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Transcriptional and immune response regulator (Thyroid cancer protein 1) (TC-1)

 TCIM_HUMAN              Reviewed;         106 AA.
Q9NR00;
19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
18-MAY-2010, sequence version 2.
20-JUN-2018, entry version 105.
RecName: Full=Transcriptional and immune response regulator {ECO:0000312|HGNC:HGNC:1357};
AltName: Full=Thyroid cancer protein 1;
Short=TC-1;
Name=TCIM {ECO:0000312|HGNC:HGNC:1357}; Synonyms=C8orf4, TC1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT ILE-10.
TISSUE=Thyroid papillary carcinoma;
PubMed=11056052; DOI=10.1006/geno.2000.6348;
Chua E.L., Young L., Wu W.M., Turtle J.R., Dong Q.;
"Cloning of TC-1 (C8orf4), a novel gene found to be overexpressed in
thyroid cancer.";
Genomics 69:342-347(2000).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16421571; DOI=10.1038/nature04406;
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
Lander E.S.;
"DNA sequence and analysis of human chromosome 8.";
Nature 439:331-335(2006).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-10.
TISSUE=Lung, and Urinary bladder;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
FUNCTION, AND SUBUNIT.
PubMed=15087392; DOI=10.1158/0008-5472.CAN-03-2093;
Sunde M., McGrath K.C.Y., Young L., Matthews J.M., Chua E.L.,
Mackay J.P., Death A.K.;
"TC-1 is a novel tumorigenic and natively disordered protein
associated with thyroid cancer.";
Cancer Res. 64:2766-2773(2004).
[5]
FUNCTION, INTERACTION WITH CBY1, TISSUE SPECIFICITY, SUBCELLULAR
LOCATION, AND MUTAGENESIS OF VAL-74; LYS-86; THR-88 AND LEU-96.
PubMed=16424001; DOI=10.1158/0008-5472.CAN-05-3124;
Jung Y., Bang S., Choi K., Kim E., Kim Y., Kim J., Park J., Koo H.,
Moon R.T., Song K., Lee I.;
"TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving
antagonistic activity of Chibby.";
Cancer Res. 66:723-728(2006).
[6]
FUNCTION, AND INDUCTION BY TNF AND IL1B.
PubMed=16730711; DOI=10.1016/j.febslet.2006.05.036;
Kim Y., Kim J., Park J., Bang S., Jung Y., Choe J., Song K., Lee I.;
"TC1(C8orf4) is upregulated by IL-1beta/TNF-alpha and enhances
proliferation of human follicular dendritic cells.";
FEBS Lett. 580:3519-3524(2006).
[7]
FUNCTION, INDUCTION BY CELLULAR STRESS, AND SUBCELLULAR LOCATION.
PubMed=17603013; DOI=10.1016/j.bbrc.2007.06.077;
Park J., Jung Y., Kim J., Kim K.Y., Ahn S.G., Song K., Lee I.;
"TC1 (C8orf4) is upregulated by cellular stress and mediates heat
shock response.";
Biochem. Biophys. Res. Commun. 360:447-452(2007).
[8]
FUNCTION, AND INDUCTION BY MITOGENS.
PubMed=18959821; DOI=10.5483/BMBRep.2008.41.10.733;
Wang Y.D., Bian G.H., Lv X.Y., Zheng R., Sun H., Zhang Z., Chen Y.,
Li Q.W., Xiao Y., Yang Q.T., Ai J.Z., Wei Y.Q., Zhou Q.;
"TC1 (C8orf4) is involved in ERK1/2 pathway-regulated G(1)- to S-phase
transition.";
BMB Rep. 41:733-738(2008).
[9]
FUNCTION, AND INDUCTION BY TNF AND IL1B.
PubMed=19684084; DOI=10.4049/jimmunol.0900956;
Kim J., Kim Y., Kim H.T., Kim D.W., Ha Y., Kim J., Kim C.H., Lee I.,
Song K.;
"TC1(C8orf4) is a novel endothelial inflammatory regulator enhancing
NF-kappaB activity.";
J. Immunol. 183:3996-4002(2009).
[10]
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=24941347; DOI=10.1371/journal.pone.0100075;
Lei J., Li W., Yang Y., Lu Q., Zhang N., Bai G., Zhong D., Su K.,
Liu B., Li X., Wang Y., Wang X.;
"TC-1 overexpression promotes cell proliferation in human non-small
cell lung cancer that can be inhibited by PD173074.";
PLoS ONE 9:E100075-E100075(2014).
[11]
INTERACTION WITH NOTCH2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=25985737; DOI=10.1038/ncomms8122;
Zhu P., Wang Y., Du Y., He L., Huang G., Zhang G., Yan X., Fan Z.;
"C8orf4 negatively regulates self-renewal of liver cancer stem cells
via suppression of NOTCH2 signalling.";
Nat. Commun. 6:7122-7122(2015).
-!- FUNCTION: Seems to be involved in the regulation of cell growth an
differentiation, may play different and opposite roles depending
on the tissue or cell type. May enhance the WNT-CTNNB1 pathway by
relieving antagonistic activity of CBY1 (PubMed:16424001,
PubMed:16730711). Enhances the proliferation of follicular
dendritic cells (PubMed:16730711). Plays a role in the mitogen-
activated MAPK2/3 signaling pathway, positively regulates G1-to-S-
phase transition of the cell cycle (PubMed:18959821). In
endothelial cells, enhances key inflammatory mediators and
inflammatory response through the modulation of NF-kappaB
transcriptional regulatory activity (PubMed:19684084). Involved in
the regulation of heat shock response, seems to play a positive
feedback with HSF1 to modulate heat-shock downstream gene
expression (PubMed:17603013). Plays a role in the regulation of
hematopoiesis even if the mechanisms are unknown (By similarity).
In cancers such as thyroid or lung cancer, it has been described
as promoter of cell proliferation, G1-to-S-phase transition and
inhibitor of apoptosis (PubMed:15087392, PubMed:24941347).
However, it negatively regulates self-renewal of liver cancer
cells via suppresion of NOTCH2 signaling (PubMed:25985737).
{ECO:0000250|UniProtKB:Q9D915, ECO:0000269|PubMed:15087392,
ECO:0000269|PubMed:16424001, ECO:0000269|PubMed:16730711,
ECO:0000269|PubMed:17603013, ECO:0000269|PubMed:18959821,
ECO:0000269|PubMed:19684084, ECO:0000269|PubMed:24941347,
ECO:0000269|PubMed:25985737, ECO:0000305}.
-!- SUBUNIT: Monomer. Interacts with NOTCH2 (via ANK repeats), the
interaction inhibits the nuclear translocation of NOTCH2 N2ICD
(PubMed:25985737). Interacts (C-terminus) with CBY1 (C-terminus),
TCIM competes with CTNNB1 for the interaction with CBY1
(PubMed:16424001). {ECO:0000269|PubMed:15087392,
ECO:0000269|PubMed:16424001, ECO:0000269|PubMed:25985737}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16424001,
ECO:0000269|PubMed:25985737}. Nucleus, nucleolus
{ECO:0000269|PubMed:16424001}. Nucleus speckle
{ECO:0000269|PubMed:16424001}. Nucleus
{ECO:0000269|PubMed:16424001}. Note=Localizes in nucleus speckles
in presence of CBY1 (PubMed:16424001). Translocates to the nucleus
upon cellular stress such as H(2)O(2) (PubMed:17603013).
{ECO:0000269|PubMed:16424001, ECO:0000269|PubMed:17603013}.
-!- TISSUE SPECIFICITY: Ubiquitous. Expressed in thyroid papillary
carcinoma. Expressed in liver, expression levels decrease in
hepatocellular carcinoma (PubMed:25985737). Slightly detected in
normal lung, its expression is highly induced in lung cancer cells
(at protein level) (PubMed:24941347).
{ECO:0000269|PubMed:11056052, ECO:0000269|PubMed:24941347,
ECO:0000269|PubMed:25985737}.
-!- INDUCTION: Induced by proinflammatory cytokines such as TNF and
IL1B, via NF-kappaB signaling (PubMed:16730711, PubMed:19684084).
Induced by cellular stresses such as heat shock, TPA,
lipopolysaccahride and UV (PubMed:17603013). Induced by mitogens
such as thrombin (PubMed:18959821). {ECO:0000269|PubMed:16730711,
ECO:0000269|PubMed:17603013, ECO:0000269|PubMed:18959821,
ECO:0000269|PubMed:19684084}.
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
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EMBL; AF268037; AAF78961.1; -; mRNA.
EMBL; AC022733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC020623; AAH20623.1; -; mRNA.
EMBL; BC021672; AAH21672.1; -; mRNA.
CCDS; CCDS6115.1; -.
RefSeq; NP_064515.1; NM_020130.4.
UniGene; Hs.591849; -.
UniGene; Hs.745031; -.
DisProt; DP00372; -.
ProteinModelPortal; Q9NR00; -.
BioGrid; 121222; 1.
IntAct; Q9NR00; 1.
STRING; 9606.ENSP00000319914; -.
iPTMnet; Q9NR00; -.
PhosphoSitePlus; Q9NR00; -.
BioMuta; C8orf4; -.
DMDM; 296434443; -.
PaxDb; Q9NR00; -.
PeptideAtlas; Q9NR00; -.
PRIDE; Q9NR00; -.
ProteomicsDB; 82240; -.
DNASU; 56892; -.
Ensembl; ENST00000315792; ENSP00000319914; ENSG00000176907.
GeneID; 56892; -.
KEGG; hsa:56892; -.
UCSC; uc003xnq.3; human.
CTD; 56892; -.
DisGeNET; 56892; -.
EuPathDB; HostDB:ENSG00000176907.4; -.
GeneCards; TCIM; -.
HGNC; HGNC:1357; TCIM.
HPA; HPA027188; -.
MIM; 607702; gene.
neXtProt; NX_Q9NR00; -.
OpenTargets; ENSG00000176907; -.
PharmGKB; PA25962; -.
eggNOG; ENOG410IXNR; Eukaryota.
eggNOG; ENOG410YPN0; LUCA.
GeneTree; ENSGT00390000003458; -.
HOGENOM; HOG000111608; -.
HOVERGEN; HBG054954; -.
InParanoid; Q9NR00; -.
OMA; VANIFEN; -.
OrthoDB; EOG091G0YFM; -.
PhylomeDB; Q9NR00; -.
TreeFam; TF338287; -.
ChiTaRS; C8orf4; human.
GeneWiki; C8orf4; -.
GenomeRNAi; 56892; -.
PRO; PR:Q9NR00; -.
Proteomes; UP000005640; Chromosome 8.
Bgee; ENSG00000176907; -.
CleanEx; HS_C8orf4; -.
Genevisible; Q9NR00; HS.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0005622; C:intracellular; IDA:CAFA.
GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:HPA.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0005112; F:Notch binding; IPI:UniProtKB.
GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
GO; GO:0002264; P:endothelial cell activation involved in immune response; IDA:UniProtKB.
GO; GO:0043066; P:negative regulation of apoptotic process; IDA:CAFA.
GO; GO:0045746; P:negative regulation of Notch signaling pathway; IDA:UniProtKB.
GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:UniProtKB.
GO; GO:0010739; P:positive regulation of protein kinase A signaling; IDA:CAFA.
GO; GO:1900020; P:positive regulation of protein kinase C activity; IDA:CAFA.
GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
GO; GO:0043620; P:regulation of DNA-templated transcription in response to stress; IDA:UniProtKB.
GO; GO:1903706; P:regulation of hemopoiesis; IEA:Ensembl.
InterPro; IPR020282; Avpi1/C8orf4.
Pfam; PF15063; TC1; 1.
ProDom; PD287216; Arg_vasopressin-induced_prot_1; 1.
1: Evidence at protein level;
Apoptosis; Complete proteome; Cytoplasm; Nucleus; Polymorphism;
Reference proteome.
CHAIN 1 106 Transcriptional and immune response
regulator.
/FTId=PRO_0000089605.
VARIANT 10 10 V -> I (in dbSNP:rs6474226).
{ECO:0000269|PubMed:11056052,
ECO:0000269|PubMed:15489334}.
/FTId=VAR_050819.
MUTAGEN 74 74 V->E: No effect on interaction with CBY1.
{ECO:0000269|PubMed:16424001}.
MUTAGEN 86 86 K->Q: Abolishes interaction with CBY1.
Forms irregular perinuclear cytoplasmic
aggregates.
{ECO:0000269|PubMed:16424001}.
MUTAGEN 88 88 T->K: Abolishes interaction with CBY1.
{ECO:0000269|PubMed:16424001}.
MUTAGEN 96 96 L->R: No effect on interaction with CBY1.
Accumulates at nucleoli periphery.
{ECO:0000269|PubMed:16424001}.
SEQUENCE 106 AA; 12337 MW; 2D5C93B7E1E7AE09 CRC64;
MKAKRSHQAV IMSTSLRVSP SIHGYHFDTA SRKKAVGNIF ENTDQESLER LFRNSGDKKA
EERAKIIFAI DQDVEEKTRA LMALKKRTKD KLFQFLKLRK YSIKVH


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