P61764 (STXB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Syntaxin-binding protein 1

Alternative name(s):
MUNC18-1
N-Sec1
Protein unc-18 homolog 1
Short name=Unc18-1
Protein unc-18 homolog A
Short name=Unc-18A
p67

Gene names

Name:	STXBP1
Synonyms:	UNC18A

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	594 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. May play a role in determining the specificity of intracellular fusion reactions.
Subunit structure	Binds SYTL4 By similarity. Interacts with STX1A. Ref.6
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein.
Tissue specificity	Brain and spinal cord. Highly enriched in axons.
Involvement in disease	Epileptic encephalopathy, early infantile, 4 (EIEE4) [MIM:612164]: A severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Affected individuals have neonatal or infantile onset of seizures, profound mental retardation, and MRI evidence of brain hypomyelination. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9
Sequence similarities	Belongs to the STXBP/unc-18/SEC1 family.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Epilepsy Mental retardation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon target recognition Inferred from sequence or structural similarity. Source: UniProtKB energy reserve metabolic process Traceable author statement. Source: Reactome glutamate secretion Traceable author statement. Source: Reactome long term synaptic depression Inferred from electronic annotation. Source: Ensembl negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Ensembl negative regulation of synaptic transmission, GABAergic Inferred from sequence or structural similarity. Source: UniProtKB neuromuscular synaptic transmission Inferred from electronic annotation. Source: Ensembl neurotransmitter secretion Traceable author statement. Source: Reactome platelet aggregation Inferred from mutant phenotype PubMed 12773094. Source: UniProtKB platelet degranulation Inferred from mutant phenotype PubMed 12773094. Source: UniProtKB positive regulation of calcium ion-dependent exocytosis Inferred from electronic annotation. Source: Ensembl protein stabilization Inferred from electronic annotation. Source: Ensembl protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of insulin secretion Traceable author statement. Source: Reactome regulation of synaptic vesicle priming Inferred from sequence or structural similarity. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome synaptic vesicle maturation Inferred from sequence or structural similarity. Source: UniProtKB vesicle docking involved in exocytosis Inferred from electronic annotation. Source: Ensembl
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB cytosol Traceable author statement. Source: Reactome extracellular vesicular exosome Inferred from direct assay PubMed 19056867. Source: UniProt mitochondrion Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from direct assay PubMed 12773094. Source: UniProtKB platelet alpha granule Inferred from direct assay PubMed 12773094. Source: UniProtKB protein complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	SNARE binding Inferred from sequence or structural similarity. Source: UniProtKB identical protein binding Inferred from sequence or structural similarity. Source: UniProtKB poly(A) RNA binding Inferred from direct assay PubMed 22658674. Source: UniProtKB syntaxin binding Inferred from physical interaction PubMed 12773094. Source: UniProtKB syntaxin-1 binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P61764-1)

Also known as: A;

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: P61764-2)

Also known as: BE; HUNC18b;

The sequence of this isoform differs from the canonical sequence as follows:
     576-594: QKLLDTLKKLNKTDEEISS → TKFLMDLRHPDFRESSRVSFEDQAPTME

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 594	594	Syntaxin-binding protein 1		PRO_0000206277
Natural variations
	Alternative sequence	576 – 594	19	QKLLD…EEISS → TKFLMDLRHPDFRESSRVSF EDQAPTME in isoform 2.		VSP_006713
	Natural variant	84	1	V → D in EIEE4; may alter protein structure. Ref.9		VAR_046205
	Natural variant	180	1	C → Y in EIEE4; reduced thermostability; decreased binding to STX1A. Ref.9		VAR_046206
	Natural variant	443	1	M → R in EIEE4; may alter protein structure. Ref.9		VAR_046207
	Natural variant	544	1	G → D in EIEE4; may alter protein structure. Ref.9		VAR_046208

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified June 7, 2004. Version 1. Checksum: 2DD0715F875CE0F3	FASTA	594	67,569
	10 20 30 40 50 60 MAPIGLKAVV GEKIMHDVIK KVKKKGEWKV LVVDQLSMRM LSSCCKMTDI MTEGITIVED 70 80 90 100 110 120 INKRREPLPS LEAVYLITPS EKSVHSLISD FKDPPTAKYR AAHVFFTDSC PDALFNELVK 130 140 150 160 170 180 SRAAKVIKTL TEINIAFLPY ESQVYSLDSA DSFQSFYSPH KAQMKNPILE RLAEQIATLC 190 200 210 220 230 240 ATLKEYPAVR YRGEYKDNAL LAQLIQDKLD AYKADDPTMG EGPDKARSQL LILDRGFDPS 250 260 270 280 290 300 SPVLHELTFQ AMSYDLLPIE NDVYKYETSG IGEARVKEVL LDEDDDLWIA LRHKHIAEVS 310 320 330 340 350 360 QEVTRSLKDF SSSKRMNTGE KTTMRDLSQM LKKMPQYQKE LSKYSTHLHL AEDCMKHYQG 370 380 390 400 410 420 TVDKLCRVEQ DLAMGTDAEG EKIKDPMRAI VPILLDANVS TYDKIRIILL YIFLKNGITE 430 440 450 460 470 480 ENLNKLIQHA QIPPEDSEII TNMAHLGVPI VTDSTLRRRS KPERKERISE QTYQLSRWTP 490 500 510 520 530 540 IIKDIMEDTI EDKLDTKHYP YISTRSSASF STTAVSARYG HWHKNKAPGE YRSGPRLIIF 550 560 570 580 590 ILGGVSLNEM RCAYEVTQAN GKWEVLIGST HILTPQKLLD TLKKLNKTDE EISS
	Isoform 2 (BE) (HUNC18b) [UniParc] [UniParc]. Checksum: 73D8337768259493	FASTA	603	68,736
	10 20 30 40 50 60 MAPIGLKAVV GEKIMHDVIK KVKKKGEWKV LVVDQLSMRM LSSCCKMTDI MTEGITIVED 70 80 90 100 110 120 INKRREPLPS LEAVYLITPS EKSVHSLISD FKDPPTAKYR AAHVFFTDSC PDALFNELVK 130 140 150 160 170 180 SRAAKVIKTL TEINIAFLPY ESQVYSLDSA DSFQSFYSPH KAQMKNPILE RLAEQIATLC 190 200 210 220 230 240 ATLKEYPAVR YRGEYKDNAL LAQLIQDKLD AYKADDPTMG EGPDKARSQL LILDRGFDPS 250 260 270 280 290 300 SPVLHELTFQ AMSYDLLPIE NDVYKYETSG IGEARVKEVL LDEDDDLWIA LRHKHIAEVS 310 320 330 340 350 360 QEVTRSLKDF SSSKRMNTGE KTTMRDLSQM LKKMPQYQKE LSKYSTHLHL AEDCMKHYQG 370 380 390 400 410 420 TVDKLCRVEQ DLAMGTDAEG EKIKDPMRAI VPILLDANVS TYDKIRIILL YIFLKNGITE 430 440 450 460 470 480 ENLNKLIQHA QIPPEDSEII TNMAHLGVPI VTDSTLRRRS KPERKERISE QTYQLSRWTP 490 500 510 520 530 540 IIKDIMEDTI EDKLDTKHYP YISTRSSASF STTAVSARYG HWHKNKAPGE YRSGPRLIIF 550 560 570 580 590 600 ILGGVSLNEM RCAYEVTQAN GKWEVLIGST HILTPTKFLM DLRHPDFRES SRVSFEDQAP TME

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A murine neural-specific homolog corrects cholinergic defects in Caenorhabditis elegans unc-18 mutants." Gengyo-Ando K., Kitayama H., Mukaida M., Ikawa Y. J. Neurosci. 16:6695-6702(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[2]	"Identification and characterization of the human ortholog of rat STXBP1, a protein implicated in vesicle trafficking and neurotransmitter release." Swanson D.A., Steel J.M., Valle D. Genomics 48:373-376(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Skin.
[6]	"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: INTERACTION WITH STX1A.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy." Saitsu H., Kato M., Mizuguchi T., Hamada K., Osaka H., Tohyama J., Uruno K., Kumada S., Nishiyama K., Nishimura A., Okada I., Yoshimura Y., Hirai S., Kumada T., Hayasaka K., Fukuda A., Ogata K., Matsumoto N. Nat. Genet. 40:782-788(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS EIEE4 ASP-84; TYR-180; ARG-443 AND ASP-544, CHARACTERIZATION OF VARIANTS EIEE4 ASP-84; TYR-180; ARG-443 AND ASP-544.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D63851 mRNA. Translation: BAA19483.1. AF004562 mRNA. Translation: AAC39688.1. AF004563 mRNA. Translation: AAC39689.1. AL162426 Genomic DNA. Translation: CAI41180.1. CH471090 Genomic DNA. Translation: EAW87681.1. BC015749 mRNA. Translation: AAH15749.1.
RefSeq	NP_001027392.1. NM_001032221.3. NP_003156.1. NM_003165.3.
UniGene	Hs.288229.
3D structure databases
ProteinModelPortal	P61764.
SMR	P61764. Positions 4-592.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	112681. 21 interactions.
IntAct	P61764. 5 interactions.
MINT	MINT-125987.
STRING	9606.ENSP00000362399.
PTM databases
PhosphoSite	P61764.
Polymorphism databases
DMDM	50403646.
Proteomic databases
PaxDb	P61764.
PRIDE	P61764.
Protocols and materials databases
DNASU	6812.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373299; ENSP00000362396; ENSG00000136854. [P61764-1] ENST00000373302; ENSP00000362399; ENSG00000136854. [P61764-2]
GeneID	6812.
KEGG	hsa:6812.
UCSC	uc004brk.2. human. [P61764-2] uc004brl.2. human.
Organism-specific databases
CTD	6812.
GeneCards	GC09P130374.
HGNC	HGNC:11444. STXBP1.
HPA	CAB034434. HPA008209. HPA023483.
MIM	602926. gene. 612164. phenotype.
neXtProt	NX_P61764.
Orphanet	1934. Early infantile epileptic encephalopathy.
PharmGKB	PA36241.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5158.
HOGENOM	HOG000232146.
HOVERGEN	HBG052710.
KO	K15292.
OMA	GVDKLCK.
OrthoDB	EOG78PV8M.
PhylomeDB	P61764.
TreeFam	TF313242.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	P61764.
Bgee	P61764.
CleanEx	HS_STXBP1.
Genevestigator	P61764.
Family and domain databases
Gene3D	3.40.50.1910. 2 hits.
InterPro	IPR027482. Sec-1-like_dom2. IPR001619. Sec1-like. [Graphical view]
PANTHER	PTHR11679. PTHR11679. 1 hit.
Pfam	PF00995. Sec1. 1 hit. [Graphical view]
PIRSF	PIRSF005715. VPS45_Sec1. 1 hit.
SUPFAM	SSF56815. SSF56815. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	STXBP1. human.
GeneWiki	STXBP1.
GenomeRNAi	6812.
NextBio	26583.
PRO	P61764.
SOURCE	Search...

Entry information

Entry name

STXB1_HUMAN

Accession

Primary (citable) accession number: P61764
Secondary accession number(s): B1AM97 , Q28208, Q62759, Q64320, Q96TG8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	April 16, 2014
This is version 103 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.