TGIF2_HUMAN
ID TGIF2_HUMAN Reviewed; 237 AA.
AC Q9GZN2; B2R9U3; E1P5T9; H0YNI0;
DT 17-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Homeobox protein TGIF2;
DE AltName: Full=5'-TG-3'-interacting factor 2;
DE AltName: Full=TGF-beta-induced transcription factor 2;
DE Short=TGFB-induced factor 2;
GN Name=TGIF2;
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] (ISOFORM 1).
RC TISSUE=Ovarian carcinoma;
RX PubMed=11006116; DOI=10.1006/bbrc.2000.3449;
RA Imoto I., Pimkhaokham A., Watanabe T., Saito-Ohara F., Soeda E.,
RA Inazawa J.;
RT "Amplification and overexpression of TGIF2, a novel homeobox gene of the
RT TALE superclass, in ovarian cancer cell lines.";
RL Biochem. Biophys. Res. Commun. 276:264-270(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [7]
RP FUNCTION, PHOSPHORYLATION AT THR-182 AND THR-186, INTERACTION WITH HDAC1
RP AND SMAD3, AND MUTAGENESIS OF THR-182 AND THR-186.
RX PubMed=11427533; DOI=10.1074/jbc.m103377200;
RA Melhuish T.A., Gallo C.M., Wotton D.;
RT "TGIF2 interacts with histone deacetylase 1 and represses transcription.";
RL J. Biol. Chem. 276:32109-32114(2001).
CC -!- FUNCTION: Transcriptional repressor, which probably repress
CC transcription by binding directly the 5'-CTGTCAA-3' DNA sequence or by
CC interacting with TGF-beta activated SMAD proteins. Probably represses
CC transcription via the recruitment of histone deacetylase proteins.
CC {ECO:0000269|PubMed:11427533}.
CC -!- SUBUNIT: Interacts with the transcriptional modulator SMAD3 and the
CC histone deacetylase HDAC1. {ECO:0000269|PubMed:11427533}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Excluded from nucleoli.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9GZN2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9GZN2-2; Sequence=VSP_047346, VSP_047347;
CC -!- TISSUE SPECIFICITY: Widely expressed. Highly expressed in heart, kidney
CC and testis. Weakly expressed in brain and prostate.
CC -!- PTM: The C-terminal part is phosphorylated in response to EGF signaling
CC by the Ras/MAPK pathway. {ECO:0000269|PubMed:11427533}.
CC -!- MISCELLANEOUS: TGIF2 is amplified and overexpressed in several ovarian
CC cancer cell lines.
CC -!- SIMILARITY: Belongs to the TALE/TGIF homeobox family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BX377269; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB042646; BAB16424.1; -; mRNA.
DR EMBL; BX377269; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK074802; BAC11216.1; -; mRNA.
DR EMBL; AK313919; BAG36640.1; -; mRNA.
DR EMBL; AL050318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76127.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76128.1; -; Genomic_DNA.
DR EMBL; BC006549; AAH06549.1; -; mRNA.
DR EMBL; BC012816; AAH12816.1; -; mRNA.
DR CCDS; CCDS13278.1; -. [Q9GZN2-1]
DR PIR; JC7392; JC7392.
DR RefSeq; NP_001186442.1; NM_001199513.1. [Q9GZN2-1]
DR RefSeq; NP_001186443.1; NM_001199514.1. [Q9GZN2-1]
DR RefSeq; NP_001186444.1; NM_001199515.1. [Q9GZN2-1]
DR RefSeq; NP_068581.1; NM_021809.6. [Q9GZN2-1]
DR AlphaFoldDB; Q9GZN2; -.
DR SMR; Q9GZN2; -.
DR BioGRID; 121908; 29.
DR BioGRID; 1529332; 5.
DR IntAct; Q9GZN2; 2.
DR STRING; 9606.ENSP00000362981; -.
DR iPTMnet; Q9GZN2; -.
DR PhosphoSitePlus; Q9GZN2; -.
DR BioMuta; TGIF2; -.
DR DMDM; 27805750; -.
DR EPD; Q9GZN2; -.
DR jPOST; Q9GZN2; -.
DR MassIVE; Q9GZN2; -.
DR MaxQB; Q9GZN2; -.
DR PaxDb; Q9GZN2; -.
DR PeptideAtlas; Q9GZN2; -.
DR PRIDE; Q9GZN2; -.
DR ProteomicsDB; 80096; -. [Q9GZN2-1]
DR Antibodypedia; 26532; 351 antibodies from 33 providers.
DR DNASU; 60436; -.
DR Ensembl; ENST00000373872.9; ENSP00000362979.3; ENSG00000118707.11. [Q9GZN2-1]
DR Ensembl; ENST00000373874.6; ENSP00000362981.2; ENSG00000118707.11. [Q9GZN2-1]
DR Ensembl; ENST00000560025.1; ENSP00000453773.1; ENSG00000118707.11. [Q9GZN2-1]
DR Ensembl; ENST00000611732.4; ENSP00000481787.1; ENSG00000118707.11. [Q9GZN2-1]
DR Ensembl; ENST00000650844.1; ENSP00000498657.1; ENSG00000118707.11. [Q9GZN2-1]
DR GeneID; 60436; -.
DR KEGG; hsa:60436; -.
DR MANE-Select; ENST00000373872.9; ENSP00000362979.3; NM_021809.7; NP_068581.1.
DR UCSC; uc002xfn.4; human. [Q9GZN2-1]
DR CTD; 60436; -.
DR DisGeNET; 60436; -.
DR GeneCards; TGIF2; -.
DR HGNC; HGNC:15764; TGIF2.
DR HPA; ENSG00000118707; Low tissue specificity.
DR MIM; 607294; gene.
DR neXtProt; NX_Q9GZN2; -.
DR OpenTargets; ENSG00000118707; -.
DR PharmGKB; PA38035; -.
DR VEuPathDB; HostDB:ENSG00000118707; -.
DR eggNOG; KOG0773; Eukaryota.
DR GeneTree; ENSGT00390000004786; -.
DR GeneTree; ENSGT00940000159849; -.
DR InParanoid; Q9GZN2; -.
DR OMA; PGQGEKP; -.
DR OrthoDB; 1573375at2759; -.
DR PhylomeDB; Q9GZN2; -.
DR TreeFam; TF314558; -.
DR TreeFam; TF318093; -.
DR PathwayCommons; Q9GZN2; -.
DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR SignaLink; Q9GZN2; -.
DR BioGRID-ORCS; 60436; 25 hits in 1095 CRISPR screens.
DR GeneWiki; TGIF2; -.
DR GenomeRNAi; 60436; -.
DR Pharos; Q9GZN2; Tbio.
DR PRO; PR:Q9GZN2; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9GZN2; protein.
DR Bgee; ENSG00000118707; Expressed in ventricular zone and 165 other tissues.
DR ExpressionAtlas; Q9GZN2; baseline and differential.
DR Genevisible; Q9GZN2; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0035881; P:amacrine cell differentiation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0038092; P:nodal signaling pathway; IEA:Ensembl.
DR GO; GO:1902871; P:positive regulation of amacrine cell differentiation; IEA:Ensembl.
DR GO; GO:0010470; P:regulation of gastrulation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR008422; Homeobox_KN_domain.
DR Pfam; PF05920; Homeobox_KN; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Homeobox; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..237
FT /note="Homeobox protein TGIF2"
FT /id="PRO_0000049321"
FT DNA_BIND 16..79
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 87..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 103..237
FT /note="Repressive function"
FT REGION 172..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 182
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11427533"
FT MOD_RES 186
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11427533"
FT VAR_SEQ 65..155
FT /note="ICNWFINARRRLLPDMLRKDGKDPNQFTISRRGGKASDVALPRGSSPSVLAV
FT SVPAPTNVLSLSVCSMPLHSGQGEKPAAPFPRGELESPK -> DEFLDVIYWFRQIIAV
FT VLGVIWGVLPLRGFLGIAGFCLINAGVLYLYFSNYLQIDEEEYGGTWELTKEGFMTSFA
FT LFMVIWIIFYTAIHYD (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_047346"
FT VAR_SEQ 156..237
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_047347"
FT MUTAGEN 182
FT /note="T->V: Decrease of phosphorylation. Strong decrease
FT of phosphorylation; when associated with V-186."
FT /evidence="ECO:0000269|PubMed:11427533"
FT MUTAGEN 186
FT /note="T->V: Decrease of phosphorylation. Strong decrease
FT of phosphorylation; when associated with V-182."
FT /evidence="ECO:0000269|PubMed:11427533"
SQ SEQUENCE 237 AA; 25878 MW; E78101CF7EF12555 CRC64;
MSDSDLGEDE GLLSLAGKRK RRGNLPKESV KILRDWLYLH RYNAYPSEQE KLSLSGQTNL
SVLQICNWFI NARRRLLPDM LRKDGKDPNQ FTISRRGGKA SDVALPRGSS PSVLAVSVPA
PTNVLSLSVC SMPLHSGQGE KPAAPFPRGE LESPKPLVTP GSTLTLLTRA EAGSPTGGLF
NTPPPTPPEQ DKEDFSSFQL LVEVALQRAA EMELQKQQDP SLPLLHTPIP LVSENPQ
