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 22-FEB-2023, entry version 164. 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 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 AGR; HGNC:11874; -. 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; 2883785at2759; -. 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 1080 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: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: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; Ribonuclease Inhibitor; 1. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR004934; TMOD. DR PANTHER; PTHR10901; TROPOMODULIN; 1. DR PANTHER; PTHR10901:SF9; TROPOMODULIN-4; 1. DR Pfam; PF03250; Tropomodulin; 1. DR SUPFAM; SSF52047; RNI-like; 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 //