Gene Symbol: SNTA1
Description: syntrophin alpha 1
Alias: LQT12, SNT1, TACIP1, dJ1187J4.5, alpha-1-syntrophin, 59 kDa dystrophin-associated protein A1 acidic component 1, acidic alpha 1 syntrophin, dystrophin-associated protein A1, 59kDa, acidic component, pro-TGF-alpha cytoplasmic domain-interacting protein 1, syntrophin-1
Species: human
Products:     SNTA1

Top Publications

  1. Castello A, Brocheriou V, Chafey P, Kahn A, Gilgenkrantz H. Characterization of the dystrophin-syntrophin interaction using the two-hybrid system in yeast. FEBS Lett. 1996;383:124-8 pubmed
    ..In addition, we have reduced the interaction domain to the distal half of alpha1 syntrophin. ..
  2. Olalla L, Aledo J, Bannenberg G, Marquez J. The C-terminus of human glutaminase L mediates association with PDZ domain-containing proteins. FEBS Lett. 2001;488:116-22 pubmed
    ..These data suggest the possibility that PDZ domain-containing proteins are involved in the regulation of glutaminase in brain. ..
  3. Blake D. Dystrobrevin dynamics in muscle-cell signalling: a possible target for therapeutic intervention in Duchenne muscular dystrophy?. Neuromuscul Disord. 2002;12 Suppl 1:S110-7 pubmed
    ..This article discusses the function of dystrobrevin in muscle and reviews its suitability as a therapeutic target for treating patients with Duchenne and Becker muscular dystrophies. ..
  4. Sadoulet Puccio H, Rajala M, Kunkel L. Dystrobrevin and dystrophin: an interaction through coiled-coil motifs. Proc Natl Acad Sci U S A. 1997;94:12413-8 pubmed
    ..From the accumulated evidence of protein-protein interactions presented here and elsewhere, we propose a partially revised model of the organization of the dystrophin-associated glycoprotein complex. ..
  5. Lumeng C, Phelps S, Crawford G, Walden P, Barald K, Chamberlain J. Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases. Nat Neurosci. 1999;2:611-7 pubmed
    ..Our data suggest that MAST205 and SAST link the dystrophin/utrophin network with microtubule filaments via the syntrophins. ..
  6. Adams M, Kramarcy N, Krall S, Rossi S, Rotundo R, Sealock R, et al. Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin. J Cell Biol. 2000;150:1385-98 pubmed
    ..Thus, alpha-syntrophin has an important role in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. ..
  7. Hillier B, Christopherson K, Prehoda K, Bredt D, Lim W. Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex. Science. 1999;284:812-5 pubmed
    ..This structure explains how PDZ domains can participate in diverse interaction modes to assemble protein networks. ..
  8. Oak S, Russo K, Petrucci T, Jarrett H. Mouse alpha1-syntrophin binding to Grb2: further evidence of a role for syntrophin in cell signaling. Biochemistry. 2001;40:11270-8 pubmed
    ..Grb2-C-SH3 domain bound syntrophin with slightly higher affinity than Grb2-N-SH3 domain. Crk-L, an SH2/SH3 protein of similar domain structure but different specificity, does not bind these syntrophin sequences. ..
  9. Ahn A, Freener C, Gussoni E, Yoshida M, Ozawa E, Kunkel L. The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. J Biol Chem. 1996;271:2724-30 pubmed

More Information


  1. Bhat H, Baba R, Bashir M, Saeed S, Kirmani D, Wani M, et al. Alpha-1-syntrophin protein is differentially expressed in human cancers. Biomarkers. 2011;16:31-6 pubmed publisher
    We studied the expression of ?1-syntrophin (SNTA1) protein in histologically confirmed esophageal, stomach, lung, colon, rectal and breast cancerous tissue samples...
  2. Hasegawa M, Cuenda A, Spillantini M, Thomas G, Buee Scherrer V, Cohen P, et al. Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. J Biol Chem. 1999;274:12626-31 pubmed
    ..Phosphorylation of a PDZ domain-containing protein by an associated protein kinase is a novel mechanism for determining both the localization and the substrate specificity of a protein kinase. ..
  3. Gee S, Madhavan R, Levinson S, Caldwell J, Sealock R, Froehner S. Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci. 1998;18:128-37 pubmed
    ..Collectively, our data suggest that syntrophins link NaChs to the actin cytoskeleton and the extracellular matrix via dystrophin and the DAPC. ..
  4. Newey S, Benson M, Ponting C, Davies K, Blake D. Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex. Curr Biol. 2000;10:1295-8 pubmed
    ..This is likely to have important consequences for the recruitment of specific signalling molecules to the DPC and ultimately for its function. ..
  5. Hogan A, Shepherd L, Chabot J, Quenneville S, Prescott S, Topham M, et al. Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions. J Biol Chem. 2001;276:26526-33 pubmed
    ..Collectively, our results suggest that gamma 1-syntrophin participates in regulating the subcellular localization of DGK-zeta to ensure correct termination of diacylglycerol signaling. ..
  6. Yang B, Jung D, Rafael J, Chamberlain J, Campbell K. Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin. J Biol Chem. 1995;270:4975-8 pubmed
    ..Our data suggest that alpha-syntrophin binds all syntrophin isoforms, and syntrophin directly interacts with dystrophin through more than one binding site in dystrophin exons 73 and 74 including amino acids 3447-3481...
  7. Munehira Y, Ohnishi T, Kawamoto S, Furuya A, Shitara K, Imamura M, et al. Alpha1-syntrophin modulates turnover of ABCA1. J Biol Chem. 2004;279:15091-5 pubmed
    ..These results suggest that alpha1-syntrophin is involved in intracellular signaling, which determines the stability of ABCA1 and modulates cellular cholesterol release...
  8. Neely J, Amiry Moghaddam M, Ottersen O, Froehner S, Agre P, Adams M. Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proc Natl Acad Sci U S A. 2001;98:14108-13 pubmed
    ..These results demonstrate that perivascular localization of AQP4 in brain requires alpha-Syn, and stability of AQP4 in the membrane is increased by the C-terminal PDZ-binding motif. ..
  9. Kilpeläinen T, Bentley A, Noordam R, Sung Y, Schwander K, Winkler T, et al. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nat Commun. 2019;10:376 pubmed publisher
    ..We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher ..
  10. La Ferla M, Mercatanti A, Rocchi G, Lodovichi S, Cervelli T, Pignata L, et al. Expression of human poly (ADP-ribose) polymerase 1 in Saccharomyces cerevisiae: Effect on survival, homologous recombination and identification of genes involved in intracellular localization. Mutat Res. 2015;774:14-24 pubmed publisher
    ..histone H1 gene HHO1, the HUL4 gene, the deubiquitination enzyme gene OTU1, the nuclear pore protein POM152 and the SNT1 that encodes for the Set3C subunit of the histone deacetylase complex...
  11. Simon M, Wang M, Murchison C, Roese N, Boespflug E, Woltjer R, et al. Transcriptional network analysis of human astrocytic endfoot genes reveals region-specific associations with dementia status and tau pathology. Sci Rep. 2018;8:12389 pubmed publisher
    ..expression of perivascular astroglial gene products dystroglycan (DAG1), dystrobrevin (DTNA) and alpha-syntrophin (SNTA1), are associated with dementia status and phosphorylated tau (P-tau) levels in temporal cortex...
  12. Marchese M, Valvo G, Moro F, Sicca F, Santorelli F. Targeted Gene Resequencing (Astrochip) to Explore the Tripartite Synapse in Autism-Epilepsy Phenotype with Macrocephaly. Neuromolecular Med. 2016;18:69-80 pubmed publisher
    ..We detected rare or previously unknown predicted deleterious missense changes in GJA1, SLC12A2, SNTA1, EFNA3, CNTNAP2, EPHA4, and STXBP1 in seven patients and two high-frequency variants in DLG1 in six individuals...
  13. Cheng J, Valdivia C, Vaidyanathan R, Balijepalli R, Ackerman M, Makielski J. Caveolin-3 suppresses late sodium current by inhibiting nNOS-dependent S-nitrosylation of SCN5A. J Mol Cell Cardiol. 2013;61:102-10 pubmed publisher
    ..A SCN5A macromolecular complex was established in HEK-293 cells by transiently expressing SCN5A, α1-syntrophin (SNTA1), nNOS, and Cav3. Compared with Cav3-WT, Cav3-F97C produced significantly larger peak INa amplitudes, and showed 3...
  14. Bhat S, Parray A, Mushtaq U, Fazili K, Khanday F. Actin depolymerization mediated loss of SNTA1 phosphorylation and Rac1 activity has implications on ROS production, cell migration and apoptosis. Apoptosis. 2016;21:737-48 pubmed publisher
    Alpha-1-syntrophin (SNTA1) and Rac1 are part of a signaling pathway via the dystrophin glycoprotein complex (DGC). Both SNTA1 and Rac1 proteins are over-expressed in various carcinomas...
  15. Allegue C, Coll M, Mates J, Campuzano O, Iglesias A, Sobrino B, et al. Genetic Analysis of Arrhythmogenic Diseases in the Era of NGS: The Complexity of Clinical Decision-Making in Brugada Syndrome. PLoS ONE. 2015;10:e0133037 pubmed publisher
  16. Sadam H, Pihlak A, Kivil A, Pihelgas S, Jaago M, Adler P, et al. Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1: Large-scale Study of Antibody Profiling. EBioMedicine. 2018;29:47-59 pubmed publisher
    ..underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1)...
  17. Miyagoe Suzuki Y, Takeda S. Association of neuronal nitric oxide synthase (nNOS) with alpha1-syntrophin at the sarcolemma. Microsc Res Tech. 2001;55:164-70 pubmed
    ..In addition, the mice would facilitate identification of other signaling molecules, which are targeted to dystrophin complex via interaction with alpha1-syntrophin. ..
  18. Tan R, Patni H, Tandon P, Luan L, Sharma B, Salhan D, et al. Nef interaction with actin compromises human podocyte actin cytoskeletal integrity. Exp Mol Pathol. 2013;94:51-7 pubmed publisher
    ..Functionally, Nef/CIHPs displayed diminished attachment and enhanced detachment to their substrate. These findings indicate that Nef interaction with actin compromises the podocyte cytoskeleton integrity. ..
  19. Cheng J, Van Norstrand D, Medeiros Domingo A, Valdivia C, Tan B, Ye B, et al. Alpha1-syntrophin mutations identified in sudden infant death syndrome cause an increase in late cardiac sodium current. Circ Arrhythm Electrophysiol. 2009;2:667-76 pubmed publisher
    ..We recently implicated mutations in alpha1-syntrophin (SNTA1) as a novel cause of long-QT syndrome, whereby mutant SNTA1 released inhibition of associated neuronal nitric ..
  20. Lanciotti A, Brignone M, Camerini S, Serafini B, Macchia G, Raggi C, et al. MLC1 trafficking and membrane expression in astrocytes: role of caveolin-1 and phosphorylation. Neurobiol Dis. 2010;37:581-95 pubmed publisher
    ..Because pathological mutations prevent MLC1 membrane expression, the identification of substances regulating MLC1 intracellular trafficking is potentially relevant for the therapy of MLC. ..
  21. Xu H, Goldfarb M. Multiple effector domains within SNT1 coordinate ERK activation and neuronal differentiation of PC12 cells. J Biol Chem. 2001;276:13049-56 pubmed
    ..differentiation factors, the neurotrophins and fibroblast growth factors, induce rapid tyrosine phosphorylation of SNT1(FRS2alpha), which in turn enables SNT1 to recruit Shp2 tyrosine phosphatase and Grb2 adaptor protein in complex ..
  22. Choi J, Wang C, Thomas M, Pitt G. α1-Syntrophin Variant Identified in Drug-Induced Long QT Syndrome Increases Late Sodium Current. PLoS ONE. 2016;11:e0152355 pubmed publisher
    ..5 Na+ channel complex have been associated with diLQTS. We tested whether a novel SNTA1 (α1-syntrophin) variant (p...
  23. Okuhira K, Fitzgerald M, Sarracino D, Manning J, Bell S, Goss J, et al. Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux. J Biol Chem. 2005;280:39653-64 pubmed
    ..The approach used to identify beta1-syntrophin as an ABCA1-binding protein should prove useful in elucidating other protein interactions upon which ABCA1 function depends...
  24. Aquilano K, Baldelli S, Ciriolo M. Nuclear recruitment of neuronal nitric-oxide synthase by ?-syntrophin is crucial for the induction of mitochondrial biogenesis. J Biol Chem. 2014;289:365-78 pubmed publisher
    ..Overall, our results indicate that altered nNOS splicing and nuclear localization could be contributing factors in human muscular diseases associated with mitochondrial impairment. ..
  25. Ueda K, Valdivia C, Medeiros Domingo A, Tester D, Vatta M, Farrugia G, et al. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci U S A. 2008;105:9355-60 pubmed publisher
    ..Direct sequencing of SNTA1, the gene encoding alpha1-syntrophin, was performed in a cohort of LQTS patients that were negative for mutations ..
  26. Albrecht D, Froehner S. DAMAGE, a novel alpha-dystrobrevin-associated MAGE protein in dystrophin complexes. J Biol Chem. 2004;279:7014-23 pubmed
    ..These results expand the role of dystrobrevin and the dystrophin complex in membrane signaling and disease. ..
  27. Hu R, Tan B, Orland K, Valdivia C, Peterson A, Pu J, et al. Digenic inheritance novel mutations in SCN5a and SNTA1 increase late I(Na) contributing to LQT syndrome. Am J Physiol Heart Circ Physiol. 2013;304:H994-H1001 pubmed publisher
    SCN5A and SNTA1 are reported susceptible genes for long QT syndrome (LQTS)...
  28. Iwata Y, Pan Y, Yoshida T, Hanada H, Shigekawa M. Alpha1-syntrophin has distinct binding sites for actin and calmodulin. FEBS Lett. 1998;423:173-7 pubmed
    ..We also found that alpha1-syntrophin binds calmodulin at two distinct sites with high (Kd 15 nM) and low (Kd 0.3 microM) affinity. ..
  29. Li C, Krishnamurthy P, Penmatsa H, Marrs K, Wang X, Zaccolo M, et al. Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia. Cell. 2007;131:940-51 pubmed
    ..Mrp4 knockout mice are more prone to CFTR-mediated secretory diarrhea. Our findings have important implications for disorders such as inflammatory bowel disease and secretory diarrhea. ..
  30. Rein Fischboeck L, Pohl R, Haberl E, Weiss T, Buechler C. The adaptor protein alpha-syntrophin is reduced in human non-alcoholic steatohepatitis but is unchanged in hepatocellular carcinoma. Exp Mol Pathol. 2017;103:204-209 pubmed publisher
    ..Present study identified associations of hepatic SNTA mRNA levels with SR-BI and features of NASH assuming a function of this protein in chronic liver disease and cholesterol metabolism. ..
  31. Chen Z, Hague C, Hall R, Minneman K. Syntrophins regulate alpha1D-adrenergic receptors through a PDZ domain-mediated interaction. J Biol Chem. 2006;281:12414-20 pubmed
    ..This direct interaction may provide new information about the regulation of alpha1D-AR signaling and the role of syntrophins in modulating G protein-coupled receptor function. ..
  32. Neculai D, Neculai A, Verrier S, Straub K, Klumpp K, Pfitzner E, et al. Structure of the unphosphorylated STAT5a dimer. J Biol Chem. 2005;280:40782-7 pubmed
    ..The separation of the dimeric arrangement, taking place upon activation and nuclear translocation of STAT5a, is demonstrated by fluorescence resonance energy transfer experiments in living cells. ..
  33. Goto M, Muramatsu H, Mihara H, Kurihara T, Esaki N, Omi R, et al. Crystal structures of Delta1-piperideine-2-carboxylate/Delta1-pyrroline-2-carboxylate reductase belonging to a new family of NAD(P)H-dependent oxidoreductases: conformational change, substrate recognition, and stereochemistry of the reaction. J Biol Chem. 2005;280:40875-84 pubmed publisher
    ..The active site structure of the catalytic form made it possible to identify the catalytic Asp:Ser:His triad and investigate the catalytic mechanism from a stereochemical point of view...
  34. Blake D, Hawkes R, Benson M, Beesley P. Different dystrophin-like complexes are expressed in neurons and glia. J Cell Biol. 1999;147:645-58 pubmed
    ..Thus, despite the similarity in primary sequence, alpha- and beta-dystrobrevin are differentially distributed in the brain where they form separate DPC-like complexes. ..
  35. Stiffler M, Grantcharova V, Sevecka M, MacBeath G. Uncovering quantitative protein interaction networks for mouse PDZ domains using protein microarrays. J Am Chem Soc. 2006;128:5913-22 pubmed
  36. Opdal S, Vege Ã, Stray Pedersen A, Rognum T. The gene encoding the inwardly rectifying potassium channel Kir4.1 may be involved in sudden infant death syndrome. Acta Paediatr. 2017;106:1474-1480 pubmed publisher
    ..1 complex can disrupt water and ion homeostasis, which may influence brain development and facilitate brain oedema formation This may be especially unfavourable during the first weeks of life. ..
  37. Stephenson J, Paavola K, Schaefer S, Kaur B, Van Meir E, Hall R. Brain-specific angiogenesis inhibitor-1 signaling, regulation, and enrichment in the postsynaptic density. J Biol Chem. 2013;288:22248-56 pubmed publisher
    ..These findings demonstrate that BAI1 is a synaptic receptor that can activate both the Rho and ERK pathways, with the N-terminal and C-terminal regions of the receptor playing key roles in the regulation of BAI1 signaling activity. ..
  38. Winkel B, Yuan L, Olesen M, Sadjadieh G, Wang Y, Risgaard B, et al. The role of the sodium current complex in a nonreferred nationwide cohort of sudden infant death syndrome. Heart Rhythm. 2015;12:1241-9 pubmed publisher
    ..5 channel complex: SCN5A, SCN1B, SCN2B, SCN3B, SCN4B, GPD1L, SNTA1, and CAV3. Patch-clamp analyses were performed on variants not previously characterized...
  39. Wu G, Ai T, Kim J, Mohapatra B, Xi Y, Li Z, et al. alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circ Arrhythm Electrophysiol. 2008;1:193-201 pubmed publisher
    ..The cytoskeletal protein syntrophin-alpha(1) (SNTA1) is known to interact with the cardiac sodium channel (hNa(v)1...
  40. Zitzer H, Richter D, Kreienkamp H. Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin-binding protein 1. J Biol Chem. 1999;274:18153-6 pubmed
    ..Our data for the first time establish a link between a G-protein coupled receptor and constituents of the cytoskeleton. ..
  41. Adams M, Mueller H, Froehner S. In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4. J Cell Biol. 2001;155:113-22 pubmed
    ..Together, these data show that the sarcolemmal localization of nNOS and aquaporin-4 in vivo depends on the presence of a dystrophin-bound alpha-syntrophin PDZ domain. ..
  42. Bhat H, Baba R, Adams M, Khanday F. Role of SNTA1 in Rac1 activation, modulation of ROS generation, and migratory potential of human breast cancer cells. Br J Cancer. 2014;110:706-14 pubmed publisher
    Alpha-1-syntrophin (SNTA1) has been implicated in the activation of Rac1. However, the underlying mechanism has not yet been explored...
  43. Harisseh R, Chatelier A, Magaud C, Déliot N, Constantin B. Involvement of TRPV2 and SOCE in calcium influx disorder in DMD primary human myotubes with a specific contribution of ?1-syntrophin and PLC/PKC in SOCE regulation. Am J Physiol Cell Physiol. 2013;304:C881-94 pubmed publisher
    ..These findings show that calcium homeostasis mishandling in DMD myotubes depends on SOCE under the influence of Ca(2+)/PLC/PKC pathway and ?1-syntrophin regulation as well as on TRPV2-dependant cation influx. ..
  44. Boor I, Nagtegaal M, Kamphorst W, van der Valk P, Pronk J, van Horssen J, et al. MLC1 is associated with the dystrophin-glycoprotein complex at astrocytic endfeet. Acta Neuropathol. 2007;114:403-10 pubmed
    ..We demonstrated a direct protein interaction between MLC1 and Kir4.1. From these results we conclude that MLC1 is associated with the DGC at astrocytic endfeet...
  45. Fernandez Larrea J, Merlos Suarez A, Urena J, Baselga J, Arribas J. A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface. Mol Cell. 1999;3:423-33 pubmed
    ..Therefore, it appears that the interaction of TACIP18 with proTGF-alpha in the early secretory pathway is necessary for the targeting of the latter to the cell surface. ..
  46. Petitprez S, Zmoos A, Ogrodnik J, Balse E, Raad N, El Haou S, et al. SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circ Res. 2011;108:294-304 pubmed publisher
    ..These data support a model with at least 2 coexisting pools of Na(v)1.5 channels in cardiomyocytes: one targeted at lateral membranes by the syntrophin-dystrophin complex, and one at intercalated discs by SAP97. ..
  47. Marchand S, Stetzkowski Marden F, Cartaud J. Differential targeting of components of the dystrophin complex to the postsynaptic membrane. Eur J Neurosci. 2001;13:221-9 pubmed
    ..This study provides the first evidence for a separate targeting of the various components of the dystrophin-associated protein complex and a step-by-step assembly at the postsynaptic membrane. ..