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DOC2A double C2 domain alpha [ Homo sapiens (human) ]

Gene ID: 8448, updated on 2-Nov-2024

Summary

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Official Symbol
DOC2Aprovided by HGNC
Official Full Name
double C2 domain alphaprovided by HGNC
Primary source
HGNC:HGNC:2985
See related
Ensembl:ENSG00000149927 MIM:604567; AllianceGenome:HGNC:2985
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
Doc2
Summary
There are at least two protein isoforms of the Double C2 protein, namely alpha (DOC2A) and beta (DOC2B), which contain two C2-like domains. DOC2A and DOC2B are encoded by different genes; these genes are at times confused with the unrelated DAB2 gene which was initially named DOC-2. DOC2A is mainly expressed in brain and is suggested to be involved in Ca(2+)-dependent neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Expression
Broad expression in brain (RPKM 11.9), testis (RPKM 7.1) and 15 other tissues See more
Orthologs
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Genomic context

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See DOC2A in Genome Data Viewer
Location:
16p11.2
Exon count:
19
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (30005514..30023228, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (30288154..30305880, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (30016835..30024917, complement)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903762 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7346 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:29985672-29986443 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:29987081-29987582 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:29987583-29988082 Neighboring gene TAO kinase 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30002153-30002740 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30004428-30004928 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30004929-30005429 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10686 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10687 Neighboring gene HIRA interacting protein 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30015046-30015830 Neighboring gene INO80 complex subunit E Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7347 Neighboring gene chromosome 16 open reading frame 92 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30039801-30040645 Neighboring gene TLC domain containing 3B Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7348 Neighboring gene MPRA-validated peak2562 silencer Neighboring gene uncharaterized LOC112694756 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30064875-30065853 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:30065854-30066831 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:30076132-30076912 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7349 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7350 Neighboring gene aldolase, fructose-bisphosphate A

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 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. Increased expression of DOC2A in human and rat temporal lobe epilepsy. Hu X, et al. Epilepsy Res, 2019 Mar. PMID 30844661
  2. Loss of Doc2-Dependent Spontaneous Neurotransmission Augments Glutamatergic Synaptic Strength. Ramirez DMO, et al. J Neurosci, 2017 Jun 28. PMID 28539418, Free PMC Article
  3. Doc2: a novel brain protein having two repeated C2-like domains. Orita S, et al. Biochem Biophys Res Commun, 1995 Jan 17. PMID 7826360
  4. Molecular cloning of an isoform of Doc2 having two C2-like domains. Sakaguchi G, et al. Biochem Biophys Res Commun, 1995 Dec 26. PMID 8554557
  5. Role of the Doc2 alpha-Munc13-1 interaction in the neurotransmitter release process. Mochida S, et al. Proc Natl Acad Sci U S A, 1998 Sep 15. PMID 9736751, Free PMC Article

See all (29) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. This study demonstrated that the DOCA2 increase expression in temporal lobe in temporal lobe epilepsy.
    Title: Increased expression of DOC2A in human and rat temporal lobe epilepsy.
  2. this study, members of the Doc2 family of presynaptic proteins were eliminated, which caused a reduction in spontaneous neurotransmission, whereas action potential-evoked neurotransmission remained relatively normal.
    Title: Loss of Doc2-Dependent Spontaneous Neurotransmission Augments Glutamatergic Synaptic Strength.
  3. Study analyzed Doc2alpha and Doc2beta and found that Doc2 responds to changes in [Ca2+], with markedly slower kinetics as compared to the cytosolic domain of syt I (syt), and operates on a timescale consistent with asynchronous neurotransmitter release.
    Title: Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release.
  4. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
    Title: Strong synaptic transmission impact by copy number variations in schizophrenia.
  5. Observational study of gene-disease association. (HuGE Navigator)
    Title: An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
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
Biological insights from 108 schizophrenia-associated genetic loci.
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

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 calcium-dependent phospholipid binding IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in calcium-dependent activation of synaptic vesicle fusion IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in calcium-dependent activation of synaptic vesicle fusion IEA
Inferred from Electronic Annotation
more info
  
involved_in chemical synaptic transmission TAS
Traceable Author Statement
more info
 PubMed 
involved_in nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of calcium ion-dependent exocytosis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of calcium ion-dependent exocytosis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cell junction IDA
Inferred from Direct Assay
more info
  
is_active_in extrinsic component of synaptic vesicle membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
  
located_in lysosome IEA
Inferred from Electronic Annotation
more info
  
located_in neuron projection IEA
Inferred from Electronic Annotation
more info
  
located_in nucleolus IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in synapse IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
double C2-like domain-containing protein alpha
Names
doc2-alpha
double C2-like domains, alpha

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_001282062.1 → NP_001268991.1  double C2-like domain-containing protein alpha

    See identical proteins and their annotated locations for NP_001268991.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1 through 4 encode the same protein.
    Source sequence(s)
    AC093512, BC055284, BC063436, DC399462
    Consensus CDS
    CCDS10666.1
    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0
    Conserved Domains (2) summary
    cd04035
    Location:90 → 213
    C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
    cd08384
    Location:254 → 386
    C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain

  2. NM_001282063.2 → NP_001268992.1  double C2-like domain-containing protein alpha

    See identical proteins and their annotated locations for NP_001268992.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an alternate terminal exon in the 5' UTR compared to variant 1. Variants 1 through 4 encode the same protein.
    Source sequence(s)
    AC093512, BC041769, BC055284
    Consensus CDS
    CCDS10666.1
    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0
    Related
    ENSP00000482870.1, ENST00000616445.4
    Conserved Domains (2) summary
    cd04035
    Location:90 → 213
    C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
    cd08384
    Location:254 → 386
    C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain

  3. NM_001282068.2 → NP_001268997.1  double C2-like domain-containing protein alpha

    See identical proteins and their annotated locations for NP_001268997.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate exons and contains an alternate terminal exon in the 5' UTR compared to variant 1. Variants 1 through 4 encode the same protein.
    Source sequence(s)
    AC093512, BC055284, BI757951, D31897
    Consensus CDS
    CCDS10666.1
    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0
    Related
    ENSP00000455624.1, ENST00000564979.5
    Conserved Domains (2) summary
    cd04035
    Location:90 → 213
    C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
    cd08384
    Location:254 → 386
    C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain

  4. NM_003586.3 → NP_003577.2  double C2-like domain-containing protein alpha

    See identical proteins and their annotated locations for NP_003577.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon and uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1 through 4 encode the same protein.
    Source sequence(s)
    BC055284
    Consensus CDS
    CCDS10666.1
    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0
    Related
    ENSP00000340017.4, ENST00000350119.9
    Conserved Domains (2) summary
    cd04035
    Location:90 → 213
    C2A_Rabphilin_Doc2; C2 domain first repeat present in Rabphilin and Double C2 domain
    cd08384
    Location:254 → 386
    C2B_Rabphilin_Doc2; C2 domain second repeat present in Rabphilin and Double C2 domain

RNA

  1. NR_104089.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks one alternate exon and uses an alternate splice site in one exon compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon found in variant 1, and the use of the 5'-most translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    BC055284, BX460259

  2. NR_104090.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) uses alternate splice sites in three exons compared to variant 1. This variant is represented as non-coding because it lacks a large portion of the coding region, including the translational start codon found in variant 1, and translation of its longest ORF would render the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC093512, AK293651, BC055284

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_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    30005514..30023228 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047434807.1 → XP_047290763.1  double C2-like domain-containing protein alpha isoform X1

    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0

  2. XM_047434804.1 → XP_047290760.1  double C2-like domain-containing protein alpha isoform X1

    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0

  3. XM_047434803.1 → XP_047290759.1  double C2-like domain-containing protein alpha isoform X1

    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0

  4. XM_047434805.1 → XP_047290761.1  double C2-like domain-containing protein alpha isoform X1

    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0

  5. XM_047434802.1 → XP_047290758.1  double C2-like domain-containing protein alpha isoform X1

    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0

  6. XM_047434806.1 → XP_047290762.1  double C2-like domain-containing protein alpha isoform X1

    UniProtKB/Swiss-Prot
    B4DEJ2, H3BNH6, Q14183, Q6P4G4, Q7Z5G0, Q8IVX0

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    30288154..30305880 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054314197.1 → XP_054170172.1  double C2-like domain-containing protein alpha isoform X1

  2. XM_054314196.1 → XP_054170171.1  double C2-like domain-containing protein alpha isoform X1

  3. XM_054314198.1 → XP_054170173.1  double C2-like domain-containing protein alpha isoform X1

  4. XM_054314195.1 → XP_054170170.1  double C2-like domain-containing protein alpha isoform X1

  5. XM_054314199.1 → XP_054170174.1  double C2-like domain-containing protein alpha isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q14183.5 GenPept UniProtKB/Swiss-Prot:Q14183

Gene LinkOut

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

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