LMOD2_MOUSE
ID LMOD2_MOUSE Reviewed; 550 AA.
AC Q3UHZ5; Q99PM7;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Leiomodin-2;
DE AltName: Full=Cardiac leiomodin;
DE Short=C-LMOD;
DE AltName: Full=Leiomodin {ECO:0000305};
GN Name=Lmod2;
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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 221-550.
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 [3]
RP SUBUNIT.
RX PubMed=17572376; DOI=10.1016/j.abb.2007.05.012;
RA Kostyukova A.S.;
RT "Leiomodin/tropomyosin interactions are isoform specific.";
RL Arch. Biochem. Biophys. 465:227-230(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-15, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart;
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 [5]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=26487682; DOI=10.1073/pnas.1508273112;
RA Pappas C.T., Mayfield R.M., Henderson C., Jamilpour N., Cover C.,
RA Hernandez Z., Hutchinson K.R., Chu M., Nam K.H., Valdez J.M., Wong P.K.,
RA Granzier H.L., Gregorio C.C.;
RT "Knockout of Lmod2 results in shorter thin filaments followed by dilated
RT cardiomyopathy and juvenile lethality.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:13573-13578(2015).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=27274810; DOI=10.1186/s13578-016-0101-y;
RA Li S., Mo K., Tian H., Chu C., Sun S., Tian L., Ding S., Li T.R., Wu X.,
RA Liu F., Zhang Z., Xu T., Sun L.V.;
RT "Lmod2 piggyBac mutant mice exhibit dilated cardiomyopathy.";
RL Cell Biosci. 6:38-38(2016).
CC -!- FUNCTION: Mediates nucleation of actin filaments and thereby promotes
CC actin polymerization (By similarity). Plays a role in the regulation of
CC actin filament length (PubMed:26487682). Required for normal sarcomere
CC organization in the heart, and for normal heart function
CC (PubMed:26487682, PubMed:27274810). {ECO:0000250|UniProtKB:Q6P5Q4,
CC ECO:0000269|PubMed:26487682, ECO:0000269|PubMed:27274810}.
CC -!- SUBUNIT: Can bind at least three actin monomers and thereby provides a
CC nucleus for actin filament formation. Interacts (via N-terminus) with
CC tropomyosin alpha (TPM1) (via N-terminus). May also interact with TPM2
CC (via N-terminus) (PubMed:17572376). {ECO:0000250|UniProtKB:Q6P5Q4,
CC ECO:0000269|PubMed:17572376}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere
CC {ECO:0000250|UniProtKB:Q6P5Q4}. Cytoplasm, myofibril
CC {ECO:0000250|UniProtKB:Q6P5Q4}. Cytoplasm, myofibril, sarcomere, M line
CC {ECO:0000250|UniProtKB:Q6P5Q4}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q6P5Q4}. Note=Colocalizes with actin filaments
CC in sarcomeres. Detected close to the M line.
CC {ECO:0000250|UniProtKB:Q6P5Q4}.
CC -!- TISSUE SPECIFICITY: Detected in neonate heart (at protein level)
CC (PubMed:26487682). Detected in embryonic heart and in pharyngeal arches
CC (PubMed:26487682). Detected in adult heart (PubMed:27274810).
CC {ECO:0000269|PubMed:26487682, ECO:0000269|PubMed:27274810}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate. All die between 15 to 33 days after birth due to early-onset
CC dilated cardiomyopathy. Cardiac muscle thin filaments are shorter than
CC in wild-type, both in embryonic heart and in pups 6 or 15 days after
CC birth. Hearts appear grossly normal at birth, but after 15 days, they
CC display enlarged left ventricles with thin ventricle walls and resuced
CC systolic performance. In contrast, there are no differences in thin
CC filament length in skeletal muscle (PubMed:26487682). Insertion of a
CC transposon in the first, non-coding exon decreases Lmod2 expression by
CC 90% in females and by over 95% in males and gives rise to a phenotype
CC that is closely similar to that of complete gene disruption, except
CC that mutant mice die between three and nine weeks after birth
CC (PubMed:27274810). {ECO:0000269|PubMed:26487682}.
CC -!- SIMILARITY: Belongs to the tropomodulin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK00789.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK147141; BAE27711.1; -; mRNA.
DR EMBL; AF237628; AAK00789.1; ALT_INIT; mRNA.
DR CCDS; CCDS19944.1; -.
DR RefSeq; NP_444328.1; NM_053098.2.
DR AlphaFoldDB; Q3UHZ5; -.
DR SMR; Q3UHZ5; -.
DR STRING; 10090.ENSMUSP00000031694; -.
DR iPTMnet; Q3UHZ5; -.
DR PhosphoSitePlus; Q3UHZ5; -.
DR MaxQB; Q3UHZ5; -.
DR PaxDb; Q3UHZ5; -.
DR PRIDE; Q3UHZ5; -.
DR ProteomicsDB; 286224; -.
DR Antibodypedia; 55328; 64 antibodies from 13 providers.
DR DNASU; 93677; -.
DR Ensembl; ENSMUST00000031694; ENSMUSP00000031694; ENSMUSG00000029683.
DR GeneID; 93677; -.
DR KEGG; mmu:93677; -.
DR UCSC; uc009bbu.1; mouse.
DR CTD; 442721; -.
DR MGI; MGI:2135672; Lmod2.
DR VEuPathDB; HostDB:ENSMUSG00000029683; -.
DR eggNOG; KOG3735; Eukaryota.
DR GeneTree; ENSGT00940000156567; -.
DR HOGENOM; CLU_031052_4_0_1; -.
DR InParanoid; Q3UHZ5; -.
DR OMA; EECFTES; -.
DR OrthoDB; 1025132at2759; -.
DR PhylomeDB; Q3UHZ5; -.
DR TreeFam; TF315841; -.
DR BioGRID-ORCS; 93677; 6 hits in 71 CRISPR screens.
DR ChiTaRS; Lmod2; mouse.
DR PRO; PR:Q3UHZ5; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q3UHZ5; protein.
DR Bgee; ENSMUSG00000029683; Expressed in interventricular septum and 70 other tissues.
DR Genevisible; Q3UHZ5; MM.
DR GO; GO:0005884; C:actin filament; ISS:UniProtKB.
DR GO; GO:0097512; C:cardiac myofibril; 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; ISO:MGI.
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; ISS:UniProtKB.
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:0030041; P:actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0045010; P:actin nucleation; ISS: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; ISS:UniProtKB.
DR GO; GO:0045214; P:sarcomere organization; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR030132; LMOD2.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR004934; TMOD.
DR PANTHER; PTHR10901; PTHR10901; 1.
DR PANTHER; PTHR10901:SF12; PTHR10901:SF12; 1.
DR Pfam; PF03250; Tropomodulin; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Coiled coil; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..550
FT /note="Leiomodin-2"
FT /id="PRO_0000311341"
FT DOMAIN 524..543
FT /note="WH2"
FT REGION 1..165
FT /note="Interaction with actin 1"
FT /evidence="ECO:0000250|UniProtKB:Q6P5Q4"
FT REGION 1..47
FT /note="Interaction with tropomyosin alpha"
FT /evidence="ECO:0000250|UniProtKB:Q6P5Q4"
FT REGION 84..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 166..500
FT /note="Interaction with actin 2"
FT /evidence="ECO:0000250|UniProtKB:Q6P5Q4"
FT REGION 359..527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..543
FT /note="Interaction with actin 3"
FT /evidence="ECO:0000250|UniProtKB:Q6P5Q4"
FT COILED 91..147
FT /evidence="ECO:0000255"
FT COMPBIAS 95..143
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..378
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 421..454
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 464..478
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 502..516
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A1A5Q0"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A1A5Q0"
FT CONFLICT 223
FT /note="V -> F (in Ref. 2; AAK00789)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 550 AA; 62018 MW; BFA34F7BDFF25A1D CRC64;
MSTFGYRRGL SKYESIDEDE LLASLSPEEL KELERELEDI EPDRNLPVGL RQKSLTEKTP
TGNFSREALM AYWEKESQKL LEKERLGECG KVAEEDKEES EEELIFTESN SEVSEEVCTE
DEEESQEEEE DSEEEEDSEE EEETTEATKH INGTVSYNSV NTDNSKPKTF KSQIENINLT
NGNSGRTQRN SESPAAIHPC GNPTVIEDAL EKIRNNDPDT TEVNLNNIEN ITTQTLSRFA
EALKENTVVK TFSLANTHAD DAAAIAIADM LKVNEHITSV NVESNFITGK GILAIMRALQ
HNTVLTELRF HNQRHIMGSQ VEMEIVKLLK ENTTLLRLGY HFELPGPRMS MTSILTRNMD
KQRQKRMQEQ KQQEGHDGGA ALRTKVWQRG TPGSSPYASP RQSPWSSPKV SKKVHTGRSR
PPSPVAPPPP PPPPPLPPHM LPPPPPPPAP PLPEKKLITR NIAEVIKQQE SAQRALQNGQ
RKKKGKKVKK QPNNILKEIK NSLRSVQEKK MEDSSRPSTP QRSVHENLME AIRGSSIRQL
RRVEVPEALR
