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    DCTN2 dynactin subunit 2 [ Homo sapiens (human) ]

    Gene ID: 10540, updated on 10-Dec-2024

    Summary

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    Official Symbol
    DCTN2provided by HGNC
    Official Full Name
    dynactin subunit 2provided by HGNC
    Primary source
    HGNC:HGNC:2712
    See related
    Ensembl:ENSG00000175203 MIM:607376; AllianceGenome:HGNC:2712
    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
    RBP50; DCTN50; HEL-S-77; DYNAMITIN
    Summary
    This gene encodes a 50-kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 4-5 copies per dynactin molecule. It contains three short alpha-helical coiled-coil domains that may mediate association with self or other dynactin subunits. It may interact directly with the largest subunit (p150) of dynactin and may affix p150 in place. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2012]
    Expression
    Ubiquitous expression in brain (RPKM 42.2), esophagus (RPKM 36.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DCTN2 in Genome Data Viewer
    Location:
    12q13.3
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (57530051..57547192, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (57498291..57515431, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (57923834..57940975, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene methionyl-tRNA synthetase 1 Neighboring gene uncharacterized LOC128125814 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:57913133-57914094 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:57914069-57915268 Neighboring gene microRNA 6758 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57916016-57916975 Neighboring gene DNA damage inducible transcript 3 Neighboring gene microRNA 616 Neighboring gene methyl-CpG binding domain protein 6 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6548 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4584 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:57944162-57944754 Neighboring gene kinesin family member 5A Neighboring gene ReSE screen-validated silencer GRCh37_chr12:57955995-57956161 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:57956855-57957072 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6549 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:57984713-57985214 Neighboring gene phosphatidylinositol-5-phosphate 4-kinase type 2 gamma

    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. Pan-cancer analysis of DCTN2 and its tumour-promoting role in HCC by modulating the AKT pathway. Xu S, et al. J Cell Mol Med, 2024 Jun. PMID 38842133, Free PMC Article
    2. Molecular and functional basis for the scaffolding role of the p50/dynamitin subunit of the microtubule-associated dynactin complex. Jacquot G, et al. J Biol Chem, 2010 Jul 23. PMID 20463029, Free PMC Article
    3. Dynamitin mutagenesis reveals protein-protein interactions important for dynactin structure. Maier KC, et al. Traffic, 2008 Apr. PMID 18182012, Free PMC Article
    4. Phenotypic changes associated with DYNACTIN-2 (DCTN2) over expression characterise SJSA-1 osteosarcoma cells. Bransfield KL, et al. Mol Carcinog, 2006 Mar. PMID 16369996
    5. Binding between ROCK1 and DCTN2 triggers diabetes‑associated centrosome amplification in colon cancer cells. Li YF, et al. Oncol Rep, 2021 Jul. PMID 34080666, Free PMC Article

    See all (181) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Pan-cancer analysis of DCTN2 and its tumour-promoting role in HCC by modulating the AKT pathway.
      Title: Pan-cancer analysis of DCTN2 and its tumour-promoting role in HCC by modulating the AKT pathway.
    2. Binding between ROCK1 and DCTN2 triggers diabetesassociated centrosome amplification in colon cancer cells.
      Title: Binding between ROCK1 and DCTN2 triggers diabetes‑associated centrosome amplification in colon cancer cells.
    3. This is the first time a haplotype on chromosome 12 containing sequence variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A has been linked to an inherited neuropathy in humans.
      Title: Variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A are associated with intermediate Charcot-Marie-Tooth disease in a Norwegian family.
    4. dynamitin is involved in the regulation of Nav1.5 cell-surface density
      Title: Dynamitin affects cell-surface expression of voltage-gated sodium channel Nav1.5.
    5. the determinants of p50/DM required for self-oligomerization of the protein and for interactions with other subunits of the dynactin complex
      Title: Molecular and functional basis for the scaffolding role of the p50/dynamitin subunit of the microtubule-associated dynactin complex.
    6. The interaction between ZW10 and dynamitin showed that the N-terminal region of ZW10 is the major binding site for dynamitin and, like full-length ZW10, could move along microtubules to the centrosomal area in a dynein-dynactin-dependent manner.
      Title: N-terminal region of ZW10 serves not only as a determinant for localization but also as a link with dynein function.
    7. Data show how dynamitin's different structural domains contribute to its ability to self-associate, interact with dynactin and assemble into a complex with its close binding partner, p24.
      Title: Dynamitin mutagenesis reveals protein-protein interactions important for dynactin structure.
    8. the Sec23p component of the COPII complex directly interacts with the dynactin complex through the carboxy-terminal cargo-binding domain of p150(Glued).
      Title: Coupling of ER exit to microtubules through direct interaction of COPII with dynactin.
    9. study does not support a major role for DCTN2 overexpression in carcinogenesis
      Title: Phenotypic changes associated with DYNACTIN-2 (DCTN2) over expression characterise SJSA-1 osteosarcoma cells.
    10. DCTN2 is required in the earliest stages of peroxisome biogenesis.
      Title: Requirement for microtubules and dynein motors in the earliest stages of peroxisome biogenesis.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Associated conditions

    Description Tests
    Charcot-Marie-Tooth disease
    MedGen: C0007959 GeneReviews: Charcot-Marie-Tooth Hereditary Neuropathy Overview
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Pr55(Gag) gag Overexpression of p50/dynamitin leads to a marked relocalization of vRNA and viral structural protein Gag to the cell periphery with late endosomes and a several fold increase in HIV-1 production PubMed
    capsid gag Over-expression of p50/dynamitin results in upregulated amounts of pelletable HIV-1 CA cores in infected cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables spectrin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in melanosome transport IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic metaphase chromosome alignment IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitotic spindle organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitotic spindle organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitotic spindle organization ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within protein localization to centrosome IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in centrosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in centrosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm 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
    		  
    part_of dynactin complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of dynactin complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of dynein complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in growth cone IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in kinetochore IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in microtubule IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    dynactin subunit 2
    Names
    50 kDa dynein-associated polypeptide
    dynactin 2 (p50)
    dynactin complex 50 kDa subunit
    epididymis secretory protein Li 77
    epididymis secretory sperm binding protein
    p50 dynamitin

    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_047120.1 RefSeqGene

      Range
      5140..22281
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001261412.2 → NP_001248341.1  dynactin subunit 2 isoform 2

      See identical proteins and their annotated locations for NP_001248341.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, compared to variant 1. The resulting isoform (2) lacks an internal segment, compared to isoform 1.
      Source sequence(s)
      AK098794, DB027733, DB569305
      Consensus CDS
      CCDS73489.1
      UniProtKB/TrEMBL
      Q53H88
      Related
      ENSP00000439376.2, ENST00000543672.6
      Conserved Domains (1) summary
      pfam04912
      Location:16 → 401
      Dynamitin; Dynamitin

    2. NM_001261413.2 → NP_001248342.1  dynactin subunit 2 isoform 3

      See identical proteins and their annotated locations for NP_001248342.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two exons in the 5' coding region but maintains the reading frame, compared to variant 1. The resulting isoform (3) lacks an internal segment, compared to isoform 1.
      Source sequence(s)
      BC009468, DB027733, DB569305
      Consensus CDS
      CCDS58245.1
      UniProtKB/Swiss-Prot
      B2RBK5, Q13561, Q86YN2, Q9BW17
      UniProtKB/TrEMBL
      A0A384MDU9, Q53H88
      Related
      ENSP00000447824.1, ENST00000548249.6
      Conserved Domains (1) summary
      pfam04912
      Location:16 → 399
      Dynamitin; Dynamitin

    3. NM_001348065.2 → NP_001334994.1  dynactin subunit 2 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC022506
      UniProtKB/TrEMBL
      Q53H88
      Conserved Domains (1) summary
      pfam04912
      Location:59 → 444
      Dynamitin

    4. NM_001348066.2 → NP_001334995.1  dynactin subunit 2 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC022506, AK096242
      UniProtKB/TrEMBL
      B3KTX4
      Conserved Domains (1) summary
      pfam04912
      Location:6 → 376
      Dynamitin

    5. NM_001348067.2 → NP_001334996.1  dynactin subunit 2 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6), as well as variant 7, encodes isoform 6.
      Source sequence(s)
      AC022506, AK292364
      Consensus CDS
      CCDS91711.1
      UniProtKB/TrEMBL
      A8K8J9, H0YI98
      Conserved Domains (1) summary
      pfam04912
      Location:2 → 312
      Dynamitin; Dynamitin

    6. NM_001348068.2 → NP_001334997.1  dynactin subunit 2 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7), as well as variant 6, encodes isoform 6.
      Source sequence(s)
      AC022506
      Consensus CDS
      CCDS91711.1
      UniProtKB/TrEMBL
      A8K8J9, H0YI98
      Related
      ENSP00000504380.1, ENST00000678653.1
      Conserved Domains (1) summary
      pfam04912
      Location:2 → 312
      Dynamitin; Dynamitin

    7. NM_006400.5 → NP_006391.1  dynactin subunit 2 isoform 1

      See identical proteins and their annotated locations for NP_006391.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1.
      Source sequence(s)
      AC022506
      Consensus CDS
      CCDS44930.1
      UniProtKB/TrEMBL
      Q53H88, V9HW58
      Related
      ENSP00000408910.3, ENST00000434715.7
      Conserved Domains (1) summary
      pfam04912
      Location:16 → 404
      Dynamitin

    RNA

    1. NR_145419.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC022506
      Related
      ENST00000552390.6

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      57530051..57547192 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047428084.1 → XP_047284040.1  dynactin subunit 2 isoform X1

      UniProtKB/TrEMBL
      F8W1I6
      Related
      ENSP00000446964.1, ENST00000550201.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      57498291..57515431 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054370781.1 → XP_054226756.1  dynactin subunit 2 isoform X1

      UniProtKB/TrEMBL
      F8W1I6
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q13561.4 GenPept UniProtKB/Swiss-Prot:Q13561

    Gene LinkOut

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

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