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Protein

DENN domain-containing protein 1B

Gene

DENND1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells (PubMed:20154091, PubMed:20937701, PubMed:24520163, PubMed:26774822). Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form (PubMed:20154091, PubMed:20937701). Plays a role in clathrin-mediated endocytosis (PubMed:20154091). Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity (PubMed:26774822). Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells (PubMed:26774822).4 Publications

GO - Molecular functioni

  • Rab guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processProtein transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs

Names & Taxonomyi

Protein namesi
Recommended name:
DENN domain-containing protein 1BImported
Alternative name(s):
Connecdenn 21 Publication
Protein FAM31BImported
Gene namesi
Name:DENND1BImported
Synonyms:C1orf218Imported, FAM31BImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000213047.11
HGNCiHGNC:28404 DENND1B
MIMi613292 gene
neXtProtiNX_Q6P3S1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle

Pathology & Biotechi

Involvement in diseasei

Asthma (ASTHMA)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. Asthma susceptibility is probably caused by decreased TCR down-modulation and recycling in TH2 cells, causing prolonged TCR signaling and increased cytokine production in TH2 lymphocytes (PubMed:26774822).1 Publication
Disease descriptionThe most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi.
See also OMIM:600807

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi489K → A: Causes only a slight reduction in AP2B1-binding. 1 Publication1
Mutagenesisi500K → A: Greatly reduce AP2B1-binding. 1 Publication1
Mutagenesisi501R → A: No effect. 1 Publication1
Mutagenesisi502K → A: Almost completely abolishes AP2B1-binding. 1 Publication1
Mutagenesisi507R → A: No effect. 1 Publication1
Mutagenesisi509K → A: Greatly reduce AP2B1-binding. 1 Publication1

Keywords - Diseasei

Asthma

Organism-specific databases

DisGeNETi163486
MIMi600807 phenotype
OpenTargetsiENSG00000213047
PharmGKBiPA134951951

Polymorphism and mutation databases

BioMutaiDENND1B
DMDMi74749089

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003046741 – 775DENN domain-containing protein 1BAdd BLAST775

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei520PhosphotyrosineBy similarity1
Modified residuei535PhosphoserineBy similarity1
Modified residuei536PhosphoserineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei552PhosphoserineBy similarity1
Modified residuei652PhosphoserineCombined sources1
Modified residuei653PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ6P3S1
PaxDbiQ6P3S1
PeptideAtlasiQ6P3S1
PRIDEiQ6P3S1
ProteomicsDBi66926
66927 [Q6P3S1-2]
66928 [Q6P3S1-3]
66929 [Q6P3S1-4]
66930 [Q6P3S1-5]

PTM databases

iPTMnetiQ6P3S1
PhosphoSitePlusiQ6P3S1

Expressioni

Tissue specificityi

Highly expressed in dendritic and natural killer cells and at lower levels in other myeloid lineage cells and in pituitary. Significantly up-regulated in effector memory T-cells as compared with naive T-cells.1 Publication

Gene expression databases

BgeeiENSG00000213047 Expressed in 222 organ(s), highest expression level in blood
CleanExiHS_DENND1B
ExpressionAtlasiQ6P3S1 baseline and differential
GenevisibleiQ6P3S1 HS

Organism-specific databases

HPAiHPA042586

Interactioni

Subunit structurei

Interacts with RAB35 (PubMed:24520163, PubMed:22065758). Interacts with clathrin heavy chain/CLTC (PubMed:20154091). Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1 (PubMed:20154091). Interacts with CD3E (By similarity).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi127867, 3 interactors
IntActiQ6P3S1, 2 interactors
STRINGi9606.ENSP00000356366

Structurei

Secondary structure

1775
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6P3S1
SMRiQ6P3S1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini14 – 143uDENNPROSITE-ProRule annotationAdd BLAST130
Domaini180 – 316cDENNPROSITE-ProRule annotationAdd BLAST137
Domaini318 – 395dDENNPROSITE-ProRule annotationAdd BLAST78

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi398 – 402FXDXF motif1 Publication5
Motifi566 – 575Clathrin box1 Publication10

Domaini

The FXDXF motif mediates interaction the AP-2 complex.By similarity
The clathrin box motif mediates interaction with clathrin.By similarity

Phylogenomic databases

eggNOGiKOG3569 Eukaryota
ENOG410XT3N LUCA
GeneTreeiENSGT00760000118819
HOVERGENiHBG059209
InParanoidiQ6P3S1
KOiK20160
OMAiFAKSHAR
OrthoDBiEOG091G083L
TreeFamiTF320336

Family and domain databases

InterProiView protein in InterPro
IPR001194 cDENN_dom
IPR005112 dDENN_dom
IPR037516 Tripartite_DENN
IPR005113 uDENN_dom
PfamiView protein in Pfam
PF03455 dDENN, 1 hit
PF02141 DENN, 1 hit
PF03456 uDENN, 1 hit
SMARTiView protein in SMART
SM00801 dDENN, 1 hit
SM00799 DENN, 1 hit
SM00800 uDENN, 1 hit
PROSITEiView protein in PROSITE
PS50211 DENN, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 5 (identifier: Q6P3S1-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MDCRTKANPD RTFDLVLKVK CHASENEDPV VLWKFPEDFG DQEILQSVPK
60 70 80 90 100
FCFPFDVERV SQNQVGQHFT FVLTDIESKQ RFGFCRLTSG GTICLCILSY
110 120 130 140 150
LPWFEVYYKL LNTLADYLAK ELENDLNETL RSLYNHPVPK ANTPVNLSVN
160 170 180 190 200
QEIFIACEQV LKDQPALVPH SYFIAPDVTG LPTIPESRNL TEYFVAVDVN
210 220 230 240 250
NMLQLYASML HERRIVIISS KLSTLTACIH GSAALLYPMY WQHIYIPVLP
260 270 280 290 300
PHLLDYCCAP MPYLIGIHSS LIERVKNKSL EDVVMLNVDT NTLESPFSDL
310 320 330 340 350
NNLPSDVVSA LKNKLKKQST ATGDGVARAF LRAQAALFGS YRDALRYKPG
360 370 380 390 400
EPITFCEESF VKHRSSVMKQ FLETAINLQL FKQFIDGRLA KLNAGRGFSD
410 420 430 440 450
VFEEEITSGG FCGGNPRSYQ QWVHTVKKGG ALFNTAMTKA TPAVRTAYKF
460 470 480 490 500
AKNHAKLGLK EVKSKLKHKE NEEDYGTCSS SVQYTPVYKL HNEKGGNSEK
510 520 530 540 550
RKLAQARLKR PLKSLDGALY DDEDDDDIER ASKLSSEDGE EASAYLYESD
560 570 580 590 600
DSVETRVKTP YSGEMDLLGE ILDTLSTHSS DQGKLAAAKS LDFFRSMDDI
610 620 630 640 650
DYKPTNKSNA PSENNLAFLC GGSGDQAEWN LGQDDSALHG KHLPPSPRKR
660 670 680 690 700
VSSSGLTDSL FILKEENSNK HLGADNVSDP TSGLDFQLTS PEVSQTDKGK
710 720 730 740 750
TEKRETLSQI SDDLLIPGLG RHSSTFVPWE KEGKEAKETS EDIGLLHEVV
760 770
SLCHMTSDFQ QSLNISDKNT NGNQT
Length:775
Mass (Da):86,552
Last modified:March 16, 2016 - v2
Checksum:iED44D8F693DF3983
GO
Isoform 2 (identifier: Q6P3S1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-169: Missing.
     415-775: NPRSYQQWVH...SDKNTNGNQT → KDKLQYDYPFSQ

Show »
Length:406
Mass (Da):46,023
Checksum:iF447B1AC261D9D1C
GO
Isoform 3 (identifier: Q6P3S1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     150-169: Missing.
     310-315: ALKNKL → MKAIQW
     316-775: Missing.

Note: No experimental confirmation available.
Show »
Length:295
Mass (Da):33,701
Checksum:iAEE0F8F8B6791EF4
GO
Isoform 4 (identifier: Q6P3S1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MDCRTKANPDRTFDLVLKVKCHASENED → MAAAPREEKRWPQPVFSN
     150-169: Missing.
     415-775: NPRSYQQWVH...SDKNTNGNQT → KDKLQYDYPFSQ

Note: No experimental confirmation available.
Show »
Length:396
Mass (Da):44,901
Checksum:iEE50301A6487BABF
GO
Isoform 1 (identifier: Q6P3S1-5) [UniParc]FASTAAdd to basket
Also known as: DENND1B-S

The sequence of this isoform differs from the canonical sequence as follows:
     415-775: NPRSYQQWVH...SDKNTNGNQT → KDKLQYDYPFSQ

Show »
Length:426
Mass (Da):48,260
Checksum:i811670F3F2F6897F
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B3KR95B3KR95_HUMAN
DENN domain-containing protein 1B
DENND1B hCG_2039668
352Annotation score:
B7ZBL5B7ZBL5_HUMAN
DENN domain-containing protein 1B
DENND1B
147Annotation score:

Sequence cautioni

The sequence AAH74735 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA90918 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB15024 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAW91280 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti340S → Y in AAH22561 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035055216V → M. Corresponds to variant dbSNP:rs7546381Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0280821 – 28MDCRT…SENED → MAAAPREEKRWPQPVFSN in isoform 4. 1 PublicationAdd BLAST28
Alternative sequenceiVSP_028083150 – 169Missing in isoform 2, isoform 3 and isoform 4. 2 PublicationsAdd BLAST20
Alternative sequenceiVSP_028084310 – 315ALKNKL → MKAIQW in isoform 3. 1 Publication6
Alternative sequenceiVSP_028085316 – 775Missing in isoform 3. 1 PublicationAdd BLAST460
Alternative sequenceiVSP_034515415 – 775NPRSY…NGNQT → KDKLQYDYPFSQ in isoform 4, isoform 2 and isoform 1. 2 PublicationsAdd BLAST361

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL139136 Genomic DNA No translation available.
AL365258 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW91280.1 Sequence problems.
CH471067 Genomic DNA Translation: EAW91281.1
CH471067 Genomic DNA Translation: EAW91285.1
BC022561 mRNA Translation: AAH22561.1
BC063877 mRNA Translation: AAH63877.1
BC074735 mRNA Translation: AAH74735.2 Different initiation.
AL831839 mRNA Translation: CAD38548.1
AK000061 mRNA Translation: BAA90918.1 Different initiation.
AK024832 mRNA Translation: BAB15024.1 Different initiation.
BK006960 mRNA Translation: DAA12502.1
CCDSiCCDS41452.2 [Q6P3S1-5]
CCDS72996.1 [Q6P3S1-4]
CCDS72997.1 [Q6P3S1-1]
RefSeqiNP_001182144.1, NM_001195215.1 [Q6P3S1-1]
NP_001182145.1, NM_001195216.1
NP_001287787.1, NM_001300858.1 [Q6P3S1-4]
NP_659414.2, NM_144977.4 [Q6P3S1-5]
UniGeneiHs.125056
Hs.745032

Genome annotation databases

EnsembliENST00000235453; ENSP00000235453; ENSG00000213047 [Q6P3S1-4]
ENST00000367396; ENSP00000356366; ENSG00000213047 [Q6P3S1-5]
ENST00000620048; ENSP00000479816; ENSG00000213047 [Q6P3S1-1]
GeneIDi163486
KEGGihsa:163486
UCSCiuc001gue.4 human [Q6P3S1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL139136 Genomic DNA No translation available.
AL365258 Genomic DNA No translation available.
CH471067 Genomic DNA Translation: EAW91280.1 Sequence problems.
CH471067 Genomic DNA Translation: EAW91281.1
CH471067 Genomic DNA Translation: EAW91285.1
BC022561 mRNA Translation: AAH22561.1
BC063877 mRNA Translation: AAH63877.1
BC074735 mRNA Translation: AAH74735.2 Different initiation.
AL831839 mRNA Translation: CAD38548.1
AK000061 mRNA Translation: BAA90918.1 Different initiation.
AK024832 mRNA Translation: BAB15024.1 Different initiation.
BK006960 mRNA Translation: DAA12502.1
CCDSiCCDS41452.2 [Q6P3S1-5]
CCDS72996.1 [Q6P3S1-4]
CCDS72997.1 [Q6P3S1-1]
RefSeqiNP_001182144.1, NM_001195215.1 [Q6P3S1-1]
NP_001182145.1, NM_001195216.1
NP_001287787.1, NM_001300858.1 [Q6P3S1-4]
NP_659414.2, NM_144977.4 [Q6P3S1-5]
UniGeneiHs.125056
Hs.745032

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TW8X-ray2.10A/C1-410[»]
ProteinModelPortaliQ6P3S1
SMRiQ6P3S1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127867, 3 interactors
IntActiQ6P3S1, 2 interactors
STRINGi9606.ENSP00000356366

PTM databases

iPTMnetiQ6P3S1
PhosphoSitePlusiQ6P3S1

Polymorphism and mutation databases

BioMutaiDENND1B
DMDMi74749089

Proteomic databases

MaxQBiQ6P3S1
PaxDbiQ6P3S1
PeptideAtlasiQ6P3S1
PRIDEiQ6P3S1
ProteomicsDBi66926
66927 [Q6P3S1-2]
66928 [Q6P3S1-3]
66929 [Q6P3S1-4]
66930 [Q6P3S1-5]

Protocols and materials databases

DNASUi163486
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000235453; ENSP00000235453; ENSG00000213047 [Q6P3S1-4]
ENST00000367396; ENSP00000356366; ENSG00000213047 [Q6P3S1-5]
ENST00000620048; ENSP00000479816; ENSG00000213047 [Q6P3S1-1]
GeneIDi163486
KEGGihsa:163486
UCSCiuc001gue.4 human [Q6P3S1-1]

Organism-specific databases

CTDi163486
DisGeNETi163486
EuPathDBiHostDB:ENSG00000213047.11
GeneCardsiDENND1B
HGNCiHGNC:28404 DENND1B
HPAiHPA042586
MIMi600807 phenotype
613292 gene
neXtProtiNX_Q6P3S1
OpenTargetsiENSG00000213047
PharmGKBiPA134951951
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3569 Eukaryota
ENOG410XT3N LUCA
GeneTreeiENSGT00760000118819
HOVERGENiHBG059209
InParanoidiQ6P3S1
KOiK20160
OMAiFAKSHAR
OrthoDBiEOG091G083L
TreeFamiTF320336

Enzyme and pathway databases

ReactomeiR-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs

Miscellaneous databases

ChiTaRSiDENND1B human
GenomeRNAii163486
PROiPR:Q6P3S1
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000213047 Expressed in 222 organ(s), highest expression level in blood
CleanExiHS_DENND1B
ExpressionAtlasiQ6P3S1 baseline and differential
GenevisibleiQ6P3S1 HS

Family and domain databases

InterProiView protein in InterPro
IPR001194 cDENN_dom
IPR005112 dDENN_dom
IPR037516 Tripartite_DENN
IPR005113 uDENN_dom
PfamiView protein in Pfam
PF03455 dDENN, 1 hit
PF02141 DENN, 1 hit
PF03456 uDENN, 1 hit
SMARTiView protein in SMART
SM00801 dDENN, 1 hit
SM00799 DENN, 1 hit
SM00800 uDENN, 1 hit
PROSITEiView protein in PROSITE
PS50211 DENN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDEN1B_HUMAN
AccessioniPrimary (citable) accession number: Q6P3S1
Secondary accession number(s): B5MD89
, D3PFD5, Q5T3B8, Q5T3B9, Q5T3C1, Q5TAI8, Q6B0I8, Q8NDT1, Q8TBE6, Q9H774, Q9NXU2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: March 16, 2016
Last modified: September 12, 2018
This is version 124 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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