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Identification
HMDB Protein ID HMDBP14645
Secondary Accession Numbers None
Name Syntaxin-1A
Synonyms
  1. Neuron-specific antigen HPC-1
  2. Synaptotagmin-associated 35 kDa protein
  3. P35A
Gene Name STX1A
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Plays an essential role in hormone and neurotransmitter calcium-dependent exocytosis and endocytosis (PubMed:7901002, PubMed:17301173, PubMed:18167541, PubMed:20484665, PubMed:22411134, PubMed:28813412). Part of the SNARE (Soluble NSF Attachment Receptor) complex composed of SNAP25, STX1A and VAMP2 which mediates the fusion of synaptic vesicles with the presynaptic plasma membrane (PubMed:14665625, PubMed:16888141, PubMed:19571812). STX1A and SNAP25 are localized on the plasma membrane while VAMP2 resides in synaptic vesicles. The pairing of the three SNAREs from the N-terminal SNARE motifs to the C-terminal anchors leads to the formation of the SNARE complex, which brings membranes into close proximity and results in final fusion (PubMed:14665625, PubMed:16888141, PubMed:19571812). Participates in the calcium-dependent regulation of acrosomal exocytosis in sperm (By similarity). Plays also an important role in the exocytosis of hormones such as insulin or glucagon-like peptide 1 (GLP-1) (By similarity).
Pathways
  • Amphetamine addiction
  • Huntington disease
  • Insulin secretion
  • Pathways of neurodegeneration - multiple diseases
  • SNARE interactions in vesicular transport
  • Synaptic vesicle cycle
Reactions Not Available
GO Classification
Biological Process
response to gravity
positive regulation of neurotransmitter secretion
positive regulation of excitatory postsynaptic membrane potential
intracellular protein transport
positive regulation of calcium ion-dependent exocytosis
synaptic vesicle fusion to presynaptic active zone membrane
vesicle docking
vesicle fusion
insulin secretion
synaptic vesicle endocytosis
protein sumoylation
neurotransmitter transport
hormone secretion
modulation of excitatory postsynaptic potential
positive regulation of catecholamine secretion
positive regulation of norepinephrine secretion
regulated exocytosis
regulation of synaptic vesicle priming
secretion by cell
SNARE complex assembly
synaptic vesicle docking
synaptic vesicle exocytosis
exocytosis
calcium ion-dependent exocytosis
regulation of exocytosis
positive regulation of exocytosis
protein localization to membrane
Cellular Component
protein-containing complex
plasma membrane
presynaptic membrane
synaptic vesicle
secretory granule
integral component of presynaptic membrane
nuclear membrane
presynaptic active zone membrane
SNARE complex
glutamatergic synapse
acrosomal vesicle
integral component of synaptic vesicle membrane
intracellular organelle
synaptobrevin 2-SNAP-25-syntaxin-1a complex
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin I complex
synaptobrevin 2-SNAP-25-syntaxin-1a-complexin II complex
endomembrane system
membrane
neuron projection
actomyosin
axon
postsynaptic density
integral to membrane
integral to plasma membrane
synaptic vesicle membrane
Molecular Function
protein N-terminus binding
protein-containing complex binding
calcium-dependent protein binding
calcium channel inhibitor activity
chloride channel inhibitor activity
ion channel binding
kinase binding
SNAP receptor activity
SNARE binding
protein domain specific binding
protein-macromolecule adaptor activity
myosin binding
myosin head/neck binding
ATP-dependent protein binding
identical protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 288
Molecular Weight 33067.145
Theoretical pI 5.236
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 266-288;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P32851
UniProtKB/Swiss-Prot Entry Name STX1A_RAT
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Chen X, Tomchick DR, Kovrigin E, Arac D, Machius M, Sudhof TC, Rizo J: Three-dimensional structure of the complexin/SNARE complex. Neuron. 2002 Jan 31;33(3):397-409. [PubMed:11832227 ]
  2. Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871. [PubMed:22673903 ]
  3. Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R: Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J. 1993 Dec;12(12):4821-8. [PubMed:7901002 ]
  4. Schiavo G, Shone CC, Bennett MK, Scheller RH, Montecucco C: Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins. J Biol Chem. 1995 May 5;270(18):10566-70. doi: 10.1074/jbc.270.18.10566. [PubMed:7737992 ]
  5. Ito H, Atsuzawa K, Morishita R, Usuda N, Sudo K, Iwamoto I, Mizutani K, Katoh-Semba R, Nozawa Y, Asano T, Nagata K: Sept8 controls the binding of vesicle-associated membrane protein 2 to synaptophysin. J Neurochem. 2009 Feb;108(4):867-80. doi: 10.1111/j.1471-4159.2008.05849.x. [PubMed:19196426 ]
  6. Zhang Z, Takeuchi H, Gao J, Wang D, James DJ, Martin TFJ, Hirata M: PRIP (phospholipase C-related but catalytically inactive protein) inhibits exocytosis by direct interactions with syntaxin 1 and SNAP-25 through its C2 domain. J Biol Chem. 2013 Mar 15;288(11):7769-7780. doi: 10.1074/jbc.M112.419317. Epub 2013 Jan 22. [PubMed:23341457 ]
  7. Tian JH, Das S, Sheng ZH: Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18. J Biol Chem. 2003 Jul 11;278(28):26265-74. doi: 10.1074/jbc.M300492200. Epub 2003 May 2. [PubMed:12730201 ]
  8. Inoue A, Obata K, Akagawa K: Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC-1. J Biol Chem. 1992 May 25;267(15):10613-9. [PubMed:1587842 ]
  9. Yoshida A, Oho C, Omori A, Kuwahara R, Ito T, Takahashi M: HPC-1 is associated with synaptotagmin and omega-conotoxin receptor. J Biol Chem. 1992 Dec 15;267(35):24925-8. [PubMed:1334074 ]
  10. Bennett MK, Calakos N, Scheller RH: Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science. 1992 Jul 10;257(5067):255-9. doi: 10.1126/science.1321498. [PubMed:1321498 ]
  11. Tang BL, Tan AE, Lim LK, Lee SS, Low DY, Hong W: Syntaxin 12, a member of the syntaxin family localized to the endosome. J Biol Chem. 1998 Mar 20;273(12):6944-50. doi: 10.1074/jbc.273.12.6944. [PubMed:9507000 ]
  12. Fasshauer D, Antonin W, Margittai M, Pabst S, Jahn R: Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties. J Biol Chem. 1999 May 28;274(22):15440-6. doi: 10.1074/jbc.274.22.15440. [PubMed:10336434 ]
  13. Haase J, Killian AM, Magnani F, Williams C: Regulation of the serotonin transporter by interacting proteins. Biochem Soc Trans. 2001 Nov;29(Pt 6):722-8. doi: 10.1042/0300-5127:0290722. [PubMed:11709063 ]
  14. Scales SJ, Hesser BA, Masuda ES, Scheller RH: Amisyn, a novel syntaxin-binding protein that may regulate SNARE complex assembly. J Biol Chem. 2002 Aug 2;277(31):28271-9. doi: 10.1074/jbc.M204929200. Epub 2002 May 24. [PubMed:12145319 ]
  15. Fasshauer D, Margittai M: A transient N-terminal interaction of SNAP-25 and syntaxin nucleates SNARE assembly. J Biol Chem. 2004 Feb 27;279(9):7613-21. doi: 10.1074/jbc.M312064200. Epub 2003 Dec 9. [PubMed:14665625 ]
  16. Singer-Lahat D, Sheinin A, Chikvashvili D, Tsuk S, Greitzer D, Friedrich R, Feinshreiber L, Ashery U, Benveniste M, Levitan ES, Lotan I: K+ channel facilitation of exocytosis by dynamic interaction with syntaxin. J Neurosci. 2007 Feb 14;27(7):1651-8. doi: 10.1523/JNEUROSCI.4006-06.2007. [PubMed:17301173 ]
  17. Singer-Lahat D, Chikvashvili D, Lotan I: Direct interaction of endogenous Kv channels with syntaxin enhances exocytosis by neuroendocrine cells. PLoS One. 2008 Jan 2;3(1):e1381. doi: 10.1371/journal.pone.0001381. [PubMed:18167541 ]
  18. Feinshreiber L, Singer-Lahat D, Friedrich R, Matti U, Sheinin A, Yizhar O, Nachman R, Chikvashvili D, Rettig J, Ashery U, Lotan I: Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells. J Cell Sci. 2010 Jun 1;123(Pt 11):1940-7. doi: 10.1242/jcs.063719. [PubMed:20484665 ]
  19. Dai XQ, Manning Fox JE, Chikvashvili D, Casimir M, Plummer G, Hajmrle C, Spigelman AF, Kin T, Singer-Lahat D, Kang Y, Shapiro AM, Gaisano HY, Lotan I, Macdonald PE: The voltage-dependent potassium channel subunit Kv2.1 regulates insulin secretion from rodent and human islets independently of its electrical function. Diabetologia. 2012 Jun;55(6):1709-20. doi: 10.1007/s00125-012-2512-6. Epub 2012 Mar 13. [PubMed:22411134 ]
  20. Sutton RB, Fasshauer D, Jahn R, Brunger AT: Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature. 1998 Sep 24;395(6700):347-53. doi: 10.1038/26412. [PubMed:9759724 ]
  21. Misura KM, Scheller RH, Weis WI: Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex. Nature. 2000 Mar 23;404(6776):355-62. doi: 10.1038/35006120. [PubMed:10746715 ]
  22. Misura KM, Scheller RH, Weis WI: Self-association of the H3 region of syntaxin 1A. Implications for intermediates in SNARE complex assembly. J Biol Chem. 2001 Apr 20;276(16):13273-82. doi: 10.1074/jbc.M009636200. Epub 2000 Dec 15. [PubMed:11118447 ]
  23. Misura KM, Gonzalez LC Jr, May AP, Scheller RH, Weis WI: Crystal structure and biophysical properties of a complex between the N-terminal SNARE region of SNAP25 and syntaxin 1a. J Biol Chem. 2001 Nov 2;276(44):41301-9. doi: 10.1074/jbc.M106853200. Epub 2001 Aug 30. [PubMed:11533035 ]
  24. Ernst JA, Brunger AT: High resolution structure, stability, and synaptotagmin binding of a truncated neuronal SNARE complex. J Biol Chem. 2003 Mar 7;278(10):8630-6. doi: 10.1074/jbc.M211889200. Epub 2002 Dec 20. [PubMed:12496247 ]
  25. Fernandez I, Ubach J, Dulubova I, Zhang X, Sudhof TC, Rizo J: Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A. Cell. 1998 Sep 18;94(6):841-9. doi: 10.1016/s0092-8674(00)81742-0. [PubMed:9753330 ]
  26. Stein A, Weber G, Wahl MC, Jahn R: Helical extension of the neuronal SNARE complex into the membrane. Nature. 2009 Jul 23;460(7254):525-8. doi: 10.1038/nature08156. Epub 2009 Jul 1. [PubMed:19571812 ]
  27. Kummel D, Krishnakumar SS, Radoff DT, Li F, Giraudo CG, Pincet F, Rothman JE, Reinisch KM: Complexin cross-links prefusion SNAREs into a zigzag array. Nat Struct Mol Biol. 2011 Jul 24;18(8):927-33. doi: 10.1038/nsmb.2101. [PubMed:21785414 ]
  28. Zhou Q, Lai Y, Bacaj T, Zhao M, Lyubimov AY, Uervirojnangkoorn M, Zeldin OB, Brewster AS, Sauter NK, Cohen AE, Soltis SM, Alonso-Mori R, Chollet M, Lemke HT, Pfuetzner RA, Choi UB, Weis WI, Diao J, Sudhof TC, Brunger AT: Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature. 2015 Sep 3;525(7567):62-7. doi: 10.1038/nature14975. Epub 2015 Aug 17. [PubMed:26280336 ]