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Q9UPW8

- UN13A_HUMAN

UniProt

Q9UPW8 - UN13A_HUMAN

Protein

Protein unc-13 homolog A

Gene

UNC13A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 4 (25 Jan 2012)
      Previous versions | rss
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    Functioni

    Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses By similarity. Also involved in secretory granule priming in insulin secretion By similarity. Interacts with FBXO45 (via SRY domain); leading to the degradation of UNC13A by the proteasome By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi567 – 5671Zinc 1By similarity
    Metal bindingi570 – 5701Zinc 1By similarity
    Metal bindingi584 – 5841Zinc 2By similarity
    Metal bindingi587 – 5871Zinc 2By similarity
    Metal bindingi595 – 5951Zinc 1By similarity
    Metal bindingi603 – 6031Zinc 2By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri553 – 60351Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. diacylglycerol binding Source: Ensembl
    2. metal ion binding Source: UniProtKB-KW

    GO - Biological processi

    1. beta-amyloid metabolic process Source: Ensembl
    2. innervation Source: Ensembl
    3. intracellular signal transduction Source: InterPro
    4. neuromuscular junction development Source: Ensembl
    5. positive regulation of neurotransmitter secretion Source: Ensembl
    6. regulation of short-term neuronal synaptic plasticity Source: Ensembl
    7. synaptic transmission, glutamatergic Source: Ensembl
    8. synaptic vesicle docking involved in exocytosis Source: Ensembl
    9. synaptic vesicle maturation Source: Ensembl

    Keywords - Biological processi

    Exocytosis

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein unc-13 homolog A
    Alternative name(s):
    Munc13-1
    Gene namesi
    Name:UNC13A
    Synonyms:KIAA1032
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:23150. UNC13A.

    Subcellular locationi

    Cytoplasm By similarity. Cell membrane By similarity; Peripheral membrane protein By similarity. Cell junctionsynapsepresynaptic cell membrane By similarity; Peripheral membrane protein By similarity
    Note: Localized to the active zone of presynaptic density. Translocated to the plasma membrane as response to phorbol ester binding By similarity.By similarity

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-KW
    2. cytoplasm Source: UniProtKB-SubCell
    3. neuromuscular junction Source: Ensembl
    4. presynaptic membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Membrane, Synapse

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134879020.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 17031703Protein unc-13 homolog APRO_0000188573Add
    BLAST

    Proteomic databases

    PaxDbiQ9UPW8.
    PRIDEiQ9UPW8.

    PTM databases

    PhosphoSiteiQ9UPW8.

    Expressioni

    Tissue specificityi

    Expressed in pancreatic islet cells.1 Publication

    Gene expression databases

    ArrayExpressiQ9UPW8.
    BgeeiQ9UPW8.
    CleanExiHS_UNC13A.
    GenevestigatoriQ9UPW8.

    Organism-specific databases

    HPAiHPA041418.

    Interactioni

    Subunit structurei

    Interacts with the N-termini of STX1A and/or STX1B1 and DOC2A. Interacts with BSN. Interacts with RIMS1 which recruits UNC13A to the active zone. Forms homodimers via its first C2 domain. Also interacts via this domain with the zinc finger domain of RIMS2. Part of a complex consisting of ERC2, RIMS1 and UNC13A. Also part of a complex consisting of UNC13A, RIMS2 and RAB3A By similarity.By similarity

    Protein-protein interaction databases

    BioGridi116665. 5 interactions.
    IntActiQ9UPW8. 1 interaction.
    STRINGi9606.ENSP00000400409.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UPW8.
    SMRiQ9UPW8. Positions 2-128, 445-479, 554-603, 674-806, 1143-1503.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 7979C2 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini663 – 769107C2 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1093 – 1236144MHD1PROSITE-ProRule annotationAdd
    BLAST
    Domaini1345 – 1512168MHD2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1532 – 1637106C2 3PROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili320 – 35738Sequence AnalysisAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi321 – 35030Glu-richAdd
    BLAST

    Domaini

    The C2 domains are not involved in calcium-dependent phospholipid binding.By similarity
    The C-terminal region containing both MHD domains and the third C2 domain is required for synaptic vesicle priming activity.By similarity

    Sequence similaritiesi

    Belongs to the unc-13 family.Curated
    Contains 3 C2 domains.PROSITE-ProRule annotation
    Contains 1 MHD1 (MUNC13 homology domain 1) domain.PROSITE-ProRule annotation
    Contains 1 MHD2 (MUNC13 homology domain 2) domain.PROSITE-ProRule annotation
    Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri553 – 60351Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Coiled coil, Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiNOG245727.
    HOGENOMiHOG000231404.
    HOVERGENiHBG057340.
    InParanoidiQ9UPW8.
    KOiK15293.
    OrthoDBiEOG76738V.
    TreeFamiTF312844.

    Family and domain databases

    Gene3Di2.60.40.150. 3 hits.
    InterProiIPR000008. C2_dom.
    IPR010439. Ca-dep_secretion_activator.
    IPR014770. Munc13_1.
    IPR014772. Munc13_dom-2.
    IPR019558. Munc13_subgr_dom-2.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR027080. Unc-13.
    [Graphical view]
    PANTHERiPTHR10480. PTHR10480. 1 hit.
    PfamiPF00130. C1_1. 1 hit.
    PF00168. C2. 3 hits.
    PF06292. DUF1041. 1 hit.
    PF10540. Membr_traf_MHD. 1 hit.
    [Graphical view]
    PRINTSiPR00360. C2DOMAIN.
    SMARTiSM00109. C1. 1 hit.
    SM00239. C2. 3 hits.
    [Graphical view]
    SUPFAMiSSF49562. SSF49562. 3 hits.
    PROSITEiPS50004. C2. 2 hits.
    PS51258. MHD1. 1 hit.
    PS51259. MHD2. 1 hit.
    PS00479. ZF_DAG_PE_1. 1 hit.
    PS50081. ZF_DAG_PE_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9UPW8-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSLLCVGVKK AKFDGAQEKF NTYVTLKVQN VKSTTIAVRG SQPSWEQDFM     50
    FEINRLDLGL TVEVWNKGLI WDTMVGTVWI PLRTIRQSNE EGPGEWLTLD 100
    SQVIMADSEI CGTKDPTFHR ILLDTRFELP LDIPEEEARY WAKKLEQLNA 150
    MRDQDEYSFQ DEQDKPLPVP SNQCCNWNYF GWGEQHNDDP DSAVDDRDSD 200
    YRSETSNSIP PPYYTTSQPN ASVHQYSVRP PPLGSRESYS DSMHSYEEFS 250
    EPQALSPTGS SRYASSGELS QGSSQLSEDF DPDEHSLQGS DMEDERDRDS 300
    YHSCHSSVSY HKDSPRWDQD EEELEEDLED FLEEEELPED EEELEEEEEE 350
    VPDDLGSYAQ REDVAVAEPK DFKRISLPPA APGKEDKAPV APTEAPDMAK 400
    VAPKPATPDK VPAAEQIPEA EPPKDEESFR PREDEEGQEG QDSMSRAKAN 450
    WLRAFNKVRM QLQEARGEGE MSKSLWFKGG PGGGLIIIDS MPDIRKRKPI 500
    PLVSDLAMSL VQSRKAGITS ALASSTLNNE ELKNHVYKKT LQALIYPISC 550
    TTPHNFEVWT ATTPTYCYEC EGLLWGIARQ GMRCTECGVK CHEKCQDLLN 600
    ADCLQRAAEK SSKHGAEDRT QNIIMVLKDR MKIRERNKPE IFELIQEIFA 650
    VTKTAHTQQM KAVKQSVLDG TSKWSAKISI TVVCAQGLQA KDKTGSSDPY 700
    VTVQVGKTKK RTKTIYGNLN PVWEENFHFE CHNSSDRIKV RVWDEDDDIK 750
    SRVKQRFKRE SDDFLGQTII EVRTLSGEMD VWYNLDKRTD KSAVSGAIRL 800
    HISVEIKGEE KVAPYHVQYT CLHENLFHFV TDVQNNGVVK IPDAKGDDAW 850
    KVYYDETAQE IVDEFAMRYG VESIYQAMTH FACLSSKYMC PGVPAVMSTL 900
    LANINAYYAH TTASTNVSAS DRFAASNFGK ERFVKLLDQL HNSLRIDLSM 950
    YRNNFPASSP ERLQDLKSTV DLLTSITFFR MKVQELQSPP RASQVVKDCV 1000
    KACLNSTYEY IFNNCHELYS REYQTDPAKK GEVLPEEQGP SIKNLDFWSK 1050
    LITLIVSIIE EDKNSYTPCL NQFPQELNVG KISAEVMWNL FAQDMKYAME 1100
    EHDKHRLCKS ADYMNLHFKV KWLYNEYVTE LPAFKDRVPE YPAWFEPFVI 1150
    QWLDENEEVS RDFLHGALER DKKDGFQQTS EHALFSCSVV DVFSQLNQSF 1200
    EIIKKLECPD PQIVGHYMRR FAKTISNVLL QYADIISKDF ASYCSKEKEK 1250
    VPCILMNNTQ QLRVQLEKMF EAMGGKELDA EASDILKELQ VKLNNVLDEL 1300
    SRVFATSFQP HIEECVKQMG DILSQVKGTG NVPASACSSV AQDADNVLQP 1350
    IMDLLDSNLT LFAKICEKTV LKRVLKELWK LVMNTMEKTI VLPPLTDQTM 1400
    IGNLLRKHGK GLEKGRVKLP SHSDGTQMIF NAAKELGQLS KLKDHMVREE 1450
    AKSLTPKQCA VVELALDTIK QYFHAGGVGL KKTFLEKSPD LQSLRYALSL 1500
    YTQATDLLIK TFVQTQSAQG LGVEDPVGEV SVHVELFTHP GTGEHKVTVK 1550
    VVAANDLKWQ TSGIFRPFIE VNIIGPQLSD KKRKFATKSK NNSWAPKYNE 1600
    SFQFTLSADA GPECYELQVC VKDYCFARED RTVGLAVLQL RELAQRGSAA 1650
    CWLPLGRRIH MDDTGLTVLR ILSQRSNDEV AKEFVKLKSD TRSAEEGGAA 1700
    PAP 1703
    Length:1,703
    Mass (Da):193,014
    Last modified:January 25, 2012 - v4
    Checksum:iC8F6CEBEEF8E050B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti1034 – 10341L → P in BAA82984. (PubMed:10470851)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti359 – 3591A → T.
    Corresponds to variant rs34752754 [ dbSNP | Ensembl ].
    VAR_061872

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC008761 Genomic DNA. No translation available.
    AB028955 mRNA. Translation: BAA82984.2.
    CCDSiCCDS46013.2.
    RefSeqiNP_001073890.2. NM_001080421.2.
    UniGeneiHs.164502.

    Genome annotation databases

    EnsembliENST00000519716; ENSP00000429562; ENSG00000130477.
    GeneIDi23025.
    KEGGihsa:23025.
    UCSCiuc031rjv.1. human.

    Polymorphism databases

    DMDMi374095515.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC008761 Genomic DNA. No translation available.
    AB028955 mRNA. Translation: BAA82984.2 .
    CCDSi CCDS46013.2.
    RefSeqi NP_001073890.2. NM_001080421.2.
    UniGenei Hs.164502.

    3D structure databases

    ProteinModelPortali Q9UPW8.
    SMRi Q9UPW8. Positions 2-128, 445-479, 554-603, 674-806, 1143-1503.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116665. 5 interactions.
    IntActi Q9UPW8. 1 interaction.
    STRINGi 9606.ENSP00000400409.

    PTM databases

    PhosphoSitei Q9UPW8.

    Polymorphism databases

    DMDMi 374095515.

    Proteomic databases

    PaxDbi Q9UPW8.
    PRIDEi Q9UPW8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000519716 ; ENSP00000429562 ; ENSG00000130477 .
    GeneIDi 23025.
    KEGGi hsa:23025.
    UCSCi uc031rjv.1. human.

    Organism-specific databases

    CTDi 23025.
    GeneCardsi GC19M017712.
    H-InvDB HIX0014898.
    HGNCi HGNC:23150. UNC13A.
    HPAi HPA041418.
    MIMi 609894. gene.
    neXtProti NX_Q9UPW8.
    PharmGKBi PA134879020.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG245727.
    HOGENOMi HOG000231404.
    HOVERGENi HBG057340.
    InParanoidi Q9UPW8.
    KOi K15293.
    OrthoDBi EOG76738V.
    TreeFami TF312844.

    Miscellaneous databases

    ChiTaRSi UNC13A. human.
    GenomeRNAii 23025.
    NextBioi 43986.
    PROi Q9UPW8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UPW8.
    Bgeei Q9UPW8.
    CleanExi HS_UNC13A.
    Genevestigatori Q9UPW8.

    Family and domain databases

    Gene3Di 2.60.40.150. 3 hits.
    InterProi IPR000008. C2_dom.
    IPR010439. Ca-dep_secretion_activator.
    IPR014770. Munc13_1.
    IPR014772. Munc13_dom-2.
    IPR019558. Munc13_subgr_dom-2.
    IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
    IPR027080. Unc-13.
    [Graphical view ]
    PANTHERi PTHR10480. PTHR10480. 1 hit.
    Pfami PF00130. C1_1. 1 hit.
    PF00168. C2. 3 hits.
    PF06292. DUF1041. 1 hit.
    PF10540. Membr_traf_MHD. 1 hit.
    [Graphical view ]
    PRINTSi PR00360. C2DOMAIN.
    SMARTi SM00109. C1. 1 hit.
    SM00239. C2. 3 hits.
    [Graphical view ]
    SUPFAMi SSF49562. SSF49562. 3 hits.
    PROSITEi PS50004. C2. 2 hits.
    PS51258. MHD1. 1 hit.
    PS51259. MHD2. 1 hit.
    PS00479. ZF_DAG_PE_1. 1 hit.
    PS50081. ZF_DAG_PE_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-1703.
      Tissue: Brain.
    3. Ohara O., Nagase T., Kikuno R.
      Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    4. Cited for: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiUN13A_HUMAN
    AccessioniPrimary (citable) accession number: Q9UPW8
    Secondary accession number(s): E5RHY9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 16, 2004
    Last sequence update: January 25, 2012
    Last modified: October 1, 2014
    This is version 118 of the entry and version 4 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 19
      Human chromosome 19: 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