    Location:351 → 416
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:142 → 319
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:57 → 137
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  7. XM_011509246.3 → XP_011507548.1  DENN domain-containing protein 1B isoform X1

    Conserved Domains (3) summary
    smart00801
    Location:371 → 436
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:142 → 339
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:57 → 137
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  8. XM_047447700.1 → XP_047303656.1  DENN domain-containing protein 1B isoform X6

  9. XM_047447715.1 → XP_047303671.1  DENN domain-containing protein 1B isoform X8

  10. XM_006711194.4 → XP_006711257.1  DENN domain-containing protein 1B isoform X9

    Conserved Domains (1) summary
    smart00801
    Location:17 → 82
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins

  11. XM_047447731.1 → XP_047303687.1  DENN domain-containing protein 1B isoform X13

    Related
    ENSP00000294737.7, ENST00000294737.11

  12. XM_047447730.1 → XP_047303686.1  DENN domain-containing protein 1B isoform X12

  13. XM_011509251.4 → XP_011507553.1  DENN domain-containing protein 1B isoform X10

    Conserved Domains (3) summary
    smart00801
    Location:371 → 434
    dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
    smart00799
    Location:142 → 339
    DENN; Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN
    smart00800
    Location:57 → 137
    uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins

  14. XM_047447726.1 → XP_047303682.1  DENN domain-containing protein 1B isoform X11

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    196766532..197041541 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054334715.1 → XP_054190690.1  DENN domain-containing protein 1B isoform X2

  2. XM_054334721.1 → XP_054190696.1  DENN domain-containing protein 1B isoform X7

  3. XM_054334718.1 → XP_054190693.1  DENN domain-containing protein 1B isoform X5

  4. XM_054334716.1 → XP_054190691.1  DENN domain-containing protein 1B isoform X3

  5. XM_054334714.1 → XP_054190689.1  DENN domain-containing protein 1B isoform X1

  6. XM_054334720.1 → XP_054190695.1  DENN domain-containing protein 1B isoform X7

  7. XM_054334717.1 → XP_054190692.1  DENN domain-containing protein 1B isoform X4

  8. XM_054334719.1 → XP_054190694.1  DENN domain-containing protein 1B isoform X6

  9. XM_054334722.1 → XP_054190697.1  DENN domain-containing protein 1B isoform X8

  10. XM_054334723.1 → XP_054190698.1  DENN domain-containing protein 1B isoform X9

  11. XM_054334727.1 → XP_054190702.1  DENN domain-containing protein 1B isoform X13

  12. XM_054334726.1 → XP_054190701.1  DENN domain-containing protein 1B isoform X12

  13. XM_054334724.1 → XP_054190699.1  DENN domain-containing protein 1B isoform X10

  14. XM_054334725.1 → XP_054190700.1  DENN domain-containing protein 1B isoform X11

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001142795.1: Suppressed sequence

    Description
    NM_001142795.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

  2. NM_019049.1: Suppressed sequence

    Description
    NM_019049.1: This RefSeq was suppressed because the CDS was partial.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6P3S1.2 GenPept UniProtKB/Swiss-Prot:Q6P3S1

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