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   27-MAR-2024, entry version 160.
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; 9606-ENSP00000263707; -.
DR   PeptideAtlas; Q9NZI6; -.
DR   ProteomicsDB; 83407; -.
DR   Antibodypedia; 18370; 311 antibodies from 33 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   AGR; HGNC:17925; -.
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; QDESCFT; -.
DR   OrthoDB; 1363858at2759; -.
DR   PhylomeDB; Q9NZI6; -.
DR   TreeFam; TF314132; -.
DR   PathwayCommons; Q9NZI6; -.
DR   SignaLink; Q9NZI6; -.
DR   BioGRID-ORCS; 29842; 15 hits in 1172 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 156 other cell types or tissues.
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; Transcription Factor, Ets-1; 1.
DR   InterPro; IPR007604; CP2.
DR   InterPro; IPR013761; SAM/pointed_sf.
DR   InterPro; IPR041418; SAM_3.
DR   InterPro; IPR040167; TF_CP2-like.
DR   InterPro; IPR037598; TFCP2L1_SAM.
DR   PANTHER; PTHR11037; TRANSCRIPTION FACTOR CP2; 1.
DR   PANTHER; PTHR11037:SF18; TRANSCRIPTION FACTOR CP2-LIKE PROTEIN 1; 1.
DR   Pfam; PF04516; CP2; 1.
DR   Pfam; PF18016; SAM_3; 1.
DR   SUPFAM; SSF47769; SAM/Pointed domain; 1.
DR   PROSITE; PS51968; GRH_CP2_DB; 1.
DR   Genevisible; Q9NZI6; HS.
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
FT                   homo-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
//