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Q14183

- DOC2A_HUMAN

UniProt

Q14183 - DOC2A_HUMAN

Protein

Double C2-like domain-containing protein alpha

Gene

DOC2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 5 (26 Jun 2007)
      Previous versions | rss
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    Functioni

    Calcium sensor which most probably regulates fusion of vesicles with membranes. Binds calcium and phospholipids. May be involved in calcium dependent neurotransmitter release through the interaction with UNC13A. May be involved in calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Regulates Ca2+-dependent secretory lysosome exocytosis in mast cells.3 Publications

    GO - Molecular functioni

    1. calcium-dependent phospholipid binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. transporter activity Source: InterPro

    GO - Biological processi

    1. nervous system development Source: ProtInc
    2. regulation of calcium ion-dependent exocytosis Source: UniProtKB
    3. synaptic transmission Source: ProtInc
    4. synaptic vesicle exocytosis Source: Ensembl

    Keywords - Biological processi

    Exocytosis

    Keywords - Ligandi

    Calcium, Calcium/phospholipid-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Double C2-like domain-containing protein alpha
    Short name:
    Doc2
    Short name:
    Doc2-alpha
    Gene namesi
    Name:DOC2A
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:2985. DOC2A.

    Subcellular locationi

    Lysosome By similarity. Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane Curated; Peripheral membrane protein Curated. Cell junctionsynapsesynaptosome
    Note: Colocalizes to synaptic vesicles.

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-KW
    2. lysosome Source: UniProtKB-SubCell
    3. neuron projection Source: UniProtKB-SubCell
    4. synaptic vesicle membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell junction, Cytoplasmic vesicle, Lysosome, Membrane, Synapse, Synaptosome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27451.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 400400Double C2-like domain-containing protein alphaPRO_0000079965Add
    BLAST

    Proteomic databases

    MaxQBiQ14183.
    PaxDbiQ14183.
    PRIDEiQ14183.

    PTM databases

    PhosphoSiteiQ14183.

    Expressioni

    Tissue specificityi

    Predominantly expressed in brain. Also expressed in testis.2 Publications

    Gene expression databases

    ArrayExpressiQ14183.
    BgeeiQ14183.
    CleanExiHS_DOC2A.
    GenevestigatoriQ14183.

    Interactioni

    Subunit structurei

    Interacts (via N-terminus) with UNC13A. Interacts with cytoplasmic dynein light chain DYNLT1. Interacts with UNC13D.3 Publications

    Protein-protein interaction databases

    BioGridi114026. 1 interaction.
    STRINGi9606.ENSP00000340017.

    Structurei

    Secondary structure

    1
    400
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi92 – 1009
    Turni101 – 1044
    Beta strandi105 – 11511
    Beta strandi127 – 1359
    Helixi139 – 1413
    Beta strandi142 – 1443
    Beta strandi155 – 1628
    Helixi167 – 1726
    Beta strandi174 – 1818
    Beta strandi190 – 1978
    Helixi198 – 2003
    Beta strandi207 – 2126

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4MJJX-ray2.00A81-217[»]
    ProteinModelPortaliQ14183.
    SMRiQ14183. Positions 55-393.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini91 – 195105C2 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini253 – 356104C2 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 8989Interaction with UNC13D and DYNLT1Add
    BLAST
    Regioni215 – 400186Interaction with UNC13DAdd
    BLAST

    Domaini

    C2 domain 1 is involved in binding calcium and phospholipids.By similarity

    Sequence similaritiesi

    Contains 2 C2 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG247952.
    HOGENOMiHOG000232127.
    HOVERGENiHBG051388.
    InParanoidiQ14183.
    OMAiDYFPRLG.
    PhylomeDBiQ14183.
    TreeFamiTF351844.

    Family and domain databases

    Gene3Di2.60.40.150. 2 hits.
    InterProiIPR000008. C2_dom.
    IPR014638. Doc2.
    IPR001565. Synaptotagmin.
    [Graphical view]
    PfamiPF00168. C2. 2 hits.
    [Graphical view]
    PIRSFiPIRSF036931. Doc2. 1 hit.
    PRINTSiPR00360. C2DOMAIN.
    PR00399. SYNAPTOTAGMN.
    SMARTiSM00239. C2. 2 hits.
    [Graphical view]
    SUPFAMiSSF49562. SSF49562. 2 hits.
    PROSITEiPS50004. C2. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q14183-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRGRRGDRMT INIQEHMAIN VCPGPIRPIR QISDYFPRGP GPEGGGGGGG    50
    EAPAHLVPLA LAPPAALLGA TTPEDGAEVD SYDSDDATAL GTLEFDLLYD 100
    RASCTLHCSI LRAKGLKPMD FNGLADPYVK LHLLPGACKA NKLKTKTQRN 150
    TLNPVWNEDL TYSGITDDDI THKVLRIAVC DEDKLSHNEF IGEIRVPLRR 200
    LKPSQKKHFN ICLERQVPLA SPSSMSAALR GISCYLKELE QAEQGQGLLE 250
    ERGRILLSLS YSSRRRGLLV GILRCAHLAA MDVNGYSDPY VKTYLRPDVD 300
    KKSKHKTCVK KKTLNPEFNE EFFYEIELST LATKTLEVTV WDYDIGKSND 350
    FIGGVSLGPG ARGEARKHWS DCLQQPDAAL ERWHTLTSEL PPAAGALSSA 400
    Length:400
    Mass (Da):43,959
    Last modified:June 26, 2007 - v5
    Checksum:i2E61A459AC373C6C
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti92 – 921T → K in BAA06695. (PubMed:7826360)Curated
    Sequence conflicti108 – 1092CS → VC in BAA06695. (PubMed:7826360)Curated
    Sequence conflicti238 – 2381E → D in BAA06695. (PubMed:7826360)Curated
    Sequence conflicti376 – 3761P → R in BAA06695. (PubMed:7826360)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti48 – 481G → S.2 Publications
    Corresponds to variant rs1140239 [ dbSNP | Ensembl ].
    VAR_019656

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D31897 mRNA. Translation: BAA06695.1.
    BC041769 mRNA. Translation: AAH41769.2.
    BC055284 mRNA. Translation: AAH55284.1.
    BC063436 mRNA. Translation: AAH63436.1.
    CCDSiCCDS10666.1.
    PIRiJC2473.
    RefSeqiNP_001268991.1. NM_001282062.1.
    NP_001268992.1. NM_001282063.1.
    NP_001268997.1. NM_001282068.1.
    NP_003577.2. NM_003586.2.
    XP_005255692.1. XM_005255635.2.
    XP_006721160.1. XM_006721097.1.
    XP_006721161.1. XM_006721098.1.
    UniGeneiHs.355281.

    Genome annotation databases

    EnsembliENST00000350119; ENSP00000340017; ENSG00000149927.
    ENST00000564944; ENSP00000455196; ENSG00000149927.
    ENST00000564979; ENSP00000455624; ENSG00000149927.
    GeneIDi8448.
    KEGGihsa:8448.
    UCSCiuc002dvn.3. human.

    Polymorphism databases

    DMDMi150421541.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D31897 mRNA. Translation: BAA06695.1 .
    BC041769 mRNA. Translation: AAH41769.2 .
    BC055284 mRNA. Translation: AAH55284.1 .
    BC063436 mRNA. Translation: AAH63436.1 .
    CCDSi CCDS10666.1.
    PIRi JC2473.
    RefSeqi NP_001268991.1. NM_001282062.1.
    NP_001268992.1. NM_001282063.1.
    NP_001268997.1. NM_001282068.1.
    NP_003577.2. NM_003586.2.
    XP_005255692.1. XM_005255635.2.
    XP_006721160.1. XM_006721097.1.
    XP_006721161.1. XM_006721098.1.
    UniGenei Hs.355281.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4MJJ X-ray 2.00 A 81-217 [» ]
    ProteinModelPortali Q14183.
    SMRi Q14183. Positions 55-393.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114026. 1 interaction.
    STRINGi 9606.ENSP00000340017.

    PTM databases

    PhosphoSitei Q14183.

    Polymorphism databases

    DMDMi 150421541.

    Proteomic databases

    MaxQBi Q14183.
    PaxDbi Q14183.
    PRIDEi Q14183.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000350119 ; ENSP00000340017 ; ENSG00000149927 .
    ENST00000564944 ; ENSP00000455196 ; ENSG00000149927 .
    ENST00000564979 ; ENSP00000455624 ; ENSG00000149927 .
    GeneIDi 8448.
    KEGGi hsa:8448.
    UCSCi uc002dvn.3. human.

    Organism-specific databases

    CTDi 8448.
    GeneCardsi GC16M030016.
    H-InvDB HIX0012939.
    HGNCi HGNC:2985. DOC2A.
    MIMi 604567. gene.
    neXtProti NX_Q14183.
    PharmGKBi PA27451.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG247952.
    HOGENOMi HOG000232127.
    HOVERGENi HBG051388.
    InParanoidi Q14183.
    OMAi DYFPRLG.
    PhylomeDBi Q14183.
    TreeFami TF351844.

    Miscellaneous databases

    GeneWikii DOC2A.
    GenomeRNAii 8448.
    NextBioi 31610.
    PROi Q14183.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q14183.
    Bgeei Q14183.
    CleanExi HS_DOC2A.
    Genevestigatori Q14183.

    Family and domain databases

    Gene3Di 2.60.40.150. 2 hits.
    InterProi IPR000008. C2_dom.
    IPR014638. Doc2.
    IPR001565. Synaptotagmin.
    [Graphical view ]
    Pfami PF00168. C2. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF036931. Doc2. 1 hit.
    PRINTSi PR00360. C2DOMAIN.
    PR00399. SYNAPTOTAGMN.
    SMARTi SM00239. C2. 2 hits.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 2 hits.
    PROSITEi PS50004. C2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Doc2, a novel synaptic vesicle protein with two repeated C2-like domains."
      Orita S., Sasaki T., Naito A., Maeda M., Igarashi H., Takai Y.
      Biochem. Biophys. Res. Commun. 206:439-448(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-48, TISSUE SPECIFICITY.
      Tissue: Brain.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-48.
      Tissue: Brain and Mammary gland.
    3. "Molecular cloning of an isoform of Doc2 having two C2-like domains."
      Sakaguchi G., Orita S., Maeda M., Igarashi H., Takai Y.
      Biochem. Biophys. Res. Commun. 217:1053-1061(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    4. "Role of the Doc2 alpha-Munc13-1 interaction in the neurotransmitter release process."
      Mochida S., Orita S., Sakaguchi G., Sasaki T., Takai Y.
      Proc. Natl. Acad. Sci. U.S.A. 95:11418-11422(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH UNC13A.
    5. "Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport."
      Nagano F., Orita S., Sasaki T., Naito A., Sakaguchi G., Maeda M., Watanabe T., Kominami E., Uchiyama Y., Takai Y.
      J. Biol. Chem. 273:30065-30068(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH DYNLT1.
    6. "Doc2 alpha and Munc13-4 regulate Ca(2+) -dependent secretory lysosome exocytosis in mast cells."
      Higashio H., Nishimura N., Ishizaki H., Miyoshi J., Orita S., Sakane A., Sasaki T.
      J. Immunol. 180:4774-4784(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH UNC13D.

    Entry informationi

    Entry nameiDOC2A_HUMAN
    AccessioniPrimary (citable) accession number: Q14183
    Secondary accession number(s): Q6P4G4, Q7Z5G0, Q8IVX0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 31, 2004
    Last sequence update: June 26, 2007
    Last modified: October 1, 2014
    This is version 124 of the entry and version 5 of the sequence. [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 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3