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Protein

T-box transcription factor TBX1

Gene

TBX1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable transcriptional regulator involved in developmental processes. Is required for normal development of the pharyngeal arch arteries (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi119 – 297179T-boxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
T-box transcription factor TBX1
Short name:
T-box protein 1
Alternative name(s):
Testis-specific T-box protein
Gene namesi
Name:TBX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:11592. TBX1.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.

DiGeorge syndrome (DGS)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:188400
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti310 – 3101G → S in DGS. 1 Publication
Corresponds to variant rs41298838 [ dbSNP | Ensembl ].
VAR_034545
Velocardiofacial syndrome (VCFS)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:192430
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti148 – 1481F → Y in CTHM and VCFS. 1 Publication
Corresponds to variant rs28939675 [ dbSNP | Ensembl ].
VAR_035025
Natural varianti194 – 1941H → Q in VCFS. 1 Publication
VAR_035026
Conotruncal heart malformations (CTHM)

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:217095
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti148 – 1481F → Y in CTHM and VCFS. 1 Publication
Corresponds to variant rs28939675 [ dbSNP | Ensembl ].
VAR_035025

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi188400. phenotype.
192430. phenotype.
217095. phenotype.
Orphaneti567. 22q11.2 deletion syndrome.
1727. 22q11.2 microduplication syndrome.
PharmGKBiPA36355.

Polymorphism and mutation databases

BioMutaiTBX1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 398398T-box transcription factor TBX1PRO_0000184423Add
BLAST

Proteomic databases

MaxQBiO43435.
PaxDbiO43435.
PRIDEiO43435.

PTM databases

PhosphoSiteiO43435.

Expressioni

Gene expression databases

BgeeiO43435.
CleanExiHS_TBX1.
ExpressionAtlasiO43435. baseline and differential.
GenevestigatoriO43435.

Organism-specific databases

HPAiHPA060863.

Interactioni

Subunit structurei

Interacts with DSCR6.By similarity

Protein-protein interaction databases

BioGridi112762. 2 interactions.
STRINGi9606.ENSP00000331791.

Structurei

Secondary structure

1
398
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi111 – 1144Combined sources
Helixi117 – 12610Combined sources
Beta strandi129 – 1313Combined sources
Beta strandi143 – 1497Combined sources
Beta strandi154 – 16512Combined sources
Beta strandi167 – 1737Combined sources
Turni174 – 1774Combined sources
Beta strandi178 – 1847Combined sources
Beta strandi200 – 2023Combined sources
Helixi203 – 2086Combined sources
Beta strandi211 – 2133Combined sources
Beta strandi217 – 2193Combined sources
Beta strandi236 – 24510Combined sources
Beta strandi260 – 2645Combined sources
Helixi266 – 2683Combined sources
Beta strandi270 – 2756Combined sources
Helixi279 – 28810Combined sources
Helixi290 – 2956Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4A04X-ray2.58A/B109-297[»]
ProteinModelPortaliO43435.
SMRiO43435. Positions 108-297.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi43 – 486Poly-Pro
Compositional biasi54 – 574Poly-Ala
Compositional biasi61 – 677Poly-Pro
Compositional biasi94 – 996Poly-Ala

Sequence similaritiesi

Contains 1 T-box DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG272513.
GeneTreeiENSGT00760000118897.
HOGENOMiHOG000286000.
HOVERGENiHBG014448.
InParanoidiO43435.
KOiK10175.
OMAiEFQRDAG.
OrthoDBiEOG7GN2PM.
PhylomeDBiO43435.
TreeFamiTF106341.

Family and domain databases

Gene3Di2.60.40.820. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiPF00907. T-box. 1 hit.
[Graphical view]
PRINTSiPR00937. TBOX.
SMARTiSM00425. TBOX. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
PROSITEiPS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A (identifier: O43435-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MHFSTVTRDM EAFTASSLSS LGAAGGFPGA ASPGADPYGP REPPPPPPRY
60 70 80 90 100
DPCAAAAPGA PGPPPPPHAY PFAPAAGAAT SAAAEPEGPG ASCAAAAKAP
110 120 130 140 150
VKKNAKVAGV SVQLEMKALW DEFNQLGTEM IVTKAGRRMF PTFQVKLFGM
160 170 180 190 200
DPMADYMLLM DFVPVDDKRY RYAFHSSSWL VAGKADPATP GRVHYHPDSP
210 220 230 240 250
AKGAQWMKQI VSFDKLKLTN NLLDDNGHII LNSMHRYQPR FHVVYVDPRK
260 270 280 290 300
DSEKYAEENF KTFVFEETRF TAVTAYQNHR ITQLKIASNP FAKGFRDCDP
310 320 330 340 350
EDWPRNHRPG ALPLMSAFAR SRNPVASPTQ PSGTEKGGHV LKDKEVKAET
360 370 380 390
SRNTPEREVE LLRDAGGCVN LGLPCPAECQ PFNTQGLVAG RTAGDRLC
Length:398
Mass (Da):43,133
Last modified:June 1, 1998 - v1
Checksum:iFAF0F3FA0CDC6176
GO
Isoform B (identifier: O43435-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     338-398: GHVLKDKEVK...AGRTAGDRLC → LVTEGSGLQPGLLDVLLKPPSKKSESLRPPHCKDT

Show »
Length:372
Mass (Da):40,353
Checksum:iDC6B41E913C8BB25
GO
Isoform C (identifier: O43435-3) [UniParc]FASTAAdd to basket

Also known as: TBX1C

The sequence of this isoform differs from the canonical sequence as follows:
     337-398: GGHVLKDKEV...AGRTAGDRLC → DAAEARREFQ...PPGSYDYCPR

Show »
Length:495
Mass (Da):52,666
Checksum:iFB0C150FEA6155FC
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti148 – 1481F → Y in CTHM and VCFS. 1 Publication
Corresponds to variant rs28939675 [ dbSNP | Ensembl ].
VAR_035025
Natural varianti194 – 1941H → Q in VCFS. 1 Publication
VAR_035026
Natural varianti310 – 3101G → S in DGS. 1 Publication
Corresponds to variant rs41298838 [ dbSNP | Ensembl ].
VAR_034545
Natural varianti337 – 3371G → E in a colorectal cancer sample; somatic mutation. 1 Publication
VAR_036065
Natural varianti350 – 3501T → M.
Corresponds to variant rs4819522 [ dbSNP | Ensembl ].
VAR_024657

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei337 – 39862GGHVL…GDRLC → DAAEARREFQRDAGGPAVLG DPAHPPQLLARVLSPSLPGA GGAGGLVPLPGAPGGRPSPP NPELRLEAPGASEPLHHHPY KYPAAAYDHYLGAKSRPAPY PLPGLRGHGYHPHAHPHHHH HPVSPAAAAAAAAAAAAAAA NMYSSAGAAPPGSYDYCPR in isoform C. 1 PublicationVSP_007423Add
BLAST
Alternative sequencei338 – 39861GHVLK…GDRLC → LVTEGSGLQPGLLDVLLKPP SKKSESLRPPHCKDT in isoform B. 1 PublicationVSP_006383Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF012130 mRNA. Translation: AAB94018.1.
AF012131 mRNA. Translation: AAB94019.1.
AF373867 mRNA. Translation: AAK58955.1.
FJ515849 Genomic DNA. Translation: ACS13741.1.
FJ515849 Genomic DNA. Translation: ACS13742.1.
CH471176 Genomic DNA. Translation: EAX03024.1.
CH471176 Genomic DNA. Translation: EAX03025.1.
CCDSiCCDS13765.1. [O43435-2]
CCDS13766.1. [O43435-1]
CCDS13767.1. [O43435-3]
RefSeqiNP_005983.1. NM_005992.1. [O43435-2]
NP_542377.1. NM_080646.1. [O43435-1]
NP_542378.1. NM_080647.1. [O43435-3]
XP_006724375.1. XM_006724312.1. [O43435-3]
UniGeneiHs.173984.

Genome annotation databases

EnsembliENST00000329705; ENSP00000331176; ENSG00000184058. [O43435-1]
ENST00000332710; ENSP00000331791; ENSG00000184058. [O43435-3]
ENST00000359500; ENSP00000352483; ENSG00000184058. [O43435-2]
ENST00000621939; ENSP00000477982; ENSG00000184058. [O43435-2]
GeneIDi6899.
KEGGihsa:6899.
UCSCiuc002zqb.3. human. [O43435-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF012130 mRNA. Translation: AAB94018.1.
AF012131 mRNA. Translation: AAB94019.1.
AF373867 mRNA. Translation: AAK58955.1.
FJ515849 Genomic DNA. Translation: ACS13741.1.
FJ515849 Genomic DNA. Translation: ACS13742.1.
CH471176 Genomic DNA. Translation: EAX03024.1.
CH471176 Genomic DNA. Translation: EAX03025.1.
CCDSiCCDS13765.1. [O43435-2]
CCDS13766.1. [O43435-1]
CCDS13767.1. [O43435-3]
RefSeqiNP_005983.1. NM_005992.1. [O43435-2]
NP_542377.1. NM_080646.1. [O43435-1]
NP_542378.1. NM_080647.1. [O43435-3]
XP_006724375.1. XM_006724312.1. [O43435-3]
UniGeneiHs.173984.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4A04X-ray2.58A/B109-297[»]
ProteinModelPortaliO43435.
SMRiO43435. Positions 108-297.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112762. 2 interactions.
STRINGi9606.ENSP00000331791.

PTM databases

PhosphoSiteiO43435.

Polymorphism and mutation databases

BioMutaiTBX1.

Proteomic databases

MaxQBiO43435.
PaxDbiO43435.
PRIDEiO43435.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329705; ENSP00000331176; ENSG00000184058. [O43435-1]
ENST00000332710; ENSP00000331791; ENSG00000184058. [O43435-3]
ENST00000359500; ENSP00000352483; ENSG00000184058. [O43435-2]
ENST00000621939; ENSP00000477982; ENSG00000184058. [O43435-2]
GeneIDi6899.
KEGGihsa:6899.
UCSCiuc002zqb.3. human. [O43435-1]

Organism-specific databases

CTDi6899.
GeneCardsiGC22P019747.
GeneReviewsiTBX1.
HGNCiHGNC:11592. TBX1.
HPAiHPA060863.
MIMi188400. phenotype.
192430. phenotype.
217095. phenotype.
602054. gene.
neXtProtiNX_O43435.
Orphaneti567. 22q11.2 deletion syndrome.
1727. 22q11.2 microduplication syndrome.
PharmGKBiPA36355.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG272513.
GeneTreeiENSGT00760000118897.
HOGENOMiHOG000286000.
HOVERGENiHBG014448.
InParanoidiO43435.
KOiK10175.
OMAiEFQRDAG.
OrthoDBiEOG7GN2PM.
PhylomeDBiO43435.
TreeFamiTF106341.

Miscellaneous databases

ChiTaRSiTBX1. human.
GenomeRNAii6899.
NextBioi26967.
PROiO43435.
SOURCEiSearch...

Gene expression databases

BgeeiO43435.
CleanExiHS_TBX1.
ExpressionAtlasiO43435. baseline and differential.
GenevestigatoriO43435.

Family and domain databases

Gene3Di2.60.40.820. 1 hit.
InterProiIPR008967. p53-like_TF_DNA-bd.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERiPTHR11267. PTHR11267. 1 hit.
PfamiPF00907. T-box. 1 hit.
[Graphical view]
PRINTSiPR00937. TBOX.
SMARTiSM00425. TBOX. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
PROSITEiPS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of a gene from the DiGeorge chromosomal region homologous to the mouse Tbx1 gene."
    Chieffo C., Garvey N., Gong W., Roe B., Zhang G., Silver L., Emanuel B.S., Budarf M.L.
    Genomics 43:267-277(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
    Tissue: Skeletal muscle and Testis.
  2. "Mutation analysis of TBX1 in 105 patients."
    Gong W., Gottlieb S., Budarf M.L.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C).
  3. NHLBI resequencing and genotyping service (RS&G)
    Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: VARIANT CTMH/VCFS TYR-148, VARIANT DGS SER-310.
  6. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-337.
  7. "Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions."
    Zweier C., Sticht H., Aydin-Yaylagul I., Campbell C.E., Rauch A.
    Am. J. Hum. Genet. 80:510-517(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT VCFS GLN-194.

Entry informationi

Entry nameiTBX1_HUMAN
AccessioniPrimary (citable) accession number: O43435
Secondary accession number(s): C6G493
, C6G494, O43436, Q96RJ2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: April 29, 2015
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.