TCHP_HUMAN
ID TCHP_HUMAN Reviewed; 498 AA.
AC Q9BT92; Q8NAG0;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Trichoplein keratin filament-binding protein;
DE Short=Protein TCHP;
DE AltName: Full=Mitochondrial protein with oncostatic activity;
DE Short=Mitostatin;
DE AltName: Full=Tumor suppressor protein;
GN Name=TCHP {ECO:0000312|EMBL:AAH04285.1};
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] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH KRT5; KRT6A; KRT8;
RP KRT14; KRT16 AND KRT18, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver {ECO:0000269|PubMed:15731013};
RX PubMed=15731013; DOI=10.1242/jcs.01667;
RA Nishizawa M., Izawa I., Inoko A., Hayashi Y., Nagata K., Yokoyama T.,
RA Usukura J., Inagaki M.;
RT "Identification of trichoplein, a novel keratin filament-binding protein.";
RL J. Cell Sci. 118:1081-1090(2005).
RN [2] {ECO:0000312|EMBL:AAG12971.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Baffa R., Croce C.M., Gomella L.G., Iozzo R.V., Vecchione A.;
RT "A novel tumor suppressor gene at 12q (TS12Q).";
RL Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:BAC03960.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine {ECO:0000312|EMBL:BAC03960.1};
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] {ECO:0000312|EMBL:AAH04285.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin {ECO:0000312|EMBL:AAH04285.1};
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANTS PRO-44 AND
RP LYS-93.
RX PubMed=18931701; DOI=10.1038/onc.2008.381;
RA Vecchione A., Fassan M., Anesti V., Morrione A., Goldoni S.,
RA Baldassarre G., Byrne D., D'Arca D., Palazzo J.P., Lloyd J., Scorrano L.,
RA Gomella L.G., Iozzo R.V., Baffa R.;
RT "MITOSTATIN, a putative tumor suppressor on chromosome 12q24.1, is
RT downregulated in human bladder and breast cancer.";
RL Oncogene 28:257-269(2009).
RN [7]
RP FUNCTION, INTERACTION WITH KCTD17, MUTAGENESIS OF LYS-50 AND LYS-57,
RP UBIQUITINATION AT LYS-50 AND LYS-57, AND UBIQUITINATION BY THE BCR(KCTD17)
RP COMPLEX.
RX PubMed=25270598; DOI=10.1038/ncomms6081;
RA Kasahara K., Kawakami Y., Kiyono T., Yonemura S., Kawamura Y., Era S.,
RA Matsuzaki F., Goshima N., Inagaki M.;
RT "Ubiquitin-proteasome system controls ciliogenesis at the initial step of
RT axoneme extension.";
RL Nat. Commun. 5:5081-5081(2014).
CC -!- FUNCTION: Tumor suppressor which has the ability to inhibit cell growth
CC and be pro-apoptotic during cell stress. Inhibits cell growth in
CC bladder and prostate cancer cells by a down-regulation of HSPB1 by
CC inhibiting its phosphorylation. May act as a 'capping' or 'branching'
CC protein for keratin filaments in the cell periphery. May regulate
CC K8/K18 filament and desmosome organization mainly at the apical or
CC peripheral regions of simple epithelial cells (PubMed:15731013,
CC PubMed:18931701). Is a negative regulator of ciliogenesis
CC (PubMed:25270598). {ECO:0000269|PubMed:15731013,
CC ECO:0000269|PubMed:18931701, ECO:0000269|PubMed:25270598}.
CC -!- SUBUNIT: Interacts specifically with keratin proteins including, KRT5,
CC KRT6A, KRT8, KRT14, KRT16 and KRT18 (PubMed:15731013). Interacts with
CC KCTD17 (PubMed:25270598). {ECO:0000269|PubMed:15731013,
CC ECO:0000269|PubMed:25270598}.
CC -!- INTERACTION:
CC Q9BT92; Q8N5M1: ATPAF2; NbExp=3; IntAct=EBI-740781, EBI-1166928;
CC Q9BT92; O75934: BCAS2; NbExp=3; IntAct=EBI-740781, EBI-1050106;
CC Q9BT92; Q9BUH8: BEGAIN; NbExp=3; IntAct=EBI-740781, EBI-742722;
CC Q9BT92; Q8NA61-2: CBY2; NbExp=3; IntAct=EBI-740781, EBI-11524851;
CC Q9BT92; Q86Z20: CCDC125; NbExp=3; IntAct=EBI-740781, EBI-11977221;
CC Q9BT92; Q8IYE1: CCDC13; NbExp=4; IntAct=EBI-740781, EBI-10961312;
CC Q9BT92; P0C7W6: CCDC172; NbExp=7; IntAct=EBI-740781, EBI-2548868;
CC Q9BT92; Q01850: CDR2; NbExp=8; IntAct=EBI-740781, EBI-1181367;
CC Q9BT92; Q86X02: CDR2L; NbExp=3; IntAct=EBI-740781, EBI-11063830;
CC Q9BT92; Q9NPF5: DMAP1; NbExp=5; IntAct=EBI-740781, EBI-399105;
CC Q9BT92; Q8WWB3: DYDC1; NbExp=6; IntAct=EBI-740781, EBI-740680;
CC Q9BT92; Q9NRA8: EIF4ENIF1; NbExp=3; IntAct=EBI-740781, EBI-301024;
CC Q9BT92; Q9NYK6-3: EURL; NbExp=3; IntAct=EBI-740781, EBI-13371226;
CC Q9BT92; Q9NP66: HMG20A; NbExp=3; IntAct=EBI-740781, EBI-740641;
CC Q9BT92; Q96ED9-2: HOOK2; NbExp=3; IntAct=EBI-740781, EBI-10961706;
CC Q9BT92; Q02363: ID2; NbExp=3; IntAct=EBI-740781, EBI-713450;
CC Q9BT92; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-740781, EBI-747204;
CC Q9BT92; Q2KHM9: KIAA0753; NbExp=4; IntAct=EBI-740781, EBI-2805604;
CC Q9BT92; P19012: KRT15; NbExp=5; IntAct=EBI-740781, EBI-739566;
CC Q9BT92; P08779: KRT16; NbExp=3; IntAct=EBI-740781, EBI-356410;
CC Q9BT92; P08727: KRT19; NbExp=3; IntAct=EBI-740781, EBI-742756;
CC Q9BT92; Q2M2I5: KRT24; NbExp=3; IntAct=EBI-740781, EBI-2952736;
CC Q9BT92; Q14532: KRT32; NbExp=3; IntAct=EBI-740781, EBI-1044146;
CC Q9BT92; O76011: KRT34; NbExp=3; IntAct=EBI-740781, EBI-1047093;
CC Q9BT92; Q92764: KRT35; NbExp=3; IntAct=EBI-740781, EBI-1058674;
CC Q9BT92; Q6A162: KRT40; NbExp=3; IntAct=EBI-740781, EBI-10171697;
CC Q9BT92; O95678: KRT75; NbExp=3; IntAct=EBI-740781, EBI-2949715;
CC Q9BT92; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-740781, EBI-741037;
CC Q9BT92; Q5JXC2: MIIP; NbExp=3; IntAct=EBI-740781, EBI-2801965;
CC Q9BT92; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-740781, EBI-2548751;
CC Q9BT92; Q13064: MKRN3; NbExp=9; IntAct=EBI-740781, EBI-2340269;
CC Q9BT92; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-740781, EBI-11522433;
CC Q9BT92; Q15742: NAB2; NbExp=7; IntAct=EBI-740781, EBI-8641936;
CC Q9BT92; Q9UHB4: NDOR1; NbExp=7; IntAct=EBI-740781, EBI-10249760;
CC Q9BT92; Q9Y5B8: NME7; NbExp=12; IntAct=EBI-740781, EBI-744782;
CC Q9BT92; Q7Z3B4: NUP54; NbExp=3; IntAct=EBI-740781, EBI-741048;
CC Q9BT92; P28074: PSMB5; NbExp=3; IntAct=EBI-740781, EBI-357828;
CC Q9BT92; Q9UJ41-4: RABGEF1; NbExp=3; IntAct=EBI-740781, EBI-14093916;
CC Q9BT92; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-740781, EBI-6257312;
CC Q9BT92; Q9H668: STN1; NbExp=3; IntAct=EBI-740781, EBI-746930;
CC Q9BT92; P14373: TRIM27; NbExp=4; IntAct=EBI-740781, EBI-719493;
CC Q9BT92; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-740781, EBI-2130429;
CC Q9BT92; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-740781, EBI-739895;
CC Q9BT92; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-740781, EBI-12040603;
CC Q9BT92; Q9NZV7: ZIM2; NbExp=3; IntAct=EBI-740781, EBI-11962760;
CC Q9BT92; Q9UDW3: ZMAT5; NbExp=3; IntAct=EBI-740781, EBI-7850213;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:15731013}. Cytoplasm {ECO:0000269|PubMed:18931701}.
CC Cell membrane {ECO:0000305|PubMed:15731013,
CC ECO:0000305|PubMed:18931701}. Mitochondrion
CC {ECO:0000269|PubMed:18931701}. Cell junction, desmosome
CC {ECO:0000269|PubMed:15731013}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in normal urothelial and
CC breast epithelial cells. Also expressed in the smooth muscle and
CC endothelial cells. Reduced expression seen in advanced bladder and
CC breast carcinomas (at protein level). Ubiquitous. Expressed at highest
CC levels in the heart, skeletal muscle, kidney, liver and testis.
CC {ECO:0000269|PubMed:18931701}.
CC -!- PTM: Ubiquitinated. Ubiquitination by the BCR(KCTD17) E3 ubiquitin
CC ligase complex results in proteasomal degradation, and induces
CC ciliogenesis. {ECO:0000269|PubMed:25270598}.
CC -!- SIMILARITY: Belongs to the TCHP 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; AY007230; AAG12971.1; -; mRNA.
DR EMBL; AK092736; BAC03960.1; -; mRNA.
DR EMBL; BC004285; AAH04285.1; -; mRNA.
DR CCDS; CCDS9137.1; -.
DR RefSeq; NP_001137324.1; NM_001143852.1.
DR RefSeq; NP_115676.1; NM_032300.4.
DR RefSeq; XP_011537138.1; XM_011538836.2.
DR RefSeq; XP_011537139.1; XM_011538837.2.
DR AlphaFoldDB; Q9BT92; -.
DR SMR; Q9BT92; -.
DR BioGRID; 123987; 123.
DR IntAct; Q9BT92; 83.
DR MINT; Q9BT92; -.
DR STRING; 9606.ENSP00000324404; -.
DR iPTMnet; Q9BT92; -.
DR PhosphoSitePlus; Q9BT92; -.
DR BioMuta; TCHP; -.
DR DMDM; 74733103; -.
DR EPD; Q9BT92; -.
DR jPOST; Q9BT92; -.
DR MassIVE; Q9BT92; -.
DR MaxQB; Q9BT92; -.
DR PaxDb; Q9BT92; -.
DR PeptideAtlas; Q9BT92; -.
DR PRIDE; Q9BT92; -.
DR ProteomicsDB; 78961; -.
DR Antibodypedia; 49415; 159 antibodies from 26 providers.
DR DNASU; 84260; -.
DR Ensembl; ENST00000312777.9; ENSP00000324404.5; ENSG00000139437.18.
DR Ensembl; ENST00000405876.9; ENSP00000384520.4; ENSG00000139437.18.
DR Ensembl; ENST00000544838.5; ENSP00000440838.1; ENSG00000139437.18.
DR GeneID; 84260; -.
DR KEGG; hsa:84260; -.
DR MANE-Select; ENST00000405876.9; ENSP00000384520.4; NM_001143852.2; NP_001137324.1.
DR UCSC; uc001tpn.4; human.
DR CTD; 84260; -.
DR DisGeNET; 84260; -.
DR GeneCards; TCHP; -.
DR HGNC; HGNC:28135; TCHP.
DR HPA; ENSG00000139437; Low tissue specificity.
DR MIM; 612654; gene.
DR neXtProt; NX_Q9BT92; -.
DR OpenTargets; ENSG00000139437; -.
DR PharmGKB; PA143485629; -.
DR VEuPathDB; HostDB:ENSG00000139437; -.
DR eggNOG; ENOG502QVSH; Eukaryota.
DR GeneTree; ENSGT01040000240563; -.
DR HOGENOM; CLU_042533_1_0_1; -.
DR InParanoid; Q9BT92; -.
DR OMA; QNSHYFR; -.
DR OrthoDB; 675049at2759; -.
DR PhylomeDB; Q9BT92; -.
DR TreeFam; TF329032; -.
DR PathwayCommons; Q9BT92; -.
DR SignaLink; Q9BT92; -.
DR BioGRID-ORCS; 84260; 17 hits in 1078 CRISPR screens.
DR ChiTaRS; TCHP; human.
DR GeneWiki; TCHP; -.
DR GenomeRNAi; 84260; -.
DR Pharos; Q9BT92; Tbio.
DR PRO; PR:Q9BT92; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9BT92; protein.
DR Bgee; ENSG00000139437; Expressed in sural nerve and 166 other tissues.
DR ExpressionAtlas; Q9BT92; baseline and differential.
DR Genevisible; Q9BT92; HS.
DR GO; GO:0045179; C:apical cortex; IDA:HGNC-UCL.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030057; C:desmosome; IEA:UniProtKB-SubCell.
DR GO; GO:0045095; C:keratin filament; IDA:HGNC-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:1902018; P:negative regulation of cilium assembly; IMP:UniProtKB.
DR InterPro; IPR043596; CFAP53/TCHP.
DR InterPro; IPR026773; TCHP.
DR InterPro; IPR043597; TPH_dom.
DR PANTHER; PTHR31183; PTHR31183; 1.
DR PANTHER; PTHR31183:SF2; PTHR31183:SF2; 1.
DR Pfam; PF13868; TPH; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cell junction; Cell membrane; Cilium biogenesis/degradation;
KW Coiled coil; Cytoplasm; Cytoskeleton; Isopeptide bond; Membrane;
KW Mitochondrion; Reference proteome; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..498
FT /note="Trichoplein keratin filament-binding protein"
FT /id="PRO_0000292609"
FT REGION 73..498
FT /note="Interaction with keratin proteins"
FT /evidence="ECO:0000269|PubMed:15731013"
FT REGION 167..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..425
FT /note="Trichohyalin/plectin homology domain"
FT /evidence="ECO:0000269|PubMed:15731013"
FT REGION 447..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 11..39
FT /evidence="ECO:0000255"
FT COILED 66..136
FT /evidence="ECO:0000255"
FT COILED 163..353
FT /evidence="ECO:0000255"
FT COILED 380..479
FT /evidence="ECO:0000255"
FT CROSSLNK 50
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:25270598"
FT CROSSLNK 57
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:25270598"
FT VARIANT 44
FT /note="S -> P (in a gastric carcinoma sample;
FT dbSNP:rs202208566)"
FT /evidence="ECO:0000269|PubMed:18931701"
FT /id="VAR_064056"
FT VARIANT 93
FT /note="E -> K (in a pancreatic carcinoma sample;
FT dbSNP:rs200027650)"
FT /evidence="ECO:0000269|PubMed:18931701"
FT /id="VAR_064057"
FT VARIANT 127
FT /note="K -> R (in dbSNP:rs10774978)"
FT /id="VAR_053924"
FT VARIANT 417
FT /note="E -> K (in dbSNP:rs16940680)"
FT /id="VAR_053925"
FT MUTAGEN 50
FT /note="K->R: Decreased ubiquitination. Negative effect on
FT ubiquitination is higher when associated with R-57."
FT /evidence="ECO:0000269|PubMed:25270598"
FT MUTAGEN 57
FT /note="K->R: Decreased ubiquitination. Negative effect on
FT ubiquitination is higher when associated with R-50."
FT /evidence="ECO:0000269|PubMed:25270598"
FT CONFLICT 326
FT /note="A -> V (in Ref. 3; BAC03960)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 498 AA; 61072 MW; 7D1E8A66C56516F8 CRC64;
MALPTLPSYW CSQQRLNQQL ARQREQEARL RQQWEQNSRY FRMSDICSSK QAEWSSKTSY
QRSMHAYQRE KMKEEKRRSL EARREKLRQL MQEEQDLLAR ELEELRLSMN LQERRIREQH
GKLKSAKEEQ RKLIAEQLLY EHWKKNNPKL REMELDLHQK HVVNSWEMQK EEKKQQEATA
EQENKRYENE YERARREALE RMKAEEERRQ LEDKLQAEAL LQQMEELKLK EVEATKLKKE
QENLLKQRWE LERLEEERKQ MEAFRQKAEL GRFLRHQYNA QLSRRTQQIQ EELEADRRIL
QALLEKEDES QRLHLARREQ VMADVAWMKQ AIEEQLQLER AREAELQMLL REEAKEMWEK
REAEWARERS ARDRLMSEVL TGRQQQIQEK IEQNRRAQEE SLKHREQLIR NLEEVRELAR
REKEESEKLK SARKQELEAQ VAERRLQAWE ADQQEEEEEE EARRVEQLSD ALLQQEAETM
AEQGYRPKPY GHPKIAWN
