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    DENND2B DENN domain containing 2B [ Homo sapiens (human) ]

    Gene ID: 6764, updated on 5-Mar-2024

    Summary

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    Official Symbol
    DENND2Bprovided by HGNC
    Official Full Name
    DENN domain containing 2Bprovided by HGNC
    Primary source
    HGNC:HGNC:11350
    See related
    Ensembl:ENSG00000166444 MIM:140750; AllianceGenome:HGNC:11350
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ST5; HTS1; p126
    Summary
    This gene was identified by its ability to suppress the tumorigenicity of Hela cells in nude mice. The protein encoded by this gene contains a C-terminal region that shares similarity with the Rab 3 family of small GTP binding proteins. This protein preferentially binds to the SH3 domain of c-Abl kinase, and acts as a regulator of MAPK1/ERK2 kinase, which may contribute to its ability to reduce the tumorigenic phenotype in cells. Three alternatively spliced transcript variants of this gene encoding distinct isoforms are identified. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in endometrium (RPKM 30.7), testis (RPKM 16.0) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    11p15.4
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (8693352..8910951, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (8775106..8995121, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (8714899..8932498, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4389 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4390 Neighboring gene Sharpr-MPRA regulatory region 3983 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:8719729-8720516 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:8720517-8721302 Neighboring gene small nucleolar RNA, H/ACA box 3A Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:8723665-8724450 Neighboring gene small nucleolar RNA, H/ACA box 3B Neighboring gene ribosomal protein L27a Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:8731697-8732198 Neighboring gene uncharacterized LOC107984308 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8780393-8780893 Neighboring gene DENND2B antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4392 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8827143-8827644 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8827645-8828144 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:8850107-8850606 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:8853387-8854188 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:8854189-8854989 Neighboring gene RNA, 5S ribosomal pseudogene 330 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8884480-8884980 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8884981-8885481 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3116 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4395 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8946857-8947641 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:8947642-8948425 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:8954113-8954951 Neighboring gene chromosome 11 open reading frame 16 Neighboring gene A-kinase interacting protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4396 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4397 Neighboring gene achaete-scute family bHLH transcription factor 3

    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. Deletion of the COOH terminus converts the ST5 p70 protein from an inhibitor of RAS signaling to an activator with transforming activity in NIH-3T3 cells. Majidi M, et al. J Biol Chem, 2000 Mar 3. PMID 10692462
    2. Expression of an isoform of the novel signal transduction protein ST5 is linked to cell morphology. Hubbs AE, et al. Oncogene, 1999 Apr 15. PMID 10229203
    3. Differential expression of the human ST5 gene in HeLa-fibroblast hybrid cell lines mediated by YY1: evidence that YY1 plays a part in tumor suppression. Lichy JH, et al. Nucleic Acids Res, 1996 Dec 1. PMID 8972856, Free PMC Article
    4. Identification of a human chromosome 11 gene which is differentially regulated in tumorigenic and nontumorigenic somatic cell hybrids of HeLa cells. Lichy JH, et al. Cell Growth Differ, 1992 Aug. PMID 1390339
    5. DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior. Ioannou MS, et al. J Cell Biol, 2015 Mar 2. PMID 25713415, Free PMC Article

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. DENND2B activates Rab35 at the intercellular bridge, regulating cytokinetic abscission and tetraploidy.
      Title: DENND2B activates Rab35 at the intercellular bridge, regulating cytokinetic abscission and tetraploidy.
    2. Findings provide evidence of suppression of tumorigenicity 5 (ST5) involvement in positive regulation of osteoclastogenesis via src Kinases (Src)/Syk Kinase (Syk)/calcium signaling.
      Title: ST5 Positively Regulates Osteoclastogenesis via Src/Syk/calcium Signaling Pathways.
    3. Here, we discover that intersectin-s binds DENND2B, a guanine nucleotide exchange factor for the exocytic GTPase Rab13, and this interaction promotes recycling of ligand-free EGFR to the cell surface. Our study thus reveals a novel mechanism controlling the fate of internalized EGFR with important implications for cancer.
      Title: Intersectin-s interaction with DENND2B facilitates recycling of epidermal growth factor receptor.
    4. DENND2B interacts with the Rab13 effector MICAL-L2 at the cell periphery, and this interaction is required for the dynamic remodeling of the cell's leading edge.
      Title: DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior.
    5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    6. Using RNA in situ hybridisation in mouse, the authors found that St5 is expressed in the frontal cortex during embryonic development. In adult mouse brain, expression of St5 was especially high in the hippocampal area and cerebellum.
      Title: Disruption of ST5 is associated with mental retardation and multiple congenital anomalies.
    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
    Genome-wide association analyses identify variants in developmental genes associated with hypospadias.
    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

    • MGC33090

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in positive regulation of ERK1 and ERK2 cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cell cortex IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in recycling endosome IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    DENN domain-containing protein 2B
    Names
    DENN/MADD domain containing 2B
    heLa tumor suppression 1
    suppression of tumorigenicity 5 protein

    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.

    Genomic

    1. NG_029450.1 RefSeqGene

      Range
      105278..222600
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001376495.1 → NP_001363424.1  DENN domain-containing protein 2B isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7791.1
      UniProtKB/Swiss-Prot
      B2R6X7, B3KXQ6, P78523, P78524, Q16492, Q7KYY2, Q7KZ12, Q8NE12, Q9BQQ6
      Conserved Domains (4) summary
      smart00801
      Location:1023 → 1089
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:697 → 784
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      PHA03247
      Location:46 → 411
      PHA03247; large tegument protein UL36; Provisional
      pfam02141
      Location:791 → 972
      DENN; DENN (AEX-3) domain

    2. NM_001376496.1 → NP_001363425.1  DENN domain-containing protein 2B isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7791.1
      UniProtKB/Swiss-Prot
      B2R6X7, B3KXQ6, P78523, P78524, Q16492, Q7KYY2, Q7KZ12, Q8NE12, Q9BQQ6
      Conserved Domains (4) summary
      smart00801
      Location:1023 → 1089
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:697 → 784
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      PHA03247
      Location:46 → 411
      PHA03247; large tegument protein UL36; Provisional
      pfam02141
      Location:791 → 972
      DENN; DENN (AEX-3) domain

    3. NM_001376497.1 → NP_001363426.1  DENN domain-containing protein 2B isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7791.1
      UniProtKB/Swiss-Prot
      B2R6X7, B3KXQ6, P78523, P78524, Q16492, Q7KYY2, Q7KZ12, Q8NE12, Q9BQQ6
      Conserved Domains (4) summary
      smart00801
      Location:1023 → 1089
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:697 → 784
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      PHA03247
      Location:46 → 411
      PHA03247; large tegument protein UL36; Provisional
      pfam02141
      Location:791 → 972
      DENN; DENN (AEX-3) domain

    4. NM_001376498.1 → NP_001363427.1  DENN domain-containing protein 2B isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Conserved Domains (3) summary
      smart00801
      Location:854 → 920
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      PHA03247
      Location:46 → 411
      PHA03247; large tegument protein UL36; Provisional
      pfam02141
      Location:622 → 803
      DENN; DENN (AEX-3) domain

    5. NM_001376499.1 → NP_001363428.1  DENN domain-containing protein 2B isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Conserved Domains (3) summary
      smart00801
      Location:843 → 909
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:517 → 604
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:611 → 792
      DENN; DENN (AEX-3) domain

    6. NM_001376500.1 → NP_001363429.1  DENN domain-containing protein 2B isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Conserved Domains (3) summary
      smart00801
      Location:796 → 862
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:470 → 557
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:564 → 745
      DENN; DENN (AEX-3) domain

    7. NM_001376501.1 → NP_001363430.1  DENN domain-containing protein 2B isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7792.1
      UniProtKB/TrEMBL
      B4DDL8
      Related
      ENSP00000436802.1, ENST00000530438.5
      Conserved Domains (3) summary
      smart00801
      Location:603 → 669
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:277 → 364
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:371 → 552
      DENN; DENN (AEX-3) domain

    8. NM_001376502.1 → NP_001363431.1  DENN domain-containing protein 2B isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7792.1
      UniProtKB/TrEMBL
      B4DDL8
      Conserved Domains (3) summary
      smart00801
      Location:603 → 669
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:277 → 364
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:371 → 552
      DENN; DENN (AEX-3) domain

    9. NM_001376503.1 → NP_001363432.1  DENN domain-containing protein 2B isoform 6

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      UniProtKB/TrEMBL
      B4DDL8
      Conserved Domains (3) summary
      smart00801
      Location:543 → 609
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:311 → 492
      DENN; DENN (AEX-3) domain
      cl04085
      Location:277 → 314
      uDENN; uDENN domain

    10. NM_001376504.1 → NP_001363433.1  DENN domain-containing protein 2B isoform 7

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      UniProtKB/TrEMBL
      B4DDL8
      Conserved Domains (3) summary
      smart00801
      Location:531 → 597
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:205 → 292
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:299 → 480
      DENN; DENN (AEX-3) domain

    11. NM_001376505.1 → NP_001363434.1  DENN domain-containing protein 2B isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS91434.1
      UniProtKB/TrEMBL
      B4DDL8
      Related
      ENSP00000432887.1, ENST00000530991.5
      Conserved Domains (3) summary
      smart00801
      Location:495 → 561
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:169 → 256
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:263 → 444
      DENN; DENN (AEX-3) domain

    12. NM_001376506.1 → NP_001363435.1  DENN domain-containing protein 2B isoform 8

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS91434.1
      UniProtKB/TrEMBL
      B4DDL8
      Conserved Domains (3) summary
      smart00801
      Location:495 → 561
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:169 → 256
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:263 → 444
      DENN; DENN (AEX-3) domain

    13. NM_005418.4 → NP_005409.3  DENN domain-containing protein 2B isoform 1

      See identical proteins and their annotated locations for NP_005409.3

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7791.1
      UniProtKB/Swiss-Prot
      B2R6X7, B3KXQ6, P78523, P78524, Q16492, Q7KYY2, Q7KZ12, Q8NE12, Q9BQQ6
      Related
      ENSP00000433528.1, ENST00000534127.5
      Conserved Domains (4) summary
      smart00801
      Location:1023 → 1089
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:697 → 784
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      PHA03247
      Location:46 → 411
      PHA03247; large tegument protein UL36; Provisional
      pfam02141
      Location:791 → 972
      DENN; DENN (AEX-3) domain

    14. NM_139157.3 → NP_631896.1  DENN domain-containing protein 2B isoform 2

      See identical proteins and their annotated locations for NP_631896.1

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053
      Consensus CDS
      CCDS7792.1
      UniProtKB/TrEMBL
      B4DDL8
      Conserved Domains (3) summary
      smart00801
      Location:603 → 669
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:277 → 364
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      pfam02141
      Location:371 → 552
      DENN; DENN (AEX-3) domain

    15. NM_213618.2 → NP_998783.1  DENN domain-containing protein 2B isoform 1

      See identical proteins and their annotated locations for NP_998783.1

      Status: REVIEWED

      Source sequence(s)
      BC036655, BX647431, U15131, U15780
      Consensus CDS
      CCDS7791.1
      UniProtKB/Swiss-Prot
      B2R6X7, B3KXQ6, P78523, P78524, Q16492, Q7KYY2, Q7KZ12, Q8NE12, Q9BQQ6
      Related
      ENSP00000319678.6, ENST00000313726.11
      Conserved Domains (4) summary
      smart00801
      Location:1023 → 1089
      dDENN; Domain always found downstream of DENN domain, found in a variety of signalling proteins
      smart00800
      Location:697 → 784
      uDENN; Domain always found upstream of DENN domain, found in a variety of signalling proteins
      PHA03247
      Location:46 → 411
      PHA03247; large tegument protein UL36; Provisional
      pfam02141
      Location:791 → 972
      DENN; DENN (AEX-3) domain

    RNA

    1. NR_164814.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    2. NR_164815.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    3. NR_164816.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    4. NR_164817.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    5. NR_164818.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    6. NR_164819.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    7. NR_164820.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    8. NR_164821.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    9. NR_164822.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC026894, AC091053

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      8693352..8910951 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      8775106..8995121 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P78524.3 GenPept UniProtKB/Swiss-Prot:P78524

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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