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   24-JAN-2024, entry version 199.
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,
RC   Pancreas, 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.ENSMUSP00000105350; -.
DR   iPTMnet; Q61234; -.
DR   PhosphoSitePlus; Q61234; -.
DR   jPOST; Q61234; -.
DR   MaxQB; Q61234; -.
DR   PaxDb; 10090-ENSMUSP00000028991; -.
DR   PeptideAtlas; Q61234; -.
DR   ProteomicsDB; 257540; -.
DR   Antibodypedia; 10673; 538 antibodies from 34 providers.
DR   Ensembl; ENSMUST00000028991.7; ENSMUSP00000028991.7; ENSMUSG00000027488.13.
DR   AGR; MGI:101772; -.
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 207 other cell types or tissues.
DR   ExpressionAtlas; Q61234; baseline and differential.
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: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; cd00992; PDZ_signaling; 1.
DR   CDD; cd01258; PHsplit_syntrophin; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 2.
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; IPR015482; Syntrophin.
DR   PANTHER; PTHR10554:SF6; ALPHA-1-SYNTROPHIN; 1.
DR   PANTHER; PTHR10554; SYNTROPHIN; 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; PDZ domain-like; 1.
DR   SUPFAM; SSF50729; PH domain-like; 1.
DR   PROSITE; PS50106; PDZ; 1.
DR   PROSITE; PS50003; PH_DOMAIN; 1.
DR   Genevisible; Q61234; MM.
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
//