SMTL1_MOUSE
ID SMTL1_MOUSE Reviewed; 459 AA.
AC Q99LM3;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Smoothelin-like protein 1;
DE AltName: Full=Calponin homology-associated smooth muscle protein;
DE Short=CHASM;
GN Name=Smtnl1;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 PHOSPHORYLATION AT SER-301, AND MUTAGENESIS OF SER-301.
RX PubMed=15327999; DOI=10.1016/j.febslet.2004.08.002;
RA Borman M.A., MacDonald J.A., Haystead T.A.;
RT "Modulation of smooth muscle contractility by CHASM, a novel member of the
RT smoothelin family of proteins.";
RL FEBS Lett. 573:207-213(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP PHOSPHORYLATION AT SER-301, DISRUPTION PHENOTYPE, INDUCTION, AND
RP MUTAGENESIS OF SER-301.
RX PubMed=18310078; DOI=10.1074/jbc.m708628200;
RA Wooldridge A.A., Fortner C.N., Lontay B., Akimoto T., Neppl R.L.,
RA Facemire C., Datto M.B., Kwon A., McCook E., Li P., Wang S., Thresher R.J.,
RA Miller S.E., Perriard J.C., Gavin T.P., Hickner R.C., Coffman T.M.,
RA Somlyo A.V., Yan Z., Haystead T.A.;
RT "Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes
RT an exercise-adapted phenotype in vascular smooth muscle.";
RL J. Biol. Chem. 283:11850-11859(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Lung;
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 [6]
RP FUNCTION, INTERACTION WITH PPP1R12A, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, PHOSPHORYLATION AT SER-301, DEVELOPMENTAL STAGE, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF SER-301.
RX PubMed=20634291; DOI=10.1074/jbc.m110.143966;
RA Lontay B., Bodoor K., Weitzel D.H., Loiselle D., Fortner C., Lengyel S.,
RA Zheng D., Devente J., Hickner R., Haystead T.A.;
RT "Smoothelin-like 1 protein regulates myosin phosphatase-targeting subunit 1
RT expression during sexual development and pregnancy.";
RL J. Biol. Chem. 285:29357-29366(2010).
RN [7]
RP STRUCTURE BY NMR OF 346-459, AND CALMODULIN BINDING.
RX PubMed=18477568; DOI=10.1074/jbc.m800627200;
RA Ishida H., Borman M.A., Ostrander J., Vogel H.J., MacDonald J.A.;
RT "Solution structure of the calponin homology (CH) domain from the
RT smoothelin-like 1 protein: a unique apocalmodulin-binding mode and the
RT possible role of the C-terminal type-2 CH-domain in smooth muscle
RT relaxation.";
RL J. Biol. Chem. 283:20569-20578(2008).
CC -!- FUNCTION: Plays a role in the regulation of contractile properties of
CC both striated and smooth muscles. When unphosphorylated, may inhibit
CC myosin dephosphorylation. Phosphorylation at Ser-301 reduces this
CC inhibitory activity. {ECO:0000269|PubMed:18310078,
CC ECO:0000269|PubMed:20634291}.
CC -!- SUBUNIT: Interacts with PPP1R12A. {ECO:0000269|PubMed:20634291}.
CC -!- INTERACTION:
CC Q99LM3; P04268: TPM1; Xeno; NbExp=3; IntAct=EBI-8073484, EBI-8073544;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, I band.
CC Cytoplasm, myofibril, sarcomere, M line. Nucleus. Note=Colocalizes with
CC MYH2. In its unphosphorylated state, localizes to the cytoplasm.
CC Phosphorylation at Ser-301 promotes translocation to the nucleus.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in
CC skeletal muscles (at protein level). Within striated muscles,
CC significantly more expressed in soleus muscle compared with plantaris
CC muscle or white vastus (at protein level). 30-40% lower expression in
CC females than in males (at protein level). Expressed in type 2a fibers,
CC but not detected in fast twitch type 2b muscle white vastus nor in
CC oxidative type I/b heart muscle (at protein level). Expressed within
CC myometrial cells of the uterus, as well as in the endometrial layer. In
CC the aorta, confined to smooth muscle cells. Not detected in endothelial
CC cells. {ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.
CC -!- DEVELOPMENTAL STAGE: Not detected in somites which give rise to
CC skeletal muscle at 10.5 dpc (at protein level). Expressed in skeletal
CC muscle of the tongue, diaphragm and axial muscles from 14.5 through
CC 17.5 dpc (at protein level). Not detected in limb buds (at protein
CC level). Overall increase by up to 10-12-fold in vascular and uterine
CC smooth muscle during pregnancy (at protein level). At day 13 of
CC pregnancy, expression increases in striated muscle by 2.5-fold compared
CC with non-pregnant mice, and by about 2-fold over levels expressed in
CC males (at protein level). At the same time, dramatically increased in
CC myometrial cells of the uterus, in the endometrial layer and in aortal
CC smooth muscle. Steadily declines through parturition and the onset of
CC lactation (at protein level). {ECO:0000269|PubMed:18310078,
CC ECO:0000269|PubMed:20634291}.
CC -!- INDUCTION: Significantly reduced by exercise in smooth and in skeletal
CC muscles. {ECO:0000269|PubMed:18310078}.
CC -!- PTM: Maximal phosphorylation of Ser-301 correlates with maximal
CC relaxation of aorta in response to acetylcholine.
CC {ECO:0000269|PubMed:15327999, ECO:0000269|PubMed:18310078,
CC ECO:0000269|PubMed:20634291}.
CC -!- DISRUPTION PHENOTYPE: Male mutant mice perform better than wild type in
CC exercise stress test after endurance training. Females do not differ
CC significantly during these tests. Even in the absence of endurance
CC exercise, mutant mice exhibit muscle fiber adaptation, i.e. more type
CC 2a fibers and lower levels of type 1b fibers. Endothelium-dependent
CC vasorelaxation of the aorta is enhanced and responses to beta-
CC adrenergic constriction are reduced. Expression of PPP1R12A is 30-40-
CC fold higher in mutant mice than in wild-type littermates and exhibits a
CC steady decline as the animals become sexually mature (at protein
CC level). During pregnancy, by day 13, PPP1R12A expression is
CC dramatically increased to 6-14 times over the levels observed in
CC pregnant wild-type littermates (at protein level). PPP1R12B expression
CC levels are unaffected. In vascular smooth muscle, force development in
CC response to phenylephrine is reduced and both the rate and extent of
CC relaxation in response to acetylcholine are promoted. Myosin
CC dephosphorylation is promoted in mutant animals.
CC {ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291}.
CC -!- SIMILARITY: Belongs to the smoothelin family. {ECO:0000305}.
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DR EMBL; AL928914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002317; AAH02317.1; -; mRNA.
DR CCDS; CCDS16195.1; -.
DR RefSeq; NP_077192.1; NM_024230.2.
DR RefSeq; XP_006500172.1; XM_006500109.3.
DR PDB; 2JV9; NMR; -; A=346-459.
DR PDB; 2K3S; NMR; -; A=346-459.
DR PDBsum; 2JV9; -.
DR PDBsum; 2K3S; -.
DR AlphaFoldDB; Q99LM3; -.
DR SMR; Q99LM3; -.
DR IntAct; Q99LM3; 4.
DR MINT; Q99LM3; -.
DR STRING; 10090.ENSMUSP00000028471; -.
DR iPTMnet; Q99LM3; -.
DR PhosphoSitePlus; Q99LM3; -.
DR PaxDb; Q99LM3; -.
DR PeptideAtlas; Q99LM3; -.
DR PRIDE; Q99LM3; -.
DR ProteomicsDB; 261282; -.
DR Antibodypedia; 48478; 73 antibodies from 15 providers.
DR DNASU; 68678; -.
DR Ensembl; ENSMUST00000028471; ENSMUSP00000028471; ENSMUSG00000027077.
DR GeneID; 68678; -.
DR KEGG; mmu:68678; -.
DR UCSC; uc008kjg.1; mouse.
DR CTD; 219537; -.
DR MGI; MGI:1915928; Smtnl1.
DR VEuPathDB; HostDB:ENSMUSG00000027077; -.
DR eggNOG; KOG4678; Eukaryota.
DR GeneTree; ENSGT00940000162276; -.
DR HOGENOM; CLU_040651_5_1_1; -.
DR InParanoid; Q99LM3; -.
DR OMA; EWPESPS; -.
DR OrthoDB; 168604at2759; -.
DR PhylomeDB; Q99LM3; -.
DR TreeFam; TF316716; -.
DR BioGRID-ORCS; 68678; 3 hits in 72 CRISPR screens.
DR EvolutionaryTrace; Q99LM3; -.
DR PRO; PR:Q99LM3; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q99LM3; protein.
DR Bgee; ENSMUSG00000027077; Expressed in tarsal region and 44 other tissues.
DR Genevisible; Q99LM3; MM.
DR GO; GO:0043292; C:contractile fiber; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031941; C:filamentous actin; IBA:GO_Central.
DR GO; GO:0031674; C:I band; IDA:MGI.
DR GO; GO:0031430; C:M band; IDA:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IPI:CAFA.
DR GO; GO:0051401; F:CH domain binding; IPI:CAFA.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0017020; F:myosin phosphatase regulator activity; ISO:MGI.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IPI:UniProtKB.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; ISO:MGI.
DR GO; GO:0043621; F:protein self-association; IDA:CAFA.
DR GO; GO:0005523; F:tropomyosin binding; IPI:CAFA.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0048644; P:muscle organ morphogenesis; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:CACAO.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:UniProtKB.
DR GO; GO:0014823; P:response to activity; IMP:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0042310; P:vasoconstriction; IMP:MGI.
DR CDD; cd00014; CH; 1.
DR DisProt; DP00742; -.
DR Gene3D; 1.10.418.10; -; 1.
DR IDEAL; IID50181; -.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR Pfam; PF00307; CH; 1.
DR SMART; SM00033; CH; 1.
DR SUPFAM; SSF47576; SSF47576; 1.
DR PROSITE; PS50021; CH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calmodulin-binding; Coiled coil; Cytoplasm; Muscle protein;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..459
FT /note="Smoothelin-like protein 1"
FT /id="PRO_0000317276"
FT DOMAIN 343..449
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REGION 1..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 441..459
FT /note="Calmodulin-binding"
FT COILED 124..154
FT /evidence="ECO:0000255"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 77..172
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..231
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..279
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 286..304
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 301
FT /note="Phosphoserine; by PKA and PKG"
FT /evidence="ECO:0000269|PubMed:15327999,
FT ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291"
FT MUTAGEN 301
FT /note="S->A: Loss of phosphorylation. Loss of nuclear
FT localization."
FT /evidence="ECO:0000269|PubMed:15327999,
FT ECO:0000269|PubMed:18310078, ECO:0000269|PubMed:20634291"
FT HELIX 346..357
FT /evidence="ECO:0007829|PDB:2JV9"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2JV9"
FT HELIX 370..372
FT /evidence="ECO:0007829|PDB:2JV9"
FT HELIX 376..383
FT /evidence="ECO:0007829|PDB:2JV9"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:2JV9"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:2JV9"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:2K3S"
FT HELIX 400..415
FT /evidence="ECO:0007829|PDB:2JV9"
FT HELIX 423..429
FT /evidence="ECO:0007829|PDB:2JV9"
FT HELIX 434..451
FT /evidence="ECO:0007829|PDB:2JV9"
SQ SEQUENCE 459 AA; 49525 MW; 9E86D60605B7F28D CRC64;
MEQTEGNSSE DGTTVSPTAG NLETPGSQGI AEEVAEGTVG TSDKEGPSDW AEHLCKAASK
SGESGGSPGE ASILDELKTD LQGEARGKDE AQGDLAEEKV GKEDTTAASQ EDTGKKEETK
PEPNEVREKE EAMLASEKQK VDEKETNLES KEKSDVNDKA KPEPKEDAGA EVTVNEAETE
SQEEADVKDQ AKPELPEVDG KETGSDTKEL VEPESPTEEQ EQGKENESEE RAAVIPSSPE
EWPESPTDEG PSLSPDGLAP ESTGETSPSA SESSPSEVPG SPTEPQPSEK KKDRAPERRV
SAPSRPRGPR AQNRKAIMDK FGGAASGPTA LFRNTKAAGA AIGGVKNMLL EWCRAMTRNY
EHVDIQNFSS SWSSGMAFCA LIHKFFPEAF DYAELDPAKR RHNFTLAFST AEKLADCAQL
LEVDDMVRLA VPDSKCVYTY IQELYRSLVQ KGLVKTKKK
