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Q9UPW8 (UN13A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein unc-13 homolog A
Alternative name(s):
Munc13-1
Gene names
Name:UNC13A
Synonyms:KIAA1032
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1703 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

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.

Tissue specificity

Expressed in pancreatic islet cells. Ref.4

Domain

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 similarities

Belongs to the unc-13 family.

Contains 3 C2 domains.

Contains 1 MHD1 (MUNC13 homology domain 1) domain.

Contains 1 MHD2 (MUNC13 homology domain 2) domain.

Contains 1 phorbol-ester/DAG-type zinc finger.

Ontologies

Keywords
   Biological processExocytosis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Membrane
Synapse
   Coding sequence diversityPolymorphism
   DomainCoiled coil
Repeat
Zinc-finger
   LigandMetal-binding
Zinc
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbeta-amyloid metabolic process

Inferred from electronic annotation. Source: Ensembl

innervation

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

neuromuscular junction development

Inferred from electronic annotation. Source: Ensembl

positive regulation of neurotransmitter secretion

Inferred from electronic annotation. Source: Ensembl

regulation of short-term neuronal synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle docking involved in exocytosis

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle maturation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

presynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functiondiacylglycerol binding

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 17031703Protein unc-13 homolog A
PRO_0000188573

Regions

Domain1 – 7979C2 1
Domain663 – 769107C2 2
Domain1093 – 1236144MHD1
Domain1345 – 1512168MHD2
Domain1532 – 1637106C2 3
Zinc finger553 – 60351Phorbol-ester/DAG-type
Coiled coil320 – 35738 Potential
Compositional bias321 – 35030Glu-rich

Sites

Metal binding5671Zinc 1 By similarity
Metal binding5701Zinc 1 By similarity
Metal binding5841Zinc 2 By similarity
Metal binding5871Zinc 2 By similarity
Metal binding5951Zinc 1 By similarity
Metal binding6031Zinc 2 By similarity

Natural variations

Natural variant3591A → T.
Corresponds to variant rs34752754 [ dbSNP | Ensembl ].
VAR_061872

Experimental info

Sequence conflict10341L → P in BAA82984. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9UPW8 [UniParc].

Last modified January 25, 2012. Version 4.
Checksum: C8F6CEBEEF8E050B

FASTA1,703193,014
        10         20         30         40         50         60 
MSLLCVGVKK AKFDGAQEKF NTYVTLKVQN VKSTTIAVRG SQPSWEQDFM FEINRLDLGL 

        70         80         90        100        110        120 
TVEVWNKGLI WDTMVGTVWI PLRTIRQSNE EGPGEWLTLD SQVIMADSEI CGTKDPTFHR 

       130        140        150        160        170        180 
ILLDTRFELP LDIPEEEARY WAKKLEQLNA MRDQDEYSFQ DEQDKPLPVP SNQCCNWNYF 

       190        200        210        220        230        240 
GWGEQHNDDP DSAVDDRDSD YRSETSNSIP PPYYTTSQPN ASVHQYSVRP PPLGSRESYS 

       250        260        270        280        290        300 
DSMHSYEEFS EPQALSPTGS SRYASSGELS QGSSQLSEDF DPDEHSLQGS DMEDERDRDS 

       310        320        330        340        350        360 
YHSCHSSVSY HKDSPRWDQD EEELEEDLED FLEEEELPED EEELEEEEEE VPDDLGSYAQ 

       370        380        390        400        410        420 
REDVAVAEPK DFKRISLPPA APGKEDKAPV APTEAPDMAK VAPKPATPDK VPAAEQIPEA 

       430        440        450        460        470        480 
EPPKDEESFR PREDEEGQEG QDSMSRAKAN WLRAFNKVRM QLQEARGEGE MSKSLWFKGG 

       490        500        510        520        530        540 
PGGGLIIIDS MPDIRKRKPI PLVSDLAMSL VQSRKAGITS ALASSTLNNE ELKNHVYKKT 

       550        560        570        580        590        600 
LQALIYPISC TTPHNFEVWT ATTPTYCYEC EGLLWGIARQ GMRCTECGVK CHEKCQDLLN 

       610        620        630        640        650        660 
ADCLQRAAEK SSKHGAEDRT QNIIMVLKDR MKIRERNKPE IFELIQEIFA VTKTAHTQQM 

       670        680        690        700        710        720 
KAVKQSVLDG TSKWSAKISI TVVCAQGLQA KDKTGSSDPY VTVQVGKTKK RTKTIYGNLN 

       730        740        750        760        770        780 
PVWEENFHFE CHNSSDRIKV RVWDEDDDIK SRVKQRFKRE SDDFLGQTII EVRTLSGEMD 

       790        800        810        820        830        840 
VWYNLDKRTD KSAVSGAIRL HISVEIKGEE KVAPYHVQYT CLHENLFHFV TDVQNNGVVK 

       850        860        870        880        890        900 
IPDAKGDDAW KVYYDETAQE IVDEFAMRYG VESIYQAMTH FACLSSKYMC PGVPAVMSTL 

       910        920        930        940        950        960 
LANINAYYAH TTASTNVSAS DRFAASNFGK ERFVKLLDQL HNSLRIDLSM YRNNFPASSP 

       970        980        990       1000       1010       1020 
ERLQDLKSTV DLLTSITFFR MKVQELQSPP RASQVVKDCV KACLNSTYEY IFNNCHELYS 

      1030       1040       1050       1060       1070       1080 
REYQTDPAKK GEVLPEEQGP SIKNLDFWSK LITLIVSIIE EDKNSYTPCL NQFPQELNVG 

      1090       1100       1110       1120       1130       1140 
KISAEVMWNL FAQDMKYAME EHDKHRLCKS ADYMNLHFKV KWLYNEYVTE LPAFKDRVPE 

      1150       1160       1170       1180       1190       1200 
YPAWFEPFVI QWLDENEEVS RDFLHGALER DKKDGFQQTS EHALFSCSVV DVFSQLNQSF 

      1210       1220       1230       1240       1250       1260 
EIIKKLECPD PQIVGHYMRR FAKTISNVLL QYADIISKDF ASYCSKEKEK VPCILMNNTQ 

      1270       1280       1290       1300       1310       1320 
QLRVQLEKMF EAMGGKELDA EASDILKELQ VKLNNVLDEL SRVFATSFQP HIEECVKQMG 

      1330       1340       1350       1360       1370       1380 
DILSQVKGTG NVPASACSSV AQDADNVLQP IMDLLDSNLT LFAKICEKTV LKRVLKELWK 

      1390       1400       1410       1420       1430       1440 
LVMNTMEKTI VLPPLTDQTM IGNLLRKHGK GLEKGRVKLP SHSDGTQMIF NAAKELGQLS 

      1450       1460       1470       1480       1490       1500 
KLKDHMVREE AKSLTPKQCA VVELALDTIK QYFHAGGVGL KKTFLEKSPD LQSLRYALSL 

      1510       1520       1530       1540       1550       1560 
YTQATDLLIK TFVQTQSAQG LGVEDPVGEV SVHVELFTHP GTGEHKVTVK VVAANDLKWQ 

      1570       1580       1590       1600       1610       1620 
TSGIFRPFIE VNIIGPQLSD KKRKFATKSK NNSWAPKYNE SFQFTLSADA GPECYELQVC 

      1630       1640       1650       1660       1670       1680 
VKDYCFARED RTVGLAVLQL RELAQRGSAA CWLPLGRRIH MDDTGLTVLR ILSQRSNDEV 

      1690       1700 
AKEFVKLKSD TRSAEEGGAA PAP 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Regulation of insulin exocytosis by Munc13-1."
Sheu L., Pasyk E.A., Ji J., Huang X., Gao X., Varoqueaux F., Brose N., Gaisano H.Y.
J. Biol. Chem. 278:27556-27563(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC008761 Genomic DNA. No translation available.
AB028955 mRNA. Translation: BAA82984.2.
CCDSCCDS46013.2.
RefSeqNP_001073890.2. NM_001080421.2.
UniGeneHs.164502.

3D structure databases

ProteinModelPortalQ9UPW8.
SMRQ9UPW8. Positions 2-128, 445-479, 554-603, 674-806, 1143-1503.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116665. 5 interactions.
IntActQ9UPW8. 1 interaction.
STRING9606.ENSP00000400409.

PTM databases

PhosphoSiteQ9UPW8.

Polymorphism databases

DMDM374095515.

Proteomic databases

PaxDbQ9UPW8.
PRIDEQ9UPW8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000519716; ENSP00000429562; ENSG00000130477.
GeneID23025.
KEGGhsa:23025.
UCSCuc031rjv.1. human.

Organism-specific databases

CTD23025.
GeneCardsGC19M017712.
H-InvDBHIX0014898.
HGNCHGNC:23150. UNC13A.
HPAHPA041418.
MIM609894. gene.
neXtProtNX_Q9UPW8.
PharmGKBPA134879020.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245727.
HOGENOMHOG000231404.
HOVERGENHBG057340.
InParanoidQ9UPW8.
KOK15293.
OrthoDBEOG76738V.
TreeFamTF312844.

Gene expression databases

ArrayExpressQ9UPW8.
BgeeQ9UPW8.
CleanExHS_UNC13A.
GenevestigatorQ9UPW8.

Family and domain databases

Gene3D2.60.40.150. 3 hits.
InterProIPR000008. 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]
PANTHERPTHR10480. PTHR10480. 1 hit.
PfamPF00130. C1_1. 1 hit.
PF00168. C2. 3 hits.
PF06292. DUF1041. 1 hit.
PF10540. Membr_traf_MHD. 1 hit.
[Graphical view]
PRINTSPR00360. C2DOMAIN.
SMARTSM00109. C1. 1 hit.
SM00239. C2. 3 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 3 hits.
PROSITEPS50004. 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]
ProtoNetSearch...

Other

ChiTaRSUNC13A. human.
GenomeRNAi23025.
NextBio43986.
PROQ9UPW8.
SOURCESearch...

Entry information

Entry nameUN13A_HUMAN
AccessionPrimary (citable) accession number: Q9UPW8
Secondary accession number(s): E5RHY9
Entry history
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 statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM