SNTA1_MOUSE
ID SNTA1_MOUSE Reviewed; 503 AA.
AC Q61234; Q8VEF3;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Alpha-1-syntrophin;
DE AltName: Full=59 kDa dystrophin-associated protein A1 acidic component 1;
DE AltName: Full=Syntrophin-1;
GN Name=Snta1; Synonyms=Snt1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 155-161; 165-171;
RP 213-228; 247-261 AND 271-307.
RC TISSUE=Muscle;
RX PubMed=7691103; DOI=10.1016/0896-6273(93)90157-m;
RA Adams M.E., Butler M.H., Dwyer T.M., Peters M.F., Murnane A.A.,
RA Froehner S.C.;
RT "Two forms of mouse syntrophin, a 58 kDa dystrophin-associated protein,
RT differ in primary structure and tissue distribution.";
RL Neuron 11:531-540(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 7-16, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP INTERACTION WITH SNTB1; SNTB2; DMD; SGCA AND SGCG.
RX PubMed=7547961; DOI=10.1021/bi00038a014;
RA Madhavan R., Jarrett H.W.;
RT "Interactions between dystrophin glycoprotein complex proteins.";
RL Biochemistry 34:12204-12209(1995).
RN [5]
RP INTERACTION WITH NOS1.
RX PubMed=8625413; DOI=10.1016/s0092-8674(00)81053-3;
RA Brenman J.E., Chao D.S., Gee S.H., McGee A.W., Craven S.E.,
RA Santillano D.R., Wu Z., Huang F., Xia H., Peters M.F., Froehner S.C.,
RA Bredt D.S.;
RT "Interaction of nitric oxide synthase with the postsynaptic density protein
RT PSD-95 and alpha1-syntrophin mediated by PDZ domains.";
RL Cell 84:757-767(1996).
RN [6]
RP INTERACTION WITH CALMODULIN.
RX PubMed=9063877; DOI=10.1021/bi962452n;
RA Newbell B.J., Anderson J.T., Jarrett H.W.;
RT "Ca2+-calmodulin binding to mouse alpha1 syntrophin: syntrophin is also a
RT Ca2+-binding protein.";
RL Biochemistry 36:1295-1305(1997).
RN [7]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH DMD; DTNA
RP AND UTRN.
RX PubMed=9214383; DOI=10.1083/jcb.138.1.81;
RA Peters M.F., Adams M.E., Froehner S.C.;
RT "Differential association of syntrophin pairs with the dystrophin
RT complex.";
RL J. Cell Biol. 138:81-93(1997).
RN [8]
RP INTERACTION WITH SCN4A AND SCN5A.
RX PubMed=9412493; DOI=10.1523/jneurosci.18-01-00128.1998;
RA Gee S.H., Madhavan R., Levinson S.R., Caldwell J.H., Sealock R.,
RA Froehner S.C.;
RT "Interaction of muscle and brain sodium channels with multiple members of
RT the syntrophin family of dystrophin-associated proteins.";
RL J. Neurosci. 18:128-137(1998).
RN [9]
RP ASSOCIATION WITH PHOSPHATIDYLINOSITOL 4,5-BIPHOSPHATE.
RX PubMed=10220348; DOI=10.1021/bi982564+;
RA Chockalingam P.S., Gee S.H., Jarrett H.W.;
RT "Pleckstrin homology domain 1 of mouse alpha 1-syntrophin binds
RT phosphatidylinositol 4,5-bisphosphate.";
RL Biochemistry 38:5596-5602(1999).
RN [10]
RP PHOSPHORYLATION BY CAM-KINASE II.
RX PubMed=10525145; DOI=10.1016/s0167-4838(99)00193-4;
RA Madhavan R., Jarrett H.W.;
RT "Phosphorylation of dystrophin and alpha-syntrophin by Ca(2+)-calmodulin
RT dependent protein kinase II.";
RL Biochim. Biophys. Acta 1434:260-274(1999).
RN [11]
RP OLIGOMERIZATION.
RX PubMed=10913299; DOI=10.1021/bi0000824;
RA Oak S.A., Jarrett H.W.;
RT "Oligomerization of mouse alpha 1-syntrophin and self-association of its
RT pleckstrin homology domain 1 containing sequences.";
RL Biochemistry 39:8870-8877(2000).
RN [12]
RP INTERACTION WITH DTNB.
RX PubMed=10893187; DOI=10.1242/jcs.113.15.2715;
RA Loh N.Y., Newey S.E., Davies K.E., Blake D.J.;
RT "Assembly of multiple dystrobrevin-containing complexes in the kidney.";
RL J. Cell Sci. 113:2715-2724(2000).
RN [13]
RP INTERACTION WITH GRB2.
RX PubMed=11551227; DOI=10.1021/bi010490n;
RA Oak S.A., Russo K., Petrucci T.C., Jarrett H.W.;
RT "Mouse alpha1-syntrophin binding to Grb2: further evidence of a role for
RT syntrophin in cell signaling.";
RL Biochemistry 40:11270-11278(2001).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-183 AND SER-187, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-95; SER-183; SER-187 AND
RP SER-194, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP INTERACTION WITH MYOC.
RX PubMed=22371502; DOI=10.1074/jbc.m111.224063;
RA Joe M.K., Kee C., Tomarev S.I.;
RT "Myocilin interacts with syntrophins and is member of dystrophin-associated
RT protein complex.";
RL J. Biol. Chem. 287:13216-13227(2012).
CC -!- FUNCTION: Adapter protein that binds to and probably organizes the
CC subcellular localization of a variety of membrane proteins. May link
CC various receptors to the actin cytoskeleton and the extracellular
CC matrix via the dystrophin glycoprotein complex. Plays an important role
CC in synapse formation and in the organization of UTRN and acetylcholine
CC receptors at the neuromuscular synapse. Binds to phosphatidylinositol
CC 4,5-bisphosphate.
CC -!- SUBUNIT: Monomer and homodimer. Interacts with MAPK12, TGFA, GA and F-
CC actin (By similarity). Interacts with the other members of the
CC syntrophin family: SNTB1 and SNTB2; with dystrophin protein DMD and
CC related proteins DTNA and UTRN; SGCG and SGCA of the dystrophin
CC glycoprotein complex; NOS1; GRB2; calmodulin and the sodium channel
CC proteins SCN4A and SCN5A. Interacts with MYOC; regulates muscle
CC hypertrophy. Interacts with DTNB (PubMed:10893187). {ECO:0000250,
CC ECO:0000269|PubMed:10893187, ECO:0000269|PubMed:11551227,
CC ECO:0000269|PubMed:22371502, ECO:0000269|PubMed:7547961,
CC ECO:0000269|PubMed:8625413, ECO:0000269|PubMed:9063877,
CC ECO:0000269|PubMed:9214383, ECO:0000269|PubMed:9412493}.
CC -!- INTERACTION:
CC Q61234; P11531: Dmd; NbExp=4; IntAct=EBI-295952, EBI-295928;
CC Q61234; Q60631: Grb2; NbExp=3; IntAct=EBI-295952, EBI-1688;
CC Q61234; P25100: ADRA1D; Xeno; NbExp=3; IntAct=EBI-295952, EBI-489993;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:9214383}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9214383}; Cytoplasmic side
CC {ECO:0000269|PubMed:9214383}. Cell junction
CC {ECO:0000269|PubMed:9214383}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:9214383}. Note=In skeletal muscle, it localizes at
CC the cytoplasmic side of the sarcolemmal membrane and at neuromuscular
CC junctions.
CC -!- TISSUE SPECIFICITY: High expression in skeletal muscle. Expressed at
CC intermediate level in heart, kidney and brain, and at low level in
CC intestine, liver, lung and testis. {ECO:0000269|PubMed:9214383}.
CC -!- DOMAIN: The PH 1 domain mediates the oligomerization in a calcium
CC dependent manner, and the association with the phosphatidylinositol
CC 4,5-bisphosphate.
CC -!- DOMAIN: The PDZ domain binds to the last three or four amino acids of
CC ion channels and receptor proteins. The association with dystrophin or
CC related proteins probably leaves the PDZ domain available to recruit
CC proteins to the membrane.
CC -!- DOMAIN: The SU domain binds calmodulin in a calcium-dependent manner.
CC -!- PTM: Phosphorylated by CaM-kinase II. Phosphorylation may inhibit the
CC interaction with DMD. {ECO:0000269|PubMed:10525145}.
CC -!- SIMILARITY: Belongs to the syntrophin family. {ECO:0000305}.
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DR EMBL; U00677; AAC52119.1; -; mRNA.
DR EMBL; BC018546; AAH18546.1; -; mRNA.
DR PIR; I84771; I84771.
DR PDB; 1QAV; X-ray; 1.90 A; A=77-164.
DR PDB; 1Z86; NMR; -; A=79-165.
DR PDB; 1Z87; NMR; -; A=2-264.
DR PDB; 2ADZ; NMR; -; A=2-264.
DR PDB; 2PDZ; NMR; -; A=79-164.
DR PDB; 4HOP; X-ray; 2.29 A; A/C/E=77-162.
DR PDBsum; 1QAV; -.
DR PDBsum; 1Z86; -.
DR PDBsum; 1Z87; -.
DR PDBsum; 2ADZ; -.
DR PDBsum; 2PDZ; -.
DR PDBsum; 4HOP; -.
DR AlphaFoldDB; Q61234; -.
DR BMRB; Q61234; -.
DR SMR; Q61234; -.
DR CORUM; Q61234; -.
DR DIP; DIP-32898N; -.
DR IntAct; Q61234; 23.
DR MINT; Q61234; -.
DR STRING; 10090.ENSMUSP00000028991; -.
DR iPTMnet; Q61234; -.
DR PhosphoSitePlus; Q61234; -.
DR jPOST; Q61234; -.
DR MaxQB; Q61234; -.
DR PaxDb; Q61234; -.
DR PeptideAtlas; Q61234; -.
DR PRIDE; Q61234; -.
DR ProteomicsDB; 257540; -.
DR Antibodypedia; 10673; 451 antibodies from 34 providers.
DR Ensembl; ENSMUST00000028991; ENSMUSP00000028991; ENSMUSG00000027488.
DR MGI; MGI:101772; Snta1.
DR VEuPathDB; HostDB:ENSMUSG00000027488; -.
DR eggNOG; KOG3551; Eukaryota.
DR GeneTree; ENSGT00950000182863; -.
DR InParanoid; Q61234; -.
DR PhylomeDB; Q61234; -.
DR TreeFam; TF317932; -.
DR ChiTaRS; Frs2; mouse.
DR EvolutionaryTrace; Q61234; -.
DR PRO; PR:Q61234; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q61234; protein.
DR Bgee; ENSMUSG00000027488; Expressed in hindlimb stylopod muscle and 203 other tissues.
DR ExpressionAtlas; Q61234; baseline and differential.
DR Genevisible; Q61234; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0016010; C:dystrophin-associated glycoprotein complex; IBA:GO_Central.
DR GO; GO:0031594; C:neuromuscular junction; ISO:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; IDA:MGI.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0051117; F:ATPase binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0017080; F:sodium channel regulator activity; ISO:MGI.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:1902083; P:negative regulation of peptidyl-cysteine S-nitrosylation; ISO:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI.
DR GO; GO:0002027; P:regulation of heart rate; ISO:MGI.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0003117; P:regulation of vasoconstriction by circulating norepinephrine; IMP:MGI.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISO:MGI.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISO:MGI.
DR CDD; cd01258; PHsplit_syntrophin; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR041428; PHsplit_syntrophin.
DR InterPro; IPR028552; SNTA1.
DR InterPro; IPR015482; Syntrophin.
DR PANTHER; PTHR10554; PTHR10554; 1.
DR PANTHER; PTHR10554:SF6; PTHR10554:SF6; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF18012; PH_17; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00233; PH; 2.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Calcium; Calmodulin-binding; Cell junction;
KW Cell membrane; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Membrane; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..503
FT /note="Alpha-1-syntrophin"
FT /id="PRO_0000184007"
FT DOMAIN 6..263
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 81..164
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 287..399
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 447..503
FT /note="SU"
FT REGION 40..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..503
FT /note="Calmodulin-binding"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13424"
FT MOD_RES 183
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 16
FT /note="R -> C (in Ref. 2; AAH18546)"
FT /evidence="ECO:0000305"
FT CONFLICT 341..344
FT /note="Missing (in Ref. 2; AAH18546)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="I -> V (in Ref. 2; AAH18546)"
FT /evidence="ECO:0000305"
FT STRAND 9..16
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 20..24
FT /evidence="ECO:0007829|PDB:2ADZ"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 37..43
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1Z87"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:2ADZ"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:1QAV"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:1QAV"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:1QAV"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:1QAV"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:1QAV"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:1Z86"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:1QAV"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:1QAV"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1Z86"
FT HELIX 142..150
FT /evidence="ECO:0007829|PDB:1QAV"
FT STRAND 154..162
FT /evidence="ECO:0007829|PDB:1QAV"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:2ADZ"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 189..193
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 207..219
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:1Z87"
FT TURN 235..238
FT /evidence="ECO:0007829|PDB:1Z87"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:1Z87"
FT HELIX 248..262
FT /evidence="ECO:0007829|PDB:1Z87"
SQ SEQUENCE 503 AA; 53665 MW; 161BA76CAF50AE96 CRC64;
MASGRRAPRT GLLELRCGAG SGAGGERWQR VLLSLAEDAL TVSPADGEPG PEPEPAQLNG
AAEPGAAPPQ LPEALLLQRR RVTVRKADAG GLGISIKGGR ENKMPILISK IFKGLAADQT
EALFVGDAIL SVNGEDLSSA THDEAVQALK KTGKEVVLEV KYMKEVSPYF KNSAGGTSVG
WDSPPASPLQ RQPSSPGPQP RNLSEAKHVS LKMAYVSRRC TPTDPEPRYL EICAADGQDA
VFLRAKDEAS ARSWAGAIQA QIGTFIPWVK DELQALLTAT GTAGSQDIKQ IGWLTEQLPS
GGTAPTLALL TEKELLFYCS LPQSREALSR PTRTAPLIAT SSAHRLVHSG PSKGSVPYDA
ELSFALRTGT RHGVDTHLFS VESPQELAAW TRQLVDGCHR AAEGIQEVST ACTWNGRPCS
LSVHIDKGFT LWAAEPGAAR AMLLRQPFEK LQMSSDDGTS LLFLDFGGAE GEIQLDLHSC
PKTMVFIIHS FLSAKVTRLG LLA
