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Protein

Protein unc-13 homolog A

Gene

Unc13a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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. Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (By similarity).By similarity7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi576Zinc 1By similarity1
Metal bindingi579Zinc 1By similarity1
Metal bindingi593Zinc 2By similarity1
Metal bindingi596Zinc 2By similarity1
Metal bindingi604Zinc 1By similarity1
Metal bindingi612Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri562 – 612Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

GO - Molecular functioni

GO - Biological processi

  • beta-amyloid metabolic process Source: MGI
  • innervation Source: MGI
  • intracellular signal transduction Source: InterPro
  • neuromuscular junction development Source: MGI
  • neurotransmitter secretion Source: ParkinsonsUK-UCL
  • positive regulation of dendrite extension Source: MGI
  • positive regulation of glutamate receptor signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of neurotransmitter secretion Source: MGI
  • positive regulation of synaptic plasticity Source: ParkinsonsUK-UCL
  • regulation of amyloid precursor protein catabolic process Source: ParkinsonsUK-UCL
  • regulation of short-term neuronal synaptic plasticity Source: MGI
  • regulation of synaptic vesicle priming Source: ParkinsonsUK-UCL
  • synaptic transmission, glutamatergic Source: MGI
  • synaptic vesicle docking Source: MGI
  • synaptic vesicle maturation Source: MGI
  • synaptic vesicle priming Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Biological processi

Differentiation, 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:Unc13aImported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:3051532. 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 in response to phorbol ester binding (By similarity).By similarity

GO - Cellular componenti

  • axon Source: MGI
  • calyx of Held Source: ParkinsonsUK-UCL
  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB-SubCell
  • neuromuscular junction Source: MGI
  • neuron projection Source: ParkinsonsUK-UCL
  • presynapse Source: MGI
  • presynaptic active zone Source: ParkinsonsUK-UCL
  • presynaptic membrane Source: ParkinsonsUK-UCL
  • synapse Source: MGI
  • terminal bouton Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice display normal synapse formation but abnormal synaptic vesicle maturation and die shortly after birth. Heterozygotes exhibit impaired insulin secretion and abnormal glucose tolerance.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi563H → V: Reduces number of fusion-competent vesicles in neurons. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003062851 – 1712Protein unc-13 homolog AAdd BLAST1712

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei239PhosphoserineBy similarity1
Modified residuei241PhosphoserineBy similarity1
Modified residuei244PhosphoserineBy similarity1
Modified residuei255PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ4KUS2.
PaxDbiQ4KUS2.
PeptideAtlasiQ4KUS2.
PRIDEiQ4KUS2.

PTM databases

iPTMnetiQ4KUS2.
PhosphoSitePlusiQ4KUS2.

Expressioni

Gene expression databases

BgeeiENSMUSG00000034799.
CleanExiMM_UNC13A.
ExpressionAtlasiQ4KUS2. baseline and differential.
GenevisibleiQ4KUS2. MM.

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). Interacts with FBXO45 (via SRY domain); leading to the degradation of UNC13A by the proteasome.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ4KUS2. 1 interactor.
STRINGi10090.ENSMUSP00000030170.

Structurei

3D structure databases

ProteinModelPortaliQ4KUS2.
SMRiQ4KUS2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 79C2 1PROSITE-ProRule annotationAdd BLAST79
Domaini672 – 778C2 2PROSITE-ProRule annotationAdd BLAST107
Domaini1102 – 1245MHD1PROSITE-ProRule annotationAdd BLAST144
Domaini1354 – 1521MHD2PROSITE-ProRule annotationAdd BLAST168
Domaini1541 – 1646C2 3PROSITE-ProRule annotationAdd BLAST106

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili321 – 360Sequence analysisAdd BLAST40

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi321 – 448Glu-richSequence analysisAdd BLAST128

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

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)DescriptionActionsGraphical viewLength
Zinc fingeri562 – 612Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Coiled coil, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1011. Eukaryota.
ENOG410XS5D. LUCA.
GeneTreeiENSGT00850000132267.
HOGENOMiHOG000231404.
HOVERGENiHBG057340.
InParanoidiQ4KUS2.
KOiK15293.
TreeFamiTF312844.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di2.60.40.150. 3 hits.
InterProiIPR000008. C2_dom.
IPR010439. CAPS_dom.
IPR014770. Munc13_1.
IPR014772. Munc13_dom-2.
IPR019558. Munc13_subgr_dom-2.
IPR002219. PE/DAG-bd.
IPR027080. Unc-13.
[Graphical view]
PANTHERiPTHR10480. PTHR10480. 2 hits.
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.
SM01145. DUF1041. 1 hit.
[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.

Q4KUS2-1 [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
SQAIMADSEI CGTKDPTFHR ILLDAHFELP LDIPEEEARY WAKKLEQLNA
160 170 180 190 200
MRDQDEYSFQ DQQDKPLPVP SSQCCNWNYF GWGEQNDDPD SAVDDRDSDY
210 220 230 240 250
RSETSNSIPP PYYTTSQPNA SVHQYSVRPP PLGSRESYSD SMHSYEEFSE
260 270 280 290 300
PRALSPTGSS RYASSGELSQ GSSQLSEDFD PDEHSLQGSE LDDERDRDSY
310 320 330 340 350
HSCHSSVSYH KDSPRWDQDD EDLEDLEDLE DEELPEEEEE LEEEGEEELE
360 370 380 390 400
EEDLEEEEEV PDDLASYTQQ EDTTVAEPKE FKRISFPTAA PQKDDKVSAV
410 420 430 440 450
PTEAPEVAKG IPKAATPEEK AAAERAQEAE PPKSEESFRS REEEEGQEGQ
460 470 480 490 500
DAMSRAKANW LRAFNKVRMQ LQEARGEGDM SKSLWFKGGP GGGLIIIDSM
510 520 530 540 550
PDIRKRKPIP LVSDLAMSLV QSRKAGITSA LASSTLNNEE LKNHVYKKTL
560 570 580 590 600
QALIYPISCT TPHNFEVWTA TTPTYCYECE GLLWGIARQG MRCTECGVKC
610 620 630 640 650
HEKCQDLLNA DCLQRAAEKS SKHGAEDRTQ NIIMVLKDRM KIRERNKPEI
660 670 680 690 700
FELIQEIFAV TKSAHTQQMK AVKQSVLDGT SKWSAKISIT VVCAQGLQAK
710 720 730 740 750
DKTGSSDPYV TVQVGKTKKR TKTIYGNLNP VWEENFHFEC HNSSDRIKVR
760 770 780 790 800
VWDEDDDIKS RVKQRFKRES DDFLGQTIIE VRTLSGEMDV WYNLDKRTDK
810 820 830 840 850
SAVSGAIRLH ISVEIKGEEK VAPYHVQYTC LHENLFHFVT DVQNNGVVKI
860 870 880 890 900
PDAKGDDAWK VYYDETAQEI VDEFAMRYGV ESIYQAMTHF ACLSSKYMCP
910 920 930 940 950
GVPAVMSTLL ANINAYYAHT TASTNVSASD RFAASNFGKE RFVKLLDQLH
960 970 980 990 1000
NSLRIDLSMY RNNFPASSPE RLQDLKSTVD LLTSITFFRM KVQELQSPPR
1010 1020 1030 1040 1050
ASQVVKDCVK ACLNSTYEYI FNNCHELYGR EYQTDPAKKG EVPPEEQGPS
1060 1070 1080 1090 1100
IKNLDFWSKL ITLIVSIIEE DKNSYTPCLN QFPQELNVGK ISAEVMWSLF
1110 1120 1130 1140 1150
AQDMKYAMEE HDKHRLCKSA DYMNLHFKVK WLYNEYVAEL PTFKDRVPEY
1160 1170 1180 1190 1200
PAWFEPFVIQ WLDENEEVSR DFLHGALERD KKDGFQQTSE HALFSCSVVD
1210 1220 1230 1240 1250
VFSQLNQSFE IIKKLECPDP QIVGHYMRRF AKTISNVLLQ YADIVSKDFA
1260 1270 1280 1290 1300
SYCSKEKEKV PCILMNNTQQ LRVQLEKMFE AMGGKELDAE ASGTLKELQV
1310 1320 1330 1340 1350
KLNNVLDELS HVFATSFQPH IEECVRQMGD ILSQVKGTGN VPASACSSVA
1360 1370 1380 1390 1400
QDADNVLQPI MDLLDSNLTL FAKICEKTVL KRVLKELWKL VMNTMEKTIV
1410 1420 1430 1440 1450
LPPLTDQTMI GTLLRKHGKG LEKGRVKLPS HSDGTQMIFN AAKELGQLSK
1460 1470 1480 1490 1500
LKDHMVREEA KSLTPKQCAV VELALDTIKQ YFHAGGVGLK KTFLEKSPDL
1510 1520 1530 1540 1550
QSLRYALSLY TQATDLLIKT FVQTQSAQGS GVEDPVGEVS VHVELFTHPG
1560 1570 1580 1590 1600
TGEQKVTVKV VAANDLKWQT SGIFRPFIEV NIVGPQLSDK KRKFATKSKN
1610 1620 1630 1640 1650
NSWAPKYNES FQFSLSADAG PECYELQVCV KDYCFAREDR TVGLAVLQLR
1660 1670 1680 1690 1700
ELAQRGSAAC WLPLGRRIHM DDTGLTVLRI LSQRSNDEVA KEFVKLKSDT
1710
RSAEEGGAAP AP
Length:1,712
Mass (Da):193,782
Last modified:July 27, 2011 - v3
Checksum:iAA498D15557454EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti127F → I in BAE27895 (PubMed:16141072).Curated1
Sequence conflicti479D → E in AAX09281 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY753536 mRNA. Translation: AAX09281.1.
AC162033 Genomic DNA. No translation available.
AK147408 mRNA. Translation: BAE27895.1.
CCDSiCCDS22402.2.
RefSeqiNP_001025044.2. NM_001029873.2.
UniGeneiMm.334606.

Genome annotation databases

EnsembliENSMUST00000030170; ENSMUSP00000030170; ENSMUSG00000034799.
GeneIDi382018.
KEGGimmu:382018.
UCSCiuc033jgb.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY753536 mRNA. Translation: AAX09281.1.
AC162033 Genomic DNA. No translation available.
AK147408 mRNA. Translation: BAE27895.1.
CCDSiCCDS22402.2.
RefSeqiNP_001025044.2. NM_001029873.2.
UniGeneiMm.334606.

3D structure databases

ProteinModelPortaliQ4KUS2.
SMRiQ4KUS2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ4KUS2. 1 interactor.
STRINGi10090.ENSMUSP00000030170.

PTM databases

iPTMnetiQ4KUS2.
PhosphoSitePlusiQ4KUS2.

Proteomic databases

MaxQBiQ4KUS2.
PaxDbiQ4KUS2.
PeptideAtlasiQ4KUS2.
PRIDEiQ4KUS2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030170; ENSMUSP00000030170; ENSMUSG00000034799.
GeneIDi382018.
KEGGimmu:382018.
UCSCiuc033jgb.1. mouse.

Organism-specific databases

CTDi23025.
MGIiMGI:3051532. Unc13a.

Phylogenomic databases

eggNOGiKOG1011. Eukaryota.
ENOG410XS5D. LUCA.
GeneTreeiENSGT00850000132267.
HOGENOMiHOG000231404.
HOVERGENiHBG057340.
InParanoidiQ4KUS2.
KOiK15293.
TreeFamiTF312844.

Miscellaneous databases

PROiQ4KUS2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034799.
CleanExiMM_UNC13A.
ExpressionAtlasiQ4KUS2. baseline and differential.
GenevisibleiQ4KUS2. MM.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di2.60.40.150. 3 hits.
InterProiIPR000008. C2_dom.
IPR010439. CAPS_dom.
IPR014770. Munc13_1.
IPR014772. Munc13_dom-2.
IPR019558. Munc13_subgr_dom-2.
IPR002219. PE/DAG-bd.
IPR027080. Unc-13.
[Graphical view]
PANTHERiPTHR10480. PTHR10480. 2 hits.
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.
SM01145. DUF1041. 1 hit.
[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]
ProtoNetiSearch...

Entry informationi

Entry nameiUN13A_MOUSE
AccessioniPrimary (citable) accession number: Q4KUS2
Secondary accession number(s): E9QKH9, Q3UHG2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 94 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.