TF2L1_HUMAN
ID TF2L1_HUMAN Reviewed; 479 AA.
AC Q9NZI6; Q4ZG43;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Transcription factor CP2-like protein 1;
DE AltName: Full=CP2-related transcriptional repressor 1;
DE Short=CRTR-1;
DE AltName: Full=Transcription factor LBP-9;
GN Name=TFCP2L1; Synonyms=CRTR1, LBP9;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=10644752; DOI=10.1074/jbc.275.4.2852;
RA Huang N., Miller W.L.;
RT "Cloning of factors related to HIV-inducible LBP proteins that regulate
RT steroidogenic factor-1-independent human placental transcription of the
RT cholesterol side-chain cleavage enzyme, P450scc.";
RL J. Biol. Chem. 275:2852-2858(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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.
RX PubMed=25215486; DOI=10.1016/j.cell.2014.08.029;
RA Takashima Y., Guo G., Loos R., Nichols J., Ficz G., Krueger F., Oxley D.,
RA Santos F., Clarke J., Mansfield W., Reik W., Bertone P., Smith A.;
RT "Resetting transcription factor control circuitry toward ground-state
RT pluripotency in human.";
RL Cell 158:1254-1269(2014).
RN [5]
RP FUNCTION, DOMAIN, SUBUNIT, AND MUTAGENESIS OF ASP-345.
RX PubMed=26906118; DOI=10.1007/s12010-016-2021-z;
RA Kim C.M., Jang T.H., Park H.H.;
RT "Functional analysis of CP2-like domain and SAM-like domain in TFCP2L1,
RT novel pluripotency factor of embryonic stem cells.";
RL Appl. Biochem. Biotechnol. 179:650-658(2016).
CC -!- FUNCTION: Transcription factor that facilitates establishment and
CC maintenance of pluripotency in embryonic stem cells (ESCs)
CC (PubMed:25215486, PubMed:26906118). 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 (By similarity).
CC Required for normal duct development in the salivary gland and kidney
CC (By similarity). 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 (By similarity).
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 (By similarity). Regulates also the
CC expression of JAG1 and subsequent notch signaling in the collecting
CC duct (By similarity). JAG1 initiates notch signaling in PCs but
CC inhibits notch signaling in ICs (By similarity). Acts as a
CC transcriptional suppressor that may suppress UBP1-mediated
CC transcriptional activation (By similarity). Modulates the placental
CC expression of CYP11A1 (PubMed:10644752). {ECO:0000250|UniProtKB:Q3UNW5,
CC ECO:0000269|PubMed:10644752, ECO:0000269|PubMed:25215486,
CC ECO:0000269|PubMed:26906118}.
CC -!- SUBUNIT: Forms homohexamers via its SAM-like domain (PubMed:26906118).
CC Interacts with MTA1; which is indispensable for TFCP2l1-mediated self-
CC renewal-promoting effect and endoderm-inhibiting action (By
CC similarity). {ECO:0000250|UniProtKB:Q3UNW5,
CC ECO:0000269|PubMed:26906118}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10644752}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placental JEG-3 cells and very
CC low levels of expression in non-steroidogenic cells. No expression was
CC seen in adrenal NCI-H295A cells or in adrenal tissue.
CC {ECO:0000269|PubMed:10644752}.
CC -!- DOMAIN: The Grh/CP2 DB domain is required for direct DNA-binding
CC (PubMed:26906118). The Grh/CP2 DB domain is essential to maintain the
CC undifferentiated state of embryonic stem cells (By similarity).
CC {ECO:0000250|UniProtKB:Q3UNW5, ECO:0000269|PubMed:26906118}.
CC -!- DOMAIN: The SAM-like domain is required for homohexamerization
CC (PubMed:26906118). {ECO:0000269|PubMed:26906118}.
CC -!- SIMILARITY: Belongs to the grh/CP2 family. CP2 subfamily.
CC {ECO:0000305}.
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DR EMBL; AF198488; AAF32275.1; -; mRNA.
DR EMBL; AC013399; AAX88871.1; -; Genomic_DNA.
DR EMBL; AC079988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064698; AAH64698.1; -; mRNA.
DR CCDS; CCDS2134.1; -.
DR RefSeq; NP_055368.1; NM_014553.2.
DR AlphaFoldDB; Q9NZI6; -.
DR SMR; Q9NZI6; -.
DR BioGRID; 118929; 8.
DR IntAct; Q9NZI6; 2.
DR STRING; 9606.ENSP00000263707; -.
DR iPTMnet; Q9NZI6; -.
DR PhosphoSitePlus; Q9NZI6; -.
DR BioMuta; TFCP2L1; -.
DR DMDM; 74734729; -.
DR EPD; Q9NZI6; -.
DR jPOST; Q9NZI6; -.
DR MassIVE; Q9NZI6; -.
DR MaxQB; Q9NZI6; -.
DR PaxDb; Q9NZI6; -.
DR PeptideAtlas; Q9NZI6; -.
DR PRIDE; Q9NZI6; -.
DR ProteomicsDB; 83407; -.
DR Antibodypedia; 18370; 285 antibodies from 32 providers.
DR DNASU; 29842; -.
DR Ensembl; ENST00000263707.6; ENSP00000263707.5; ENSG00000115112.8.
DR GeneID; 29842; -.
DR KEGG; hsa:29842; -.
DR MANE-Select; ENST00000263707.6; ENSP00000263707.5; NM_014553.3; NP_055368.1.
DR UCSC; uc002tmx.4; human.
DR CTD; 29842; -.
DR DisGeNET; 29842; -.
DR GeneCards; TFCP2L1; -.
DR HGNC; HGNC:17925; TFCP2L1.
DR HPA; ENSG00000115112; Tissue enhanced (kidney, salivary gland).
DR MIM; 609785; gene.
DR neXtProt; NX_Q9NZI6; -.
DR OpenTargets; ENSG00000115112; -.
DR PharmGKB; PA134980544; -.
DR VEuPathDB; HostDB:ENSG00000115112; -.
DR eggNOG; KOG4091; Eukaryota.
DR GeneTree; ENSGT00940000159158; -.
DR HOGENOM; CLU_015127_2_0_1; -.
DR InParanoid; Q9NZI6; -.
DR OMA; LVQVCGP; -.
DR OrthoDB; 386296at2759; -.
DR PhylomeDB; Q9NZI6; -.
DR TreeFam; TF314132; -.
DR PathwayCommons; Q9NZI6; -.
DR SignaLink; Q9NZI6; -.
DR BioGRID-ORCS; 29842; 12 hits in 1092 CRISPR screens.
DR ChiTaRS; TFCP2L1; human.
DR GenomeRNAi; 29842; -.
DR Pharos; Q9NZI6; Tbio.
DR PRO; PR:Q9NZI6; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NZI6; protein.
DR Bgee; ENSG00000115112; Expressed in parotid gland and 154 other tissues.
DR Genevisible; Q9NZI6; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0007028; P:cytoplasm organization; IEA:Ensembl.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0002070; P:epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045927; P:positive regulation of growth; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0007431; P:salivary gland development; IEA:Ensembl.
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_0000228006"
FT DOMAIN 43..280
FT /note="Grh/CP2 DB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01313,
FT ECO:0000305|PubMed:26906118"
FT REGION 219..245
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..365
FT /note="SAM2-like domain"
FT /evidence="ECO:0000305|PubMed:26906118"
FT REGION 271..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..244
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..287
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 345
FT /note="D->G: Impairs the formation of oligomeric homo-
FT complexes in solution."
FT /evidence="ECO:0000269|PubMed:26906118"
SQ SEQUENCE 479 AA; 54627 MW; C2D0B56D0705AE75 CRC64;
MLFWHTQPEH YNQHNSGSYL RDVLALPIFK QEEPQLSPEN EARLPPLQYV LCAATSPAVK
LHEETLTYLN QGQSYEIRLL ENRKLGDFQD LNTKYVKSII RVVFHDRRLQ YTEHQQLEGW
RWSRPGDRIL DIDIPLSVGI LDPRASPTQL NAVEFLWDPA KRASAFIQVH CISTEFTPRK
HGGEKGVPFR VQIDTFKQNE NGEYTEHLHS ASCQIKVFKP KGADRKQKTD REKMEKRTAQ
EKEKYQPSYE TTILTECSPW PDVAYQVNSA PSPSYNGSPN SFGLGEGNAS PTHPVEALPV
GSDHLLPSAS IQDAQQWLHR NRFSQFCRLF ASFSGADLLK MSRDDLVQIC GPADGIRLFN
AIKGRNVRPK MTIYVCQELE QNRVPLQQKR DGSGDSNLSV YHAIFLEELT TLELIEKIAN
LYSISPQHIH RVYRQGPTGI HVVVSNEMVQ NFQDESCFVL STIKAESNDG YHIILKCGL
