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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

DENND1B Gene

protein-coding GIFtS: 43
GCID: GC01M197473

DENN/MADD domain containing 1B

(Previous names: family with sequence similarity 31, member B, chromosome...)
(Previous symbols: FAM31B, C1orf218)

Explore 4 diseases affiliated with
DENND1B via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
DENN/MADD Domain Containing 1B¹ ²		MGC27044¹
FAM31B¹ ² ³ ⁵		Chromosome 1 Open Reading Frame 218¹
C1orf218¹ ² ³		C1ORF18²
Family With Sequence Similarity 31, Member B¹ ²		DENN Domain-Containing Protein 1B²
Connecdenn 2² ³		Protein FAM31B³
FLJ20054¹		C1orf18⁵

External Ids:	HGNC: 28404¹	Entrez Gene: 163486²	Ensembl: ENSG00000213047⁷	OMIM: 613292⁵	UniProtKB: Q6P3S1³

Export aliases for DENND1B gene to outside databases

Previous GC identifers: GC01M194253 GC01M195746 GC01M195788 GC01M168677

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for DENND1B:

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)

UniProtKB/Swiss-Prot: DEN1B_HUMAN, Q6P3S1

Function: Guanine nucleotide exchange factor (GEF) for RAB35. Promotes the exchange of GDP to GTP, converting inactive

GDP-bound RAB35 into its active GTP-bound form. May play a role in clathrin-mediated endocytosis

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000001.10 NC_018912.1 NT_004487.19

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the DENND1B gene promoter:
STAT1 STAT4 Nkx2-2 STAT1beta NF-kappaB STAT1alpha C/EBPalpha STAT2 STAT3 NF-kappaB1
Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids

Search SABiosciences Chromatin IP Primers for DENND1B

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat DENND1B

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 1q31.3 Ensembl cytogenetic band: 1q31.3 HGNC cytogenetic band: 1q31.3

DENND1B Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
DENND1B gene location

GeneLoc information about chromosome 1 GeneLoc Exon Structure

GeneLoc location for GC01M197473: view genomic region (about GC identifiers)

Start:	197,473,878 bp from pter	End:	197,744,826 bp from pter
Size:	270,949 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: DEN1B_HUMAN, Q6P3S1 (See protein sequence)

Recommended Name: DENN domain-containing protein 1B

Size: 426 amino acids; 48260 Da

Subunit: Interacts with RAB35. Interacts with clathrin heavy chain/CLTC and with AP2A2. Isoform 5 interacts with AP2B1

Subcellular location: Cytoplasm, cytosol (By similarity). Cytoplasmic vesicle, clathrin-coated vesicle (By similarity)

Sequence caution: Sequence=AAH74735.2; Type=Erroneous initiation; Note=Translation N-terminally extended;

Sequence=BAA90918.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAB15024.1;

Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=EAW91280.1; Type=Erroneous gene model

prediction;

1 PDB 3D structure from and Proteopedia for DENND1B:

3TW8 (3D)

Secondary accessions: B5MD89 D3PFD5 Q5T3B8 Q5T3B9 Q5T3C1 Q5TAI8 Q6B0I8 Q8NDT1 Q8TBE6 Q9H774 Q9NXU2

Alternative splicing: 5 isoforms: Q6P3S1-1 Q6P3S1-2 Q6P3S1-3 Q6P3S1-4 Q6P3S1-5 (Mutations at Lys-502 almost completely abolishes AP2B1-binding, mutations at Lys-500 and Lys-509 greatly reduce AP2B1-binding. Mutations at Lys-489 causes only a slight reduction in AP2B1-binding, while mutations at Arg-501 or Arg-507 have no effect. Ref.9 (DAA12502) sequence is in conflict in position: 664:K->R. Contains a phosphoserine at position 652)

Explore the universe of human proteins at neXtProt for DENND1B: NX_Q6P3S1

Post-translational modifications:

Isoform 5 is phosphorylated on Tyr-475, Tyr-484, Ser-514 and Ser-652¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q6P3S1

DENND1B Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_001182144.1 NP_001182145.1 NP_659414.2

ENSEMBL proteins:

ENSP00000375839 ENSP00000294737 ENSP00000235453 ENSP00000356366 ENSP00000410025

ENSP00000383751

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	Uscn Proteins for DENND1B

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005829	cytosol	IEA	--
GO:0030136	clathrin-coated vesicle	IEA	--

DENND1B for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for DENND1B

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

DENND1B for domains About GeneDecksing

3 InterPro domains/families:

IPR005113 uDENN_dom

IPR005112 dDENN_dom

IPR001194 DENN_dom

Graphical View of Domain Structure for InterPro Entry Q6P3S1

ProtoNet protein and cluster: Q6P3S1

UniProtKB/Swiss-Prot: DEN1B_HUMAN, Q6P3S1

Similarity: Contains 1 dDENN domain

Similarity: Contains 1 DENN domain

Similarity: Contains 1 uDENN domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: DEN1B_HUMAN, Q6P3S1

Function: Guanine nucleotide exchange factor (GEF) for RAB35. Promotes the exchange of GDP to GTP, converting inactive

GDP-bound RAB35 into its active GTP-bound form. May play a role in clathrin-mediated endocytosis

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Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005085	guanyl-nucleotide exchange factor activity	--	--
GO:0017112	Rab guanyl-nucleotide exchange factor activity	IDA	--

DENND1B for ontologies About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

Search SABiosciences Gene Network Central^TM Interacting Genes and Proteins Networks for DENND1B

Gene Ontology (GO): 1 biological process term (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0015031	protein transport	IEA	--

DENND1B for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for DENND1B
Search CenterWatch for drugs/clinical trials and news about DENND1B / DEN1B

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for DENND1B gene (5 alternative transcripts):

NM_001142795.1 NM_019049.1 NM_001195215.1 NM_001195216.1 NM_144977.4

Unigene Clusters for DENND1B:

DENN/MADD domain containing 1B

Hs.125056 [show with all ESTs], Hs.743766 [show with all ESTs]

Unigene Representative Sequences: NM_001195215, AK024832

12 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000391979(uc021pgu.1 uc010ppf.2) ENST00000294737 ENST00000463124

ENST00000235453(uc001gue.3) ENST00000367396(uc001guf.3) ENST00000496935(uc001gug.4)

ENST00000422998 ENST00000294738 ENST00000468589(uc021pgv.1) ENST00000495550

ENST00000477581 ENST00000400967

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		8/113 QIAGEN miScript miRNA Assays for microRNAs that regulate DENND1B (see all 113):
		hsa-miR-548j hsa-miR-579 hsa-miR-520f hsa-miR-15a hsa-miR-128 hsa-miR-938 hsa-miR-374a hsa-miR-3653

		SwitchGear 3'UTR luciferase reporter plasmids (see all 2): DENND1B 3' UTR sequence

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Additional cDNA sequence:

AK024832.1 BC074735.2

10 DOTS entries:

DT.211363 DT.309530 DT.100016665 DT.91863843 DT.100657727 DT.40221209 DT.99932909 DT.102826067

DT.95147979 DT.95190205

24/57 AceView cDNA sequences (see all 57):

CD243988 AI480253 BC074735 AL831839 AK091207 BC063456 BC063877 AA809946

AI948992 CR622563 AX746849 BC016588 NM_019049 BX356941 AK000061 NM_144977

R81505 AI636062 CF552552 BG287134 BC022561 CB962211 AA171951 BI759326

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

DENND1B expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TCAAGTCACC

About this image
See DENND1B Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for DENND1B

SOURCE GeneReport for Unigene clusters: Hs.125056 Hs.743766

UniProtKB/Swiss-Prot: DEN1B_HUMAN, Q6P3S1

Tissue specificity: 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

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for DENND1B gene from 5/19 species (see all 19) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	DENND1B¹	DENN/MADD domain containing 1B	75.71(n) 76.01(a)		424351 XM_422194.3 XP_422194.3
lizard (Anolis carolinensis)	Reptilia	DENND1B⁶ DENND1A⁶	--	44(a) 10(a)	1 ↔ 1 possible ortholog	GL343432.1(504020-631741) GL344112.1(17882-67755)
zebrafish (Danio rerio)	Actinopterygii	dennd1b¹	DENN/MADD domain containing 1B	62.21(n) 61.87(a)		560720 XM_684120.5 XP_689212.5
fruit fly (Drosophila melanogaster)	Insecta	CG18659⁶	--	17(a)	possible ortholog	2R(5010809-5019486)
worm (Caenorhabditis elegans)	Secernentea	rme-4⁶	Receptor Mediated Endocytosis family member (rme-4...	20(a)	possible ortholog	X(10373170-10377692)

ENSEMBL Gene Tree for DENND1B (if available)
TreeFam Gene Tree for DENND1B (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for DENND1B gene

ST5² DENND5A² DENND2D² DENND2A² DENND3² DENND4A² DENND1C² DENND4B²

DENND1A² DENND5B² DENND4C² DENND2C²

3 SIMAP similar genes for DENND1B using alignment to 5 protein entries: DEN1B_HUMAN (see all proteins):

DENND1A DENND1C ST5

DENND1B for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 1 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs182889454^1,2		--	197473384(+)	`AATAAG/TAAAGG`	1	--	int¹		0	--	--	--	--
rs13375098^1,2	C,F,H,	--	197473403(+)	`ATTAAT/ACCCAG`	1	--	int¹		7		NS EA WA CSA	538
rs141000398^1,2		--	197473423(+)	`ACCCAC/GAGGGA`	1	--	int¹		0	--	--	--	--
rs186170802^1,2		--	197473553(+)	`TTTCAC/TCTCTG`	1	--	int¹		0	--	--	--	--
rs201075702^1,2		--	197473963(+)	`GCATA-/TTTTTT`	1	--	ut3¹		0	--	--	--	--
rs1024920^1,2	C,F,A,H,	--	197473969(-)	`TTTTTA/TAAAAA`	1	--	ut3¹		12		NS EA NA WA	786
rs78494700^1,2		--	197474238(+)	`CTTTAC/TGCATT`	1	--	ut3¹		0	--	--	--	--
rs191413291^1,2		--	197474381(+)	`AAGTTA/GCACTG`	1	--	ut3¹		0	--	--	--	--
rs7553327^1,2	C,F,H,	--	197474565(+)	`AAAGAG/AGTAAT`	1	--	ut3¹		21		NS EA NA WA CSA	1358
rs59091965^1,2		--	197474642(+)	`ACATAA/GCATTC`	1	--	ut3¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for DENND1B (197473878 - 197723878 bp, first 250kb of DENND1B)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 11 variations for DENND1B
8 CNVs: 23346 43500 97606 34752 60919 1022 43753 39026
3 Indels: 84779 84778 74851

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing DENND1B

DNA2.0 Custom Variant and Variant Library Synthesis for DENND1B

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

DENND1B for disorders           About GeneDecksing

OMIM gene information: 613292    OMIM disorders: --

4 diseases for DENND1B:    About MalaCards

primary biliary cirrhosis crohn's disease asthma obesity

Human Genome Epidemiology (HuGE) Navigator: DENND1B (4 documents)

Export disorders for DENND1B gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for DENND1B gene, integrated from 9 sources (see all 18):
(articles sorted by number of sources associating them with DENND1B)

Utopia: connect your pdf to the dynamic
world of online information

Insights regarding guanine nucleotide exchange from t he structure of a DENN-domain protein complexed with its Rab GTPase substrate. (PubMed id 22065758)^{1, 2} Wu X....Reinisch K.M. (2011)
The connecdenn family: Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery. (PubMed id 20154091)^{1, 2} Marat A.L. and McPherson P.S. (2010)
Variants of DENND1B associated with asthma in childre n. (PubMed id 20032318)^{1, 2} Sleiman P.M....Hakonarson H. (2010)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)
Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PubMed id 12477932)^{1, 3} Strausberg R.L....Marra M.A. (2002)
Genome-wide association study identifies 12 new susce ptibility loci for primary biliary cirrhosis. (PubMed id 21399635)¹ Mells G.F....Anderson C.A. (2011)
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. (PubMed id 21102463)¹ Franke A....Parkes M. (2010)
Analyses of shared genetic factors between asthma and obesity in children. (PubMed id 20816195)¹ MelAcn E....Lasky-Su J. (2010)
Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors. (PubMed id 20937701)² Yoshimura S.... Barr F.A. (2010)
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. (PubMed id 19690332)² Mayya V.... Han D.K. (2009)

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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 163486	HGNC: 28404	AceView: FLJ20054	Ensembl:ENSG00000213047	euGenes: HUgn163486
ECgene: DENND1B	H-InvDB: DENND1B

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for DENND1B	Pharmacogenomics, SNPs, Pathways

Intellectual Property for DENND1B gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for DENND1B gene:
Search GeneIP for patents involving DENND1B

GeneCards and IP:
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(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
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DENN/MADD domain containing 1B

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