O43435 (TBX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-box transcription factor TBX1
Short name=T-box protein 1

Alternative name(s):
Testis-specific T-box protein

Gene names

Name:

TBX1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	398 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	DNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis 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 blood vessel remodeling Inferred from electronic annotation. Source: Compara 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 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 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 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 otic vesicle morphogenesis Inferred from electronic annotation. Source: Compara outer ear 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 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 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: Compara 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-dependent Inferred from direct assay Ref.7. Source: UniProtKB regulation of organ morphogenesis 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW vagus nerve morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	nucleus Inferred from direct assay PubMed 15703190. Source: UniProtKB
Molecular_function	DNA 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 398

398

T-box transcription factor TBX1

PRO_0000184423

Regions

DNA binding

119 – 297

179

T-box

Compositional bias

43 – 48

6

Poly-Pro

Compositional bias

54 – 57

4

Poly-Ala

Compositional bias

61 – 67

7

Poly-Pro

Compositional bias

94 – 99

6

Poly-Ala

Natural variations

Alternative sequence

337 – 398

62

GGHVL…GDRLC → DAAEARREFQRDAGGPAVLG DPAHPPQLLARVLSPSLPGA GGAGGLVPLPGAPGGRPSPP NPELRLEAPGASEPLHHHPY KYPAAAYDHYLGAKSRPAPY PLPGLRGHGYHPHAHPHHHH HPVSPAAAAAAAAAAAAAAA NMYSSAGAAPPGSYDYCPR in isoform C.

VSP_007423

Alternative sequence

338 – 398

61

GHVLK…GDRLC → LVTEGSGLQPGLLDVLLKPP SKKSESLRPPHCKDT in isoform B.

VSP_006383

Natural variant

148

1

F → Y in CTHM and VCFS. Ref.5
Corresponds to variant rs28939675 [ dbSNP | Ensembl ].

VAR_035025

Natural variant

194

1

H → Q in VCFS. Ref.7

VAR_035026

Natural variant

310

1

G → S in DGS. Ref.5
Corresponds to variant rs41298838 [ dbSNP | Ensembl ].

VAR_034545

Natural variant

337

1

G → E in a colorectal cancer sample; somatic mutation. Ref.6

VAR_036065

Natural variant

350

1

T → M.
Corresponds to variant rs4819522 [ dbSNP | Ensembl ].

VAR_024657

Secondary structure

1

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398

Helix Strand Turn

Details...

Beta strand

111 – 114

4

Helix

117 – 126

10

Beta strand

129 – 131

3

Beta strand

143 – 149

7

Beta strand

154 – 165

12

Beta strand

167 – 173

7

Turn

174 – 177

4

Beta strand

178 – 184

7

Beta strand

200 – 202

3

Helix

203 – 208

6

Beta strand

211 – 213

3

Beta strand

217 – 219

3

Beta strand

236 – 245

10

Beta strand

260 – 264

5

Helix

266 – 268

3

Beta strand

270 – 275

6

Helix

279 – 288

10

Helix

290 – 295

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified June 1, 1998. Version 1. Checksum: FAF0F3FA0CDC6176	FASTA	398	43,133
	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
	Isoform B [UniParc]. Checksum: DC6B41E913C8BB25	FASTA	372	40,353
	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 PSGTEKGLVT EGSGLQPGLL DVLLKPPSKK 370 SESLRPPHCK DT
	Isoform C (TBX1C) [UniParc]. Checksum: FB0C150FEA6155FC	FASTA	495	52,666
	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 PSGTEKDAAE ARREFQRDAG GPAVLGDPAH 370 380 390 400 410 420 PPQLLARVLS PSLPGAGGAG GLVPLPGAPG GRPSPPNPEL RLEAPGASEP LHHHPYKYPA 430 440 450 460 470 480 AAYDHYLGAK SRPAPYPLPG LRGHGYHPHA HPHHHHHPVS PAAAAAAAAA AAAAAANMYS 490 SAGAAPPGSY DYCPR

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

IPI

IPI00045335.
IPI00395723.
IPI00411964.

RefSeq

NP_005983.1. NM_005992.1.
NP_542377.1. NM_080646.1.
NP_542378.1. NM_080647.1.

UniGene

Hs.173984.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4A04	X-ray	2.58	A/B	109-297	[»]

ProteinModelPortal

O43435.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000331791.

PTM databases

PhosphoSite

O43435.

Proteomic databases

PaxDb

O43435.

PRIDE

O43435.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000329705; ENSP00000331176; ENSG00000184058.
ENST00000332710; ENSP00000331791; ENSG00000184058.
ENST00000359500; ENSP00000352483; ENSG00000184058.

GeneID

6899.

KEGG

hsa:6899.

UCSC

uc002zqb.3. human.

Organism-specific databases

CTD

6899.

GeneCards

GC22P019747.

HGNC

HGNC:11592. TBX1.

MIM

188400. phenotype.
192430. phenotype.
217095. phenotype.
602054. gene.

neXtProt

NX_O43435.

Orphanet

1727. 22q11.2 microduplication syndrome.
567. Monosomy 22q11.

PharmGKB

PA36355.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG272513.

HOGENOM

HOG000286000.

HOVERGEN

HBG014448.

KO

K10175.

OMA

ANMYSAT.

Gene expression databases

ArrayExpress

O43435.

Bgee

O43435.

CleanEx

HS_TBX1.

Genevestigator

O43435.

GermOnline

ENSG00000184058. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.820. 1 hit.

InterPro

IPR008967. p53-like_TF_DNA-bd.
IPR001699. TF_T-box.
IPR018186. TF_T-box_CS.
[Graphical view]

PANTHER

PTHR11267. PTHR11267. 1 hit.

Pfam

PF00907. T-box. 1 hit.
[Graphical view]

PRINTS

PR00937. TBOX.

SMART

SM00425. TBOX. 1 hit.
[Graphical view]

SUPFAM

SSF49417. P53_like_DNA_bnd. 1 hit.

PROSITE

PS01283. TBOX_1. 1 hit.
PS01264. TBOX_2. 1 hit.
PS50252. TBOX_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

6899.

NextBio

26967.

SOURCE

Search...

Entry information

Entry name

TBX1_HUMAN

Accession

Primary (citable) accession number: O43435
Secondary accession number(s): C6G493 , C6G494, O43436, Q96RJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.