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   27-MAR-2024, entry version 187.
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   PDB; 8F8T; EM; 3.26 A; T=1-359.
DR   PDBsum; 4PKG; -.
DR   PDBsum; 4PKH; -.
DR   PDBsum; 4PKI; -.
DR   PDBsum; 4Z8G; -.
DR   PDBsum; 4Z94; -.
DR   PDBsum; 8F8T; -.
DR   AlphaFoldDB; P28289; -.
DR   EMDB; EMD-28936; -.
DR   SMR; P28289; -.
DR   BioGRID; 112966; 214.
DR   IntAct; P28289; 68.
DR   MINT; P28289; -.
DR   STRING; 9606.ENSP00000259365; -.
DR   GlyGen; P28289; 1 site, 1 O-linked glycan (1 site).
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; 9606-ENSP00000259365; -.
DR   PeptideAtlas; P28289; -.
DR   ProteomicsDB; 54457; -. [P28289-1]
DR   ProteomicsDB; 64694; -.
DR   Pumba; P28289; -.
DR   Antibodypedia; 28841; 356 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   AGR; HGNC:11871; -.
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; NHINEEG; -.
DR   OrthoDB; 3662163at2759; -.
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; 13 hits in 1162 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 188 other cell types or tissues.
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: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; Ribonuclease Inhibitor; 1.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   InterPro; IPR004934; TMOD.
DR   PANTHER; PTHR10901; TROPOMODULIN; 1.
DR   PANTHER; PTHR10901:SF8; TROPOMODULIN-1; 1.
DR   Pfam; PF03250; Tropomodulin; 1.
DR   SUPFAM; SSF52047; RNI-like; 1.
DR   Genevisible; P28289; HS.
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
//