Q16623 (STX1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Syntaxin-1A

Alternative name(s):
Neuron-specific antigen HPC-1

Gene names

Name:	STX1A
Synonyms:	STX1

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	288 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Potentially involved in docking of synaptic vesicles at presynaptic active zones. May play a critical role in neurotransmitter exocytosis. May mediate Ca2+-regulation of exocytosis acrosomal reaction in sperm.
Subunit structure	Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A. This complex binds to CPLX1. Binds SYTL4 and STXBP6. Found in a ternary complex with STX1A and SNAP25. Interacts with OTOF and LGI3. Interacts with SLC6A4. Interacts with SYT6 and SYT8; the interaction is Ca2+-dependent By similarity. Found in a complex with VAMP8 and SNAP23. Interacts with VAPA and SYBU. Interacts with STXBP1 and DAPK1. Ref.10 Ref.11 Ref.12
Subcellular location	Cytoplasmic vesicle › secretory vesicle › synaptic vesicle membrane; Single-pass type IV membrane protein By similarity. Cell junction › synapse › synaptosome By similarity. Isoform 2: Secreted Probable.
Tissue specificity	Isoform 1 is highly expressed in embryonic spinal chord and ganglia and in adult cerebellum and cerebral cortex. Isoform 2 is expressed in heart, liver, fat, skeletal muscle, kidney and brain. Ref.9
Post-translational modification	Phosphorylated by CK2 By similarity. Phosphorylation at Ser-188 by DAPK1 significantly decreases its interaction with STXBP1. Ref.11
Involvement in disease	STX1A is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
Sequence similarities	Belongs to the syntaxin family. Contains 1 t-SNARE coiled-coil homology domain.
Sequence caution	The sequence AAA20940.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Exocytosis Neurotransmitter transport Transport
Cellular component	Cell junction Cytoplasmic vesicle Membrane Secreted Synapse Synaptosome
Coding sequence diversity	Alternative splicing
Disease	Williams-Beuren syndrome
Domain	Coiled coil Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion-dependent exocytosis Inferred from electronic annotation. Source: Compara energy reserve metabolic process Traceable author statement. Source: Reactome glutamate secretion Traceable author statement. Source: Reactome intracellular protein transport Inferred from electronic annotation. Source: InterPro neurotransmitter secretion Traceable author statement. Source: Reactome positive regulation of exocytosis Inferred from electronic annotation. Source: Compara positive regulation of neurotransmitter secretion Inferred from electronic annotation. Source: Compara regulation of insulin secretion Traceable author statement PubMed 15537656. Source: UniProtKB response to gravity Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome synaptic vesicle docking involved in exocytosis Inferred from electronic annotation. Source: Compara
Cellular_component	SNARE complex Inferred from direct assay PubMed 19546860. Source: UniProtKB actomyosin Inferred from electronic annotation. Source: Compara cell junction Inferred from electronic annotation. Source: UniProtKB-KW extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection Inferred from direct assay PubMed 12115694. Source: MGI plasma membrane Traceable author statement. Source: Reactome secretory granule Inferred from electronic annotation. Source: Compara synaptic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell synaptobrevin 2-SNAP-25-syntaxin-1a complex Inferred from electronic annotation. Source: Compara synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex Inferred from electronic annotation. Source: Compara
Molecular_function	calcium channel inhibitor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q16623-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q16623-2)

Also known as: 1C;

The sequence of this isoform differs from the canonical sequence as follows:
     227-288: GEMIDRIEYN...IASTVGGIFA → PQGAFLKSCPEPQPNREEGALWSSGAPGPAGRDD

Isoform 3 (identifier: Q16623-3)

The sequence of this isoform differs from the canonical sequence as follows:
     227-288: GEMIDRIEYN...IASTVGGIFA → TMWRGPCLTPRRPSSTRARRAGRKS

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 288	288	Syntaxin-1A		PRO_0000210186
Regions
	Topological domain	1 – 265	265	Cytoplasmic Potential
	Transmembrane	266 – 286	21	Helical; Anchor for type IV membrane protein; Potential
	Topological domain	287 – 288	2	Extracellular Potential
	Domain	192 – 254	63	t-SNARE coiled-coil homology
	Coiled coil	68 – 109	42	Potential
Amino acid modifications
	Modified residue	14	1	Phosphoserine Ref.13
	Modified residue	188	1	Phosphoserine; by DAPK1 Ref.11
Natural variations
	Alternative sequence	227 – 288	62	GEMID…GGIFA → PQGAFLKSCPEPQPNREEGA LWSSGAPGPAGRDD in isoform 2.		VSP_006338
	Alternative sequence	227 – 288	62	GEMID…GGIFA → TMWRGPCLTPRRPSSTRARR AGRKS in isoform 3.		VSP_006339
Experimental info
	Sequence conflict	73	1	E → V in AAA20940. Ref.8
	Sequence conflict	140	1	D → V in AAA20940. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 8AC787EFCE65ACA1	FASTA	288	33,023
	10 20 30 40 50 60 MKDRTQELRT AKDSDDDDDV AVTVDRDRFM DEFFEQVEEI RGFIDKIAEN VEEVKRKHSA 70 80 90 100 110 120 ILASPNPDEK TKEELEELMS DIKKTANKVR SKLKSIEQSI EQEEGLNRSS ADLRIRKTQH 130 140 150 160 170 180 STLSRKFVEV MSEYNATQSD YRERCKGRIQ RQLEITGRTT TSEELEDMLE SGNPAIFASG 190 200 210 220 230 240 IIMDSSISKQ ALSEIETRHS EIIKLENSIR ELHDMFMDMA MLVESQGEMI DRIEYNVEHA 250 260 270 280 VDYVERAVSD TKKAVKYQSK ARRKKIMIII CCVILGIVIA STVGGIFA
	Isoform 2 (1C) [UniParc]. Checksum: 546C1582FE83499E	FASTA	260	29,632
	10 20 30 40 50 60 MKDRTQELRT AKDSDDDDDV AVTVDRDRFM DEFFEQVEEI RGFIDKIAEN VEEVKRKHSA 70 80 90 100 110 120 ILASPNPDEK TKEELEELMS DIKKTANKVR SKLKSIEQSI EQEEGLNRSS ADLRIRKTQH 130 140 150 160 170 180 STLSRKFVEV MSEYNATQSD YRERCKGRIQ RQLEITGRTT TSEELEDMLE SGNPAIFASG 190 200 210 220 230 240 IIMDSSISKQ ALSEIETRHS EIIKLENSIR ELHDMFMDMA MLVESQPQGA FLKSCPEPQP 250 260 NREEGALWSS GAPGPAGRDD
	Isoform 3 [UniParc]. Checksum: C885D46384137E0B	FASTA	251	28,995
	10 20 30 40 50 60 MKDRTQELRT AKDSDDDDDV AVTVDRDRFM DEFFEQVEEI RGFIDKIAEN VEEVKRKHSA 70 80 90 100 110 120 ILASPNPDEK TKEELEELMS DIKKTANKVR SKLKSIEQSI EQEEGLNRSS ADLRIRKTQH 130 140 150 160 170 180 STLSRKFVEV MSEYNATQSD YRERCKGRIQ RQLEITGRTT TSEELEDMLE SGNPAIFASG 190 200 210 220 230 240 IIMDSSISKQ ALSEIETRHS EIIKLENSIR ELHDMFMDMA MLVESQTMWR GPCLTPRRPS 250 STRARRAGRK S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequence analysis of a cDNA encoding human syntaxin 1A, a polypeptide essential for exocytosis." Zhang R.-D., Maksymowych A.B., Simpson L.L. Gene 159:293-294(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome." Osborne L.R., Soder S., Shi X.-M., Pober B., Costa T., Scherer S.W., Tsui L.-C. Am. J. Hum. Genet. 61:449-452(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
[3]	"Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients." Wu Y.-Q., Bejjani B.A., Tsui L.-C., Mandel A., Osborne L.R., Shaffer L.G. Am. J. Med. Genet. 109:121-124(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), SEQUENCE REVISION TO 144.
[4]	"Novel isoform of syntaxin 1 is expressed in mammalian cells." Jagadish M.N., Tellam J.T., Macaulay S.L., Gough K.H., James D.E., Ward C.W. Biochem. J. 321:151-156(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Adipose tissue.
[5]	"Mapping of the human HPC-1/syntaxin 1A gene (STX1A) to chromosome 7 band q11.2." Nakayama T., Fujiwara T., Miyazawa A., Asakawa S., Shimizu N., Shimizu Y., Mikoshiba K., Akagawa K. Genomics 42:173-176(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Brain and Lung.
[8]	"Human syntaxin is homologous with rat syntaxin A and digested by BoNT C." Zhang R.-D., Simpson L. Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 15-288 (ISOFORM 1). Tissue: Brain.
[9]	"Expression analysis of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome." Botta A., Calza L., Giardino L., Potenza S., Novelli G., Dallapiccola B. Genomics 62:525-528(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[10]	"Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion." Polgar J., Chung S.H., Reed G.L. Blood 100:1081-1083(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH VAMP8 AND SNAP23.
[11]	"Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18." Tian J.H., Das S., Sheng Z.H. J. Biol. Chem. 278:26265-26274(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-188, INTERACTION WITH DAPK1 AND STXBP1.
[12]	"Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons." Su Q., Cai Q., Gerwin C., Smith C.L., Sheng Z.-H. Nat. Cell Biol. 6:941-953(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SYBU.
[13]	"Phosphoproteomic analysis of synaptosomes from human cerebral cortex." DeGiorgis J.A., Jaffe H., Moreira J.E., Carlotti C.G. Jr., Leite J.P., Pant H.C., Dosemeci A. J. Proteome Res. 4:306-315(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L37792 mRNA. Translation: AAA53519.1. U87315 , AF297001, AF297002, U87310, AF297003, U87314 Genomic DNA. Translation: AAK54507.2. U87315 , AF297001, AF297002, U87310, AF297003, U87314 Genomic DNA. Translation: AAB65500.2. D37932 mRNA. Translation: BAA07151.1. BC000444 mRNA. No translation available. AC073846 Genomic DNA. Translation: AAS07470.1. BC003011 mRNA. Translation: AAH03011.1. BC064644 mRNA. Translation: AAH64644.1. U12918 mRNA. Translation: AAA20940.1. Different initiation.
IPI	IPI00003370. IPI00221098. IPI00221099.
RefSeq	NP_001159375.1. NM_001165903.1. NP_004594.1. NM_004603.3.
UniGene	Hs.647024.
3D structure databases
ProteinModelPortal	Q16623.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-390N.
IntAct	Q16623. 5 interactions.
MINT	MINT-255942.
STRING	9606.ENSP00000222812.
Protein family/group databases
TCDB	1.F.1.1.1. synaptosomal vesicle fusion pore (SVF-Pore) family.
PTM databases
PhosphoSite	Q16623.
Polymorphism databases
DMDM	2501084.
Proteomic databases
PaxDb	Q16623.
PRIDE	Q16623.
Protocols and materials databases
DNASU	6804.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222812; ENSP00000222812; ENSG00000106089. ENST00000395156; ENSP00000378585; ENSG00000106089. ENST00000572494; ENSP00000459531; ENSG00000263024. ENST00000574942; ENSP00000459444; ENSG00000263024.
GeneID	6804.
KEGG	hsa:6804.
UCSC	uc003tyx.3. human. uc003tyy.3. human.
Organism-specific databases
CTD	6804.
GeneCards	GC07M073113.
HGNC	HGNC:11433. STX1A.
HPA	CAB008372.
MIM	186590. gene.
neXtProt	NX_Q16623.
PharmGKB	PA36233.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5074.
HOGENOM	HOG000286023.
HOVERGEN	HBG000497.
InParanoid	Q16623.
KO	K04560.
OMA	HVINASH.
OrthoDB	EOG4PC9SV.
PhylomeDB	Q16623.
Enzyme and pathway databases
Pathway_Interaction_DB	botulinumtoxinpathway. Effects of Botulinum toxin.
Reactome	REACT_111217. Metabolism. REACT_116125. Disease. REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q16623.
Bgee	Q16623.
CleanEx	HS_STX1A.
Genevestigator	Q16623.
GermOnline	ENSG00000106089. Homo sapiens.
Family and domain databases
InterPro	IPR015709. Syntaxin-1. IPR006012. Syntaxin/epimorphin_CS. IPR006011. Syntaxin_N. IPR010989. t-SNARE. IPR000727. T_SNARE_dom. [Graphical view]
PANTHER	PTHR19957:SF35. PTHR19957:SF35. 1 hit.
Pfam	PF05739. SNARE. 1 hit. PF00804. Syntaxin. 1 hit. [Graphical view]
SMART	SM00503. SynN. 1 hit. SM00397. t_SNARE. 1 hit. [Graphical view]
SUPFAM	SSF47661. t-snare. 1 hit.
PROSITE	PS00914. SYNTAXIN. 1 hit. PS50192. T_SNARE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6804.
NextBio	26565.
SOURCE	Search...

Entry information

Entry name

STX1A_HUMAN

Accession

Primary (citable) accession number: Q16623
Secondary accession number(s): O15447 , O15448, Q12936, Q75MD9, Q9BPZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 133 of the entry and version 1 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.