LMOD3_MOUSE
ID LMOD3_MOUSE Reviewed; 571 AA.
AC E9QA62; A0AUN8; A0JP45;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Leiomodin-3;
GN Name=Lmod3 {ECO:0000312|MGI:MGI:2444169};
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].
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 INTERACTION WITH KLHL40, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=24960163; DOI=10.1172/jci74994;
RA Garg A., O'Rourke J., Long C., Doering J., Ravenscroft G.,
RA Bezprozvannaya S., Nelson B.R., Beetz N., Li L., Chen S., Laing N.G.,
RA Grange R.W., Bassel-Duby R., Olson E.N.;
RT "KLHL40 deficiency destabilizes thin filament proteins and promotes
RT nemaline myopathy.";
RL J. Clin. Invest. 124:3529-3539(2014).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=25774500; DOI=10.1172/jci80115;
RA Cenik B.K., Garg A., McAnally J.R., Shelton J.M., Richardson J.A.,
RA Bassel-Duby R., Olson E.N., Liu N.;
RT "Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3.";
RL J. Clin. Invest. 125:1569-1578(2015).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26035871; DOI=10.1242/dmm.019430;
RA Tian L., Ding S., You Y., Li T.R., Liu Y., Wu X., Sun L., Xu T.;
RT "Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber
RT atrophy.";
RL Dis. Model. Mech. 8:635-641(2015).
CC -!- FUNCTION: Essential for the organization of sarcomeric actin thin
CC filaments in skeletal muscle (PubMed:25774500, PubMed:26035871).
CC Increases the rate of actin polymerization (By similarity).
CC {ECO:0000250|UniProtKB:Q0VAK6, ECO:0000269|PubMed:26035871}.
CC -!- SUBUNIT: May interact with tropomyosin alpha (TPM1/2) N-terminus (By
CC similarity). Interacts with KLHL40; leading to stabilization
CC (PubMed:24960163). {ECO:0000250|UniProtKB:Q0VAK6,
CC ECO:0000269|PubMed:24960163}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q0VAK6}.
CC Cytoplasm, myofibril, sarcomere, A band {ECO:0000269|PubMed:24960163}.
CC Cytoplasm, myofibril, sarcomere, M line {ECO:0000250|UniProtKB:Q0VAK6}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q0VAK6}. Note=Highly
CC expressed in nonstriated areas of developing myotubes, where it shows a
CC granular cytoplasmic pattern. In sarcomeres, highly expressed in the M
CC band region and, at lower levels, along actin thin filaments. Not
CC detected in Z-disks. In sarcomeres, may be located near, but not at,
CC actin thin filament pointed end. {ECO:0000250|UniProtKB:Q0VAK6}.
CC -!- TISSUE SPECIFICITY: Skeletal muscle and heart-specific (at protein
CC level). {ECO:0000269|PubMed:25774500}.
CC -!- DEVELOPMENTAL STAGE: Expressed by 15.5 dpc in both skeletal muscle and
CC heart. Expression is maintained throughout adulthood.
CC {ECO:0000269|PubMed:25774500}.
CC -!- INDUCTION: Expression is regulated by SRF and MEF2.
CC {ECO:0000269|PubMed:25774500}.
CC -!- PTM: Ubiquitinated, leading to its degradation. Interaction with KLHL40
CC negatively regulates ubiquitination and degradation.
CC {ECO:0000269|PubMed:24960163}.
CC -!- DISRUPTION PHENOTYPE: Mice show severe muscle weakness and postnatal
CC growth retardation. Skeletal muscles show the presence of nemaline
CC bodies and have disorganized sarcomeric structures. Muscle atrophy is
CC specific to the fast fibers. {ECO:0000269|PubMed:25774500,
CC ECO:0000269|PubMed:26035871}.
CC -!- SIMILARITY: Belongs to the tropomodulin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI17773.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC155724; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117772; AAI17773.1; ALT_INIT; mRNA.
DR EMBL; BC127157; AAI27158.1; -; mRNA.
DR CCDS; CCDS39576.1; -.
DR RefSeq; NP_001074626.1; NM_001081157.1.
DR RefSeq; XP_006506333.1; XM_006506270.3.
DR RefSeq; XP_006506334.1; XM_006506271.3.
DR AlphaFoldDB; E9QA62; -.
DR SMR; E9QA62; -.
DR STRING; 10090.ENSMUSP00000093315; -.
DR iPTMnet; E9QA62; -.
DR PhosphoSitePlus; E9QA62; -.
DR jPOST; E9QA62; -.
DR MaxQB; E9QA62; -.
DR PaxDb; E9QA62; -.
DR PRIDE; E9QA62; -.
DR ProteomicsDB; 252482; -.
DR Antibodypedia; 46385; 47 antibodies from 18 providers.
DR DNASU; 320502; -.
DR Ensembl; ENSMUST00000095655; ENSMUSP00000093315; ENSMUSG00000044086.
DR GeneID; 320502; -.
DR KEGG; mmu:320502; -.
DR UCSC; uc009das.1; mouse.
DR CTD; 56203; -.
DR MGI; MGI:2444169; Lmod3.
DR VEuPathDB; HostDB:ENSMUSG00000044086; -.
DR eggNOG; KOG3735; Eukaryota.
DR GeneTree; ENSGT00940000159731; -.
DR HOGENOM; CLU_031052_4_1_1; -.
DR InParanoid; E9QA62; -.
DR OMA; PPGMWER; -.
DR OrthoDB; 1025132at2759; -.
DR PhylomeDB; E9QA62; -.
DR TreeFam; TF315841; -.
DR BioGRID-ORCS; 320502; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Lmod3; mouse.
DR PRO; PR:E9QA62; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; E9QA62; protein.
DR Bgee; ENSMUSG00000044086; Expressed in soleus muscle and 109 other tissues.
DR Genevisible; E9QA62; MM.
DR GO; GO:0031672; C:A band; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0031430; C:M band; ISO:MGI.
DR GO; GO:0030016; C:myofibril; IBA:GO_Central.
DR GO; GO:0005865; C:striated muscle thin filament; ISO:MGI.
DR GO; GO:0003785; F:actin monomer binding; ISO:MGI.
DR GO; GO:0005523; F:tropomyosin binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0045010; P:actin nucleation; ISO:MGI.
DR GO; GO:0006936; P:muscle contraction; IBA:GO_Central.
DR GO; GO:0030239; P:myofibril assembly; IBA:GO_Central.
DR GO; GO:0051694; P:pointed-end actin filament capping; IEA:InterPro.
DR GO; GO:0048743; P:positive regulation of skeletal muscle fiber development; ISO:MGI.
DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:UniProtKB.
DR GO; GO:0030240; P:skeletal muscle thin filament assembly; ISO:MGI.
DR GO; GO:0006941; P:striated muscle contraction; ISO:MGI.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR030131; LMOD3.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR004934; TMOD.
DR PANTHER; PTHR10901; PTHR10901; 1.
DR PANTHER; PTHR10901:SF3; PTHR10901:SF3; 1.
DR Pfam; PF03250; Tropomodulin; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Coiled coil; Cytoplasm; Cytoskeleton; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..571
FT /note="Leiomodin-3"
FT /id="PRO_0000439646"
FT DOMAIN 545..564
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 46..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 397..436
FT /evidence="ECO:0000255"
FT COMPBIAS 140..178
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..207
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..228
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 93
FT /note="S -> N (in Ref. 2; AAI27158)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="Missing (in Ref. 2; AAI27158)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="Y -> C (in Ref. 2; AAI27158)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="H -> D (in Ref. 2; AAI27158)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 571 AA; 65689 MW; 7DEEE7D4AE05D6F5 CRC64;
MSGHSRNSEQ EDTLSEELDE DELLANLSPE ELKELQSEME VMAPDPHLPV GMIQKDQTDK
APTGNFNHKS LVDYMYLQKA SRRMLEDERV PVSFVQSEKN TQNQREVGDK GIKNMPQFLK
EKLNSEILAK KRESNGSNNV QEAEDDDEDE EEEEEDDEDE EEEEEDEEDD EGEEDEDGEQ
ANREKNDAKE QIHNNPGTYQ QLATKTAHEQ KDTSETKEKG EKKIAKLDPK KLALDTSFLK
VSARPSGNQT DLDGSLRRVR QNDPDMKELN LNNIENIPKE MLLDFVNAMK KNKHIKTFSL
ANVGADESVA FALANMLREN RSVTTLNIES NFITGKGIVA IMRCLQFNET LTELRFHNQR
HMLGHHAEME ISRLLKANTT LLKMGYHFEL PGPRMVVTNL LTRNQDKRRQ KRQEEQQQQQ
LKEQRKLIAM LENGLGLPPG MWERLGGPMP DPRMQEFFQP ASGRPLDAQE VPFGSRKEMI
KNPPQPPQCK TDPDSFRVVK LKRIQRKSRM PEAREAQEKT NLKDVIKTLK PVPRNRPPPL
VEITPRDQLL NDIRHSNVAY LKPVQLPKEL E
