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Protein

Protein unc-13 homolog A

Gene

UNC13A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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). Plays a role in dendrite formation by melanocytes (PubMed:23999003).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi567Zinc 1By similarity1
Metal bindingi570Zinc 1By similarity1
Metal bindingi584Zinc 2By similarity1
Metal bindingi587Zinc 2By similarity1
Metal bindingi595Zinc 1By similarity1
Metal bindingi603Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri553 – 603Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processDifferentiation, Exocytosis
LigandMetal-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
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000130477.14
HGNCiHGNC:23150 UNC13A
MIMi609894 gene
neXtProtiNX_Q9UPW8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane, Synapse

Pathology & Biotechi

Organism-specific databases

DisGeNETi23025
MalaCardsiUNC13A
OpenTargetsiENSG00000130477
Orphaneti803 Amyotrophic lateral sclerosis
PharmGKBiPA134879020

Polymorphism and mutation databases

BioMutaiUNC13A
DMDMi374095515

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001885731 – 1703Protein unc-13 homolog AAdd BLAST1703

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei240PhosphoserineBy similarity1
Modified residuei242PhosphoserineBy similarity1
Modified residuei245PhosphoserineBy similarity1
Modified residuei256PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UPW8
MaxQBiQ9UPW8
PaxDbiQ9UPW8
PeptideAtlasiQ9UPW8
PRIDEiQ9UPW8
ProteomicsDBi85464

PTM databases

iPTMnetiQ9UPW8
PhosphoSitePlusiQ9UPW8

Expressioni

Tissue specificityi

Expressed in pancreatic islet cells (PubMed:12871971). Expressed in melanocytes (PubMed:23999003).2 Publications

Gene expression databases

BgeeiENSG00000130477 Expressed in 192 organ(s), highest expression level in cingulate cortex
CleanExiHS_UNC13A
ExpressionAtlasiQ9UPW8 baseline and differential
GenevisibleiQ9UPW8 HS

Organism-specific databases

HPAiHPA041418
HPA077242

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116665, 7 interactors
IntActiQ9UPW8, 2 interactors
STRINGi9606.ENSP00000429562

Structurei

3D structure databases

ProteinModelPortaliQ9UPW8
SMRiQ9UPW8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 79C2 1PROSITE-ProRule annotationAdd BLAST79
Domaini663 – 769C2 2PROSITE-ProRule annotationAdd BLAST107
Domaini1093 – 1236MHD1PROSITE-ProRule annotationAdd BLAST144
Domaini1345 – 1512MHD2PROSITE-ProRule annotationAdd BLAST168
Domaini1532 – 1637C2 3PROSITE-ProRule annotationAdd BLAST106

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili320 – 357Sequence analysisAdd BLAST38

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi321 – 350Glu-richAdd BLAST30

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri553 – 603Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1011 Eukaryota
ENOG410XS5D LUCA
GeneTreeiENSGT00920000149033
HOGENOMiHOG000231404
HOVERGENiHBG057340
InParanoidiQ9UPW8
KOiK15293
TreeFamiTF312844

Family and domain databases

CDDicd00029 C1, 1 hit
cd04027 C2B_Munc13, 1 hit
Gene3Di2.60.40.150, 3 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR010439 CAPS_dom
IPR014770 Munc13_1
IPR014772 Munc13_dom-2
IPR019558 Munc13_subgr_dom-2
IPR002219 PE/DAG-bd
IPR027080 Unc-13
IPR037302 Unc-13_C2B
IPR027082 Unc13A
PANTHERiPTHR10480 PTHR10480, 1 hit
PTHR10480:SF1 PTHR10480:SF1, 1 hit
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF00168 C2, 3 hits
PF06292 DUF1041, 1 hit
PF10540 Membr_traf_MHD, 1 hit
PRINTSiPR00360 C2DOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00239 C2, 3 hits
SM01145 DUF1041, 1 hit
PROSITEiView protein in PROSITE
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

Q9UPW8-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSLLCVGVKK AKFDGAQEKF NTYVTLKVQN VKSTTIAVRG SQPSWEQDFM
60 70 80 90 100
FEINRLDLGL TVEVWNKGLI WDTMVGTVWI PLRTIRQSNE EGPGEWLTLD
110 120 130 140 150
SQVIMADSEI CGTKDPTFHR ILLDTRFELP LDIPEEEARY WAKKLEQLNA
160 170 180 190 200
MRDQDEYSFQ DEQDKPLPVP SNQCCNWNYF GWGEQHNDDP DSAVDDRDSD
210 220 230 240 250
YRSETSNSIP PPYYTTSQPN ASVHQYSVRP PPLGSRESYS DSMHSYEEFS
260 270 280 290 300
EPQALSPTGS SRYASSGELS QGSSQLSEDF DPDEHSLQGS DMEDERDRDS
310 320 330 340 350
YHSCHSSVSY HKDSPRWDQD EEELEEDLED FLEEEELPED EEELEEEEEE
360 370 380 390 400
VPDDLGSYAQ REDVAVAEPK DFKRISLPPA APGKEDKAPV APTEAPDMAK
410 420 430 440 450
VAPKPATPDK VPAAEQIPEA EPPKDEESFR PREDEEGQEG QDSMSRAKAN
460 470 480 490 500
WLRAFNKVRM QLQEARGEGE MSKSLWFKGG PGGGLIIIDS MPDIRKRKPI
510 520 530 540 550
PLVSDLAMSL VQSRKAGITS ALASSTLNNE ELKNHVYKKT LQALIYPISC
560 570 580 590 600
TTPHNFEVWT ATTPTYCYEC EGLLWGIARQ GMRCTECGVK CHEKCQDLLN
610 620 630 640 650
ADCLQRAAEK SSKHGAEDRT QNIIMVLKDR MKIRERNKPE IFELIQEIFA
660 670 680 690 700
VTKTAHTQQM KAVKQSVLDG TSKWSAKISI TVVCAQGLQA KDKTGSSDPY
710 720 730 740 750
VTVQVGKTKK RTKTIYGNLN PVWEENFHFE CHNSSDRIKV RVWDEDDDIK
760 770 780 790 800
SRVKQRFKRE SDDFLGQTII EVRTLSGEMD VWYNLDKRTD KSAVSGAIRL
810 820 830 840 850
HISVEIKGEE KVAPYHVQYT CLHENLFHFV TDVQNNGVVK IPDAKGDDAW
860 870 880 890 900
KVYYDETAQE IVDEFAMRYG VESIYQAMTH FACLSSKYMC PGVPAVMSTL
910 920 930 940 950
LANINAYYAH TTASTNVSAS DRFAASNFGK ERFVKLLDQL HNSLRIDLSM
960 970 980 990 1000
YRNNFPASSP ERLQDLKSTV DLLTSITFFR MKVQELQSPP RASQVVKDCV
1010 1020 1030 1040 1050
KACLNSTYEY IFNNCHELYS REYQTDPAKK GEVLPEEQGP SIKNLDFWSK
1060 1070 1080 1090 1100
LITLIVSIIE EDKNSYTPCL NQFPQELNVG KISAEVMWNL FAQDMKYAME
1110 1120 1130 1140 1150
EHDKHRLCKS ADYMNLHFKV KWLYNEYVTE LPAFKDRVPE YPAWFEPFVI
1160 1170 1180 1190 1200
QWLDENEEVS RDFLHGALER DKKDGFQQTS EHALFSCSVV DVFSQLNQSF
1210 1220 1230 1240 1250
EIIKKLECPD PQIVGHYMRR FAKTISNVLL QYADIISKDF ASYCSKEKEK
1260 1270 1280 1290 1300
VPCILMNNTQ QLRVQLEKMF EAMGGKELDA EASDILKELQ VKLNNVLDEL
1310 1320 1330 1340 1350
SRVFATSFQP HIEECVKQMG DILSQVKGTG NVPASACSSV AQDADNVLQP
1360 1370 1380 1390 1400
IMDLLDSNLT LFAKICEKTV LKRVLKELWK LVMNTMEKTI VLPPLTDQTM
1410 1420 1430 1440 1450
IGNLLRKHGK GLEKGRVKLP SHSDGTQMIF NAAKELGQLS KLKDHMVREE
1460 1470 1480 1490 1500
AKSLTPKQCA VVELALDTIK QYFHAGGVGL KKTFLEKSPD LQSLRYALSL
1510 1520 1530 1540 1550
YTQATDLLIK TFVQTQSAQG LGVEDPVGEV SVHVELFTHP GTGEHKVTVK
1560 1570 1580 1590 1600
VVAANDLKWQ TSGIFRPFIE VNIIGPQLSD KKRKFATKSK NNSWAPKYNE
1610 1620 1630 1640 1650
SFQFTLSADA GPECYELQVC VKDYCFARED RTVGLAVLQL RELAQRGSAA
1660 1670 1680 1690 1700
CWLPLGRRIH MDDTGLTVLR ILSQRSNDEV AKEFVKLKSD TRSAEEGGAA

PAP
Length:1,703
Mass (Da):193,014
Last modified:January 25, 2012 - v4
Checksum:iC8F6CEBEEF8E050B
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8W059F8W059_HUMAN
Protein unc-13 homolog A
UNC13A
1,722Annotation score:
F8VZH8F8VZH8_HUMAN
Protein unc-13 homolog A
UNC13A
1,676Annotation score:
F8W0P6F8W0P6_HUMAN
Protein unc-13 homolog A
UNC13A
1,697Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1034L → P in BAA82984 (PubMed:10470851).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061872359A → T. Corresponds to variant dbSNP:rs34752754Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
UCSCiuc060vkq.1 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC008761 Genomic DNA No translation available.
AB028955 mRNA Translation: BAA82984.2
CCDSiCCDS46013.2
RefSeqiNP_001073890.2, NM_001080421.2
UniGeneiHs.164502

3D structure databases

ProteinModelPortaliQ9UPW8
SMRiQ9UPW8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116665, 7 interactors
IntActiQ9UPW8, 2 interactors
STRINGi9606.ENSP00000429562

PTM databases

iPTMnetiQ9UPW8
PhosphoSitePlusiQ9UPW8

Polymorphism and mutation databases

BioMutaiUNC13A
DMDMi374095515

Proteomic databases

EPDiQ9UPW8
MaxQBiQ9UPW8
PaxDbiQ9UPW8
PeptideAtlasiQ9UPW8
PRIDEiQ9UPW8
ProteomicsDBi85464

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000519716; ENSP00000429562; ENSG00000130477
GeneIDi23025
KEGGihsa:23025
UCSCiuc060vkq.1 human

Organism-specific databases

CTDi23025
DisGeNETi23025
EuPathDBiHostDB:ENSG00000130477.14
GeneCardsiUNC13A
H-InvDBiHIX0014898
HGNCiHGNC:23150 UNC13A
HPAiHPA041418
HPA077242
MalaCardsiUNC13A
MIMi609894 gene
neXtProtiNX_Q9UPW8
OpenTargetsiENSG00000130477
Orphaneti803 Amyotrophic lateral sclerosis
PharmGKBiPA134879020
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1011 Eukaryota
ENOG410XS5D LUCA
GeneTreeiENSGT00920000149033
HOGENOMiHOG000231404
HOVERGENiHBG057340
InParanoidiQ9UPW8
KOiK15293
TreeFamiTF312844

Miscellaneous databases

ChiTaRSiUNC13A human
GenomeRNAii23025
PROiPR:Q9UPW8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130477 Expressed in 192 organ(s), highest expression level in cingulate cortex
CleanExiHS_UNC13A
ExpressionAtlasiQ9UPW8 baseline and differential
GenevisibleiQ9UPW8 HS

Family and domain databases

CDDicd00029 C1, 1 hit
cd04027 C2B_Munc13, 1 hit
Gene3Di2.60.40.150, 3 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR010439 CAPS_dom
IPR014770 Munc13_1
IPR014772 Munc13_dom-2
IPR019558 Munc13_subgr_dom-2
IPR002219 PE/DAG-bd
IPR027080 Unc-13
IPR037302 Unc-13_C2B
IPR027082 Unc13A
PANTHERiPTHR10480 PTHR10480, 1 hit
PTHR10480:SF1 PTHR10480:SF1, 1 hit
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF00168 C2, 3 hits
PF06292 DUF1041, 1 hit
PF10540 Membr_traf_MHD, 1 hit
PRINTSiPR00360 C2DOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00239 C2, 3 hits
SM01145 DUF1041, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiUN13A_HUMAN
AccessioniPrimary (citable) accession number: Q9UPW8
Secondary accession number(s): E5RHY9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: January 25, 2012
Last modified: November 7, 2018
This is version 153 of the entry and version 4 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
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