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Q9UPW8

- UN13A_HUMAN

UniProt

Q9UPW8 - UN13A_HUMAN

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Protein

Protein unc-13 homolog A

Gene
UNC13A, KIAA1032
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

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.

Sites

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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri553 – 60351Phorbol-ester/DAG-typeAdd
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
Complete GO annotation...

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; Peripheral membrane protein By similarity. Cell junctionsynapsepresynaptic cell membrane; 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.

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
Complete GO annotation...

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.

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 7979C2 1Add
BLAST
Domaini663 – 769107C2 2Add
BLAST
Domaini1093 – 1236144MHD1Add
BLAST
Domaini1345 – 1512168MHD2Add
BLAST
Domaini1532 – 1637106C2 3Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili320 – 35738 Reviewed predictionAdd
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.
Contains 3 C2 domains.

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri553 – 60351Phorbol-ester/DAG-typeAdd
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

Natural variant

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1034 – 10341L → P in BAA82984. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 117 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

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