ID TGIF1_HUMAN Reviewed; 401 AA. AC Q15583; A6NE42; A6NLU7; F8VZB6; Q6ICR0; Q8N5X9; Q9NRS0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 11-NOV-2015, entry version 169. DE RecName: Full=Homeobox protein TGIF1; DE AltName: Full=5'-TG-3'-interacting factor 1; GN Name=TGIF1; Synonyms=TGIF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Liver; RX PubMed=8537382; DOI=10.1074/jbc.270.52.31178; RA Bertolino E., Reimund B., Wildt-Perinic D., Clerc R.G.; RT "A novel homeobox protein which recognizes a TGT core and functionally RT interferes with a retinoid-responsive motif."; RL J. Biol. Chem. 270:31178-31188(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT SER-292. RC TISSUE=Brain; RX PubMed=10764806; DOI=10.1074/jbc.M908382199; RA Yang Y., Hwang C.K., D'Souza U.M., Lee S.-H., Junn E., Mouradian M.M.; RT "Three-amino acid extension loop homeodomain proteins Meis2 and TGIF RT differentially regulate transcription."; RL J. Biol. Chem. 275:20734-20741(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP SER-292. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-137 (ISOFORM 4). RC TISSUE=Brain, Placenta, and Rhabdomyosarcoma; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP STRUCTURE BY NMR OF 171-248. RG Northeast structural genomics consortium (NESG); RT "Solution NMR structure of homeobox domain (171-248) of human homeobox RT protein TGIF1, northeast structural genomics consortium target RT hr4411b."; RL Submitted (OCT-2011) to the PDB data bank. RN [9] RP VARIANTS HPE4 CYS-157; ARG-192; ALA-280 AND PHE-291. RX PubMed=10835638; DOI=10.1038/76074; RA Gripp K.W., Wotton D., Edwards M.C., Roessler E., Ades L., RA Meinecke P., Richieri-Costa A., Zackai E.H., Massague J., Muenke M., RA Elledge S.J.; RT "Mutations in TGIF cause holoprosencephaly and link NODAL signalling RT to human neural axis determination."; RL Nat. Genet. 25:205-208(2000). RN [10] RP VARIANT HPE4 LEU-236. RX PubMed=15221788; DOI=10.1002/humu.20056; RA Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., RA Le Duff F., Durou M.-R., Odent S., David V.; RT "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients RT with features of holoprosencephaly spectrum: mutation review and RT genotype-phenotype correlations."; RL Hum. Mutat. 24:43-51(2004). CC -!- FUNCTION: Binds to a retinoid X receptor (RXR) responsive element CC from the cellular retinol-binding protein II promoter (CRBPII- CC RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha CC transcription activation of the retinoic acid responsive element. CC Active transcriptional corepressor of SMAD2. Links the nodal CC signaling pathway to the bifurcation of the forebrain and the CC establishment of ventral midline structures. May participate in CC the transmission of nuclear signals during development and in the CC adult, as illustrated by the down-modulation of the RXR alpha CC activities. CC -!- SUBUNIT: Interacts with CTBP, SMAD2, SMAD3 and HDAC1. CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-714215, EBI-10171858; CC P56545:CTBP2; NbExp=5; IntAct=EBI-714215, EBI-741533; CC O00214:LGALS8; NbExp=10; IntAct=EBI-714215, EBI-740058; CC Q99750:MDFI; NbExp=4; IntAct=EBI-714215, EBI-724076; CC P29590:PML; NbExp=3; IntAct=EBI-714215, EBI-295890; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q15583-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15583-2; Sequence=VSP_013020, VSP_013021; CC Name=3; CC IsoId=Q15583-3; Sequence=VSP_043108, VSP_043109; CC Name=4; CC IsoId=Q15583-4; Sequence=VSP_046848; CC Note=No experimental confirmation available.; CC -!- DISEASE: Holoprosencephaly 4 (HPE4) [MIM:142946]: A structural CC anomaly of the brain, in which the developing forebrain fails to CC correctly separate into right and left hemispheres. CC Holoprosencephaly is genetically heterogeneous and associated with CC several distinct facies and phenotypic variability. CC {ECO:0000269|PubMed:10835638, ECO:0000269|PubMed:15221788}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the TALE/TGIF homeobox family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. 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; X89750; CAA61897.1; -; mRNA. DR EMBL; AF179900; AAF81643.1; -; mRNA. DR EMBL; CR450333; CAG29329.1; -; mRNA. DR EMBL; AK291112; BAF83801.1; -; mRNA. DR EMBL; AP001025; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471113; EAX01672.1; -; Genomic_DNA. DR EMBL; BC000814; AAH00814.1; -; mRNA. DR EMBL; BC031268; AAH31268.1; -; mRNA. DR EMBL; BE296707; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS11832.1; -. [Q15583-3] DR CCDS; CCDS11833.1; -. [Q15583-2] DR CCDS; CCDS11834.1; -. [Q15583-1] DR CCDS; CCDS11835.1; -. [Q15583-4] DR RefSeq; NP_001265611.1; NM_001278682.1. DR RefSeq; NP_001265613.1; NM_001278684.1. [Q15583-2] DR RefSeq; NP_001265615.1; NM_001278686.1. [Q15583-4] DR RefSeq; NP_003235.1; NM_003244.3. [Q15583-2] DR RefSeq; NP_733796.2; NM_170695.3. [Q15583-1] DR RefSeq; NP_775299.1; NM_173207.2. [Q15583-3] DR RefSeq; NP_775300.1; NM_173208.2. [Q15583-2] DR RefSeq; NP_775301.1; NM_173209.2. [Q15583-4] DR RefSeq; NP_775302.1; NM_173210.2. [Q15583-4] DR RefSeq; NP_775303.1; NM_173211.1. [Q15583-4] DR RefSeq; NP_777480.1; NM_174886.2. [Q15583-4] DR RefSeq; XP_011524037.1; XM_011525735.1. [Q15583-4] DR UniGene; Hs.373550; -. DR PDB; 2LK2; NMR; -; A=171-248. DR PDBsum; 2LK2; -. DR ProteinModelPortal; Q15583; -. DR SMR; Q15583; 171-248. DR BioGrid; 112908; 21. DR IntAct; Q15583; 9. DR MINT; MINT-145985; -. DR STRING; 9606.ENSP00000327959; -. DR PhosphoSite; Q15583; -. DR BioMuta; TGIF1; -. DR DMDM; 215274200; -. DR MaxQB; Q15583; -. DR PaxDb; Q15583; -. DR PRIDE; Q15583; -. DR Ensembl; ENST00000330513; ENSP00000327959; ENSG00000177426. [Q15583-1] DR Ensembl; ENST00000343820; ENSP00000339631; ENSG00000177426. [Q15583-2] DR Ensembl; ENST00000345133; ENSP00000343969; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000400167; ENSP00000383031; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000401449; ENSP00000385206; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000405385; ENSP00000384970; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000407501; ENSP00000384133; ENSG00000177426. [Q15583-2] DR Ensembl; ENST00000472042; ENSP00000449501; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000548489; ENSP00000447747; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000551541; ENSP00000450025; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000618001; ENSP00000483499; ENSG00000177426. [Q15583-3] DR GeneID; 7050; -. DR KEGG; hsa:7050; -. DR UCSC; uc002klu.3; human. [Q15583-1] DR UCSC; uc002klv.3; human. [Q15583-3] DR UCSC; uc002klw.3; human. [Q15583-2] DR CTD; 7050; -. DR GeneCards; TGIF1; -. DR GeneReviews; TGIF1; -. DR H-InvDB; HIX0174209; -. DR HGNC; HGNC:11776; TGIF1. DR HPA; CAB004596; -. DR HPA; HPA062160; -. DR MIM; 142946; phenotype. DR MIM; 602630; gene. DR neXtProt; NX_Q15583; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR Orphanet; 93924; Lobar holoprosencephaly. DR Orphanet; 280200; Microform holoprosencephaly. DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly. DR Orphanet; 220386; Semilobar holoprosencephaly. DR Orphanet; 280195; Septopreoptic holoprosencephaly. DR PharmGKB; PA36489; -. DR eggNOG; KOG0773; Eukaryota. DR eggNOG; ENOG410XPMQ; LUCA. DR GeneTree; ENSGT00550000074260; -. DR HOGENOM; HOG000232039; -. DR HOVERGEN; HBG001143; -. DR InParanoid; Q15583; -. DR KO; K19383; -. DR OMA; IAANNFT; -. DR PhylomeDB; Q15583; -. DR TreeFam; TF318093; -. 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; Q15583; -. DR EvolutionaryTrace; Q15583; -. DR GeneWiki; Homeobox_protein_TGIF1; -. DR GenomeRNAi; 7050; -. DR NextBio; 27551; -. DR PRO; PR:Q15583; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; Q15583; -. DR CleanEx; HS_TGIF1; -. DR ExpressionAtlas; Q15583; baseline and differential. DR Genevisible; Q15583; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0038092; P:nodal signaling pathway; IEA:Ensembl. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0010470; P:regulation of gastrulation; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; TAS:Reactome. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR008422; Homeobox_KN_domain. DR InterPro; IPR009057; Homeodomain-like. 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 3D-structure; Alternative splicing; Complete proteome; KW Disease mutation; DNA-binding; Holoprosencephaly; Homeobox; Nucleus; KW Polymorphism; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 401 Homeobox protein TGIF1. FT /FTId=PRO_0000049318. FT DNA_BIND 164 226 Homeobox; TALE-type. FT {ECO:0000255|PROSITE-ProRule:PRU00108}. FT MOTIF 153 157 CTBP-binding motif. FT COMPBIAS 165 168 Poly-Arg. FT VAR_SEQ 1 149 Missing (in isoform 4). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_046848. FT VAR_SEQ 1 129 Missing (in isoform 2). FT {ECO:0000303|PubMed:10764806, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8537382, FT ECO:0000303|Ref.3}. FT /FTId=VSP_013020. FT VAR_SEQ 1 115 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043108. FT VAR_SEQ 116 134 PSQGAQGPAPRRRLLETMK -> MTCSGKSCALARSSLTSS FT Q (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043109. FT VAR_SEQ 130 133 LETM -> MKGK (in isoform 2). FT {ECO:0000303|PubMed:10764806, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8537382, FT ECO:0000303|Ref.3}. FT /FTId=VSP_013021. FT VARIANT 157 157 S -> C (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009961. FT VARIANT 192 192 P -> R (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009962. FT VARIANT 236 236 Q -> L (in HPE4). FT {ECO:0000269|PubMed:15221788}. FT /FTId=VAR_023803. FT VARIANT 280 280 T -> A (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009963. FT VARIANT 289 289 P -> S (in dbSNP:rs11571512). FT /FTId=VAR_047363. FT VARIANT 291 291 S -> F (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009964. FT VARIANT 292 292 P -> L (in dbSNP:rs2229333). FT /FTId=VAR_020151. FT VARIANT 292 292 P -> S (in dbSNP:rs4468717). FT {ECO:0000269|PubMed:10764806, FT ECO:0000269|Ref.3}. FT /FTId=VAR_061268. FT CONFLICT 96 96 P -> Q (in Ref. 7; AAH31268). FT {ECO:0000305}. FT HELIX 173 185 {ECO:0000244|PDB:2LK2}. FT HELIX 188 190 {ECO:0000244|PDB:2LK2}. FT HELIX 194 203 {ECO:0000244|PDB:2LK2}. FT STRAND 204 206 {ECO:0000244|PDB:2LK2}. FT HELIX 208 230 {ECO:0000244|PDB:2LK2}. SQ SEQUENCE 401 AA; 43013 MW; 4D9C76AFB37A29F0 CRC64; MVLAQSRVSA GVGSPHCSGS GGGGSDSFPW PASHPGNPQC SFSTAFLASP RLSRGTLAYL PPAPWSSLAT PSALLGSSCA PPPPPARCPQ PRALSPELGT KAGPRRPHRW ELPRSPSQGA QGPAPRRRLL ETMKGIVAAS GSETEDEDSM DIPLDLSSSA GSGKRRRRGN LPKESVQILR DWLYEHRYNA YPSEQEKALL SQQTHLSTLQ VCNWFINARR RLLPDMLRKD GKDPNQFTIS RRGAKISETS SVESVMGIKN FMPALEETPF HSCTAGPNPT LGRPLSPKPS SPGSVLARPS VICHTTVTAL KDVPFSLCQS VGVGQNTDIQ QIAAKNFTDT SLMYPEDTCK SGPSTNTQSG LFNTPPPTPP DLNQDFSGFQ LLVDVALKRA AEMELQAKLT A //