LMOD3_HUMAN
ID LMOD3_HUMAN Reviewed; 560 AA.
AC Q0VAK6; B4DT85; Q0JTT2; Q5JPG6; Q8IUK4; Q96LS4;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Leiomodin-3;
DE AltName: Full=Leiomodin, fetal form;
GN Name=LMOD3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Pericardium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [4]
RP FUNCTION, INTERACTION WITH TPM1/2, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND VARIANT NEM10 ARG-326.
RX PubMed=25250574; DOI=10.1172/jci75199;
RA Yuen M., Sandaradura S.A., Dowling J.J., Kostyukova A.S., Moroz N.,
RA Quinlan K.G., Lehtokari V.L., Ravenscroft G., Todd E.J., Ceyhan-Birsoy O.,
RA Gokhin D.S., Maluenda J., Lek M., Nolent F., Pappas C.T., Novak S.M.,
RA D'Amico A., Malfatti E., Thomas B.P., Gabriel S.B., Gupta N., Daly M.J.,
RA Ilkovski B., Houweling P.J., Davidson A.E., Swanson L.C., Brownstein C.A.,
RA Gupta V.A., Medne L., Shannon P., Martin N., Bick D.P., Flisberg A.,
RA Holmberg E., Van den Bergh P., Lapunzina P., Waddell L.B., Sloboda D.D.,
RA Bertini E., Chitayat D., Telfer W.R., Laquerriere A., Gregorio C.C.,
RA Ottenheijm C.A., Boennemann C.G., Pelin K., Beggs A.H., Hayashi Y.K.,
RA Romero N.B., Laing N.G., Nishino I., Wallgren-Pettersson C., Melki J.,
RA Fowler V.M., MacArthur D.G., North K.N., Clarke N.F.;
RT "Leiomodin-3 dysfunction results in thin filament disorganization and
RT nemaline myopathy.";
RL J. Clin. Invest. 124:4693-4708(2014).
CC -!- FUNCTION: Essential for the organization of sarcomeric actin thin
CC filaments in skeletal muscle (PubMed:25250574). Increases the rate of
CC actin polymerization (PubMed:25250574). {ECO:0000269|PubMed:25250574}.
CC -!- SUBUNIT: May interact with tropomyosin alpha (TPM1/2) N-terminus
CC (PubMed:25250574). Interacts with KLHL40; leading to stabilization (By
CC similarity). {ECO:0000250|UniProtKB:E9QA62,
CC ECO:0000269|PubMed:25250574}.
CC -!- INTERACTION:
CC Q0VAK6; P25791-3: LMO2; NbExp=3; IntAct=EBI-23685399, EBI-11959475;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25250574}.
CC Cytoplasm, myofibril, sarcomere, M line {ECO:0000269|PubMed:25250574}.
CC Cytoplasm, myofibril, sarcomere, A band {ECO:0000250|UniProtKB:E9QA62}.
CC Cytoplasm, cytoskeleton {ECO:0000269|PubMed:25250574}. 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:0000269|PubMed:25250574}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q0VAK6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q0VAK6-2; Sequence=VSP_021664, VSP_021665, VSP_021666,
CC VSP_021667;
CC -!- TISSUE SPECIFICITY: Expressed in cardiac and at higher levels in
CC skeletal muscles (at protein level). {ECO:0000269|PubMed:25250574}.
CC -!- DEVELOPMENTAL STAGE: Expressed soon after the start of myoblast
CC differentiation and in skeletal muscle throughout life from at least 14
CC weeks gestation (at protein level). {ECO:0000269|PubMed:25250574}.
CC -!- PTM: Ubiquitinated, leading to its degradation. Interaction with KLHL40
CC negatively regulates ubiquitination and degradation.
CC {ECO:0000250|UniProtKB:E9QA62}.
CC -!- DISEASE: Nemaline myopathy 10 (NEM10) [MIM:616165]: An autosomal
CC recessive severe form of nemaline myopathy. Nemaline myopathies are
CC muscular disorders characterized by muscle weakness of varying severity
CC and onset, and abnormal thread-like or rod-shaped structures in muscle
CC fibers on histologic examination. NEM10 is characterized by early-onset
CC generalized muscle weakness and hypotonia with respiratory
CC insufficiency and feeding difficulties. Additional features include
CC arthrogryposis or congenital contractures, ophthalmoplegia, a history
CC of prematurity, reduced fetal movements, and polyhydramnios. Most
CC patients die of respiratory failure in early infancy.
CC {ECO:0000269|PubMed:25250574}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tropomodulin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH39202.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305};
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DR EMBL; AK057852; BAB71596.1; -; mRNA.
DR EMBL; AK300096; BAG61897.1; -; mRNA.
DR EMBL; AL832709; CAI46110.1; -; mRNA.
DR EMBL; AM393202; CAL38080.1; -; mRNA.
DR EMBL; BC039202; AAH39202.1; ALT_SEQ; mRNA.
DR EMBL; BC121019; AAI21020.1; -; mRNA.
DR CCDS; CCDS46862.1; -. [Q0VAK6-1]
DR RefSeq; NP_001291347.1; NM_001304418.1. [Q0VAK6-1]
DR RefSeq; NP_938012.2; NM_198271.4. [Q0VAK6-1]
DR AlphaFoldDB; Q0VAK6; -.
DR SMR; Q0VAK6; -.
DR BioGRID; 121107; 4.
DR IntAct; Q0VAK6; 1.
DR STRING; 9606.ENSP00000414670; -.
DR iPTMnet; Q0VAK6; -.
DR PhosphoSitePlus; Q0VAK6; -.
DR BioMuta; LMOD3; -.
DR DMDM; 118572771; -.
DR EPD; Q0VAK6; -.
DR MassIVE; Q0VAK6; -.
DR MaxQB; Q0VAK6; -.
DR PaxDb; Q0VAK6; -.
DR PeptideAtlas; Q0VAK6; -.
DR PRIDE; Q0VAK6; -.
DR ProteomicsDB; 58797; -. [Q0VAK6-1]
DR ProteomicsDB; 58798; -. [Q0VAK6-2]
DR Antibodypedia; 46385; 47 antibodies from 18 providers.
DR DNASU; 56203; -.
DR Ensembl; ENST00000420581.7; ENSP00000414670.3; ENSG00000163380.16. [Q0VAK6-1]
DR Ensembl; ENST00000475434.1; ENSP00000418645.1; ENSG00000163380.16. [Q0VAK6-1]
DR Ensembl; ENST00000489031.5; ENSP00000417210.1; ENSG00000163380.16. [Q0VAK6-1]
DR GeneID; 56203; -.
DR KEGG; hsa:56203; -.
DR MANE-Select; ENST00000420581.7; ENSP00000414670.3; NM_198271.5; NP_938012.2.
DR UCSC; uc003dns.3; human. [Q0VAK6-1]
DR CTD; 56203; -.
DR DisGeNET; 56203; -.
DR GeneCards; LMOD3; -.
DR HGNC; HGNC:6649; LMOD3.
DR HPA; ENSG00000163380; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR MalaCards; LMOD3; -.
DR MIM; 616112; gene.
DR MIM; 616165; phenotype.
DR neXtProt; NX_Q0VAK6; -.
DR OpenTargets; ENSG00000163380; -.
DR Orphanet; 171430; Severe congenital nemaline myopathy.
DR Orphanet; 171436; Typical nemaline myopathy.
DR PharmGKB; PA30415; -.
DR VEuPathDB; HostDB:ENSG00000163380; -.
DR eggNOG; KOG3735; Eukaryota.
DR GeneTree; ENSGT00940000159731; -.
DR HOGENOM; CLU_031052_4_1_1; -.
DR InParanoid; Q0VAK6; -.
DR OMA; PPGMWER; -.
DR OrthoDB; 1025132at2759; -.
DR PhylomeDB; Q0VAK6; -.
DR TreeFam; TF315841; -.
DR PathwayCommons; Q0VAK6; -.
DR SignaLink; Q0VAK6; -.
DR BioGRID-ORCS; 56203; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; LMOD3; human.
DR GeneWiki; LMOD3; -.
DR GenomeRNAi; 56203; -.
DR Pharos; Q0VAK6; Tbio.
DR PRO; PR:Q0VAK6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q0VAK6; protein.
DR Bgee; ENSG00000163380; Expressed in biceps brachii and 119 other tissues.
DR Genevisible; Q0VAK6; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0031430; C:M band; IDA:UniProtKB.
DR GO; GO:0030016; C:myofibril; IBA:GO_Central.
DR GO; GO:0005865; C:striated muscle thin filament; IDA:UniProtKB.
DR GO; GO:0003785; F:actin monomer binding; IMP:UniProtKB.
DR GO; GO:0005523; F:tropomyosin binding; IMP:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0045010; P:actin nucleation; IMP:UniProtKB.
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; IMP:UniProtKB.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISS:UniProtKB.
DR GO; GO:0030240; P:skeletal muscle thin filament assembly; IMP:UniProtKB.
DR GO; GO:0006941; P:striated muscle contraction; IMP:UniProtKB.
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 Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton;
KW Disease variant; Nemaline myopathy; Reference proteome; Ubl conjugation.
FT CHAIN 1..560
FT /note="Leiomodin-3"
FT /id="PRO_0000261175"
FT DOMAIN 534..553
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 1..49
FT /note="Interaction with tropomyosin alpha"
FT /evidence="ECO:0000269|PubMed:25250574"
FT REGION 45..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 437..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 494..530
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 16..42
FT /evidence="ECO:0000255"
FT COILED 386..425
FT /evidence="ECO:0000255"
FT COMPBIAS 142..169
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 194..217
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..459
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 494..514
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021664"
FT VAR_SEQ 101..122
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021665"
FT VAR_SEQ 443..444
FT /note="MQ -> IA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021666"
FT VAR_SEQ 445..560
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_021667"
FT VARIANT 83
FT /note="R -> H (in dbSNP:rs35740823)"
FT /id="VAR_061863"
FT VARIANT 263
FT /note="I -> T (in dbSNP:rs9835034)"
FT /id="VAR_052401"
FT VARIANT 326
FT /note="G -> R (in NEM10)"
FT /evidence="ECO:0000269|PubMed:25250574"
FT /id="VAR_072643"
FT VARIANT 438
FT /note="K -> M (in dbSNP:rs6810145)"
FT /id="VAR_034083"
FT VARIANT 560
FT /note="A -> V (in dbSNP:rs17005363)"
FT /id="VAR_029088"
FT CONFLICT 213
FT /note="I -> V (in Ref. 2; CAL38080)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="S -> G (in Ref. 2; CAI46110)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="A -> V (in Ref. 2; CAL38080)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 560 AA; 64914 MW; 762412021EDEDE08 CRC64;
MSEHSRNSDQ EELLDEEINE DEILANLSAE ELKELQSEME VMAPDPSLPV GMIQKDQTDK
PPTGNFNHKS LVDYMYWEKA SRRMLEEERV PVTFVKSEEK TQEEHEEIEK RNKNMAQYLK
EKLNNEIVAN KRESKGSSNI QETDEEDEEE EDDDDDDEGE DDGEESEETN REEEGKAKEQ
IRNCENNCQQ VTDKAFKEQR DRPEAQEQSE KKISKLDPKK LALDTSFLKV STRPSGNQTD
LDGSLRRVRK NDPDMKELNL NNIENIPKEM LLDFVNAMKK NKHIKTFSLA NVGADENVAF
ALANMLRENR SITTLNIESN FITGKGIVAI MRCLQFNETL TELRFHNQRH MLGHHAEMEI
ARLLKANNTL LKMGYHFELP GPRMVVTNLL TRNQDKQRQK RQEEQKQQQL KEQKKLIAML
ENGLGLPPGM WELLGGPKPD SRMQEFFQPP PPRPPNPQNV PFSQRSEMMK KPSQAPKYRT
DPDSFRVVKL KRIQRKSRMP EAREPPEKTN LKDVIKTLKP VPRNRPPPLV EITPRDQLLN
DIRHSSVAYL KPVQLPKELA
