Syntrophin, alpha 1

SNTA1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1QAV, 1Z86, 1Z87, 2ADZ, 2PDZ, 4HOP
Identifiers
Aliases	SNTA1 , LQT12, SNT1, TACIP1, dJ1187J4.5, Syntrophin, alpha 1, syntrophin alpha 1
External IDs	OMIM: 601017 MGI: 101772 HomoloGene: 2331 GeneCards: SNTA1
Gene location (Human)
Chr.	Chromosome 20 (human)
End	33,443,763 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	154,250,019 bp
RNA expression pattern
	Top expressed in
	gastrocnemius muscle; ; left ventricle; ; putamen; ; caudate nucleus; ; nucleus accumbens; ; amygdala; ; right lobe of thyroid gland; ; triceps brachii muscle; ; left lobe of thyroid gland; ; cingulate gyrus;
	Top expressed in
	extensor digitorum longus muscle; ; triceps brachii muscle; ; ankle; ; sternocleidomastoid muscle; ; skeletal muscle tissue; ; plantaris muscle; ; temporal muscle; ; masseter muscle; ; tibialis anterior muscle; ; vastus lateralis muscle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	sodium channel regulator activity ; nitric-oxide synthase binding ; transmembrane transporter binding ; ATPase binding ; structural molecule activity ; calmodulin binding ; protein binding ; actin binding ; PDZ domain binding ;
Cellular component	cytoplasm ; lateral plasma membrane ; membrane ; neuromuscular junction ; plasma membrane ; intracellular anatomical structure ; cell junction ; sarcolemma ; syntrophin complex ; cytoskeleton ; protein-containing complex ; dystrophin-associated glycoprotein complex ; synapse ;
Biological process	muscle contraction ; negative regulation of peptidyl-cysteine S-nitrosylation ; ventricular cardiac muscle cell action potential ; regulation of heart rate ; regulation of sodium ion transmembrane transport ; regulation of ventricular cardiac muscle cell membrane repolarization ;
	Sources:Amigo / QuickGO
Orthologs
	6640
	20648
	ENSG00000101400
	ENSMUSG00000027488
	Q13424
	Q61234
	NM_003098
	NM_009228
	NP_003089
	NP_033254
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated January 05, 2024

Alpha-1-syntrophin is a protein that in humans is encoded by the SNTA1 gene.^[5]^[6]^[7] Alpha-1 syntrophin is a signal transducing adaptor protein and serves as a scaffold for various signaling molecules. Alpha-1 syntrophin contains a PDZ domain, two Pleckstrin homology domain and a 'syntrophin unique' domain.

Function

Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in Duchenne Muscular Dystrophy patients and is present in reduced amounts in Becker Muscular Dystrophy patients. The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related proteins. This gene is a member of the syntrophin gene family, which contains at least two other structurally related genes.^[7] The PDZ domain of syntrophin-α1(SNTA1), the most abundant isoform in the heart, has been reported to bind to the C-terminal domain of murine cardiac voltage-gated sodium channels (SkM2) causing altering ion channel activity leading to Long QT syndrome.^[8]^[9]

Interactions

Syntrophin, alpha 1 has been shown to interact with Dystrophin,^[5]^[10]^[11] Nav1.1 ^[11] and Nav1.5,^[11] and Aquaporin 4.^[12]

Related Research Articles

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. It has a molecular weight of 427 kDa

Utrophin is a protein that in humans is encoded by the UTRN gene. The name is a short form for ubiquitous dystrophin.

Dystrobrevin is a protein that binds to dystrophin in the costamere of skeletal muscle cells. In humans, there are at least two isoforms of dystrobrevin, dystrobrevin alpha and dystrobrevin beta.

PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene.

Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the DLG2 gene.

Syntenin-1 is a protein that in humans is encoded by the SDCBP gene.

The alpha-1B adrenergic receptor (α_1B-adrenoreceptor), also known as ADRA1B, is an alpha-1 adrenergic receptor, and also denotes the human gene encoding it. The crystal structure of the α_1B-adrenergic receptor has been determined in complex with the inverse agonist (+)-cyclazosin.

Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.

Alpha-actinin-4 is a protein that in humans is encoded by the ACTN4 gene.

GIPC PDZ domain containing family, member 1 (GIPC1) is a protein that in humans is encoded by the GIPC1 gene. GIPC was originally identified as it binds specifically to the C terminus of RGS-GAIP, a protein involved in the regulation of G protein signaling. GIPC is an acronym for "GAIP Interacting Protein C-terminus". RGS proteins are "Regulators of G protein Signaling" and RGS-GAIP is a "GTPase Activator protein for Gαi/Gαq", which are two major subtypes of Gα proteins. The human GIPC1 molecule is 333 amino acids or about 36 kDa in molecular size and consists of a central PDZ domain, a compact protein module which mediates specific protein-protein interactions. The RGS-GAIP protein interacts with this domain and many other proteins interact here or at other parts of the GIPC1 molecule. As a result, GIPC1 was independently discovered by several other groups and has a variety of alternate names, including synectin, C19orf3, RGS19IP1 and others. The GIPC1 gene family in mammals consisting of three members, so the first discovered, originally named GIPC, is now generally called GIPC1, with the other two being named GIPC2 and GIPC3. The three human proteins are about 60% identical in protein sequence. GIPC1 has been shown to interact with a variety of other receptor and cytoskeletal proteins including the GLUT1 receptor, ACTN1, KIF1B, MYO6, PLEKHG5, SDC4/syndecan-4, SEMA4C/semaphorin-4 and HTLV-I Tax. The general function of GIPC family proteins therefore appears to be mediating specific interactions between proteins involved in G protein signaling and membrane translocation.

Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or K_ir2.3, is a human gene.

Beta-2-syntrophin is a protein that in humans is encoded by the SNTB2 gene.

Beta-1-syntrophin is a protein that in humans is encoded by the SNTB1 gene.

Microtubule-associated serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the MAST2 gene. The protein encoded by this gene controls TRAF6 and NF-kappaB activity.

Lin-7 homolog B is a protein that in humans is encoded by the LIN7B gene.

Cysteine-rich PDZ-binding protein is a protein that in humans is encoded by the CRIPT gene.

Gamma-1-syntrophin is a protein that in humans is encoded by the SNTG1 gene.

Dystrobrevin alpha is a protein that in humans is encoded by the DTNA gene.

Dystrobrevin beta is a protein which in humans is encoded by the DTNB gene.

Stanley C. Froehner is an American physiologist and biophysicist currently the UW Medicine Distinguished Professor at University of Washington and an Elected Fellow of the American Association for the Advancement of Science.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000101400 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027488 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM (Mar 1996). "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. 271 (5): 2724–30. doi: 10.1074/jbc.271.5.2724 . PMID 8576247.
↑ Castelló A, Brochériou V, Chafey P, Kahn A, Gilgenkrantz H (Jun 1996). "Characterization of the dystrophin-syntrophin interaction using the two-hybrid system in yeast". FEBS Lett. 383 (1–2): 124–8. doi: 10.1016/0014-5793(96)00214-1 . PMID 8612778. S2CID 27278535.
1 2 "Entrez Gene: SNTA1 syntrophin, alpha 1 (dystrophin-associated protein A1, 59kDa, acidic component)".
↑ Wu G, Ai T, Kim JJ, Mohapatra B, Xi Y, Li Z, Abbasi S, Purevjav E, Samani K, Ackerman MJ, Qi M, Moss AJ, Shimizu W, Towbin JA, Cheng J, Vatta M (Aug 2008). "Alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption". Circ Arrhythmia Electrophysiol. 1 (3): 193–201. doi:10.1161/CIRCEP.108.769224. PMC 2726717 . PMID 19684871.
↑ Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M (2009). "The genetic basis of long QT and short QT syndromes: a mutation update". Human Mutation. 30 (11): 1486–511. doi: 10.1002/humu.21106 . PMID 19862833. S2CID 19122696.
↑ Yang B, Jung D, Rafael JA, Chamberlain JS, Campbell KP (Mar 1995). "Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin". J. Biol. Chem. 270 (10): 4975–8. doi: 10.1074/jbc.270.10.4975 . PMID 7890602.
1 2 3 Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (Jan 1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". J. Neurosci. 18 (1): 128–37. doi: 10.1523/jneurosci.18-01-00128.1998 . PMC 6793384 . PMID 9412493.
↑ Neely JD, Amiry-Moghaddam M, Ottersen OP, Froehner SC, Agre P, Adams ME (November 2001). "Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein". Proc. Natl. Acad. Sci. U.S.A. 98 (24): 14108–13. Bibcode:2001PNAS...9814108N. doi: 10.1073/pnas.241508198 . PMC 61176 . PMID 11717465.

Miyagoe-Suzuki Y, Takeda SI (2002). "Association of neuronal nitric oxide synthase (nNOS) with alpha1-syntrophin at the sarcolemma". Microsc. Res. Tech. 55 (3): 164–70. doi:10.1002/jemt.1167. PMID 11747091. S2CID 28225242.
Blake DJ (2002). "Dystrobrevin dynamics in muscle-cell signalling: a possible target for therapeutic intervention in Duchenne muscular dystrophy?". Neuromuscul. Disord. 12 (Suppl 1): S110–7. doi:10.1016/S0960-8966(02)00091-3. PMID 12206805. S2CID 9188156.
Yang B, Jung D, Rafael JA, Chamberlain JS, Campbell KP (1995). "Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin". J. Biol. Chem. 270 (10): 4975–8. doi: 10.1074/jbc.270.10.4975 . PMID 7890602.
Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". J. Neurosci. 18 (1): 128–37. doi: 10.1523/jneurosci.18-01-00128.1998 . PMC 6793384 . PMID 9412493.
Iwata Y, Pan Y, Yoshida T, Hanada H, Shigekawa M (1998). "Alpha1-syntrophin has distinct binding sites for actin and calmodulin". FEBS Lett. 423 (2): 173–7. doi:10.1016/S0014-5793(98)00085-4. PMID 9512352. S2CID 26209999.
Hasegawa M, Cuenda A, Spillantini MG, Thomas GM, Buée-Scherrer V, Cohen P, Goedert M (1999). "Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition". J. Biol. Chem. 274 (18): 12626–31. doi: 10.1074/jbc.274.18.12626 . PMID 10212242.
Hillier BJ, Christopherson KS, Prehoda KE, Bredt DS, Lim WA (1999). "Unexpected modes of PDZ domain scaffolding revealed by structure of nNOS-syntrophin complex". Science. 284 (5415): 812–5. doi:10.1126/science.284.5415.812. PMID 10221915.
Fernández-Larrea J, Merlos-Suárez A, Ureña JM, Baselga J, Arribas J (1999). "A role for a PDZ protein in the early secretory pathway for the targeting of proTGF-alpha to the cell surface". Mol. Cell. 3 (4): 423–33. doi: 10.1016/S1097-2765(00)80470-0 . PMID 10230395.
Lumeng C, Phelps S, Crawford GE, Walden PD, Barald K, Chamberlain JS (1999). "Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases". Nat. Neurosci. 2 (7): 611–7. doi:10.1038/10165. PMID 10404183. S2CID 20910888.
Adams ME, Kramarcy N, Krall SP, Rossi SG, Rotundo RL, Sealock R, Froehner SC (2000). "Absence of alpha-syntrophin leads to structurally aberrant neuromuscular synapses deficient in utrophin". J. Cell Biol. 150 (6): 1385–98. doi:10.1083/jcb.150.6.1385. PMC 2150701 . PMID 10995443.
Newey SE, Benson MA, Ponting CP, Davies KE, Blake DJ (2001). "Alternative splicing of dystrobrevin regulates the stoichiometry of syntrophin binding to the dystrophin protein complex". Curr. Biol. 10 (20): 1295–8. doi: 10.1016/S0960-9822(00)00760-0 . PMID 11069112. S2CID 18104833.
Olalla L, Aledo JC, Bannenberg G, Márquez J (2001). "The C-terminus of human glutaminase L mediates association with PDZ domain-containing proteins". FEBS Lett. 488 (3): 116–22. doi:10.1016/S0014-5793(00)02373-5. PMID 11163757. S2CID 11614189.
Marchand S, Stetzkowski-Marden F, Cartaud J (2001). "Differential targeting of components of the dystrophin complex to the postsynaptic membrane". Eur. J. Neurosci. 13 (2): 221–9. doi:10.1046/j.1460-9568.2001.01373.x. PMID 11168526.
Xu H, Goldfarb M (2001). "Multiple effector domains within SNT1 coordinate ERK activation and neuronal differentiation of PC12 cells". J. Biol. Chem. 276 (16): 13049–56. doi: 10.1074/jbc.M009925200 . PMID 11278583.
Hogan A, Shepherd L, Chabot J, Quenneville S, Prescott SM, Topham MK, Gee SH (2001). "Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions". J. Biol. Chem. 276 (28): 26526–33. doi: 10.1074/jbc.M104156200 . PMID 11352924.
Oak SA, Russo K, Petrucci TC, Jarrett HW (2001). "Mouse alpha1-syntrophin binding to Grb2: further evidence of a role for syntrophin in cell signaling". Biochemistry. 40 (37): 11270–8. doi:10.1021/bi010490n. PMID 11551227.
Adams ME, Mueller HA, Froehner SC (2001). "In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4". J. Cell Biol. 155 (1): 113–22. doi:10.1083/jcb.200106158. PMC 2150783 . PMID 11571312.
Neely JD, Amiry-Moghaddam M, Ottersen OP, Froehner SC, Agre P, Adams ME (2002). "Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein". Proc. Natl. Acad. Sci. U.S.A. 98 (24): 14108–13. Bibcode:2001PNAS...9814108N. doi: 10.1073/pnas.241508198 . PMC 61176 . PMID 11717465.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000101400 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027488 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8576247-5] 1 2 Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM (Mar 1996). "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. 271 (5): 2724–30. doi: 10.1074/jbc.271.5.2724 . PMID 8576247.

[pmid8612778-6] Castelló A, Brochériou V, Chafey P, Kahn A, Gilgenkrantz H (Jun 1996). "Characterization of the dystrophin-syntrophin interaction using the two-hybrid system in yeast". FEBS Lett. 383 (1–2): 124–8. doi: 10.1016/0014-5793(96)00214-1 . PMID 8612778. S2CID 27278535.

[entrez-7] 1 2 "Entrez Gene: SNTA1 syntrophin, alpha 1 (dystrophin-associated protein A1, 59kDa, acidic component)".

[pmid19684871-8] Wu G, Ai T, Kim JJ, Mohapatra B, Xi Y, Li Z, Abbasi S, Purevjav E, Samani K, Ackerman MJ, Qi M, Moss AJ, Shimizu W, Towbin JA, Cheng J, Vatta M (Aug 2008). "Alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption". Circ Arrhythmia Electrophysiol. 1 (3): 193–201. doi:10.1161/CIRCEP.108.769224. PMC 2726717 . PMID 19684871.

[pmid19862833-9] Hedley PL, Jørgensen P, Schlamowitz S, Wangari R, Moolman-Smook J, Brink PA, Kanters JK, Corfield VA, Christiansen M (2009). "The genetic basis of long QT and short QT syndromes: a mutation update". Human Mutation. 30 (11): 1486–511. doi: 10.1002/humu.21106 . PMID 19862833. S2CID 19122696.

[pmid7890602-10] Yang B, Jung D, Rafael JA, Chamberlain JS, Campbell KP (Mar 1995). "Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, and utrophin". J. Biol. Chem. 270 (10): 4975–8. doi: 10.1074/jbc.270.10.4975 . PMID 7890602.

[pmid9412493-11] 1 2 3 Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC (Jan 1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". J. Neurosci. 18 (1): 128–37. doi: 10.1523/jneurosci.18-01-00128.1998 . PMC 6793384 . PMID 9412493.

[pmid11717465-12] Neely JD, Amiry-Moghaddam M, Ottersen OP, Froehner SC, Agre P, Adams ME (November 2001). "Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein". Proc. Natl. Acad. Sci. U.S.A. 98 (24): 14108–13. Bibcode:2001PNAS...9814108N. doi: 10.1073/pnas.241508198 . PMC 61176 . PMID 11717465.

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Syntrophin, alpha 1

Contents

Function

Interactions

Related Research Articles

References

Further reading