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Q14184

- DOC2B_HUMAN

UniProt

Q14184 - DOC2B_HUMAN

Protein

Double C2-like domain-containing protein beta

Gene

DOC2B

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    Functioni

    Calcium sensor which positively regulates SNARE-dependent fusion of vesicles with membranes. Binds phospholipids in a calcium-dependent manner and may act at the priming stage of fusion by modifying membrane curvature to stimulate fusion. Involved in calcium-triggered exocytosis in chromaffin cells and calcium-dependent spontaneous release of neurotransmitter in absence of action potentials in neuronal cells. Involved both in glucose-stimulated insulin secretion in pancreatic cells and insulin-dependent GLUT4 transport to the plasma membrane in adipocytes By similarity.By similarity

    GO - Molecular functioni

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

    GO - Biological processi

    1. calcium ion-dependent exocytosis of neurotransmitter Source: UniProtKB
    2. positive regulation of calcium ion-dependent exocytosis Source: UniProtKB
    3. positive regulation of insulin secretion Source: UniProtKB
    4. positive regulation of vesicle fusion Source: UniProtKB
    5. protein localization Source: UniProtKB

    Keywords - Ligandi

    Calcium, Calcium/phospholipid-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Double C2-like domain-containing protein beta
    Short name:
    Doc2-beta
    Gene namesi
    Name:DOC2B
    Synonyms:DOC2BL
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:2986. DOC2B.

    Subcellular locationi

    Cytoplasm. Cytoplasmic granule By similarity. Cell membrane By similarity; Peripheral membrane protein By similarity
    Note: Translocates to the plasma membrane in a calcium-dependent manner.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. plasma membrane Source: UniProtKB
    3. synaptic vesicle Source: InterPro

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27452.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 412412Double C2-like domain-containing protein betaPRO_0000079968Add
    BLAST

    Proteomic databases

    PaxDbiQ14184.
    PRIDEiQ14184.

    PTM databases

    PhosphoSiteiQ14184.

    Expressioni

    Tissue specificityi

    Widely expressed with highest levels in brain and kidney. Expressed in pancreatic islet cells (at protein level).2 Publications

    Gene expression databases

    BgeeiQ14184.
    CleanExiHS_DOC2B.
    GenevestigatoriQ14184.

    Organism-specific databases

    HPAiHPA043168.

    Interactioni

    Subunit structurei

    Interacts with the SNARE (soluble N-ethylmaleimide-sensitive factor attached protein receptor) complex composed of SNAP25, STX1A and VAMP2; the interaction is calcium-dependent and competitive with SYT1. Interacts with STX4; the interaction is calcium-dependent, increased by insulin and glucose, and mediates vesicle fusion with plasma membrane in pancreatic cells and adipocytes. Interacts with STXBP3; the interaction is direct, occurs at the cell membrane and regulates glucose-stimulated insulin secretion. May interact with UNC13A; the interaction mediates targeting to the plasma membrane By similarity. Interacts with cytoplasmic dynein light chain DYNLT1.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi114025. 1 interaction.
    IntActiQ14184. 1 interaction.
    MINTiMINT-7006088.
    STRINGi9606.ENSP00000343665.

    Structurei

    3D structure databases

    ProteinModelPortaliQ14184.
    SMRiQ14184. Positions 125-412.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini128 – 232105C2 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini268 – 371104C2 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 9090Mediates interaction with DYNLT1Add
    BLAST
    Regioni1 – 3636Negatively regulates targeting to plasma membraneBy similarityAdd
    BLAST
    Regioni257 – 375119Mediates interaction with STXBP3By similarityAdd
    BLAST

    Domaini

    C2 domain 1 is involved in binding calcium and phospholipids. C2 domain 2 may also play a role in the calcium-dependent targeting to membranes By similarity.By similarity

    Sequence similaritiesi

    Contains 2 C2 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG247952.
    HOGENOMiHOG000232127.
    HOVERGENiHBG051388.
    InParanoidiQ14184.
    OrthoDBiEOG7CZK67.
    PhylomeDBiQ14184.
    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.

    Q14184-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTLRRRGEKA TISIQEHMAI DVCPGPIRPI KQISDYFPRF PRGLPPDAGP    50
    RAAAPPDAPA RPAVAGAGRR SPSDGAREDD EDVDQLFGAY GSSPGPSPGP 100
    SPARPPAKPP EDEPDADGYE SDDCTALGTL DFSLLYDQEN NALHCTITKA 150
    KGLKPMDHNG LADPYVKLHL LPGASKANKL RTKTLRNTLN PTWNETLTYY 200
    GITDEDMIRK TLRISVCDED KFRHNEFIGE TRVPLKKLKP NHTKTFNICL 250
    EKQLPVDKTE DKSLEERGRI LISLKYSSQK QGLLVGIVRC AHLAAMDANG 300
    YSDPYVKTYL RPDVDKKSKH KTAVKKKTLN PEFNEEFCYE IKHGDLAKKS 350
    LEVTVWDYDI GKSNDFIGGV VLGIHAKGER LKHWFDCLKN KDKRIERWHT 400
    LTSELPGAVL SD 412
    Length:412
    Mass (Da):45,949
    Last modified:November 1, 1996 - v1
    Checksum:i679592A874542ED3
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti209 – 2091R → L in a patient with amyotrophic lateral sclerosis. 1 Publication
    VAR_065743

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D70830 mRNA. Translation: BAA11107.1.
    RefSeqiNP_003576.2. NM_003585.4.
    UniGeneiHs.551705.

    Genome annotation databases

    GeneIDi8447.
    KEGGihsa:8447.
    UCSCiuc010vpx.1. human.

    Polymorphism databases

    DMDMi51701386.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D70830 mRNA. Translation: BAA11107.1 .
    RefSeqi NP_003576.2. NM_003585.4.
    UniGenei Hs.551705.

    3D structure databases

    ProteinModelPortali Q14184.
    SMRi Q14184. Positions 125-412.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114025. 1 interaction.
    IntActi Q14184. 1 interaction.
    MINTi MINT-7006088.
    STRINGi 9606.ENSP00000343665.

    PTM databases

    PhosphoSitei Q14184.

    Polymorphism databases

    DMDMi 51701386.

    Proteomic databases

    PaxDbi Q14184.
    PRIDEi Q14184.

    Protocols and materials databases

    DNASUi 8447.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 8447.
    KEGGi hsa:8447.
    UCSCi uc010vpx.1. human.

    Organism-specific databases

    CTDi 8447.
    GeneCardsi GC17M000007.
    HGNCi HGNC:2986. DOC2B.
    HPAi HPA043168.
    MIMi 604568. gene.
    neXtProti NX_Q14184.
    PharmGKBi PA27452.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG247952.
    HOGENOMi HOG000232127.
    HOVERGENi HBG051388.
    InParanoidi Q14184.
    OrthoDBi EOG7CZK67.
    PhylomeDBi Q14184.
    TreeFami TF351844.

    Miscellaneous databases

    GeneWikii DOC2B.
    GenomeRNAii 8447.
    NextBioi 31606.
    PROi Q14184.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q14184.
    CleanExi HS_DOC2B.
    Genevestigatori Q14184.

    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. "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: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    2. "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.
    3. "Doc2beta is a novel Munc18c-interacting partner and positive effector of syntaxin 4-mediated exocytosis."
      Ke B., Oh E., Thurmond D.C.
      J. Biol. Chem. 282:21786-21797(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    4. "Resequencing of 29 candidate genes in patients with familial and sporadic amyotrophic lateral sclerosis."
      Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D., Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A., Rouleau G.A.
      Arch. Neurol. 68:587-593(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LEU-209.

    Entry informationi

    Entry nameiDOC2B_HUMAN
    AccessioniPrimary (citable) accession number: Q14184
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 31, 2004
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 115 of the entry and version 1 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 17
      Human chromosome 17: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3