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O43435 (TBX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
T-box transcription factor TBX1

Short name=T-box protein 1
Alternative name(s):
Testis-specific T-box protein
Gene names
Name:TBX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length398 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

Interacts with DSCR6 By similarity.

Subcellular location

Nucleus Potential.

Involvement in disease

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. Ref.5

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

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.

Sequence similarities

Contains 1 T-box DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

anterior/posterior pattern specification

Inferred from sequence or structural similarity. Source: UniProtKB

aorta morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

artery morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

blood vessel development

Inferred from sequence or structural similarity. Source: UniProtKB

blood vessel morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

blood vessel remodeling

Inferred from electronic annotation. Source: Ensembl

cell fate specification

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to fibroblast growth factor stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to retinoic acid

Inferred from sequence or structural similarity. Source: UniProtKB

cochlea morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

coronary artery morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

determination of left/right symmetry

Inferred from sequence or structural similarity. Source: UniProtKB

ear morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic cranial skeleton morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

embryonic viscerocranium morphogenesis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

enamel mineralization

Inferred from sequence or structural similarity. Source: UniProtKB

epithelial cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

face morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

heart development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

heart morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

inner ear morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

lymph vessel development

Inferred from sequence or structural similarity. Source: UniProtKB

mesenchymal cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

mesoderm development

Inferred from sequence or structural similarity. Source: UniProtKB

middle ear morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

muscle cell fate commitment

Inferred from sequence or structural similarity. Source: UniProtKB

muscle organ development

Inferred from sequence or structural similarity. Source: UniProtKB

muscle organ morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

muscle tissue morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of mesenchymal cell apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

neural crest cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

odontogenesis of dentin-containing tooth

Inferred from sequence or structural similarity. Source: UniProtKB

otic vesicle morphogenesis

Inferred from electronic annotation. Source: Ensembl

outer ear morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

outflow tract septum morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

parathyroid gland development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

pattern specification process

Inferred from sequence or structural similarity. Source: UniProtKB

pharyngeal system development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of epithelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mesenchymal cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of secondary heart field cardioblast proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of tongue muscle cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of organ morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

retinoic acid receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

semicircular canal morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

sensory perception of sound

Inferred from sequence or structural similarity. Source: UniProtKB

social behavior

Inferred from sequence or structural similarity. Source: UniProtKB

soft palate development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

thymus development

Inferred from mutant phenotype Ref.5. Source: UniProtKB

thyroid gland development

Inferred from sequence or structural similarity. Source: UniProtKB

tongue morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

vagus nerve morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentnucleus

Inferred from direct assay PubMed 15703190. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.7. Source: UniProtKB

protein dimerization activity

Traceable author statement Ref.7. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 11111039. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay PubMed 11111039. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: O43435-1)

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.
Isoform B (identifier: O43435-2)

The sequence of this isoform differs from the canonical sequence as follows:
     338-398: GHVLKDKEVK...AGRTAGDRLC → LVTEGSGLQPGLLDVLLKPPSKKSESLRPPHCKDT
Isoform C (identifier: O43435-3)

Also known as: TBX1C;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 398398T-box transcription factor TBX1
PRO_0000184423

Regions

DNA binding119 – 297179T-box
Compositional bias43 – 486Poly-Pro
Compositional bias54 – 574Poly-Ala
Compositional bias61 – 677Poly-Pro
Compositional bias94 – 996Poly-Ala

Natural variations

Alternative sequence337 – 39862GGHVL…GDRLC → DAAEARREFQRDAGGPAVLG DPAHPPQLLARVLSPSLPGA GGAGGLVPLPGAPGGRPSPP NPELRLEAPGASEPLHHHPY KYPAAAYDHYLGAKSRPAPY PLPGLRGHGYHPHAHPHHHH HPVSPAAAAAAAAAAAAAAA NMYSSAGAAPPGSYDYCPR in isoform C.
VSP_007423
Alternative sequence338 – 39861GHVLK…GDRLC → LVTEGSGLQPGLLDVLLKPP SKKSESLRPPHCKDT in isoform B.
VSP_006383
Natural variant1481F → Y in CTHM and VCFS. Ref.5
Corresponds to variant rs28939675 [ dbSNP | Ensembl ].
VAR_035025
Natural variant1941H → Q in VCFS. Ref.7
VAR_035026
Natural variant3101G → S in DGS. Ref.5
Corresponds to variant rs41298838 [ dbSNP | Ensembl ].
VAR_034545
Natural variant3371G → E in a colorectal cancer sample; somatic mutation. Ref.6
VAR_036065
Natural variant3501T → M.
Corresponds to variant rs4819522 [ dbSNP | Ensembl ].
VAR_024657

Secondary structure

.................................. 398
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: FAF0F3FA0CDC6176

FASTA39843,133
        10         20         30         40         50         60 
MHFSTVTRDM EAFTASSLSS LGAAGGFPGA ASPGADPYGP REPPPPPPRY DPCAAAAPGA 

        70         80         90        100        110        120 
PGPPPPPHAY PFAPAAGAAT SAAAEPEGPG ASCAAAAKAP VKKNAKVAGV SVQLEMKALW 

       130        140        150        160        170        180 
DEFNQLGTEM IVTKAGRRMF PTFQVKLFGM DPMADYMLLM DFVPVDDKRY RYAFHSSSWL 

       190        200        210        220        230        240 
VAGKADPATP GRVHYHPDSP AKGAQWMKQI VSFDKLKLTN NLLDDNGHII LNSMHRYQPR 

       250        260        270        280        290        300 
FHVVYVDPRK DSEKYAEENF KTFVFEETRF TAVTAYQNHR ITQLKIASNP FAKGFRDCDP 

       310        320        330        340        350        360 
EDWPRNHRPG ALPLMSAFAR SRNPVASPTQ PSGTEKGGHV LKDKEVKAET SRNTPEREVE 

       370        380        390 
LLRDAGGCVN LGLPCPAECQ PFNTQGLVAG RTAGDRLC 

« Hide

Isoform B [UniParc].

Checksum: DC6B41E913C8BB25
Show »

FASTA37240,353
Isoform C (TBX1C) [UniParc].

Checksum: FB0C150FEA6155FC
Show »

FASTA49552,666

References

« Hide 'large scale' references
[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]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. expand/collapse author list , 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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Role of TBX1 in human del22q11.2 syndrome."
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.
Lancet 362:1366-1373(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTMH/VCFS TYR-148, VARIANT DGS SER-310.
[6]"The consensus coding sequences of human breast and colorectal cancers."
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. expand/collapse author list , 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.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS13765.1. [O43435-2]
CCDS13766.1. [O43435-1]
CCDS13767.1. [O43435-3]
RefSeqNP_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]
UniGeneHs.173984.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4A04X-ray2.58A/B109-297[»]
ProteinModelPortalO43435.
SMRO43435. Positions 108-297.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112762. 2 interactions.
STRING9606.ENSP00000331791.

PTM databases

PhosphoSiteO43435.

Proteomic databases

MaxQBO43435.
PaxDbO43435.
PRIDEO43435.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329705; ENSP00000331176; ENSG00000184058. [O43435-1]
ENST00000332710; ENSP00000331791; ENSG00000184058. [O43435-3]
ENST00000359500; ENSP00000352483; ENSG00000184058. [O43435-2]
GeneID6899.
KEGGhsa:6899.
UCSCuc002zqb.3. human. [O43435-1]

Organism-specific databases

CTD6899.
GeneCardsGC22P019747.
GeneReviewsTBX1.
HGNCHGNC:11592. TBX1.
HPAHPA060863.
MIM188400. phenotype.
192430. phenotype.
217095. phenotype.
602054. gene.
neXtProtNX_O43435.
Orphanet567. 22q11.2 deletion syndrome.
1727. 22q11.2 microduplication syndrome.
PharmGKBPA36355.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG272513.
HOGENOMHOG000286000.
HOVERGENHBG014448.
KOK10175.
OMAANMYSAT.
OrthoDBEOG7GN2PM.
PhylomeDBO43435.
TreeFamTF106341.

Gene expression databases

ArrayExpressO43435.
BgeeO43435.
CleanExHS_TBX1.
GenevestigatorO43435.

Family and domain databases

Gene3D2.60.40.820. 1 hit.
InterProIPR008967. p53-like_TF_DNA-bd.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]
PANTHERPTHR11267. PTHR11267. 1 hit.
PfamPF00907. T-box. 1 hit.
[Graphical view]
PRINTSPR00937. TBOX.
SMARTSM00425. TBOX. 1 hit.
[Graphical view]
SUPFAMSSF49417. SSF49417. 1 hit.
PROSITEPS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi6899.
NextBio26967.
PROO43435.
SOURCESearch...

Entry information

Entry nameTBX1_HUMAN
AccessionPrimary (citable) accession number: O43435
Secondary accession number(s): C6G493 expand/collapse secondary AC list , C6G494, O43436, Q96RJ2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM