TMOD1_HUMAN
ID TMOD1_HUMAN Reviewed; 359 AA.
AC P28289; B2RB77; Q5T7W3; Q9BUF1;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Tropomodulin-1;
DE AltName: Full=Erythrocyte tropomodulin;
DE Short=E-Tmod;
GN Name=TMOD1; Synonyms=D9S57E, TMOD;
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), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Fetal liver;
RX PubMed=1370827; DOI=10.1016/s0021-9258(18)45926-1;
RA Sung L.A., Fowler V.M., Lambert K., Sussman M.A., Karr D., Chien S.;
RT "Molecular cloning and characterization of human fetal liver tropomodulin.
RT A tropomyosin-binding protein.";
RL J. Biol. Chem. 267:2616-2621(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11054557; DOI=10.1016/s0378-1119(00)00327-9;
RA Chu X., Thompson D., Yee L.J., Sung L.A.;
RT "Genomic organization of mouse and human erythrocyte tropomodulin genes
RT encoding the pointed end capping protein for the actin filaments.";
RL Gene 256:271-281(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [6]
RP FUNCTION, AND INTERACTION WITH TPM3.
RX PubMed=8002995; DOI=10.1006/bbrc.1994.1747;
RA Sung L.A., Lin J.J.-C.;
RT "Erythrocyte tropomodulin binds to the N-terminus of hTM5, a tropomyosin
RT isoform encoded by the gamma-tropomyosin gene.";
RL Biochem. Biophys. Res. Commun. 201:627-634(1994).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
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. May play an important role in
CC regulating the organization of actin filaments by preferentially
CC binding to a specific tropomyosin isoform at its N-terminus.
CC {ECO:0000269|PubMed:8002995}.
CC -!- SUBUNIT: Binds to the N-terminus of isoforms 2/3 of TPM3 and to actin.
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=P28289-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28289-2; Sequence=VSP_056863, VSP_056864;
CC -!- TISSUE SPECIFICITY: Highly expressed in the erythrocyte, heart and
CC skeletal muscle.
CC -!- SIMILARITY: Belongs to the tropomodulin family. {ECO:0000305}.
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DR EMBL; M77016; AAA61224.1; -; mRNA.
DR EMBL; AF288155; AAG30124.1; -; Genomic_DNA.
DR EMBL; AF288147; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288148; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288149; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288150; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288151; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288152; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288153; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AF288154; AAG30124.1; JOINED; Genomic_DNA.
DR EMBL; AK095748; BAG53119.1; -; mRNA.
DR EMBL; AK314533; BAG37124.1; -; mRNA.
DR EMBL; AL162385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002660; AAH02660.1; -; mRNA.
DR CCDS; CCDS6726.1; -. [P28289-1]
DR PIR; A42336; A42336.
DR RefSeq; NP_001159588.1; NM_001166116.1. [P28289-1]
DR RefSeq; NP_003266.1; NM_003275.3. [P28289-1]
DR PDB; 4PKG; X-ray; 1.80 A; G=50-101.
DR PDB; 4PKH; X-ray; 2.15 A; B/E/G/J=50-101.
DR PDB; 4PKI; X-ray; 2.30 A; G=160-349.
DR PDB; 4Z8G; X-ray; 2.10 A; A=163-228.
DR PDB; 4Z94; X-ray; 2.40 A; G=160-228.
DR PDBsum; 4PKG; -.
DR PDBsum; 4PKH; -.
DR PDBsum; 4PKI; -.
DR PDBsum; 4Z8G; -.
DR PDBsum; 4Z94; -.
DR AlphaFoldDB; P28289; -.
DR SMR; P28289; -.
DR BioGRID; 112966; 203.
DR IntAct; P28289; 67.
DR MINT; P28289; -.
DR STRING; 9606.ENSP00000259365; -.
DR iPTMnet; P28289; -.
DR PhosphoSitePlus; P28289; -.
DR BioMuta; TMOD1; -.
DR DMDM; 135922; -.
DR EPD; P28289; -.
DR jPOST; P28289; -.
DR MassIVE; P28289; -.
DR MaxQB; P28289; -.
DR PaxDb; P28289; -.
DR PeptideAtlas; P28289; -.
DR PRIDE; P28289; -.
DR ProteomicsDB; 54457; -. [P28289-1]
DR ProteomicsDB; 64694; -.
DR Antibodypedia; 28841; 296 antibodies from 28 providers.
DR DNASU; 7111; -.
DR Ensembl; ENST00000259365.9; ENSP00000259365.3; ENSG00000136842.14. [P28289-1]
DR Ensembl; ENST00000375175.1; ENSP00000364318.1; ENSG00000136842.14. [P28289-2]
DR Ensembl; ENST00000395211.6; ENSP00000378637.2; ENSG00000136842.14. [P28289-1]
DR GeneID; 7111; -.
DR KEGG; hsa:7111; -.
DR MANE-Select; ENST00000259365.9; ENSP00000259365.3; NM_003275.4; NP_003266.1.
DR UCSC; uc004axk.3; human. [P28289-1]
DR CTD; 7111; -.
DR DisGeNET; 7111; -.
DR GeneCards; TMOD1; -.
DR HGNC; HGNC:11871; TMOD1.
DR HPA; ENSG00000136842; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 190930; gene.
DR neXtProt; NX_P28289; -.
DR OpenTargets; ENSG00000136842; -.
DR PharmGKB; PA36572; -.
DR VEuPathDB; HostDB:ENSG00000136842; -.
DR eggNOG; KOG3735; Eukaryota.
DR GeneTree; ENSGT00940000158695; -.
DR HOGENOM; CLU_031052_0_0_1; -.
DR InParanoid; P28289; -.
DR OMA; ELCDIAX; -.
DR OrthoDB; 1025132at2759; -.
DR PhylomeDB; P28289; -.
DR TreeFam; TF315841; -.
DR PathwayCommons; P28289; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; P28289; -.
DR SIGNOR; P28289; -.
DR BioGRID-ORCS; 7111; 10 hits in 1084 CRISPR screens.
DR ChiTaRS; TMOD1; human.
DR GeneWiki; TMOD1; -.
DR GenomeRNAi; 7111; -.
DR Pharos; P28289; Tbio.
DR PRO; PR:P28289; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P28289; protein.
DR Bgee; ENSG00000136842; Expressed in type B pancreatic cell and 186 other tissues.
DR Genevisible; P28289; HS.
DR GO; GO:0005884; C:actin filament; IDA:UniProtKB.
DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0030016; C:myofibril; IDA:UniProtKB.
DR GO; GO:0030017; C:sarcomere; IDA:UniProtKB.
DR GO; GO:0005865; C:striated muscle thin filament; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; 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:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0070307; P:lens fiber cell development; IEA:Ensembl.
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; IPR030135; TMOD1.
DR PANTHER; PTHR10901; PTHR10901; 1.
DR PANTHER; PTHR10901:SF8; PTHR10901:SF8; 1.
DR Pfam; PF03250; Tropomodulin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Reference proteome.
FT CHAIN 1..359
FT /note="Tropomodulin-1"
FT /id="PRO_0000186128"
FT REGION 36..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..138
FT /note="Tropomyosin-binding"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..6
FT /note="MSYRRE -> MSQVLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056863"
FT VAR_SEQ 7..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056864"
FT CONFLICT 17
FT /note="E -> K (in Ref. 5; AAH02660)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="K -> E (in Ref. 3; BAG37124)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="N -> S (in Ref. 3; BAG37124)"
FT /evidence="ECO:0000305"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:4PKG"
FT HELIX 180..191
FT /evidence="ECO:0007829|PDB:4Z8G"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:4Z8G"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:4Z8G"
FT STRAND 228..230
FT /evidence="ECO:0007829|PDB:4PKI"
FT HELIX 238..248
FT /evidence="ECO:0007829|PDB:4PKI"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:4PKI"
FT HELIX 266..274
FT /evidence="ECO:0007829|PDB:4PKI"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:4PKI"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:4PKI"
FT HELIX 296..306
FT /evidence="ECO:0007829|PDB:4PKI"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:4PKI"
FT HELIX 322..345
FT /evidence="ECO:0007829|PDB:4PKI"
FT TURN 346..348
FT /evidence="ECO:0007829|PDB:4PKI"
SQ SEQUENCE 359 AA; 40569 MW; 732B7D7798B88A48 CRC64;
MSYRRELEKY RDLDEDEILG ALTEEELRTL ENELDELDPD NALLPAGLRQ KDQTTKAPTG
PFKREELLDH LEKQAKEFKD REDLVPYTGE KRGKVWVPKQ KPLDPVLESV TLEPELEEAL
ANASDAELCD IAAILGMHTL MSNQQYYQAL SSSSIMNKEG LNSVIKPTQY KPVPDEEPNS
TDVEETLERI KNNDPKLEEV NLNNIRNIPI PTLKAYAEAL KENSYVKKFS IVGTRSNDPV
AYALAEMLKE NKVLKTLNVE SNFISGAGIL RLVEALPYNT SLVEMKIDNQ SQPLGNKVEM
EIVSMLEKNA TLLKFGYHFT QQGPRLRASN AMMNNNDLVR KRRLADLTGP IIPKCRSGV
