Q9UPW8 (UN13A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein unc-13 homolog A

Alternative name(s):
Munc13-1

Gene names

Name:	UNC13A
Synonyms:	KIAA1032

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1703 AA.
Sequence status	Complete.
Protein existence	Evidence 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 junction › synapse › presynaptic 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 process	Exocytosis
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Synapse
Coding sequence diversity	Polymorphism
Domain	Coiled coil Repeat Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	beta-amyloid metabolic process Inferred from electronic annotation. Source: Compara innervation Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro neuromuscular junction development Inferred from electronic annotation. Source: Compara positive regulation of neurotransmitter secretion Inferred from electronic annotation. Source: Compara regulation of short-term neuronal synaptic plasticity Inferred from electronic annotation. Source: Compara synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara synaptic vesicle docking involved in exocytosis Inferred from electronic annotation. Source: Compara synaptic vesicle maturation Inferred from electronic annotation. Source: Compara synaptic vesicle priming Inferred from electronic annotation. Source: InterPro
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell neuromuscular junction Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	diacylglycerol binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1703	1703	Protein unc-13 homolog A		PRO_0000188573
Regions
	Domain	1 – 79	79	C2 1
	Domain	663 – 769	107	C2 2
	Domain	1093 – 1236	144	MHD1
	Domain	1345 – 1512	168	MHD2
	Domain	1532 – 1637	106	C2 3
	Zinc finger	553 – 603	51	Phorbol-ester/DAG-type
	Coiled coil	320 – 357	38	Potential
	Compositional bias	321 – 350	30	Glu-rich
Sites
	Metal binding	567	1	Zinc 1 By similarity
	Metal binding	570	1	Zinc 1 By similarity
	Metal binding	584	1	Zinc 2 By similarity
	Metal binding	587	1	Zinc 2 By similarity
	Metal binding	595	1	Zinc 1 By similarity
	Metal binding	603	1	Zinc 2 By similarity
Amino acid modifications
	Modified residue	245	1	Phosphoserine By similarity
Natural variations
	Natural variant	359	1	A → T. Corresponds to variant rs34752754 [ dbSNP | Ensembl ].		VAR_061872
Experimental info
	Sequence conflict	1034	1	L → P in BAA82984. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9UPW8 [UniParc]. Last modified January 25, 2012. Version 4. Checksum: C8F6CEBEEF8E050B	FASTA	1,703	193,014
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI01018254.
RefSeq	NP_001073890.2. NM_001080421.2.
UniGene	Hs.164502.
3D structure databases
ProteinModelPortal	Q9UPW8.
SMR	Q9UPW8. Positions 2-128, 445-479, 554-603, 674-806, 1143-1503.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UPW8. 1 interaction.
STRING	9606.ENSP00000400409.
PTM databases
PhosphoSite	Q9UPW8.
Polymorphism databases
DMDM	71153185.
Proteomic databases
PaxDb	Q9UPW8.
PRIDE	Q9UPW8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000519716; ENSP00000429562; ENSG00000130477.
GeneID	23025.
KEGG	hsa:23025.
Organism-specific databases
CTD	23025.
GeneCards	GC19M017712.
H-InvDB	HIX0014898.
HGNC	HGNC:23150. UNC13A.
HPA	HPA041418.
MIM	609894. gene.
neXtProt	NX_Q9UPW8.
PharmGKB	PA134879020.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245727.
HOGENOM	HOG000231404.
HOVERGEN	HBG057340.
InParanoid	Q9UPW8.
KO	K15293.
OrthoDB	EOG4GTKC1.
Gene expression databases
ArrayExpress	Q9UPW8.
Bgee	Q9UPW8.
CleanEx	HS_UNC13A.
Genevestigator	Q9UPW8.
GermOnline	ENSG00000130477. Homo sapiens.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR020477. C2_dom. IPR018029. C2_membr_targeting. 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. IPR027082. Unc13A. [Graphical view]
PANTHER	PTHR10480. PTHR10480. 1 hit. PTHR10480:SF1. PTHR10480:SF1. 1 hit.
Pfam	PF00130. C1_1. 1 hit. PF00168. C2. 3 hits. PF06292. DUF1041. 1 hit. PF10540. Membr_traf_MHD. 1 hit. [Graphical view]
PRINTS	PR00360. C2DOMAIN.
SMART	SM00109. C1. 1 hit. SM00239. C2. 3 hits. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 3 hits.
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. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UNC13A. human.
GenomeRNAi	23025.
NextBio	43986.
SOURCE	Search...

Entry information

Entry name

UN13A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 105 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.