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T-box transcription factor TBX1 (T-box protein 1) (Testis-specific T-box protein)

 TBX1_HUMAN              Reviewed;         398 AA.
O43435; C6G493; C6G494; O43436; Q96RJ2;
15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
01-JUN-1998, sequence version 1.
20-JUN-2018, entry version 158.
RecName: Full=T-box transcription factor TBX1;
Short=T-box protein 1;
AltName: Full=Testis-specific T-box protein;
Name=TBX1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
TISSUE=Skeletal muscle, and Testis;
PubMed=9268629; DOI=10.1006/geno.1997.4829;
Chieffo C., Garvey N., Gong W., Roe B., Zhang G., Silver L.,
Emanuel B.S., Budarf M.L.;
"Isolation and characterization of a gene from the DiGeorge
chromosomal region homologous to the mouse Tbx1 gene.";
Genomics 43:267-277(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
Gong W., Gottlieb S., Budarf M.L.;
"Mutation analysis of TBX1 in 105 patients.";
Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NHLBI resequencing and genotyping service (RS&G);
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[5]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[6]
VARIANT CTMH/VCFS TYR-148, AND VARIANT DGS SER-310.
PubMed=14585638; DOI=10.1016/S0140-6736(03)14632-6;
Yagi H., Furutani Y., Hamada H., Sasaki T., Asakawa S., Minoshima S.,
Ichida F., Joo K., Kimura M., Imamura S., Kamatani N., Momma K.,
Takao A., Nakazawa M., Shimizu N., Matsuoka R.;
"Role of TBX1 in human del22q11.2 syndrome.";
Lancet 362:1366-1373(2003).
[7]
VARIANT [LARGE SCALE ANALYSIS] GLU-337.
PubMed=16959974; DOI=10.1126/science.1133427;
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
Vogelstein B., Kinzler K.W., Velculescu V.E.;
"The consensus coding sequences of human breast and colorectal
cancers.";
Science 314:268-274(2006).
[8]
VARIANT VCFS GLN-194.
PubMed=17273972; DOI=10.1086/511993;
Zweier C., Sticht H., Aydin-Yaylagul I., Campbell C.E., Rauch A.;
"Human TBX1 missense mutations cause gain of function resulting in the
same phenotype as 22q11.2 deletions.";
Am. J. Hum. Genet. 80:510-517(2007).
-!- FUNCTION: Probable transcriptional regulator involved in
developmental processes. Is required for normal development of the
pharyngeal arch arteries (By similarity). {ECO:0000250}.
-!- SUBUNIT: Interacts with DSCR6. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00201}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=A;
IsoId=O43435-1; Sequence=Displayed;
Name=B;
IsoId=O43435-2; Sequence=VSP_006383;
Name=C; Synonyms=TBX1C;
IsoId=O43435-3; Sequence=VSP_007423;
-!- DISEASE: Note=Haploinsufficiency of the TBX1 gene is responsible
for most of the physical malformations present in DiGeorge
syndrome (DGS) and velocardiofacial syndrome (VCFS). DGS is
characterized by the association of several malformations:
hypoplastic thymus and parathyroid glands, congenital conotruncal
cardiopathy, and a subtle but characteristic facial dysmorphology.
VCFS is marked by the association of congenital conotruncal heart
defects, cleft palate or velar insufficiency, facial dysmorpholgy
and learning difficulties. It is now accepted that these two
syndromes represent two forms of clinical expression of the same
entity manifesting at different stages of life.
-!- DISEASE: DiGeorge syndrome (DGS) [MIM:188400]: A congenital
syndrome characterized by a wide spectrum of characteristics
including parathyroid hypoplasia resulting in hypocalcemia, thymic
hypoplasia resulting in T-cell immunodeficiency, defects in the
outflow tract of the heart, and craniofacial anomalies.
Disturbance of cervical neural crest migration into the
derivatives of the pharyngeal arches and pouches can account for
the phenotype. {ECO:0000269|PubMed:14585638}. Note=The disease is
caused by mutations affecting the gene represented in this entry.
-!- DISEASE: Velocardiofacial syndrome (VCFS) [MIM:192430]: A syndrome
characterized by abnormal pharyngeal arch development that results
in defective development of the parathyroid glands, thymus, and
conotruncal region of the heart. The phenotype is highly variable,
with no single clinical feature present in every patient. Affected
individuals may present with structural or functional palatal
abnormalities, cardiac defects, unique facial characteristics,
hypernasal speech, hypotonia, and defective thymic development
associated with impaired immune function. In addition, affected
individuals may present with learning disabilities, overt
developmental delay, and psychiatric disorders.
{ECO:0000269|PubMed:14585638, ECO:0000269|PubMed:17273972}.
Note=The disease is caused by mutations affecting the gene
represented in this entry.
-!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A
group of congenital heart defects involving the outflow tracts.
Examples include truncus arteriosus communis, double-outlet right
ventricle and transposition of great arteries. Truncus arteriosus
communis is characterized by a single outflow tract instead of a
separate aorta and pulmonary artery. In transposition of the great
arteries, the aorta arises from the right ventricle and the
pulmonary artery from the left ventricle. In double outlet of the
right ventricle, both the pulmonary artery and aorta arise from
the right ventricle. Note=The disease is caused by mutations
affecting the gene represented in this entry.
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EMBL; AF012130; AAB94018.1; -; mRNA.
EMBL; AF012131; AAB94019.1; -; mRNA.
EMBL; AF373867; AAK58955.1; -; mRNA.
EMBL; FJ515849; ACS13741.1; -; Genomic_DNA.
EMBL; FJ515849; ACS13742.1; -; Genomic_DNA.
EMBL; CH471176; EAX03024.1; -; Genomic_DNA.
EMBL; CH471176; EAX03025.1; -; Genomic_DNA.
CCDS; CCDS13765.1; -. [O43435-2]
CCDS; CCDS13766.1; -. [O43435-1]
CCDS; CCDS13767.1; -. [O43435-3]
RefSeq; NP_005983.1; NM_005992.1. [O43435-2]
RefSeq; NP_542377.1; NM_080646.1. [O43435-1]
RefSeq; NP_542378.1; NM_080647.1. [O43435-3]
RefSeq; XP_006724375.1; XM_006724312.2. [O43435-3]
RefSeq; XP_016884415.1; XM_017028926.1. [O43435-3]
UniGene; Hs.173984; -.
PDB; 4A04; X-ray; 2.58 A; A/B=109-297.
PDBsum; 4A04; -.
ProteinModelPortal; O43435; -.
SMR; O43435; -.
BioGrid; 112762; 4.
iPTMnet; O43435; -.
PhosphoSitePlus; O43435; -.
BioMuta; TBX1; -.
MaxQB; O43435; -.
PeptideAtlas; O43435; -.
PRIDE; O43435; -.
ProteomicsDB; 48946; -.
ProteomicsDB; 48947; -. [O43435-2]
ProteomicsDB; 48948; -. [O43435-3]
Ensembl; ENST00000329705; ENSP00000331176; ENSG00000184058. [O43435-1]
Ensembl; ENST00000332710; ENSP00000331791; ENSG00000184058. [O43435-3]
Ensembl; ENST00000359500; ENSP00000352483; ENSG00000184058. [O43435-2]
GeneID; 6899; -.
KEGG; hsa:6899; -.
UCSC; uc002zqa.2; human. [O43435-1]
CTD; 6899; -.
DisGeNET; 6899; -.
EuPathDB; HostDB:ENSG00000184058.12; -.
GeneCards; TBX1; -.
GeneReviews; TBX1; -.
HGNC; HGNC:11592; TBX1.
HPA; HPA029330; -.
MalaCards; TBX1; -.
MIM; 188400; phenotype.
MIM; 192430; phenotype.
MIM; 217095; phenotype.
MIM; 602054; gene.
neXtProt; NX_O43435; -.
OpenTargets; ENSG00000184058; -.
Orphanet; 567; 22q11.2 deletion syndrome.
Orphanet; 1727; 22q11.2 microduplication syndrome.
PharmGKB; PA36355; -.
GeneTree; ENSGT00760000118897; -.
HOGENOM; HOG000286000; -.
HOVERGEN; HBG014448; -.
InParanoid; O43435; -.
KO; K10175; -.
OMA; PAHQLMS; -.
PhylomeDB; O43435; -.
TreeFam; TF106341; -.
SIGNOR; O43435; -.
ChiTaRS; TBX1; human.
GenomeRNAi; 6899; -.
PRO; PR:O43435; -.
Proteomes; UP000005640; Chromosome 22.
Bgee; ENSG00000184058; -.
CleanEx; HS_TBX1; -.
ExpressionAtlas; O43435; baseline and differential.
Genevisible; O43435; HS.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
GO; GO:0046983; F:protein dimerization activity; TAS:UniProtKB.
GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; ISA:NTNU_SB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
GO; GO:0009952; P:anterior/posterior pattern specification; ISS:UniProtKB.
GO; GO:0035909; P:aorta morphogenesis; ISS:UniProtKB.
GO; GO:0048844; P:artery morphogenesis; ISS:UniProtKB.
GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB.
GO; GO:0001708; P:cell fate specification; ISS:UniProtKB.
GO; GO:0008283; P:cell proliferation; ISS:UniProtKB.
GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISS:UniProtKB.
GO; GO:0071300; P:cellular response to retinoic acid; ISS:UniProtKB.
GO; GO:0090103; P:cochlea morphogenesis; ISS:UniProtKB.
GO; GO:0060982; P:coronary artery morphogenesis; ISS:UniProtKB.
GO; GO:0007368; P:determination of left/right symmetry; ISS:UniProtKB.
GO; GO:0042471; P:ear morphogenesis; ISS:UniProtKB.
GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:UniProtKB.
GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IMP:UniProtKB.
GO; GO:0070166; P:enamel mineralization; ISS:UniProtKB.
GO; GO:0030855; P:epithelial cell differentiation; ISS:UniProtKB.
GO; GO:0060325; P:face morphogenesis; ISS:UniProtKB.
GO; GO:0007507; P:heart development; IMP:UniProtKB.
GO; GO:0003007; P:heart morphogenesis; ISS:UniProtKB.
GO; GO:0042472; P:inner ear morphogenesis; ISS:UniProtKB.
GO; GO:0001945; P:lymph vessel development; ISS:UniProtKB.
GO; GO:0097152; P:mesenchymal cell apoptotic process; ISS:UniProtKB.
GO; GO:0007498; P:mesoderm development; ISS:UniProtKB.
GO; GO:0042474; P:middle ear morphogenesis; ISS:UniProtKB.
GO; GO:0042693; P:muscle cell fate commitment; ISS:UniProtKB.
GO; GO:0007517; P:muscle organ development; ISS:UniProtKB.
GO; GO:0048644; P:muscle organ morphogenesis; ISS:UniProtKB.
GO; GO:0060415; P:muscle tissue morphogenesis; ISS:UniProtKB.
GO; GO:0045596; P:negative regulation of cell differentiation; ISS:UniProtKB.
GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; ISS:UniProtKB.
GO; GO:0001755; P:neural crest cell migration; ISS:UniProtKB.
GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:UniProtKB.
GO; GO:0042473; P:outer ear morphogenesis; ISS:UniProtKB.
GO; GO:0003151; P:outflow tract morphogenesis; ISS:UniProtKB.
GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:UniProtKB.
GO; GO:0060017; P:parathyroid gland development; IMP:UniProtKB.
GO; GO:0007389; P:pattern specification process; ISS:UniProtKB.
GO; GO:0060037; P:pharyngeal system development; IMP:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
GO; GO:2001037; P:positive regulation of tongue muscle cell differentiation; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:2000027; P:regulation of organ morphogenesis; ISS:UniProtKB.
GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
GO; GO:0048384; P:retinoic acid receptor signaling pathway; ISS:UniProtKB.
GO; GO:0048752; P:semicircular canal morphogenesis; ISS:UniProtKB.
GO; GO:0007605; P:sensory perception of sound; ISS:UniProtKB.
GO; GO:0035176; P:social behavior; ISS:UniProtKB.
GO; GO:0060023; P:soft palate development; IMP:UniProtKB.
GO; GO:0048538; P:thymus development; IMP:UniProtKB.
GO; GO:0030878; P:thyroid gland development; ISS:UniProtKB.
GO; GO:0043587; P:tongue morphogenesis; ISS:UniProtKB.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
GO; GO:0021644; P:vagus nerve morphogenesis; ISS:UniProtKB.
CDD; cd00182; TBOX; 1.
Gene3D; 2.60.40.820; -; 1.
InterPro; IPR008967; p53-like_TF_DNA-bd.
InterPro; IPR036960; T-box_sf.
InterPro; IPR001699; TF_T-box.
InterPro; IPR018186; TF_T-box_CS.
PANTHER; PTHR11267; PTHR11267; 1.
Pfam; PF00907; T-box; 1.
PRINTS; PR00937; TBOX.
SMART; SM00425; TBOX; 1.
SUPFAM; SSF49417; SSF49417; 1.
PROSITE; PS01283; TBOX_1; 1.
PROSITE; PS01264; TBOX_2; 1.
PROSITE; PS50252; TBOX_3; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome;
Developmental protein; Disease mutation; DNA-binding; Nucleus;
Polymorphism; Reference proteome; Transcription;
Transcription regulation.
CHAIN 1 398 T-box transcription factor TBX1.
/FTId=PRO_0000184423.
DNA_BIND 119 297 T-box. {ECO:0000255|PROSITE-
ProRule:PRU00201}.
COMPBIAS 43 48 Poly-Pro.
COMPBIAS 54 57 Poly-Ala.
COMPBIAS 61 67 Poly-Pro.
COMPBIAS 94 99 Poly-Ala.
VAR_SEQ 337 398 GGHVLKDKEVKAETSRNTPEREVELLRDAGGCVNLGLPCPA
ECQPFNTQGLVAGRTAGDRLC -> DAAEARREFQRDAGGP
AVLGDPAHPPQLLARVLSPSLPGAGGAGGLVPLPGAPGGRP
SPPNPELRLEAPGASEPLHHHPYKYPAAAYDHYLGAKSRPA
PYPLPGLRGHGYHPHAHPHHHHHPVSPAAAAAAAAAAAAAA
ANMYSSAGAAPPGSYDYCPR (in isoform C).
{ECO:0000303|Ref.2}.
/FTId=VSP_007423.
VAR_SEQ 338 398 GHVLKDKEVKAETSRNTPEREVELLRDAGGCVNLGLPCPAE
CQPFNTQGLVAGRTAGDRLC -> LVTEGSGLQPGLLDVLL
KPPSKKSESLRPPHCKDT (in isoform B).
{ECO:0000303|PubMed:9268629}.
/FTId=VSP_006383.
VARIANT 148 148 F -> Y (in CTHM and VCFS;
dbSNP:rs28939675).
{ECO:0000269|PubMed:14585638}.
/FTId=VAR_035025.
VARIANT 194 194 H -> Q (in VCFS; dbSNP:rs74315522).
{ECO:0000269|PubMed:17273972}.
/FTId=VAR_035026.
VARIANT 310 310 G -> S (in DGS; dbSNP:rs41298838).
{ECO:0000269|PubMed:14585638}.
/FTId=VAR_034545.
VARIANT 337 337 G -> E (in a colorectal cancer sample;
somatic mutation).
{ECO:0000269|PubMed:16959974}.
/FTId=VAR_036065.
VARIANT 350 350 T -> M (in dbSNP:rs4819522).
/FTId=VAR_024657.
STRAND 111 114 {ECO:0000244|PDB:4A04}.
HELIX 117 126 {ECO:0000244|PDB:4A04}.
STRAND 129 131 {ECO:0000244|PDB:4A04}.
STRAND 143 149 {ECO:0000244|PDB:4A04}.
STRAND 154 165 {ECO:0000244|PDB:4A04}.
STRAND 167 173 {ECO:0000244|PDB:4A04}.
TURN 174 177 {ECO:0000244|PDB:4A04}.
STRAND 178 184 {ECO:0000244|PDB:4A04}.
STRAND 200 202 {ECO:0000244|PDB:4A04}.
HELIX 203 208 {ECO:0000244|PDB:4A04}.
STRAND 211 213 {ECO:0000244|PDB:4A04}.
STRAND 217 219 {ECO:0000244|PDB:4A04}.
STRAND 236 245 {ECO:0000244|PDB:4A04}.
STRAND 260 264 {ECO:0000244|PDB:4A04}.
HELIX 266 268 {ECO:0000244|PDB:4A04}.
STRAND 270 275 {ECO:0000244|PDB:4A04}.
HELIX 279 288 {ECO:0000244|PDB:4A04}.
HELIX 290 295 {ECO:0000244|PDB:4A04}.
SEQUENCE 398 AA; 43133 MW; FAF0F3FA0CDC6176 CRC64;
MHFSTVTRDM EAFTASSLSS LGAAGGFPGA ASPGADPYGP REPPPPPPRY DPCAAAAPGA
PGPPPPPHAY PFAPAAGAAT SAAAEPEGPG ASCAAAAKAP VKKNAKVAGV SVQLEMKALW
DEFNQLGTEM IVTKAGRRMF PTFQVKLFGM DPMADYMLLM DFVPVDDKRY RYAFHSSSWL
VAGKADPATP GRVHYHPDSP AKGAQWMKQI VSFDKLKLTN NLLDDNGHII LNSMHRYQPR
FHVVYVDPRK DSEKYAEENF KTFVFEETRF TAVTAYQNHR ITQLKIASNP FAKGFRDCDP
EDWPRNHRPG ALPLMSAFAR SRNPVASPTQ PSGTEKGGHV LKDKEVKAET SRNTPEREVE
LLRDAGGCVN LGLPCPAECQ PFNTQGLVAG RTAGDRLC


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