LMOD1_HUMAN
ID LMOD1_HUMAN Reviewed; 600 AA.
AC P29536; B1APV6; C4AMB1; Q68EN2;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 3.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Leiomodin-1;
DE AltName: Full=64 kDa autoantigen 1D;
DE AltName: Full=64 kDa autoantigen 1D3;
DE AltName: Full=64 kDa autoantigen D1 {ECO:0000303|PubMed:2026759};
DE AltName: Full=Leiomodin, muscle form;
DE AltName: Full=Smooth muscle leiomodin;
DE Short=SM-Lmod;
DE AltName: Full=Thyroid-associated ophthalmopathy autoantigen;
GN Name=LMOD1;
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 [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Thyroid;
RX PubMed=2026759; DOI=10.1210/jcem-72-6-1375;
RA Dong Q., Ludgate M., Vassart G.;
RT "Cloning and sequencing of a novel 64-kDa autoantigen recognized by
RT patients with autoimmune thyroid disease.";
RL J. Clin. Endocrinol. Metab. 72:1375-1381(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=PNS;
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 TISSUE SPECIFICITY.
RX PubMed=11318603; DOI=10.1006/geno.2000.6501;
RA Conley C.A., Fritz-Six K.L., Almenar-Queralt A., Fowler V.M.;
RT "Leiomodins: larger members of the tropomodulin (Tmod) gene family.";
RL Genomics 73:127-139(2001).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=27144530; DOI=10.1371/journal.pone.0153780;
RA Sahoo S., Meijles D.N., Al Ghouleh I., Tandon M., Cifuentes-Pagano E.,
RA Sembrat J., Rojas M., Goncharova E., Pagano P.J.;
RT "MEF2C-MYOCD and leiomodin1 suppression by miRNA-214 promotes smooth muscle
RT cell phenotype switching in pulmonary arterial hypertension.";
RL PLoS ONE 11:E0153780-E0153780(2016).
RN [6] {ECO:0007744|PDB:4Z79, ECO:0007744|PDB:4Z8G, ECO:0007744|PDB:4Z94}
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 299-486, FUNCTION, ACTIN-BINDING,
RP AND SUBCELLULAR LOCATION.
RX PubMed=26370058; DOI=10.1038/ncomms9314;
RA Boczkowska M., Rebowski G., Kremneva E., Lappalainen P., Dominguez R.;
RT "How Leiomodin and Tropomodulin use a common fold for different actin
RT assembly functions.";
RL Nat. Commun. 6:8314-8314(2015).
RN [7]
RP VARIANT MMIHS3 370-ARG--GLN-600 DEL, INVOLVEMENT IN MMIHS3,
RP CHARACTERIZATION OF VARIANT MMIHS3 370-ARG--GLN-600 DEL, AND FUNCTION.
RX PubMed=28292896; DOI=10.1073/pnas.1620507114;
RA Halim D., Wilson M.P., Oliver D., Brosens E., Verheij J.B., Han Y.,
RA Nanda V., Lyu Q., Doukas M., Stoop H., Brouwer R.W., van Ijcken W.F.,
RA Slivano O.J., Burns A.J., Christie C.K., de Mesy Bentley K.L., Brooks A.S.,
RA Tibboel D., Xu S., Jin Z.G., Djuwantono T., Yan W., Alves M.M.,
RA Hofstra R.M., Miano J.M.;
RT "Loss of LMOD1 impairs smooth muscle cytocontractility and causes
RT megacystis microcolon intestinal hypoperistalsis syndrome in humans and
RT mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E2739-E2747(2017).
CC -!- FUNCTION: Required for proper contractility of visceral smooth muscle
CC cells (PubMed:28292896). Mediates nucleation of actin filaments.
CC {ECO:0000269|PubMed:26370058, ECO:0000269|PubMed:28292896}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere
CC {ECO:0000269|PubMed:26370058}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:A0A0G2K0D3}. Note=Colocalizes with actin
CC filaments in sarcomeres. {ECO:0000250|UniProtKB:A0A0G2K0D3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P29536-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P29536-2; Sequence=VSP_035745;
CC -!- TISSUE SPECIFICITY: Detected in lung vascular smooth muscle (at protein
CC level) (PubMed:27144530). Detected in thyroid and extraocular smooth
CC muscle, but not skeletal muscle (PubMed:2026759). Detected in heart,
CC aorta, skeletal muscle, colon, urinary bladder, uterus, stomach, and
CC small intestine (PubMed:11318603). {ECO:0000269|PubMed:2026759,
CC ECO:0000269|PubMed:27144530}.
CC -!- DISEASE: Megacystis-microcolon-intestinal hypoperistalsis syndrome 3
CC (MMIHS3) [MIM:619362]: A form of megacystis-microcolon-intestinal
CC hypoperistalsis syndrome, a congenital visceral myopathy primarily
CC affecting females, and characterized by loss of smooth muscle
CC contraction in the bladder and intestine. Affected individuals present
CC at birth with functional obstruction of intestine, microcolon, dilation
CC of bladder, and secondary hydronephrosis. The majority of cases have a
CC fatal outcome due to malnutrition and sepsis, followed by multiorgan
CC failure. MMIHS3 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:28292896}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the tropomodulin family. {ECO:0000305}.
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DR EMBL; X54162; CAA38101.1; -; mRNA.
DR EMBL; AC099676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL513217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC080187; AAH80187.1; -; mRNA.
DR CCDS; CCDS53457.1; -. [P29536-1]
DR PIR; S18732; S18732.
DR RefSeq; NP_036266.2; NM_012134.2. [P29536-1]
DR PDB; 4Z79; X-ray; 1.54 A; A=299-486.
DR PDB; 4Z8G; X-ray; 2.10 A; A=364-486.
DR PDB; 4Z94; X-ray; 2.40 A; G=364-486.
DR PDBsum; 4Z79; -.
DR PDBsum; 4Z8G; -.
DR PDBsum; 4Z94; -.
DR AlphaFoldDB; P29536; -.
DR SMR; P29536; -.
DR BioGRID; 117334; 5.
DR IntAct; P29536; 3.
DR MINT; P29536; -.
DR STRING; 9606.ENSP00000356257; -.
DR iPTMnet; P29536; -.
DR MetOSite; P29536; -.
DR PhosphoSitePlus; P29536; -.
DR BioMuta; LMOD1; -.
DR DMDM; 325511399; -.
DR EPD; P29536; -.
DR jPOST; P29536; -.
DR MassIVE; P29536; -.
DR MaxQB; P29536; -.
DR PaxDb; P29536; -.
DR PeptideAtlas; P29536; -.
DR PRIDE; P29536; -.
DR ProteomicsDB; 54584; -. [P29536-1]
DR ProteomicsDB; 54585; -. [P29536-2]
DR Antibodypedia; 34518; 163 antibodies from 28 providers.
DR DNASU; 25802; -.
DR Ensembl; ENST00000367288.5; ENSP00000356257.4; ENSG00000163431.13. [P29536-1]
DR GeneID; 25802; -.
DR KEGG; hsa:25802; -.
DR MANE-Select; ENST00000367288.5; ENSP00000356257.4; NM_012134.3; NP_036266.2.
DR UCSC; uc057oju.1; human. [P29536-1]
DR CTD; 25802; -.
DR DisGeNET; 25802; -.
DR GeneCards; LMOD1; -.
DR HGNC; HGNC:6647; LMOD1.
DR HPA; ENSG00000163431; Low tissue specificity.
DR MalaCards; LMOD1; -.
DR MIM; 602715; gene.
DR MIM; 619362; phenotype.
DR neXtProt; NX_P29536; -.
DR OpenTargets; ENSG00000163431; -.
DR Orphanet; 2241; Megacystis-microcolon-intestinal hypoperistalsis syndrome.
DR PharmGKB; PA30413; -.
DR VEuPathDB; HostDB:ENSG00000163431; -.
DR eggNOG; KOG3735; Eukaryota.
DR GeneTree; ENSGT00940000159825; -.
DR HOGENOM; CLU_031052_4_0_1; -.
DR InParanoid; P29536; -.
DR OMA; ELKMDMM; -.
DR OrthoDB; 1025132at2759; -.
DR PhylomeDB; P29536; -.
DR TreeFam; TF315841; -.
DR PathwayCommons; P29536; -.
DR Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR SignaLink; P29536; -.
DR BioGRID-ORCS; 25802; 21 hits in 1071 CRISPR screens.
DR ChiTaRS; LMOD1; human.
DR GenomeRNAi; 25802; -.
DR Pharos; P29536; Tbio.
DR PRO; PR:P29536; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P29536; protein.
DR Bgee; ENSG00000163431; Expressed in popliteal artery and 168 other tissues.
DR ExpressionAtlas; P29536; baseline and differential.
DR Genevisible; P29536; HS.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0030016; C:myofibril; IDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; ISS:UniProtKB.
DR GO; GO:0005865; C:striated muscle thin filament; IBA:GO_Central.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0005523; F:tropomyosin binding; IBA:GO_Central.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0045010; P:actin nucleation; IDA: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:0030838; P:positive regulation of actin filament polymerization; IDA:UniProtKB.
DR DisProt; DP02368; -.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR030136; LMOD1.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR004934; TMOD.
DR InterPro; IPR003124; WH2_dom.
DR PANTHER; PTHR10901; PTHR10901; 1.
DR PANTHER; PTHR10901:SF5; PTHR10901:SF5; 1.
DR Pfam; PF03250; Tropomodulin; 1.
DR Pfam; PF02205; WH2; 1.
DR SMART; SM00246; WH2; 1.
DR PROSITE; PS51082; WH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Disease variant; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..600
FT /note="Leiomodin-1"
FT /id="PRO_0000084453"
FT REPEAT 165..180
FT /note="1"
FT REPEAT 181..196
FT /note="2"
FT REPEAT 197..212
FT /note="3"
FT REPEAT 213..228
FT /note="4"
FT REPEAT 229..244
FT /note="5"
FT REPEAT 245..260
FT /note="6"
FT REPEAT 261..276
FT /note="7"
FT REPEAT 277..293
FT /note="8"
FT DOMAIN 574..593
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 38..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 165..293
FT /note="8 X approximate tandem repeats"
FT REGION 472..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..527
FT /note="5 X 4 AA approximate tandem repeats"
FT COMPBIAS 80..291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 305..324
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..499
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 510..545
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0A0G2K0D3"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0A0G2K0D3"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0A0G2K0D3"
FT MOD_RES 555
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A0A0G2K0D3"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2026759"
FT /id="VSP_035745"
FT VARIANT 295
FT /note="T -> M (in dbSNP:rs2820312)"
FT /id="VAR_021839"
FT VARIANT 370..600
FT /note="Missing (in MMIHS3; markedly reduced LMOD1 protein
FT levels in homozygous patient cells)"
FT /evidence="ECO:0000269|PubMed:28292896"
FT /id="VAR_085835"
FT CONFLICT 102
FT /note="E -> Q (in Ref. 1; CAA38101)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="D -> N (in Ref. 1; CAA38101)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="S -> G (in Ref. 1; CAA38101)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="T -> S (in Ref. 1; CAA38101)"
FT /evidence="ECO:0000305"
FT HELIX 319..326
FT /evidence="ECO:0007829|PDB:4Z79"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:4Z79"
FT HELIX 345..355
FT /evidence="ECO:0007829|PDB:4Z79"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:4Z79"
FT HELIX 373..385
FT /evidence="ECO:0007829|PDB:4Z79"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:4Z79"
FT HELIX 401..410
FT /evidence="ECO:0007829|PDB:4Z79"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:4Z79"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:4Z79"
FT HELIX 431..441
FT /evidence="ECO:0007829|PDB:4Z79"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:4Z79"
FT HELIX 457..484
FT /evidence="ECO:0007829|PDB:4Z79"
SQ SEQUENCE 600 AA; 67030 MW; 79103ED8AB8231D4 CRC64;
MSRVAKYRRQ VSEDPDIDSL LETLSPEEME ELEKELDVVD PDGSVPVGLR QRNQTEKQST
GVYNREAMLN FCEKETKKLM QREMSMDESK QVETKTDAKN GEERGRDASK KALGPRRDSD
LGKEPKRGGL KKSFSRDRDE AGGKSGEKPK EEKIIRGIDK GRVRAAVDKK EAGKDGRGEE
RAVATKKEEE KKGSDRNTGL SRDKDKKREE MKEVAKKEDD EKVKGERRNT DTRKEGEKMK
RAGGNTDMKK EDEKVKRGTG NTDTKKDDEK VKKNEPLHEK EAKDDSKTKT PEKQTPSGPT
KPSEGPAKVE EEAAPSIFDE PLERVKNNDP EMTEVNVNNS DCITNEILVR FTEALEFNTV
VKLFALANTR ADDHVAFAIA IMLKANKTIT SLNLDSNHIT GKGILAIFRA LLQNNTLTEL
RFHNQRHICG GKTEMEIAKL LKENTTLLKL GYHFELAGPR MTVTNLLSRN MDKQRQKRLQ
EQRQAQEAKG EKKDLLEVPK AGAVAKGSPK PSPQPSPKPS PKNSPKKGGA PAAPPPPPPP
LAPPLIMENL KNSLSPATQR KMGDKVLPAQ EKNSRDQLLA AIRSSNLKQL KKVEVPKLLQ
