ID GT2D1_HUMAN Reviewed; 959 AA. AC Q9UHL9; O95444; Q75MX7; Q86UM3; Q8WVC4; Q9UHK8; Q9UI91; DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 21-MAR-2012, entry version 113. DE RecName: Full=General transcription factor II-I repeat domain-containing protein 1; DE Short=GTF2I repeat domain-containing protein 1; DE AltName: Full=General transcription factor III; DE AltName: Full=MusTRD1/BEN; DE AltName: Full=Muscle TFII-I repeat domain-containing protein 1; DE AltName: Full=Slow-muscle-fiber enhancer-binding protein; DE AltName: Full=USE B1-binding protein; DE AltName: Full=Williams-Beuren syndrome chromosomal region 11 protein; DE AltName: Full=Williams-Beuren syndrome chromosomal region 12 protein; GN Name=GTF2IRD1; GN Synonyms=CREAM1, GTF3, MUSTRD1, RBAP2, WBSCR11, WBSCR12; 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=Muscle; RX MEDLINE=98449952; PubMed=9774679; RA O'Mahoney J.V., Guven K.L., Lin J., Joya J.E., Robinson C.S., RA Wade R.P., Hardeman E.C.; RT "Identification of a novel slow-muscle-fiber enhancer binding protein, RT MUSTRD1."; RL Mol. Cell. Biol. 18:6641-6652(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Colon carcinoma; RX MEDLINE=99216421; PubMed=10198167; DOI=10.1006/geno.1999.5784; RA Osborne L.R., Campbell T., Daradich A., Scherer S.W., Tsui L.-C.; RT "Identification of a putative transcription factor gene (WBSCR11) that RT is commonly deleted in Williams-Beuren syndrome."; RL Genomics 57:279-284(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX MEDLINE=20037629; PubMed=10573005; DOI=10.1038/sj.ejhg.5200396; RA Tassabehji M., Carette M., Wilmot C., Donnai D., Read A.P., RA Metcalfe K.; RT "A transcription factor involved in skeletal muscle gene expression is RT deleted in patients with Williams syndrome."; RL Eur. J. Hum. Genet. 7:737-747(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT VAL-652. RX MEDLINE=20044629; PubMed=10575229; RA Franke Y., Peoples R.J., Francke U.; RT "Identification of GTF2IRD1, a putative transcription factor within RT the Williams-Beuren syndrome deletion at 7q11.23."; RL Cytogenet. Cell Genet. 86:296-304(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH RB1, RP MUTAGENESIS, AND VARIANT VAL-652. RC TISSUE=Cervix carcinoma, Fetal spleen, and Placenta; RX MEDLINE=20115113; PubMed=10642537; DOI=10.1042/0264-6021:3450749; RA Yan X., Zhao X., Qian M., Guo N., Gong X., Zhu X.; RT "Characterization and gene structure of a novel retinoblastoma- RT protein-associated protein similar to the transcription regulator RT TFII-I."; RL Biochem. J. 345:749-757(2000). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP VAL-652. RC TISSUE=Uterus; 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 FUNCTION. RX MEDLINE=21332325; PubMed=11438732; DOI=10.1073/pnas.141222298; RA Tussie-Luna M.I., Bayarsaihan D., Ruddle F.H., Roy A.L.; RT "Repression of TFII-I-dependent transcription by nuclear exclusion."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7789-7794(2001). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-654, AND MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-448, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP STRUCTURE BY NMR OF 128-203 AND 565-877. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of RSGI RUH-048 and RUH-057, a GTF2I domain in RT human."; RL Submitted (MAR-2007) to the PDB data bank. CC -!- FUNCTION: May be a transcription regulator involved in cell-cycle CC progression and skeletal muscle differentiation. May repress GTF2I CC transcriptional functions, by preventing its nuclear residency, or CC by inhibiting its transcriptional activation. May contribute to CC slow-twitch fiber type specificity during myogenesis and in CC regenerating muscles. Binds troponin I slow-muscle fiber enhancer CC (USE B1). Binds specifically and with high affinity to the EFG CC sequences derived from the early enhancer of HOXC8 (By CC similarity). CC -!- SUBUNIT: Interacts with the retinoblastoma protein (RB1) via its CC C-terminus. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UHL9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UHL9-2; Sequence=VSP_003873; CC -!- TISSUE SPECIFICITY: Highly expressed in adult skeletal muscle, CC heart, fibroblast, bone and fetal tissues. Expressed at lower CC levels in all other tissues tested. CC -!- DEVELOPMENTAL STAGE: Highly expressed in developing and CC regenerating muscles, at the time of myofiber diversification. CC -!- DOMAIN: The N-terminal half may have an activating activity. CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- DISEASE: Note=GTF2IRD1 is located in the Williams-Beuren syndrome CC (WBS) critical region. WBS results from a hemizygous deletion of CC several genes on chromosome 7q11.23, thought to arise as a CC consequence of unequal crossing over between highly homologous CC low-copy repeat sequences flanking the deleted region. CC Haploinsufficiency of GTF2IRD1 may be the cause of certain CC cardiovascular and musculo-skeletal abnormalities observed in the CC disease. CC -!- SIMILARITY: Belongs to the TFII-I family. CC -!- SIMILARITY: Contains 5 GTF2I-like repeats. 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; AF118270; AAD14687.2; -; mRNA. DR EMBL; AF104923; AAD27668.1; -; mRNA. DR EMBL; AF151354; AAF19786.1; -; mRNA. DR EMBL; AF156489; AAF17358.1; -; mRNA. DR EMBL; AF089107; AAF21796.1; -; mRNA. DR EMBL; AC004851; AAS00362.1; -; Genomic_DNA. DR EMBL; AC005231; AAP21877.1; -; Genomic_DNA. DR EMBL; BC018136; AAH18136.1; -; mRNA. DR IPI; IPI00069694; -. DR IPI; IPI00472179; -. DR RefSeq; NP_001186136.1; NM_001199207.1. DR RefSeq; NP_005676.3; NM_005685.3. DR RefSeq; NP_057412.1; NM_016328.2. DR UniGene; Hs.647056; -. DR PDB; 2D99; NMR; -; A=128-203. DR PDB; 2DN5; NMR; -; A=802-877. DR PDB; 2DZQ; NMR; -; A=565-650. DR PDB; 2DZR; NMR; -; A=705-790. DR PDBsum; 2D99; -. DR PDBsum; 2DN5; -. DR PDBsum; 2DZQ; -. DR PDBsum; 2DZR; -. DR ProteinModelPortal; Q9UHL9; -. DR SMR; Q9UHL9; 128-203, 351-431, 565-656, 702-790, 802-880. DR IntAct; Q9UHL9; 2. DR MINT; MINT-1209004; -. DR STRING; Q9UHL9; -. DR PhosphoSite; Q9UHL9; -. DR DMDM; 21263630; -. DR PRIDE; Q9UHL9; -. DR DNASU; 9569; -. DR Ensembl; ENST00000265755; ENSP00000265755; ENSG00000006704. DR GeneID; 9569; -. DR KEGG; hsa:9569; -. DR UCSC; uc003uap.1; human. DR UCSC; uc003uaq.1; human. DR CTD; 9569; -. DR GeneCards; GC07P073868; -. DR H-InvDB; HIX0006766; -. DR HGNC; HGNC:4661; GTF2IRD1. DR HPA; HPA044254; -. DR MIM; 604318; gene. DR neXtProt; NX_Q9UHL9; -. DR Orphanet; 904; Williams syndrome. DR PharmGKB; PA29047; -. DR eggNOG; NOG29608; -. DR GeneTree; ENSGT00530000063863; -. DR HOVERGEN; HBG051855; -. DR InParanoid; Q9UHL9; -. DR KO; K03121; -. DR OrthoDB; EOG4NKBV2; -. DR PhylomeDB; Q9UHL9; -. DR NextBio; 35885; -. DR ArrayExpress; Q9UHL9; -. DR Bgee; Q9UHL9; -. DR CleanEx; HS_GTF2IRD1; -. DR Genevestigator; Q9UHL9; -. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003705; F:sequence-specific distal enhancer binding RNA polymerase II transcription factor activity; NAS:UniProtKB. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR InterPro; IPR004212; GTF2I. DR InterPro; IPR016659; TF_II-I. DR Gene3D; G3DSA:3.90.1460.10; GTF2I; 5. DR Pfam; PF02946; GTF2I; 5. DR PIRSF; PIRSF016441; TF_II-I; 1. DR SUPFAM; SSF117773; SSF117773; 5. DR PROSITE; PS51139; GTF2I; 5. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Developmental protein; DNA-binding; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Transcription; KW Transcription regulation; Williams-Beuren syndrome. FT CHAIN 1 959 General transcription factor II-I repeat FT domain-containing protein 1. FT /FTId=PRO_0000083870. FT REPEAT 119 213 GTF2I-like 1. FT REPEAT 342 436 GTF2I-like 2. FT REPEAT 556 650 GTF2I-like 3. FT REPEAT 696 790 GTF2I-like 4. FT REPEAT 793 887 GTF2I-like 5. FT MOTIF 898 905 Nuclear localization signal (Potential). FT COMPBIAS 906 930 Ser-rich. FT MOD_RES 448 448 Phosphoserine. FT MOD_RES 654 654 Phosphoserine. FT VAR_SEQ 656 670 Missing (in isoform 2). FT /FTId=VSP_003873. FT VARIANT 652 652 M -> V (in dbSNP:rs2301895). FT /FTId=VAR_013446. FT MUTAGEN 898 959 Missing: Cytoplasmic localization. FT CONFLICT 111 111 G -> S (in Ref. 1; AAD14687 and 2; FT AAD27668). FT CONFLICT 378 378 R -> Q (in Ref. 5; AAF21796). FT HELIX 128 144 FT HELIX 154 159 FT TURN 161 163 FT STRAND 164 168 FT TURN 178 180 FT HELIX 183 192 FT TURN 193 195 FT STRAND 197 203 FT HELIX 565 580 FT HELIX 591 596 FT TURN 598 600 FT STRAND 601 605 FT TURN 615 617 FT HELIX 620 628 FT TURN 629 632 FT STRAND 634 638 FT HELIX 640 642 FT HELIX 705 721 FT HELIX 731 736 FT STRAND 738 745 FT HELIX 755 757 FT HELIX 760 769 FT TURN 770 772 FT STRAND 774 777 FT HELIX 802 817 FT HELIX 828 833 FT STRAND 837 842 FT STRAND 852 854 FT HELIX 857 864 FT TURN 865 869 FT STRAND 871 876 SQ SEQUENCE 959 AA; 106057 MW; 7DA3097879701540 CRC64; MALLGKRCDV PTNGCGPDRW NSAFTRKDEI ITSLVSALDS MCSALSKLNA EVACVAVHDE SAFVVGTEKG RMFLNARKEL QSDFLRFCRG PPWKDPEAEH PKKVQRGEGG GRSLPRSSLE HGSDVYLLRK MVEEVFDVLY SEALGRASVV PLPYERLLRE PGLLAVQGLP EGLAFRRPAE YDPKALMAIL EHSHRIRFKL KRPLEDGGRD SKALVELNGV SLIPKGSRDC GLHGQAPKVP PQDLPPTATS SSMASFLYST ALPNHAIREL KQEAPSCPLA PSDLGLSRPM PEPKATGAQD FSDCCGQKPT GPGGPLIQNV HASKRILFSI VHDKSEKWDA FIKETEDINT LRECVQILFN SRYAEALGLD HMVPVPYRKI ACDPEAVEIV GIPDKIPFKR PCTYGVPKLK RILEERHSIH FIIKRMFDER IFTGNKFTKD TTKLEPASPP EDTSAEVSRA TVLDLAGNAR SDKGSMSEDC GPGTSGELGG LRPIKIEPED LDIIQVTVPD PSPTSEEMTD SMPGHLPSED SGYGMEMLTD KGLSEDARPE ERPVEDSHGD VIRPLRKQVE LLFNTRYAKA IGISEPVKVP YSKFLMHPEE LFVVGLPEGI SLRRPNCFGI AKLRKILEAS NSIQFVIKRP ELLTEGVKEP IMDSQGTASS LGFSPPALPP ERDSGDPLVD ESLKRQGFQE NYDARLSRID IANTLREQVQ DLFNKKYGEA LGIKYPVQVP YKRIKSNPGS VIIEGLPPGI PFRKPCTFGS QNLERILAVA DKIKFTVTRP FQGLIPKPDE DDANRLGEKV ILREQVKELF NEKYGEALGL NRPVLVPYKL IRDSPDAVEV TGLPDDIPFR NPNTYDIHRL EKILKAREHV RMVIINQLQP FAEICNDAKV PAKDSSIPKR KRKRVSEGNS VSSSSSSSSS SSSNPDSVAS ANQISLVQWP MYMVDYAGLN VQLPGPLNY //