TCIM_HUMAN
ID TCIM_HUMAN Reviewed; 106 AA.
AC Q9NR00;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Transcriptional and immune response regulator {ECO:0000312|HGNC:HGNC:1357};
DE AltName: Full=Thyroid cancer protein 1;
DE Short=TC-1;
GN Name=TCIM {ECO:0000312|HGNC:HGNC:1357}; Synonyms=C8orf4, TC1;
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], TISSUE SPECIFICITY, AND VARIANT ILE-10.
RC TISSUE=Thyroid papillary carcinoma;
RX PubMed=11056052; DOI=10.1006/geno.2000.6348;
RA Chua E.L., Young L., Wu W.M., Turtle J.R., Dong Q.;
RT "Cloning of TC-1 (C8orf4), a novel gene found to be overexpressed in
RT thyroid cancer.";
RL Genomics 69:342-347(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-10.
RC TISSUE=Lung, and Urinary bladder;
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 [4]
RP FUNCTION, AND SUBUNIT.
RX PubMed=15087392; DOI=10.1158/0008-5472.can-03-2093;
RA Sunde M., McGrath K.C.Y., Young L., Matthews J.M., Chua E.L., Mackay J.P.,
RA Death A.K.;
RT "TC-1 is a novel tumorigenic and natively disordered protein associated
RT with thyroid cancer.";
RL Cancer Res. 64:2766-2773(2004).
RN [5]
RP FUNCTION, INTERACTION WITH CBY1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF VAL-74; LYS-86; THR-88 AND LEU-96.
RX PubMed=16424001; DOI=10.1158/0008-5472.can-05-3124;
RA Jung Y., Bang S., Choi K., Kim E., Kim Y., Kim J., Park J., Koo H.,
RA Moon R.T., Song K., Lee I.;
RT "TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving
RT antagonistic activity of Chibby.";
RL Cancer Res. 66:723-728(2006).
RN [6]
RP FUNCTION, AND INDUCTION BY TNF AND IL1B.
RX PubMed=16730711; DOI=10.1016/j.febslet.2006.05.036;
RA Kim Y., Kim J., Park J., Bang S., Jung Y., Choe J., Song K., Lee I.;
RT "TC1(C8orf4) is upregulated by IL-1beta/TNF-alpha and enhances
RT proliferation of human follicular dendritic cells.";
RL FEBS Lett. 580:3519-3524(2006).
RN [7]
RP FUNCTION, INDUCTION BY CELLULAR STRESS, AND SUBCELLULAR LOCATION.
RX PubMed=17603013; DOI=10.1016/j.bbrc.2007.06.077;
RA Park J., Jung Y., Kim J., Kim K.Y., Ahn S.G., Song K., Lee I.;
RT "TC1 (C8orf4) is upregulated by cellular stress and mediates heat shock
RT response.";
RL Biochem. Biophys. Res. Commun. 360:447-452(2007).
RN [8]
RP FUNCTION, AND INDUCTION BY MITOGENS.
RX PubMed=18959821; DOI=10.5483/bmbrep.2008.41.10.733;
RA Wang Y.D., Bian G.H., Lv X.Y., Zheng R., Sun H., Zhang Z., Chen Y.,
RA Li Q.W., Xiao Y., Yang Q.T., Ai J.Z., Wei Y.Q., Zhou Q.;
RT "TC1 (C8orf4) is involved in ERK1/2 pathway-regulated G(1)- to S-phase
RT transition.";
RL BMB Rep. 41:733-738(2008).
RN [9]
RP FUNCTION, AND INDUCTION BY TNF AND IL1B.
RX PubMed=19684084; DOI=10.4049/jimmunol.0900956;
RA Kim J., Kim Y., Kim H.T., Kim D.W., Ha Y., Kim J., Kim C.H., Lee I.,
RA Song K.;
RT "TC1(C8orf4) is a novel endothelial inflammatory regulator enhancing NF-
RT kappaB activity.";
RL J. Immunol. 183:3996-4002(2009).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24941347; DOI=10.1371/journal.pone.0100075;
RA Lei J., Li W., Yang Y., Lu Q., Zhang N., Bai G., Zhong D., Su K., Liu B.,
RA Li X., Wang Y., Wang X.;
RT "TC-1 overexpression promotes cell proliferation in human non-small cell
RT lung cancer that can be inhibited by PD173074.";
RL PLoS ONE 9:E100075-E100075(2014).
RN [11]
RP INTERACTION WITH NOTCH2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=25985737; DOI=10.1038/ncomms8122;
RA Zhu P., Wang Y., Du Y., He L., Huang G., Zhang G., Yan X., Fan Z.;
RT "C8orf4 negatively regulates self-renewal of liver cancer stem cells via
RT suppression of NOTCH2 signalling.";
RL Nat. Commun. 6:7122-7122(2015).
CC -!- FUNCTION: Seems to be involved in the regulation of cell growth an
CC differentiation, may play different and opposite roles depending on the
CC tissue or cell type. May enhance the WNT-CTNNB1 pathway by relieving
CC antagonistic activity of CBY1 (PubMed:16424001, PubMed:16730711).
CC Enhances the proliferation of follicular dendritic cells
CC (PubMed:16730711). Plays a role in the mitogen-activated MAPK2/3
CC signaling pathway, positively regulates G1-to-S-phase transition of the
CC cell cycle (PubMed:18959821). In endothelial cells, enhances key
CC inflammatory mediators and inflammatory response through the modulation
CC of NF-kappaB transcriptional regulatory activity (PubMed:19684084).
CC Involved in the regulation of heat shock response, seems to play a
CC positive feedback with HSF1 to modulate heat-shock downstream gene
CC expression (PubMed:17603013). Plays a role in the regulation of
CC hematopoiesis even if the mechanisms are unknown (By similarity). In
CC cancers such as thyroid or lung cancer, it has been described as
CC promoter of cell proliferation, G1-to-S-phase transition and inhibitor
CC of apoptosis (PubMed:15087392, PubMed:24941347). However, it negatively
CC regulates self-renewal of liver cancer cells via suppresion of NOTCH2
CC signaling (PubMed:25985737). {ECO:0000250|UniProtKB:Q9D915,
CC ECO:0000269|PubMed:15087392, ECO:0000269|PubMed:16424001,
CC ECO:0000269|PubMed:16730711, ECO:0000269|PubMed:17603013,
CC ECO:0000269|PubMed:18959821, ECO:0000269|PubMed:19684084,
CC ECO:0000269|PubMed:24941347, ECO:0000269|PubMed:25985737, ECO:0000305}.
CC -!- SUBUNIT: Monomer. Interacts with NOTCH2 (via ANK repeats), the
CC interaction inhibits the nuclear translocation of NOTCH2 N2ICD
CC (PubMed:25985737). Interacts (C-terminus) with CBY1 (C-terminus), TCIM
CC competes with CTNNB1 for the interaction with CBY1 (PubMed:16424001).
CC {ECO:0000269|PubMed:15087392, ECO:0000269|PubMed:16424001,
CC ECO:0000269|PubMed:25985737}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16424001,
CC ECO:0000269|PubMed:25985737}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:16424001}. Nucleus speckle
CC {ECO:0000269|PubMed:16424001}. Nucleus {ECO:0000269|PubMed:16424001}.
CC Note=Localizes in nucleus speckles in presence of CBY1
CC (PubMed:16424001). Translocates to the nucleus upon cellular stress
CC such as H(2)O(2) (PubMed:17603013). {ECO:0000269|PubMed:16424001,
CC ECO:0000269|PubMed:17603013}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in thyroid papillary
CC carcinoma. Expressed in liver, expression levels decrease in
CC hepatocellular carcinoma (PubMed:25985737). Slightly detected in normal
CC lung, its expression is highly induced in lung cancer cells (at protein
CC level) (PubMed:24941347). {ECO:0000269|PubMed:11056052,
CC ECO:0000269|PubMed:24941347, ECO:0000269|PubMed:25985737}.
CC -!- INDUCTION: Induced by pro-inflammatory cytokines such as TNF and IL1B,
CC via NF-kappaB signaling (PubMed:16730711, PubMed:19684084). Induced by
CC cellular stresses such as heat shock, TPA, lipopolysaccharide and UV
CC (PubMed:17603013). Induced by mitogens such as thrombin
CC (PubMed:18959821). {ECO:0000269|PubMed:16730711,
CC ECO:0000269|PubMed:17603013, ECO:0000269|PubMed:18959821,
CC ECO:0000269|PubMed:19684084}.
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; AF268037; AAF78961.1; -; mRNA.
DR EMBL; AC022733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020623; AAH20623.1; -; mRNA.
DR EMBL; BC021672; AAH21672.1; -; mRNA.
DR CCDS; CCDS6115.1; -.
DR RefSeq; NP_064515.1; NM_020130.4.
DR AlphaFoldDB; Q9NR00; -.
DR BMRB; Q9NR00; -.
DR BioGRID; 121222; 3.
DR IntAct; Q9NR00; 2.
DR STRING; 9606.ENSP00000319914; -.
DR iPTMnet; Q9NR00; -.
DR PhosphoSitePlus; Q9NR00; -.
DR BioMuta; TCIM; -.
DR DMDM; 296434443; -.
DR MassIVE; Q9NR00; -.
DR PaxDb; Q9NR00; -.
DR PeptideAtlas; Q9NR00; -.
DR PRIDE; Q9NR00; -.
DR ProteomicsDB; 82240; -.
DR Antibodypedia; 23908; 71 antibodies from 20 providers.
DR DNASU; 56892; -.
DR Ensembl; ENST00000315792.5; ENSP00000319914.3; ENSG00000176907.5.
DR GeneID; 56892; -.
DR KEGG; hsa:56892; -.
DR MANE-Select; ENST00000315792.5; ENSP00000319914.3; NM_020130.5; NP_064515.2.
DR UCSC; uc003xnq.3; human.
DR CTD; 56892; -.
DR DisGeNET; 56892; -.
DR GeneCards; TCIM; -.
DR HGNC; HGNC:1357; TCIM.
DR HPA; ENSG00000176907; Low tissue specificity.
DR MIM; 607702; gene.
DR neXtProt; NX_Q9NR00; -.
DR OpenTargets; ENSG00000176907; -.
DR PharmGKB; PA25962; -.
DR VEuPathDB; HostDB:ENSG00000176907; -.
DR eggNOG; ENOG502S1N0; Eukaryota.
DR GeneTree; ENSGT00390000003458; -.
DR HOGENOM; CLU_172922_0_0_1; -.
DR InParanoid; Q9NR00; -.
DR OMA; ILDTDQD; -.
DR OrthoDB; 1548471at2759; -.
DR PhylomeDB; Q9NR00; -.
DR TreeFam; TF338287; -.
DR PathwayCommons; Q9NR00; -.
DR SignaLink; Q9NR00; -.
DR BioGRID-ORCS; 56892; 12 hits in 1059 CRISPR screens.
DR GeneWiki; C8orf4; -.
DR GenomeRNAi; 56892; -.
DR Pharos; Q9NR00; Tbio.
DR PRO; PR:Q9NR00; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q9NR00; protein.
DR Bgee; ENSG00000176907; Expressed in parotid gland and 177 other tissues.
DR Genevisible; Q9NR00; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0002264; P:endothelial cell activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:CAFA.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0010739; P:positive regulation of protein kinase A signaling; IDA:CAFA.
DR GO; GO:1900020; P:positive regulation of protein kinase C activity; IDA:CAFA.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR GO; GO:0043620; P:regulation of DNA-templated transcription in response to stress; IDA:UniProtKB.
DR GO; GO:1903706; P:regulation of hemopoiesis; IEA:Ensembl.
DR DisProt; DP00372; -.
DR InterPro; IPR020282; Avpi1/C8orf4_dom.
DR InterPro; IPR039580; Tcim.
DR PANTHER; PTHR32358; PTHR32358; 1.
DR Pfam; PF15063; TC1; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..106
FT /note="Transcriptional and immune response regulator"
FT /id="PRO_0000089605"
FT VARIANT 10
FT /note="V -> I (in dbSNP:rs6474226)"
FT /evidence="ECO:0000269|PubMed:11056052,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_050819"
FT MUTAGEN 74
FT /note="V->E: No effect on interaction with CBY1."
FT /evidence="ECO:0000269|PubMed:16424001"
FT MUTAGEN 86
FT /note="K->Q: Abolishes interaction with CBY1. Forms
FT irregular perinuclear cytoplasmic aggregates."
FT /evidence="ECO:0000269|PubMed:16424001"
FT MUTAGEN 88
FT /note="T->K: Abolishes interaction with CBY1."
FT /evidence="ECO:0000269|PubMed:16424001"
FT MUTAGEN 96
FT /note="L->R: No effect on interaction with CBY1.
FT Accumulates at nucleoli periphery."
FT /evidence="ECO:0000269|PubMed:16424001"
SQ SEQUENCE 106 AA; 12337 MW; 2D5C93B7E1E7AE09 CRC64;
MKAKRSHQAV IMSTSLRVSP SIHGYHFDTA SRKKAVGNIF ENTDQESLER LFRNSGDKKA
EERAKIIFAI DQDVEEKTRA LMALKKRTKD KLFQFLKLRK YSIKVH
