TMOD4_HUMAN
ID TMOD4_HUMAN Reviewed; 345 AA.
AC Q9NZQ9; B7Z6N9; Q5JR83; Q8WVL3; Q9UKH2;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Tropomodulin-4;
DE AltName: Full=Skeletal muscle tropomodulin;
DE Short=Sk-Tmod;
GN Name=TMOD4;
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 1).
RX PubMed=10497209; DOI=10.1074/jbc.274.40.28466;
RA Almenar-Queralt A., Lee A., Conley C.A., Ribas de Pouplana L., Fowler V.M.;
RT "Identification of a novel tropomodulin isoform, skeletal tropomodulin,
RT that caps actin filament pointed ends in fast skeletal muscle.";
RL J. Biol. Chem. 274:28466-28475(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=10662549; DOI=10.1006/geno.1999.6061;
RA Cox P.R., Zoghbi H.Y.;
RT "Sequencing, expression analysis, and mapping of three unique human
RT tropomodulin genes and their mouse orthologs.";
RL Genomics 63:97-107(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Durling H.J., Laing N.G.;
RT "Homo sapiens tropomodulin 4 (TMOD4) genomic sequence.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Cox P.R., Siddique T., Zoghbi H.Y.;
RT "Genomic organization of tropomodulins 2 and 4 and intergenic splicing of
RT YL-1 and TMOD4.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skeletal muscle;
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
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 [9]
RP SUBCELLULAR LOCATION.
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: Blocks the elongation and depolymerization of the actin
CC filaments at the pointed end. The Tmod/TM complex contributes to the
CC formation of the short actin protofilament, which in turn defines the
CC geometry of the membrane skeleton.
CC -!- SUBUNIT: Binds to the N-terminus of tropomyosin and to actin.
CC -!- INTERACTION:
CC Q9NZQ9; Q99757: TXN2; NbExp=3; IntAct=EBI-9393504, EBI-2932492;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:25250574}. Note=In myofibrils with sarcomeric
CC structure, localizes to the pointed end of actin thin filaments
CC (PubMed:25250574). {ECO:0000269|PubMed:25250574}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NZQ9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZQ9-2; Sequence=VSP_056865;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle.
CC {ECO:0000269|PubMed:10662549}.
CC -!- SIMILARITY: Belongs to the tropomodulin family. {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; AF165217; AAF01277.1; -; mRNA.
DR EMBL; AF177173; AAF31672.1; -; mRNA.
DR EMBL; AF321183; AAK06765.1; -; Genomic_DNA.
DR EMBL; AF393375; AAM73676.1; -; Genomic_DNA.
DR EMBL; AK300675; BAH13325.1; -; mRNA.
DR EMBL; AL592424; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53465.1; -; Genomic_DNA.
DR EMBL; BC017810; AAH17810.1; -; mRNA.
DR CCDS; CCDS988.1; -. [Q9NZQ9-1]
DR RefSeq; NP_037485.2; NM_013353.2. [Q9NZQ9-1]
DR RefSeq; XP_011507751.1; XM_011509449.1. [Q9NZQ9-1]
DR RefSeq; XP_016856578.1; XM_017001089.1.
DR AlphaFoldDB; Q9NZQ9; -.
DR SMR; Q9NZQ9; -.
DR BioGRID; 118898; 28.
DR IntAct; Q9NZQ9; 24.
DR STRING; 9606.ENSP00000295314; -.
DR iPTMnet; Q9NZQ9; -.
DR PhosphoSitePlus; Q9NZQ9; -.
DR BioMuta; TMOD4; -.
DR DMDM; 23396885; -.
DR MassIVE; Q9NZQ9; -.
DR PaxDb; Q9NZQ9; -.
DR PeptideAtlas; Q9NZQ9; -.
DR PRIDE; Q9NZQ9; -.
DR ProteomicsDB; 6792; -.
DR ProteomicsDB; 83489; -. [Q9NZQ9-1]
DR Antibodypedia; 34056; 169 antibodies from 26 providers.
DR DNASU; 29765; -.
DR Ensembl; ENST00000295314.9; ENSP00000295314.4; ENSG00000163157.15. [Q9NZQ9-1]
DR GeneID; 29765; -.
DR KEGG; hsa:29765; -.
DR MANE-Select; ENST00000295314.9; ENSP00000295314.4; NM_013353.3; NP_037485.2.
DR UCSC; uc001exc.5; human. [Q9NZQ9-1]
DR CTD; 29765; -.
DR DisGeNET; 29765; -.
DR GeneCards; TMOD4; -.
DR HGNC; HGNC:11874; TMOD4.
DR HPA; ENSG00000163157; Group enriched (skeletal muscle, tongue).
DR MIM; 605834; gene.
DR neXtProt; NX_Q9NZQ9; -.
DR OpenTargets; ENSG00000163157; -.
DR PharmGKB; PA36575; -.
DR VEuPathDB; HostDB:ENSG00000163157; -.
DR eggNOG; KOG3735; Eukaryota.
DR GeneTree; ENSGT00940000158734; -.
DR HOGENOM; CLU_031052_0_1_1; -.
DR InParanoid; Q9NZQ9; -.
DR OMA; SIIRFGY; -.
DR OrthoDB; 1025132at2759; -.
DR PhylomeDB; Q9NZQ9; -.
DR TreeFam; TF315841; -.
DR PathwayCommons; Q9NZQ9; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; Q9NZQ9; -.
DR BioGRID-ORCS; 29765; 13 hits in 1019 CRISPR screens.
DR GeneWiki; TMOD4; -.
DR GenomeRNAi; 29765; -.
DR Pharos; Q9NZQ9; Tbio.
DR PRO; PR:Q9NZQ9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NZQ9; protein.
DR Bgee; ENSG00000163157; Expressed in vastus lateralis and 108 other tissues.
DR ExpressionAtlas; Q9NZQ9; baseline and differential.
DR Genevisible; Q9NZQ9; HS.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0030016; C:myofibril; IBA:GO_Central.
DR GO; GO:0005865; C:striated muscle thin filament; IDA:UniProtKB.
DR GO; GO:0051015; F:actin filament binding; IEA:InterPro.
DR GO; GO:0005523; F:tropomyosin binding; IBA:GO_Central.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
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 Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR004934; TMOD.
DR InterPro; IPR030129; TMOD4.
DR PANTHER; PTHR10901; PTHR10901; 1.
DR PANTHER; PTHR10901:SF9; PTHR10901:SF9; 1.
DR Pfam; PF03250; Tropomodulin; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Reference proteome.
FT CHAIN 1..345
FT /note="Tropomodulin-4"
FT /id="PRO_0000186136"
FT REGION 42..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 95..163
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056865"
FT VARIANT 336
FT /note="N -> S (in dbSNP:rs11800088)"
FT /id="VAR_052400"
FT CONFLICT 283
FT /note="T -> I (in Ref. 1; AAF01277)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="C -> R (in Ref. 8; AAH17810)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 345 AA; 39335 MW; 3ACE2692EF52E2CB CRC64;
MSSYQKELEK YRDIDEDEIL RTLSPEELEQ LDCELQEMDP ENMLLPAGLR QRDQTKKSPT
GPLDREALLQ YLEQQALEVK ERDDLVPFTG EKKGKPYIQP KREIPAEEQI TLEPELEEAL
AHATDAEMCD IAAILDMYTL MSNKQYYDAL CSGEICNTEG ISSVVQPDKY KPVPDEPPNP
TNIEEILKRV RSNDKELEEV NLNNIQDIPI PMLSELCEAM KANTYVRSFS LVATRSGDPI
ANAVADMLRE NRSLQSLNIE SNFISSTGLM AVLKAVRENA TLTELRVDNQ RQWPGDAVEM
EMATVLEQCP SIVRFGYHFT QQGPRARAAQ AMTRNNELRR QQKKR
