ID   TCIM_MOUSE              Reviewed;         106 AA.
AC   Q9D915;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   03-AUG-2022, entry version 113.
DE   RecName: Full=Transcriptional and immune response regulator;
GN   Name=Tcim {ECO:0000312|MGI:MGI:1916318}; Synonyms=Tc1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Pancreas;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=129, C57BL/6J, and FVB/N; TISSUE=Mammary tumor;
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   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=24937306; DOI=10.1371/journal.pone.0100311;
RA   Jung Y., Kim M., Soh H., Lee S., Kim J., Park S., Song K., Lee I.;
RT   "TC1(C8orf4) regulates hematopoietic stem/progenitor cells and
RT   hematopoiesis.";
RL   PLoS ONE 9:E100311-E100311(2014).
RN   [4]
RP   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. Enhances the proliferation of follicular
CC       dendritic cells. Plays a role in the mitogen-activated MAPK2/3
CC       signaling pathway, positively regulates G1-to-S-phase transition of the
CC       cell cycle. In endothelial cells, enhances key inflammatory mediators
CC       and inflammatory response through the modulation of NF-kappaB
CC       transcriptional regulatory activity. Involved in the regulation of heat
CC       shock response, seems to play a positive feedback with HSF1 to modulate
CC       heat-shock downstream gene expression (By similarity). Plays a role in
CC       the regulation of hematopoiesis even if the mechanisms are unknown
CC       (PubMed:24937306). In cancers such as thyroid or lung cancer, it has
CC       been described as promoter of cell proliferation, G1-to-S-phase
CC       transition and inhibitor of apoptosis. However, it negatively regulates
CC       self-renewal of liver cancer cells via suppresion of NOTCH2 signaling
CC       (By similarity). {ECO:0000250|UniProtKB:Q9NR00,
CC       ECO:0000269|PubMed:24937306}.
CC   -!- SUBUNIT: Monomer. Interacts with NOTCH2 (via ANK repeats), the
CC       interaction inhibits the nuclear translocation of NOTCH2 N2ICD.
CC       Interacts (C-terminus) with CBY1 (C-terminus), TCIM competes with
CC       CTNNB1 for the interaction with CBY1. {ECO:0000250|UniProtKB:Q9NR00}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24937306}. Nucleus
CC       {ECO:0000269|PubMed:24937306}. Nucleus, nucleolus
CC       {ECO:0000250|UniProtKB:Q9NR00}. Nucleus speckle
CC       {ECO:0000250|UniProtKB:Q9NR00}. Note=Localizes in nucleus speckles in
CC       presence of CBY1. Translocates to the nucleus upon cellular stress such
CC       as H(2)O(2). {ECO:0000250|UniProtKB:Q9NR00}.
CC   -!- TISSUE SPECIFICITY: Expressed in liver, expression levels decrease in
CC       regenerating liver (PubMed:25985737). In bone marrow, expressed in
CC       large progenitor-like cells, cells with ring-shaped nuclei and, at
CC       lower, levels in hematopietic stem cell-like cells with round nuclei
CC       (at protein level) (PubMed:24937306). {ECO:0000269|PubMed:24937306,
CC       ECO:0000269|PubMed:25985737}.
CC   -!- DISRUPTION PHENOTYPE: Mice have increased number of myeloid and
CC       lymphoid cells on peripheral blood compared to wild type controls. Red
CC       blood cells are small-sized but increased in number. In bone marrow,
CC       cells show higher colony forming units. {ECO:0000269|PubMed:24937306}.
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; AK007441; BAB25041.1; -; mRNA.
DR   EMBL; BC016562; AAH16562.1; -; mRNA.
DR   CCDS; CCDS22194.1; -.
DR   RefSeq; NP_081207.1; NM_026931.2.
DR   AlphaFoldDB; Q9D915; -.
DR   STRING; 10090.ENSMUSP00000058631; -.
DR   iPTMnet; Q9D915; -.
DR   PhosphoSitePlus; Q9D915; -.
DR   MaxQB; Q9D915; -.
DR   PaxDb; Q9D915; -.
DR   PRIDE; Q9D915; -.
DR   ProteomicsDB; 254834; -.
DR   Antibodypedia; 23908; 71 antibodies from 20 providers.
DR   DNASU; 69068; -.
DR   Ensembl; ENSMUST00000052622; ENSMUSP00000058631; ENSMUSG00000056313.
DR   GeneID; 69068; -.
DR   KEGG; mmu:69068; -.
DR   UCSC; uc009lex.1; mouse.
DR   CTD; 56892; -.
DR   MGI; MGI:1916318; Tcim.
DR   VEuPathDB; HostDB:ENSMUSG00000056313; -.
DR   eggNOG; ENOG502S1N0; Eukaryota.
DR   GeneTree; ENSGT00390000003458; -.
DR   HOGENOM; CLU_172922_0_0_1; -.
DR   InParanoid; Q9D915; -.
DR   OMA; ILDTDQD; -.
DR   OrthoDB; 1548471at2759; -.
DR   PhylomeDB; Q9D915; -.
DR   TreeFam; TF338287; -.
DR   BioGRID-ORCS; 69068; 2 hits in 71 CRISPR screens.
DR   ChiTaRS; Tcim; mouse.
DR   PRO; PR:Q9D915; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q9D915; protein.
DR   Bgee; ENSMUSG00000056313; Expressed in parotid gland and 200 other tissues.
DR   Genevisible; Q9D915; MM.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR   GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0005112; F:Notch binding; ISO:MGI.
DR   GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
DR   GO; GO:0002264; P:endothelial cell activation involved in immune response; ISS:UniProtKB.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0045746; P:negative regulation of Notch signaling pathway; ISS:UniProtKB.
DR   GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR   GO; GO:0010739; P:positive regulation of protein kinase A signaling; ISO:MGI.
DR   GO; GO:1900020; P:positive regulation of protein kinase C activity; ISO:MGI.
DR   GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; ISS:UniProtKB.
DR   GO; GO:0043620; P:regulation of DNA-templated transcription in response to stress; ISS:UniProtKB.
DR   GO; GO:1903706; P:regulation of hemopoiesis; IDA:MGI.
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_0000089606"
SQ   SEQUENCE   106 AA;  12215 MW;  46D87C0D259DFDB0 CRC64;
     MKAKPSHQAT SMSSSLRVSP SIHGYHFDTA ARKKAVGNIF ENIDQESLQR LFRNSGDKKA
     EERAKIIFAI DQDLEEKTRA LMALKKRTKD KLLQFLKLRK YSIKVH