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Q9UPW8

- UN13A_HUMAN

UniProt

Q9UPW8 - UN13A_HUMAN

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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

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
  3. protein N-terminus binding Source: ParkinsonsUK-UCL
  4. syntaxin-1 binding Source: ParkinsonsUK-UCL

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. neurotransmitter secretion Source: ParkinsonsUK-UCL
  6. positive regulation of neurotransmitter secretion Source: Ensembl
  7. regulation of short-term neuronal synaptic plasticity Source: Ensembl
  8. regulation of synaptic transmission, glutamatergic Source: ParkinsonsUK-UCL
  9. synaptic transmission, glutamatergic Source: Ensembl
  10. synaptic vesicle docking involved in exocytosis Source: Ensembl
  11. 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 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. axon Source: Ensembl
  2. cell junction Source: UniProtKB-KW
  3. cytoplasm Source: UniProtKB-KW
  4. neuromuscular junction Source: Ensembl
  5. neuron projection Source: ParkinsonsUK-UCL
  6. presynaptic active zone Source: ParkinsonsUK-UCL
  7. presynaptic membrane Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Membrane, Synapse

Pathology & Biotechi

Organism-specific databases

Orphaneti803. Amyotrophic lateral sclerosis.
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

BgeeiQ9UPW8.
CleanExiHS_UNC13A.
ExpressionAtlasiQ9UPW8. baseline and differential.
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.
GeneTreeiENSGT00730000110590.
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. 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

        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

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:
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.
UCSCiuc031rjv.1. human.

Polymorphism databases

DMDMi374095515.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
Orphaneti 803. Amyotrophic lateral sclerosis.
PharmGKBi PA134879020.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG245727.
GeneTreei ENSGT00730000110590.
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

Bgeei Q9UPW8.
CleanExi HS_UNC13A.
ExpressionAtlasi Q9UPW8. baseline and differential.
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. 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: October 29, 2014
This is version 119 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