TF2L1_MOUSE
ID TF2L1_MOUSE Reviewed; 479 AA.
AC Q3UNW5; Q14AW3; Q99PF2;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Transcription factor CP2-like protein 1;
DE AltName: Full=CP2-related transcriptional repressor 1;
DE Short=CRTR-1;
GN Name=Tfcp2l1; Synonyms=Crtr1, Tcfcp2l1;
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 [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=129/Ola;
RX PubMed=11073954; DOI=10.1074/jbc.m008167200;
RA Rodda S., Sharma S., Scherer M., Chapman G., Rathjen P.;
RT "CRTR-1, a developmentally regulated transcriptional repressor related to
RT the CP2 family of transcription factors.";
RL J. Biol. Chem. 276:3324-3332(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=17079272; DOI=10.1242/dev.02658;
RA Yamaguchi Y., Yonemura S., Takada S.;
RT "Grainyhead-related transcription factor is required for duct maturation in
RT the salivary gland and the kidney of the mouse.";
RL Development 133:4737-4748(2006).
RN [7]
RP FUNCTION.
RX PubMed=23942238; DOI=10.1038/emboj.2013.175;
RA Ye S., Li P., Tong C., Ying Q.L.;
RT "Embryonic stem cell self-renewal pathways converge on the transcription
RT factor Tfcp2l1.";
RL EMBO J. 32:2548-2560(2013).
RN [8]
RP FUNCTION.
RX PubMed=23942233; DOI=10.1038/emboj.2013.177;
RA Martello G., Bertone P., Smith A.;
RT "Identification of the missing pluripotency mediator downstream of
RT leukaemia inhibitory factor.";
RL EMBO J. 32:2561-2574(2013).
RN [9]
RP FUNCTION.
RX PubMed=26321140; DOI=10.1016/j.stemcr.2015.07.014;
RA Qiu D., Ye S., Ruiz B., Zhou X., Liu D., Zhang Q., Ying Q.L.;
RT "Klf2 and Tfcp2l1, two Wnt/beta-catenin targets, act synergistically to
RT induce and maintain naive pluripotency.";
RL Stem Cell Reports 5:314-322(2015).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=28577314; DOI=10.7554/elife.24265;
RA Werth M., Schmidt-Ott K.M., Leete T., Qiu A., Hinze C., Viltard M.,
RA Paragas N., Shawber C.J., Yu W., Lee P., Chen X., Sarkar A., Mu W.,
RA Rittenberg A., Lin C.S., Kitajewski J., Al-Awqati Q., Barasch J.;
RT "Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting
RT ducts.";
RL Elife 6:0-0(2017).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, DOMAIN, AND INTERACTION WITH MTA1.
RX PubMed=28982712; DOI=10.1242/jcs.206532;
RA Liu K., Zhang Y., Liu D., Ying Q.L., Ye S.;
RT "Tfcp2l1 represses multiple lineage commitment of mouse embryonic stem
RT cells through MTA1 and LEF1.";
RL J. Cell Sci. 130:3809-3817(2017).
CC -!- FUNCTION: Transcription factor that facilitates establishment and
CC maintenance of pluripotency in embryonic stem cells (ESCs)
CC (PubMed:23942233, PubMed:26321140). With Klf2, acts as the major
CC effector of self-renewal that mediates induction of pluripotency
CC downstream of LIF/Stat3 and Wnt/beta-catenin signaling
CC (PubMed:23942238, PubMed:23942233, PubMed:26321140). Required for
CC normal duct development in the salivary gland and kidney
CC (PubMed:17079272). Coordinates the development of the kidney collecting
CC ducts intercalated (IC) and principal (PC) cells, which regulate acid-
CC base and salt-water homeostasis, respectively (PubMed:28577314).
CC Regulates the expression of IC genes including subunits B1 and D2 of
CC the V-ATPase complex, Oxgr1, Ca12, Slc4a1, Aqp6 and IC-specific
CC transcription factor Foxi1 (PubMed:28577314). Regulates also the
CC expression of Jag1 and subsequent notch signaling in the collecting
CC duct (PubMed:28577314). Jag1 initiates notch signaling in PCs but
CC inhibits notch signaling in ICs (PubMed:28577314). Acts as a
CC transcriptional suppressor that may suppress UBP1-mediated
CC transcriptional activation (PubMed:11073954). Modulates the placental
CC expression of CYP11A1 (By similarity). {ECO:0000250|UniProtKB:Q9NZI6,
CC ECO:0000269|PubMed:11073954, ECO:0000269|PubMed:17079272,
CC ECO:0000269|PubMed:23942233, ECO:0000269|PubMed:23942238,
CC ECO:0000269|PubMed:26321140, ECO:0000269|PubMed:28577314}.
CC -!- SUBUNIT: Forms homohexamers via its SAM-like domain (By similarity).
CC Interacts with Mta1; which is indispensable for Tfcp2l1-mediated self-
CC renewal-promoting effect and endoderm-inhibiting action
CC (PubMed:28982712). {ECO:0000250|UniProtKB:Q9NZI6,
CC ECO:0000269|PubMed:28982712}.
CC -!- INTERACTION:
CC Q3UNW5; Q61539: Esrrb; NbExp=4; IntAct=EBI-5691372, EBI-2312731;
CC Q3UNW5; Q9ERA0: Tfcp2; NbExp=3; IntAct=EBI-5691372, EBI-5717242;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28577314}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, testis, small
CC intestine, kidney and stomach (PubMed:11073954, PubMed:17079272). Low
CC levels of expression in lung, mesenteric lymph nodes, muscle, ovary,
CC and thymus (PubMed:11073954). No expression was detected in brain,
CC heart, liver, and spleen (PubMed:11073954). Expressed in eccrine glands
CC in the palm (PubMed:11073954). Expression is prominent in both kidney
CC collecting ducts intercalated (IC) and principal (PC) cells
CC (PubMed:28577314). Also expressed in the thick limb of Henle and
CC connecting segments of the nephron (PubMed:28577314).
CC {ECO:0000269|PubMed:11073954, ECO:0000269|PubMed:17079272,
CC ECO:0000269|PubMed:28577314}.
CC -!- DEVELOPMENTAL STAGE: Expressed at low levels in 10.5- and 11.5-dpc
CC embryos. Expression was not detected at 12.5- and 13.5-dpc. Highly
CC expressed in the epithelial monolayer lining in a subset of tubules of
CC embryonic kidney cortex. Low levels of expression were detected in
CC 16.5-dpc embryonic intestine, limb, lung, and skin. No expression was
CC detected in the brain. Expression is regulated in at least two distinct
CC sites, the pluripotent cells of the developing embryo and the
CC epithelial cells lining the embryonic kidney distal convoluted tubules.
CC Expressed in the ducts of submandibular and sublingual glands, isolated
CC submandibular gland, parotid and lachrymal glands and nasal gland in 16
CC dpc embryos. At birth, the expression is detected in minor nasal glands
CC in the olfactory epithelium, ducts of the mammary gland, male
CC reproductive system, endolymphatic sac and lung. Expressed during renal
CC development; first detected in the ureteric epithelium, at the distal
CC end of the S-shaped body in nephron and subsequently in all nephric
CC tubule, with expression localizing to more distal regions in the
CC nephron during the maturation of the kidney.
CC {ECO:0000269|PubMed:11073954, ECO:0000269|PubMed:17079272}.
CC -!- DOMAIN: The Grh/CP2 DB domain is required for direct DNA-binding (By
CC similarity). The Grh/CP2 DB domain is essential to maintain the
CC undifferentiated state of embryonic stem cells (PubMed:28982712).
CC {ECO:0000250|UniProtKB:Q9NZI6, ECO:0000269|PubMed:28982712}.
CC -!- DOMAIN: The SAM-like domain is required for homohexamerization (By
CC similarity). {ECO:0000250|UniProtKB:Q9NZI6}.
CC -!- DISRUPTION PHENOTYPE: Approximately half of the mutant mice die before
CC weaning and show growth retardation during early postnatal stages. Mice
CC display defects in the morphology of the submandibular ducts,
CC abnormalities in the maturation of renal tubules and abnormal
CC composition of saliva and urine (PubMed:17079272). Leads to a decrease
CC in the expression of pluripotency genes (Nanog, Oct4, Sox2 and Esrrb),
CC while resulted in up-regulation of some endoderm (Sox17, Gata4 and
CC Gata6), mesoderm (T and Mixl1) and trophectoderm (Cdx2, Eomes, and
CC Elf5) markers (PubMed:28982712). {ECO:0000269|PubMed:17079272,
CC ECO:0000269|PubMed:28982712}.
CC -!- SIMILARITY: Belongs to the grh/CP2 family. CP2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF311309; AAK01150.1; -; mRNA.
DR EMBL; AK143960; BAE25632.1; -; mRNA.
DR EMBL; AC109271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109294; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466520; EDL39825.1; -; Genomic_DNA.
DR EMBL; BC116663; AAI16664.1; -; mRNA.
DR CCDS; CCDS35691.1; -.
DR RefSeq; NP_076244.2; NM_023755.2.
DR AlphaFoldDB; Q3UNW5; -.
DR SMR; Q3UNW5; -.
DR BioGRID; 219895; 92.
DR IntAct; Q3UNW5; 138.
DR MINT; Q3UNW5; -.
DR STRING; 10090.ENSMUSP00000027629; -.
DR iPTMnet; Q3UNW5; -.
DR PhosphoSitePlus; Q3UNW5; -.
DR MaxQB; Q3UNW5; -.
DR PaxDb; Q3UNW5; -.
DR PeptideAtlas; Q3UNW5; -.
DR PRIDE; Q3UNW5; -.
DR ProteomicsDB; 259013; -.
DR Antibodypedia; 18370; 285 antibodies from 32 providers.
DR DNASU; 81879; -.
DR Ensembl; ENSMUST00000027629; ENSMUSP00000027629; ENSMUSG00000026380.
DR GeneID; 81879; -.
DR KEGG; mmu:81879; -.
DR UCSC; uc007cil.1; mouse.
DR CTD; 29842; -.
DR MGI; MGI:2444691; Tfcp2l1.
DR VEuPathDB; HostDB:ENSMUSG00000026380; -.
DR eggNOG; KOG4091; Eukaryota.
DR GeneTree; ENSGT00940000159158; -.
DR HOGENOM; CLU_015127_2_0_1; -.
DR InParanoid; Q3UNW5; -.
DR OMA; LVQVCGP; -.
DR OrthoDB; 386296at2759; -.
DR PhylomeDB; Q3UNW5; -.
DR TreeFam; TF314132; -.
DR BioGRID-ORCS; 81879; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Tfcp2l1; mouse.
DR PRO; PR:Q3UNW5; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q3UNW5; protein.
DR Bgee; ENSMUSG00000026380; Expressed in submandibular gland and 136 other tissues.
DR Genevisible; Q3UNW5; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; ISA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IC:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000902; P:cell morphogenesis; IMP:MGI.
DR GO; GO:0007028; P:cytoplasm organization; IMP:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR GO; GO:0002070; P:epithelial cell maturation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045927; P:positive regulation of growth; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0007431; P:salivary gland development; IMP:MGI.
DR CDD; cd09590; SAM_LBP9; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR007604; CP2.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR041418; SAM_3.
DR InterPro; IPR037598; TFCP2L1_SAM.
DR Pfam; PF04516; CP2; 1.
DR Pfam; PF18016; SAM_3; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR PROSITE; PS51968; GRH_CP2_DB; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..479
FT /note="Transcription factor CP2-like protein 1"
FT /id="PRO_0000228007"
FT DOMAIN 43..280
FT /note="Grh/CP2 DB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01313"
FT REGION 1..52
FT /note="Mediate transcriptional repression"
FT REGION 219..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..365
FT /note="SAM2-like domain"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI6"
FT COMPBIAS 219..244
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 60
FT /note="K -> R (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="T -> A (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 201..212
FT /note="SGDYSEHLHSAS -> KWGLLGASTLLPA (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 217
FT /note="V -> G (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 220..227
FT /note="PKGADRKQ -> AQGELIGNK (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 269..270
FT /note="NT -> TP (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="N -> T (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="N -> I (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="Missing (in Ref. 2; BAE25632)"
FT /evidence="ECO:0000305"
FT CONFLICT 468
FT /note="N -> S (in Ref. 1; AAK01150)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 479 AA; 54737 MW; 4765C41F5ECCB8C6 CRC64;
MLFWHTQPEH YNQHNSGSYL RDVLALPIFK QEEPQLSPEN GARLPPLQYV LCAATSPAVK
LHEETLTYLN QGQSYEIRLL ENRKLGDFQD LNTKYVKSII RVVFHDRRLQ YTEYQQLEGW
RWSRPGDRIL DIDIPLSVGI LDPRASPTQL NAVEFLWDPS KRASAFIQVH CISTEFTPRK
HGGEKGVPFR VQIDTFKQNE SGDYSEHLHS ASCQIKVFKP KGADRKQKTD REKMEKRTAQ
EKEKYQPSYE TTILTECSPW PDVPYQANNT PSPSYNGSPN SFGLREGNSS PNHPVEPLPL
GSDHLLPSAS IQDAQQWLHR NRFSQFCWLF ASFSGADLLK MSRDDLVQVC GPADGIRLFN
AIKGRNVRPK MTIYVCQELE QNQLPLPQKQ DDSGDNSLCV YHAIFLEELT TLELTEKIAS
LYSIPPQHIH RVYRQGPAGI HVVVSNEMVQ NFQDESCFIL STLKAESNDG YHIILKCGL
