Q15833 (STXB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Syntaxin-binding protein 2

Alternative name(s):
Protein unc-18 homolog 2
Short name=Unc18-2
Protein unc-18 homolog B
Short name=Unc-18B

Gene names

Name:	STXBP2
Synonyms:	UNC18B

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

General annotation (Comments)

Function	Involved in intracellular vesicle trafficking and vesicle fusion with membranes. Contributes to the granule exocytosis machinery through interaction with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins that regulate membrane fusion. Regulates cytotoxic granule exocytosis in natural killer (NK) cells. Ref.6 Ref.7
Subunit structure	Interacts with STX1A, STX2 and STX3 By similarity. Interacts with STX11. Ref.6 Ref.7
Tissue specificity	Placenta, lung, liver, kidney and pancreas, as well as in peripheral blood lymphocytes.
Involvement in disease	Familial hemophagocytic lymphohistiocytosis 5 (FHL5) [MIM:613101]: A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7
Sequence similarities	Belongs to the STXBP/unc-18/SEC1 family.

Ontologies

Keywords
Biological process	Exocytosis Protein transport Transport
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	leukocyte mediated cytotoxicity Inferred from mutant phenotype Ref.7. Source: UniProtKB neutrophil degranulation Inferred from expression pattern PubMed 18588921. Source: UniProtKB protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of mast cell degranulation Inferred from sequence or structural similarity. Source: UniProtKB vesicle docking involved in exocytosis Inferred from electronic annotation. Source: InterPro
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara azurophil granule Inferred from direct assay PubMed 18588921. Source: UniProtKB cytolytic granule Inferred from direct assay Ref.6. Source: UniProtKB cytosol Inferred from direct assay PubMed 18588921. Source: UniProtKB plasma membrane Inferred from direct assay PubMed 18588921. Source: UniProtKB specific granule Inferred from direct assay PubMed 18588921. Source: UniProtKB tertiary granule Inferred from direct assay PubMed 18588921. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q15833-1)

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: Q15833-2)

The sequence of this isoform differs from the canonical sequence as follows:
     83-85: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 593	593	Syntaxin-binding protein 2		PRO_0000206281
Natural variations
	Alternative sequence	83 – 85	3	Missing in isoform 2.		VSP_040121
	Natural variant	209	1	L → P in FHL5. Ref.6		VAR_063814
	Natural variant	232	1	Missing in FHL5; leads to a complete loss of the ability to interact with STX11. Ref.6		VAR_063815
	Natural variant	292	1	R → H in FHL5; leads to a complete loss of the ability to interact with STX11. Ref.6		VAR_063816
	Natural variant	405	1	R → Q in FHL5; leads to a complete loss of the ability to interact with STX11. Ref.6		VAR_063817
	Natural variant	405	1	R → W in FHL5; leads to a complete loss of the ability to interact with STX11. Ref.6		VAR_063818
	Natural variant	477	1	P → L in FHL5; leads to a complete loss of the ability to interact with STX11. Ref.6 Ref.7		VAR_063819
	Natural variant	526	1	I → V. Ref.1 Corresponds to variant rs6791 [ dbSNP | Ensembl ].		VAR_014934

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 98E27B55309168A9	FASTA	593	66,453
	10 20 30 40 50 60 MAPSGLKAVV GEKILSGVIR SVKKDGEWKV LIMDHPSMRI LSSCCKMSDI LAEGITIVED 70 80 90 100 110 120 INKRREPIPS LEAIYLLSPT EKSVQALIKD FQGTPTFTYK AAHIFFTDTC PEPLFSELGR 130 140 150 160 170 180 SRLAKVVKTL KEIHLAFLPY EAQVFSLDAP HSTYNLYCPF RAEERTRQLE VLAQQIATLC 190 200 210 220 230 240 ATLQEYPAIR YRKGPEDTAQ LAHAVLAKLN AFKADTPSLG EGPEKTRSQL LIMDRAADPV 250 260 270 280 290 300 SPLLHELTFQ AMAYDLLDIE QDTYRYETTG LSEAREKAVL LDEDDDLWVE LRHMHIADVS 310 320 330 340 350 360 KKVTELLRTF CESKRLTTDK ANIKDLSQIL KKMPQYQKEL NKYSTHLHLA DDCMKHFKGS 370 380 390 400 410 420 VEKLCSVEQD LAMGSDAEGE KIKDSMKLIV PVLLDAAVPA YDKIRVLLLY ILLRNGVSEE 430 440 450 460 470 480 NLAKLIQHAN VQAHSSLIRN LEQLGGTVTN PGGSGTSSRL EPRERMEPTY QLSRWTPVIK 490 500 510 520 530 540 DVMEDAVEDR LDRNLWPFVS DPAPTASSQA AVSARFGHWH KNKAGIEARA GPRLIVYVMG 550 560 570 580 590 GVAMSEMRAA YEVTRATEGK WEVLIGSSHI LTPTRFLDDL KALDKKLEDI ALP
	Isoform 2 [UniParc]. Checksum: C9A58E0240FCF3B2	FASTA	590	66,138
	10 20 30 40 50 60 MAPSGLKAVV GEKILSGVIR SVKKDGEWKV LIMDHPSMRI LSSCCKMSDI LAEGITIVED 70 80 90 100 110 120 INKRREPIPS LEAIYLLSPT EKALIKDFQG TPTFTYKAAH IFFTDTCPEP LFSELGRSRL 130 140 150 160 170 180 AKVVKTLKEI HLAFLPYEAQ VFSLDAPHST YNLYCPFRAE ERTRQLEVLA QQIATLCATL 190 200 210 220 230 240 QEYPAIRYRK GPEDTAQLAH AVLAKLNAFK ADTPSLGEGP EKTRSQLLIM DRAADPVSPL 250 260 270 280 290 300 LHELTFQAMA YDLLDIEQDT YRYETTGLSE AREKAVLLDE DDDLWVELRH MHIADVSKKV 310 320 330 340 350 360 TELLRTFCES KRLTTDKANI KDLSQILKKM PQYQKELNKY STHLHLADDC MKHFKGSVEK 370 380 390 400 410 420 LCSVEQDLAM GSDAEGEKIK DSMKLIVPVL LDAAVPAYDK IRVLLLYILL RNGVSEENLA 430 440 450 460 470 480 KLIQHANVQA HSSLIRNLEQ LGGTVTNPGG SGTSSRLEPR ERMEPTYQLS RWTPVIKDVM 490 500 510 520 530 540 EDAVEDRLDR NLWPFVSDPA PTASSQAAVS ARFGHWHKNK AGIEARAGPR LIVYVMGGVA 550 560 570 580 590 MSEMRAAYEV TRATEGKWEV LIGSSHILTP TRFLDDLKAL DKKLEDIALP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization of a nonneuronal human UNC18 homolog." Ziegler S.F., Mortrud M.T., Swartz A.R., Baker E., Sutherland G.R., Burmeister M., Mulligan J.T. Genomics 37:19-23(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-526.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"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].
[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 (SEP-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 2). Tissue: Lung.
[6]	"Familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) is caused by mutations in Munc18-2 and impaired binding to syntaxin 11." zur Stadt U., Rohr J., Seifert W., Koch F., Grieve S., Pagel J., Strauss J., Kasper B., Nuernberg G., Becker C., Maul-Pavicic A., Beutel K., Janka G., Griffiths G., Ehl S., Hennies H.C. Am. J. Hum. Genet. 85:482-492(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STX11, VARIANTS FHL5 PRO-209; ILE-232 DEL; HIS-292; TRP-405; GLN-405 AND LEU-477, CHARACTERIZATION OF VARIANTS FHL5 ILE-232 DEL; HIS-292; TRP-405; GLN-405 AND LEU-477.
[7]	"Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells." Cote M., Menager M.M., Burgess A., Mahlaoui N., Picard C., Schaffner C., Al-Manjomi F., Al-Harbi M., Alangari A., Le Deist F., Gennery A.R., Prince N., Cariou A., Nitschke P., Blank U., El-Ghazali G., Menasche G., Latour S., Fischer A., de Saint Basile G. J. Clin. Invest. 119:3765-3773(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STX11, VARIANT FHL5 LEU-477.
[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].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U63533 mRNA. Translation: AAC50762.1. BT006915 mRNA. Translation: AAP35561.1. AC008763 Genomic DNA. No translation available. CH471139 Genomic DNA. Translation: EAW69018.1. BC002869 mRNA. Translation: AAH02869.1.
IPI	IPI00642310. IPI00943192.
RefSeq	NP_001120868.1. NM_001127396.2. NP_001258963.1. NM_001272034.1. NP_008880.2. NM_006949.3.
UniGene	Hs.515104.
3D structure databases
ProteinModelPortal	Q15833.
SMR	Q15833. Positions 5-590.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000221283.
PTM databases
PhosphoSite	Q15833.
Polymorphism databases
DMDM	2501513.
2D gel databases
OGP	Q15833.
Proteomic databases
PaxDb	Q15833.
PRIDE	Q15833.
Protocols and materials databases
DNASU	6813.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000221283; ENSP00000221283; ENSG00000076944. ENST00000414284; ENSP00000409471; ENSG00000076944.
GeneID	6813.
KEGG	hsa:6813.
UCSC	uc002mha.4. human. uc002mhb.4. human.
Organism-specific databases
CTD	6813.
GeneCards	GC19P007701.
H-InvDB	HIX0021726.
HGNC	HGNC:11445. STXBP2.
HPA	HPA015564.
MIM	601717. gene. 613101. phenotype.
neXtProt	NX_Q15833.
Orphanet	540. Familial hemophagocytic lymphohistiocytosis.
PharmGKB	PA36242.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5158.
HOGENOM	HOG000232146.
HOVERGEN	HBG052710.
InParanoid	Q15833.
KO	K15300.
OrthoDB	EOG4K6G3W.
PhylomeDB	Q15833.
Gene expression databases
ArrayExpress	Q15833.
Bgee	Q15833.
CleanEx	HS_STXBP2.
Genevestigator	Q15833.
GermOnline	ENSG00000076944. Homo sapiens.
Family and domain databases
InterPro	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. Sec1-like. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	6813.
NextBio	26589.
SOURCE	Search...

Entry information

Entry name

STXB2_HUMAN

Accession

Primary (citable) accession number: Q15833
Secondary accession number(s): Q9BU65

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 107 of the entry and version 2 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.