TBR1_HUMAN
ID TBR1_HUMAN Reviewed; 682 AA.
AC Q16650; B0AZS4; B2R6G5; Q14DC5; Q53TH0; Q56A81;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=T-box brain protein 1;
DE Short=T-brain-1;
DE Short=TBR-1;
DE AltName: Full=TES-56;
GN Name=TBR1;
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=Fetal brain;
RX PubMed=7619531; DOI=10.1016/0896-6273(95)90065-9;
RA Bulfone A., Smiga S.M., Shimamura K., Peterson A., Puelles L.,
RA Rubenstein J.L.R.;
RT "T-brain-1: a homolog of Brachyury whose expression defines molecularly
RT distinct domains within the cerebral cortex.";
RL Neuron 15:63-78(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, HOMODIMERIZATION, INTERACTION WITH FOXP2,
RP INVOLVEMENT IN IDDAS, VARIANTS IDDAS GLU-178; GLU-228; ARG-418 AND ARG-542,
RP AND CHARACTERIZATION OF VARIANTS IDDAS GLU-178; GLU-228; MET-356; HIS-374;
RP ARG-418 AND ARG-542.
RX PubMed=25232744; DOI=10.1038/ncomms5954;
RA Deriziotis P., O'Roak B.J., Graham S.A., Estruch S.B., Dimitropoulou D.,
RA Bernier R.A., Gerdts J., Shendure J., Eichler E.E., Fisher S.E.;
RT "De novo TBR1 mutations in sporadic autism disrupt protein functions.";
RL Nat. Commun. 5:4954-4954(2014).
RN [6]
RP INVOLVEMENT IN IDDAS.
RX PubMed=30268909; DOI=10.1016/j.ejmg.2018.09.012;
RA Vegas N., Cavallin M., Kleefstra T., de Boer L., Philbert M., Maillard C.,
RA Boddaert N., Munnich A., Hubert L., Bery A., Besmond C., Bahi-Buisson N.;
RT "Mutations in TBR1 gene leads to cortical malformations and intellectual
RT disability.";
RL Eur. J. Med. Genet. 61:759-764(2018).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FOXP1; FOXP2 AND BCL11A,
RP CHARACTERIZATION OF VARIANTS IDDAS GLU-228; ARG-271; CYS-271; MET-356;
RP HIS-374; GLU-389; ARG-418 AND ARG-542, AND MUTAGENESIS OF 394-ASN--SER-682
RP AND 568-SER--SER-682.
RX PubMed=30250039; DOI=10.1038/s41598-018-32053-6;
RA den Hoed J., Sollis E., Venselaar H., Estruch S.B., Deriziotis P.,
RA Fisher S.E.;
RT "Functional characterization of TBR1 variants in neurodevelopmental
RT disorder.";
RL Sci. Rep. 8:14279-14279(2018).
RN [8]
RP VARIANT IDDAS MET-356.
RX PubMed=14593429; DOI=10.1038/sj.mp.4001340;
RG International Molecular Genetic Study of Autism Consortium (IMGSAC);
RA Bacchelli E., Blasi F., Biondolillo M., Lamb J.A., Bonora E., Barnby G.,
RA Parr J., Beyer K.S., Klauck S.M., Poustka A., Bailey A.J., Monaco A.P.,
RA Maestrini E.;
RT "Screening of nine candidate genes for autism on chromosome 2q reveals rare
RT nonsynonymous variants in the cAMP-GEFII gene.";
RL Mol. Psychiatry 8:916-924(2003).
RN [9]
RP VARIANT IDDAS HIS-374.
RX PubMed=22495311; DOI=10.1038/nature11011;
RA Neale B.M., Kou Y., Liu L., Ma'ayan A., Samocha K.E., Sabo A., Lin C.F.,
RA Stevens C., Wang L.S., Makarov V., Polak P., Yoon S., Maguire J.,
RA Crawford E.L., Campbell N.G., Geller E.T., Valladares O., Schafer C.,
RA Liu H., Zhao T., Cai G., Lihm J., Dannenfelser R., Jabado O., Peralta Z.,
RA Nagaswamy U., Muzny D., Reid J.G., Newsham I., Wu Y., Lewis L., Han Y.,
RA Voight B.F., Lim E., Rossin E., Kirby A., Flannick J., Fromer M.,
RA Shakir K., Fennell T., Garimella K., Banks E., Poplin R., Gabriel S.,
RA DePristo M., Wimbish J.R., Boone B.E., Levy S.E., Betancur C., Sunyaev S.,
RA Boerwinkle E., Buxbaum J.D., Cook E.H. Jr., Devlin B., Gibbs R.A.,
RA Roeder K., Schellenberg G.D., Sutcliffe J.S., Daly M.J.;
RT "Patterns and rates of exonic de novo mutations in autism spectrum
RT disorders.";
RL Nature 485:242-245(2012).
RN [10]
RP VARIANT IDDAS GLU-228.
RX PubMed=23160955; DOI=10.1126/science.1227764;
RA O'Roak B.J., Vives L., Fu W., Egertson J.D., Stanaway I.B., Phelps I.G.,
RA Carvill G., Kumar A., Lee C., Ankenman K., Munson J., Hiatt J.B.,
RA Turner E.H., Levy R., O'Day D.R., Krumm N., Coe B.P., Martin B.K.,
RA Borenstein E., Nickerson D.A., Mefford H.C., Doherty D., Akey J.M.,
RA Bernier R., Eichler E.E., Shendure J.;
RT "Multiplex targeted sequencing identifies recurrently mutated genes in
RT autism spectrum disorders.";
RL Science 338:1619-1622(2012).
RN [11]
RP VARIANTS IDDAS GLU-228; CYS-271; HIS-374 AND GLU-389.
RX PubMed=25418537; DOI=10.1038/ncomms6595;
RA O'Roak B.J., Stessman H.A., Boyle E.A., Witherspoon K.T., Martin B.,
RA Lee C., Vives L., Baker C., Hiatt J.B., Nickerson D.A., Bernier R.,
RA Shendure J., Eichler E.E.;
RT "Recurrent de novo mutations implicate novel genes underlying simplex
RT autism risk.";
RL Nat. Commun. 5:5595-5595(2014).
RN [12]
RP VARIANT IDDAS CYS-271.
RX PubMed=25363760; DOI=10.1038/nature13772;
RG DDD Study;
RG Homozygosity Mapping Collaborative for Autism;
RG UK10K Consortium;
RA De Rubeis S., He X., Goldberg A.P., Poultney C.S., Samocha K., Cicek A.E.,
RA Kou Y., Liu L., Fromer M., Walker S., Singh T., Klei L., Kosmicki J.,
RA Shih-Chen F., Aleksic B., Biscaldi M., Bolton P.F., Brownfeld J.M., Cai J.,
RA Campbell N.G., Carracedo A., Chahrour M.H., Chiocchetti A.G., Coon H.,
RA Crawford E.L., Curran S.R., Dawson G., Duketis E., Fernandez B.A.,
RA Gallagher L., Geller E., Guter S.J., Hill R.S., Ionita-Laza J.,
RA Jimenz Gonzalez P., Kilpinen H., Klauck S.M., Kolevzon A., Lee I., Lei I.,
RA Lei J., Lehtimaeki T., Lin C.F., Ma'ayan A., Marshall C.R., McInnes A.L.,
RA Neale B., Owen M.J., Ozaki N., Parellada M., Parr J.R., Purcell S.,
RA Puura K., Rajagopalan D., Rehnstroem K., Reichenberg A., Sabo A.,
RA Sachse M., Sanders S.J., Schafer C., Schulte-Ruether M., Skuse D.,
RA Stevens C., Szatmari P., Tammimies K., Valladares O., Voran A., Li-San W.,
RA Weiss L.A., Willsey A.J., Yu T.W., Yuen R.K., Cook E.H., Freitag C.M.,
RA Gill M., Hultman C.M., Lehner T., Palotie A., Schellenberg G.D., Sklar P.,
RA State M.W., Sutcliffe J.S., Walsh C.A., Scherer S.W., Zwick M.E.,
RA Barett J.C., Cutler D.J., Roeder K., Devlin B., Daly M.J., Buxbaum J.D.;
RT "Synaptic, transcriptional and chromatin genes disrupted in autism.";
RL Nature 515:209-215(2014).
RN [13]
RP VARIANT IDDAS ARG-271.
RX PubMed=25356899; DOI=10.1371/journal.pgen.1004772;
RA Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L.,
RA Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E.,
RA Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S.,
RA Rouleau G.A., Michaud J.L.;
RT "De novo mutations in moderate or severe intellectual disability.";
RL PLoS Genet. 10:E1004772-E1004772(2014).
CC -!- FUNCTION: Transcriptional repressor involved in multiple aspects of
CC cortical development, including neuronal migration, laminar and areal
CC identity, and axonal projection (PubMed:25232744, PubMed:30250039). As
CC transcriptional repressor of FEZF2, it blocks the formation of the
CC corticospinal (CS) tract from layer 6 projection neurons, thereby
CC restricting the origin of CS axons specifically to layer 5 neurons (By
CC similarity). {ECO:0000250|UniProtKB:Q64336,
CC ECO:0000269|PubMed:25232744, ECO:0000269|PubMed:30250039}.
CC -!- SUBUNIT: Homodimer (PubMed:25232744). Part of a complex containing
CC CASK, TBR1 and TSPYL2; may modulate gene expression in response to
CC neuronal synaptic activity (By similarity). Interacts with FOXP2
CC (PubMed:25232744, PubMed:30250039). Interacts with FOXP1
CC (PubMed:30250039). Interacts with BCL11A (PubMed:30250039).
CC {ECO:0000250|UniProtKB:Q64336, ECO:0000269|PubMed:25232744,
CC ECO:0000269|PubMed:30250039}.
CC -!- INTERACTION:
CC Q16650; P05067: APP; NbExp=3; IntAct=EBI-1047158, EBI-77613;
CC Q16650; P05067-2: APP; NbExp=3; IntAct=EBI-1047158, EBI-17264467;
CC Q16650; P54253: ATXN1; NbExp=7; IntAct=EBI-1047158, EBI-930964;
CC Q16650; P42858: HTT; NbExp=12; IntAct=EBI-1047158, EBI-466029;
CC Q16650; O60260-5: PRKN; NbExp=6; IntAct=EBI-1047158, EBI-21251460;
CC Q16650; P37840: SNCA; NbExp=3; IntAct=EBI-1047158, EBI-985879;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25232744,
CC ECO:0000269|PubMed:30250039}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16650-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16650-2; Sequence=VSP_056591;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DISEASE: Intellectual developmental disorder with autism and speech
CC delay (IDDAS) [MIM:606053]: An autosomal dominant neurodevelopmental
CC disorder characterized by varying degrees of intellectual disability,
CC autism spectrum disorder, and language deficits.
CC {ECO:0000269|PubMed:14593429, ECO:0000269|PubMed:22495311,
CC ECO:0000269|PubMed:23160955, ECO:0000269|PubMed:25232744,
CC ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:25363760,
CC ECO:0000269|PubMed:25418537, ECO:0000269|PubMed:30250039}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; U49250; AAA92010.1; -; mRNA.
DR EMBL; AK297438; BAH12582.1; -; mRNA.
DR EMBL; AK312567; BAG35462.1; -; mRNA.
DR EMBL; AK315865; BAF98756.1; -; mRNA.
DR EMBL; AK316161; BAH14532.1; -; mRNA.
DR EMBL; AC009487; AAY15017.1; -; Genomic_DNA.
DR EMBL; BC029289; AAH29289.1; -; mRNA.
DR EMBL; BC104844; AAI04845.1; -; mRNA.
DR EMBL; BC113418; AAI13419.1; -; mRNA.
DR CCDS; CCDS33310.1; -. [Q16650-1]
DR RefSeq; NP_006584.1; NM_006593.3. [Q16650-1]
DR AlphaFoldDB; Q16650; -.
DR SMR; Q16650; -.
DR BioGRID; 115942; 111.
DR IntAct; Q16650; 94.
DR MINT; Q16650; -.
DR STRING; 9606.ENSP00000374205; -.
DR GlyGen; Q16650; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q16650; -.
DR PhosphoSitePlus; Q16650; -.
DR BioMuta; TBR1; -.
DR DMDM; 2501122; -.
DR jPOST; Q16650; -.
DR MassIVE; Q16650; -.
DR PaxDb; Q16650; -.
DR PeptideAtlas; Q16650; -.
DR PRIDE; Q16650; -.
DR ProteomicsDB; 2534; -.
DR ProteomicsDB; 61001; -. [Q16650-1]
DR Antibodypedia; 35331; 201 antibodies from 32 providers.
DR DNASU; 10716; -.
DR Ensembl; ENST00000389554.8; ENSP00000374205.3; ENSG00000136535.15. [Q16650-1]
DR Ensembl; ENST00000410035.1; ENSP00000387023.1; ENSG00000136535.15. [Q16650-2]
DR GeneID; 10716; -.
DR KEGG; hsa:10716; -.
DR MANE-Select; ENST00000389554.8; ENSP00000374205.3; NM_006593.4; NP_006584.1.
DR UCSC; uc002ubw.2; human. [Q16650-1]
DR CTD; 10716; -.
DR DisGeNET; 10716; -.
DR GeneCards; TBR1; -.
DR HGNC; HGNC:11590; TBR1.
DR HPA; ENSG00000136535; Tissue enriched (brain).
DR MalaCards; TBR1; -.
DR MIM; 604616; gene.
DR MIM; 606053; phenotype.
DR neXtProt; NX_Q16650; -.
DR OpenTargets; ENSG00000136535; -.
DR Orphanet; 1617; 2q24 microdeletion syndrome.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA36354; -.
DR VEuPathDB; HostDB:ENSG00000136535; -.
DR eggNOG; KOG3585; Eukaryota.
DR GeneTree; ENSGT00940000156994; -.
DR HOGENOM; CLU_014430_8_1_1; -.
DR InParanoid; Q16650; -.
DR OMA; NRALGYY; -.
DR OrthoDB; 374561at2759; -.
DR PhylomeDB; Q16650; -.
DR TreeFam; TF106341; -.
DR PathwayCommons; Q16650; -.
DR SignaLink; Q16650; -.
DR SIGNOR; Q16650; -.
DR BioGRID-ORCS; 10716; 7 hits in 1086 CRISPR screens.
DR GeneWiki; TBR1; -.
DR GenomeRNAi; 10716; -.
DR Pharos; Q16650; Tbio.
DR PRO; PR:Q16650; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q16650; protein.
DR Bgee; ENSG00000136535; Expressed in cortical plate and 39 other tissues.
DR ExpressionAtlas; Q16650; baseline and differential.
DR Genevisible; Q16650; HS.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0021764; P:amygdala development; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; TAS:ProtInc.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl.
DR GO; GO:0006338; P:chromatin remodeling; IEA:Ensembl.
DR GO; GO:0021902; P:commitment of neuronal cell to specific neuron type in forebrain; IBA:GO_Central.
DR GO; GO:0001661; P:conditioned taste aversion; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0030902; P:hindbrain development; IEA:Ensembl.
DR GO; GO:0016575; P:histone deacetylation; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:1902667; P:regulation of axon guidance; IEA:Ensembl.
DR GO; GO:0010975; P:regulation of neuron projection development; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0010092; P:specification of animal organ identity; IEA:Ensembl.
DR CDD; cd00182; TBOX; 1.
DR Gene3D; 2.60.40.820; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR032385; T-box_assoc.
DR InterPro; IPR046360; T-box_DNA-bd.
DR InterPro; IPR036960; T-box_sf.
DR InterPro; IPR001699; TF_T-box.
DR InterPro; IPR018186; TF_T-box_CS.
DR PANTHER; PTHR11267; PTHR11267; 1.
DR Pfam; PF00907; T-box; 1.
DR Pfam; PF16176; T-box_assoc; 1.
DR PRINTS; PR00937; TBOX.
DR SMART; SM00425; TBOX; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS01283; TBOX_1; 1.
DR PROSITE; PS01264; TBOX_2; 1.
DR PROSITE; PS50252; TBOX_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autism spectrum disorder; Disease variant;
KW DNA-binding; Intellectual disability; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..682
FT /note="T-box brain protein 1"
FT /id="PRO_0000184457"
FT DNA_BIND 213..393
FT /note="T-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00201"
FT REGION 43..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 108..127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 447..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 588..658
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 612..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 408
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q64336"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64336"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64336"
FT MOD_RES 641
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64336"
FT VAR_SEQ 1..287
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056591"
FT VARIANT 178
FT /note="Q -> E (in IDDAS; unknown pathological significance;
FT does not affect nuclear localization; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; does not affect interaction with FOXP2;
FT dbSNP:rs771354583)"
FT /evidence="ECO:0000269|PubMed:25232744"
FT /id="VAR_081757"
FT VARIANT 228
FT /note="K -> E (in IDDAS; de novo variant; localizes to the
FT nucleus but forms abnormal aggregates; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; abolishes interaction with FOXP2; does
FT not affect interaction with BCL11A)"
FT /evidence="ECO:0000269|PubMed:23160955,
FT ECO:0000269|PubMed:25232744, ECO:0000269|PubMed:25418537"
FT /id="VAR_081758"
FT VARIANT 271
FT /note="W -> C (in IDDAS; de novo variant; localizes to the
FT nucleus but forms abnormal aggregates; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; severely decreased interaction with
FT FOXP2; loss of interaction with FOXP1; does not affect
FT interaction with BCL11A; dbSNP:rs1559060428)"
FT /evidence="ECO:0000269|PubMed:25363760,
FT ECO:0000269|PubMed:25418537, ECO:0000269|PubMed:30250039"
FT /id="VAR_081759"
FT VARIANT 271
FT /note="W -> R (in IDDAS; de novo variant; does not affect
FT nuclear localization; no effect on transcriptional
FT repression of FEZF2; does not affect homodimerization; does
FT not affect interaction with FOXP2; does not affect
FT interaction with BCL11A; dbSNP:rs1553510301)"
FT /evidence="ECO:0000269|PubMed:25356899,
FT ECO:0000269|PubMed:30250039"
FT /id="VAR_078646"
FT VARIANT 289
FT /note="H -> Q (in dbSNP:rs12994035)"
FT /id="VAR_052264"
FT VARIANT 356
FT /note="V -> M (in IDDAS; unknown pathological significance;
FT does not affect nuclear localization; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; does not affect interaction with FOXP2;
FT does not affect interaction with BCL11A;
FT dbSNP:rs147026901)"
FT /evidence="ECO:0000269|PubMed:14593429,
FT ECO:0000269|PubMed:25232744, ECO:0000269|PubMed:30250039"
FT /id="VAR_081760"
FT VARIANT 374
FT /note="N -> H (in IDDAS; de novo variant; localizes to the
FT nucleus but forms abnormal aggregates; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; abolishes interaction with FOXP2; does
FT not affect interaction with BCL11A)"
FT /evidence="ECO:0000269|PubMed:22495311,
FT ECO:0000269|PubMed:25232744, ECO:0000269|PubMed:25418537,
FT ECO:0000269|PubMed:30250039"
FT /id="VAR_081761"
FT VARIANT 389
FT /note="K -> E (in IDDAS; de novo variant; localizes to the
FT nucleus but forms abnormal aggregates; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; severely decreased interaction with
FT FOXP2; loss of interaction with FOXP1; does not affect
FT interaction with BCL11A; dbSNP:rs1553510677)"
FT /evidence="ECO:0000269|PubMed:25418537,
FT ECO:0000269|PubMed:30250039"
FT /id="VAR_081762"
FT VARIANT 418
FT /note="Q -> R (in IDDAS; unknown pathological significance;
FT does not affect nuclear localization; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; decreased interaction with FOXP2; loss of
FT interaction with BCL11A; dbSNP:rs1173646549)"
FT /evidence="ECO:0000269|PubMed:25232744,
FT ECO:0000269|PubMed:30250039"
FT /id="VAR_081763"
FT VARIANT 542
FT /note="P -> R (in IDDAS; unknown pathological significance;
FT does not affect nuclear localization; no effect on
FT transcriptional repression of FEZF2; does not affect
FT homodimerization; does not affect interaction with FOXP2;
FT does not affect interaction with BCL11A)"
FT /evidence="ECO:0000269|PubMed:25232744,
FT ECO:0000269|PubMed:30250039"
FT /id="VAR_081764"
FT MUTAGEN 394..682
FT /note="Missing: Decreased interaction with BCL11A."
FT /evidence="ECO:0000269|PubMed:30250039"
FT MUTAGEN 568..682
FT /note="Missing: No effect on interaction with BCL11A."
FT /evidence="ECO:0000269|PubMed:30250039"
FT CONFLICT 619
FT /note="S -> P (in Ref. 2; BAG35462)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 682 AA; 74053 MW; E1C8D84206EFBBB5 CRC64;
MQLEHCLSPS IMLSKKFLNV SSSYPHSGGS ELVLHDHPII STTDNLERSS PLKKITRGMT
NQSDTDNFPD SKDSPGDVQR SKLSPVLDGV SELRHSFDGS AADRYLLSQS SQPQSAATAP
SAMFPYPGQH GPAHPAFSIG SPSRYMAHHP VITNGAYNSL LSNSSPQGYP TAGYPYPQQY
GHSYQGAPFY QFSSTQPGLV PGKAQVYLCN RPLWLKFHRH QTEMIITKQG RRMFPFLSFN
ISGLDPTAHY NIFVDVILAD PNHWRFQGGK WVPCGKADTN VQGNRVYMHP DSPNTGAHWM
RQEISFGKLK LTNNKGASNN NGQMVVLQSL HKYQPRLHVV EVNEDGTEDT SQPGRVQTFT
FPETQFIAVT AYQNTDITQL KIDHNPFAKG FRDNYDTIYT GCDMDRLTPS PNDSPRSQIV
PGARYAMAGS FLQDQFVSNY AKARFHPGAG AGPGPGTDRS VPHTNGLLSP QQAEDPGAPS
PQRWFVTPAN NRLDFAASAY DTATDFAGNA ATLLSYAAAG VKALPLQAAG CTGRPLGYYA
DPSGWGARSP PQYCGTKSGS VLPCWPNSAA AAARMAGANP YLGEEAEGLA AERSPLPPGA
AEDAKPKDLS DSSWIETPSS IKSIDSSDSG IYEQAKRRRI SPADTPVSES SSPLKSEVLA
QRDCEKNCAK DISGYYGFYS HS
