Q99593 (TBX5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
T-box transcription factor TBX5
Short name=T-box protein 5

Gene names

Name:

TBX5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	518 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the transcriptional regulation of genes required for mesoderm differentiation. Probably plays a role in limb pattern formation.
Subunit structure	Monomer. Ref.5
Subcellular location	Nucleus Potential.
Involvement in disease	Defects in TBX5 are the cause of Holt-Oram syndrome (HOS) [MIM:142900]. HOS is a developmental disorder affecting the heart and upper limbs. It is characterized by thumb anomaly and atrial septal defects. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8
Sequence similarities	Contains 1 T-box DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cardiac left ventricle formation Inferred from sequence or structural similarity. Source: BHF-UCL cell migration involved in coronary vasculogenesis Traceable author statement. Source: DFLAT cell-cell signaling Inferred from direct assay. Source: UniProtKB embryonic arm morphogenesis Inferred from mutant phenotype. Source: UniProtKB induction of apoptosis Inferred from direct assay. Source: UniProtKB negative regulation of cardiac muscle cell proliferation Inferred from direct assay. Source: UniProtKB negative regulation of cell migration Inferred from direct assay. Source: UniProtKB negative regulation of epithelial to mesenchymal transition Traceable author statement. Source: DFLAT pericardium development Inferred from direct assay. Source: UniProtKB positive regulation of cardioblast differentiation Inferred from direct assay. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ventricular septum development Inferred from sequence or structural similarity. Source: BHF-UCL
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	protein binding Inferred from physical interaction. Source: IntAct sequence-specific DNA binding Inferred from direct assay. Source: UniProtKB sequence-specific DNA binding transcription factor activity Inferred from direct assay. Source: UniProtKB transcription factor binding Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Gata4	Q08369	2	EBI-297043,EBI-297008	From a different organism.
NKX2-5	P52952	6	EBI-304423,EBI-936601

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: Q99593-1)

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 Short (identifier: Q99593-2)

The sequence of this isoform differs from the canonical sequence as follows:
     328-349: EEECSTTDHPYKKPYMETSPSE → GECDHPWSICFLSYLFLSLGWG
     350-518: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 518

518

T-box transcription factor TBX5

PRO_0000184435

Regions

DNA binding

58 – 238

181

T-box

Natural variations

Alternative sequence

328 – 349

22

EEECS…TSPSE → GECDHPWSICFLSYLFLSLG WG in isoform Short.

VSP_006387

Alternative sequence

350 – 518

169

Missing in isoform Short.

VSP_006388

Natural variant

49

1

Q → K in HOS. Ref.7

VAR_015381

Natural variant

54

1

I → T in HOS. Ref.7

VAR_015382

Natural variant

80

1

G → R in HOS; significant cardiac malformations but only minor skeletal abnormalities; reduced protein stability and strongly reduced affinity for DNA. Ref.5 Ref.6

VAR_009701

Natural variant

237

1

R → Q in HOS; extensive upper limb malformations; affects transcriptional regulation of MYH6. Ref.2 Ref.6 Ref.8

VAR_007456

Natural variant

237

1

R → W in HOS; extensive upper limb malformations; strongly reduced affinity for DNA. Ref.5 Ref.6

VAR_009702

Experimental info

Sequence conflict

7 – 49

43

GFGLA…AFTQQ → ALAGAHLWSLTQKTCLRFEP RARSGPPASPPGRPRSRLHP A in CAA70592. Ref.1

Sequence conflict

71

1

Missing in CAA70592. Ref.1

Sequence conflict

94

1

L → I in CAA70592. Ref.1

Sequence conflict

122

1

S → C in CAA70592. Ref.1

Sequence conflict

132

1

P → A in CAA70592. Ref.1

Sequence conflict

418 – 460

43

MDRLP…QHQTS → WTGYPTSTSPLTSPRGPWSL GWLAWQPWLPTAGRGNVPST RPP in CAA70592. Ref.1

Sequence conflict

468 – 470

3

RQC → SSV in CAA70592. Ref.1

Sequence conflict

494 – 518

25

PRTLS…WSDNS → QGLYPLISTTLCTELAWCRV ERQ in CAA70592. Ref.1

Secondary structure

1

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518

Helix Strand Turn

Details...

Beta strand

55 – 58

4

Helix

61 – 69

9

Beta strand

73 – 75

3

Beta strand

88 – 92

5

Beta strand

96 – 98

3

Beta strand

100 – 117

18

Beta strand

120 – 123

4

Helix

147 – 150

4

Beta strand

151 – 154

4

Beta strand

159 – 161

3

Beta strand

177 – 187

11

Beta strand

201 – 204

4

Helix

207 – 209

3

Beta strand

211 – 216

6

Helix

220 – 229

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified December 1, 2000. Version 2. Checksum: 70118AD84FF5C00F	FASTA	518	57,711
	10 20 30 40 50 60 MADADEGFGL AHTPLEPDAK DLPCDSKPES ALGAPSKSPS SPQAAFTQQG MEGIKVFLHE 70 80 90 100 110 120 RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY ILLMDIVPAD DHRYKFADNK 130 140 150 160 170 180 WSVTGKAEPA MPGRLYVHPD SPATGAHWMR QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ 190 200 210 220 230 240 PRLHIVKADE NNGFGSKNTA FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD 250 260 270 280 290 300 DMELHRMSRM QSKEYPVVPR STVRQKVASN HSPFSSESRA LSTSSNLGSQ YQCENGVSGP 310 320 330 340 350 360 SQDLLPPPNP YPLPQEHSQI YHCTKRKEEE CSTTDHPYKK PYMETSPSEE DSFYRSSYPQ 370 380 390 400 410 420 QQGLGASYRT ESAQRQACMY ASSAPPSEPV PSLEDISCNT WPSMPSYSSC TVTTVQPMDR 430 440 450 460 470 480 LPYQHFSAHF TSGPLVPRLA GMANHGSPQL GEGMFQHQTS VAHQPVVRQC GPQTGLQSPG 490 500 510 TLQPPEFLYS HGVPRTLSPH QYHSVHGVGM VPEWSDNS
	Isoform Short [UniParc]. Checksum: 50CE556CD97ACD76	FASTA	349	39,196
	10 20 30 40 50 60 MADADEGFGL AHTPLEPDAK DLPCDSKPES ALGAPSKSPS SPQAAFTQQG MEGIKVFLHE 70 80 90 100 110 120 RELWLKFHEV GTEMIITKAG RRMFPSYKVK VTGLNPKTKY ILLMDIVPAD DHRYKFADNK 130 140 150 160 170 180 WSVTGKAEPA MPGRLYVHPD SPATGAHWMR QLVSFQKLKL TNNHLDPFGH IILNSMHKYQ 190 200 210 220 230 240 PRLHIVKADE NNGFGSKNTA FCTHVFPETA FIAVTSYQNH KITQLKIENN PFAKGFRGSD 250 260 270 280 290 300 DMELHRMSRM QSKEYPVVPR STVRQKVASN HSPFSSESRA LSTSSNLGSQ YQCENGVSGP 310 320 330 340 SQDLLPPPNP YPLPQEHSQI YHCTKRKGEC DHPWSICFLS YLFLSLGWG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family." Li Q.Y., Newbury-Ecob R., Terrett J.A., Wilson D.I., Curtis A., Yi C.H., Bullen P.J., Strachan T., Robson S., Bonnet D., Young I.E., Raeburn J.A., Buckler A.J., Gebuhr T., Law D.J., Brook J.D. Nat. Genet. 15:21-29(1997) [PubMed: 8988164] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome." Basson C.T., Bachinsky D.R., Lin R.C., Levi T., Elkins J.A., Soults J., Grayzel D., Kroumpouzou E., Traill T.A., Leblanc-Straceski J., Renault B., Kucherlapati R., Seidman J.G., Seidman C.E. Nat. Genet. 15:30-35(1997) [PubMed: 8988165] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, VARIANT HOS GLN-237.
[3]	"The mutation spectrum in Holt-Oram syndrome." Cross S.J., Ching Y.-H., Li Q.Y., Armstrong-Buisseret L., Spranger S., Lyonnet S., Bonnet D., Penttinen M., Jonveaux P., Leheup B., Mortier G., Van Ravenswaaij C., Gardiner C.A. J. Med. Genet. 37:785-787(2000) [PubMed: 11183182] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Spleen.
[5]	"Structural basis of TBX5-DNA recognition: the T-box domain in its DNA-bound and -unbound form." Stirnimann C.U., Ptchelkine D., Grimm C., Muller C.W. J. Mol. Biol. 400:71-81(2010) [PubMed: 20450920] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 51-251 IN COMPLEX WITH DNA, CHARACTERIZATION OF VARIANTS HOS ARG-80 AND TRP-237, SUBUNIT.
[6]	"Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations." Basson C.T., Huang T., Lin R.C., Bachinksy D.R., Weremowicz S., Vaglio A., Bruzzone R., Quadrelli R., Lerone M., Romeo G., Silengo M., Pereira A., Krieger J., Mesquita S.F., Kamisago M., Morton C.C., Pierpont M.E.M., Muller C.W., Seidman J.G., Seidman C.E. Proc. Natl. Acad. Sci. U.S.A. 96:2919-2924(1999) [PubMed: 10077612] [Abstract] Cited for: VARIANTS HOS ARG-80; GLN-237 AND TRP-237.
[7]	"Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome." Yang J., Hu D., Xia J., Yang Y., Ying B., Hu J., Zhou X. Am. J. Med. Genet. 92:237-240(2000) [PubMed: 10842287] [Abstract] Cited for: VARIANTS HOS LYS-49 AND THR-54.
[8]	"Mutation in myosin heavy chain 6 causes atrial septal defect." Ching Y.-H., Ghosh T.K., Cross S.J., Packham E.A., Honeyman L., Loughna S., Robinson T.E., Dearlove A.M., Ribas G., Bonser A.J., Thomas N.R., Scotter A.J., Caves L.S.D., Tyrrell G.P., Newbury-Ecob R.A., Munnich A., Bonnet D., Brook J.D. Nat. Genet. 37:423-428(2005) [PubMed: 15735645] [Abstract] Cited for: CHARACTERIZATION OF VARIANT HOS GLN-237.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Y09445 mRNA. Translation: CAA70592.1.
U89353 mRNA. Translation: AAC04619.1.
U80987 mRNA. Translation: AAC51644.1.
AF221714 mRNA. Translation: AAF34659.1.
BC027942 mRNA. Translation: AAH27942.1.

IPI

IPI00216449.
IPI00218492.

RefSeq

NP_000183.2. NM_000192.3.
NP_542448.1. NM_080717.2.
NP_542449.1. NM_080718.1.
NP_852259.1. NM_181486.1.

UniGene

Hs.381715.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X6U	X-ray	1.90	A	51-251	[»]
2X6V	X-ray	2.20	A/B	51-251	[»]

ProteinModelPortal

Q99593.

SMR

Q99593. Positions 52-230.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q99593. 4 interactions.

STRING

Q99593.

PTM databases

PhosphoSite

Q99593.

Polymorphism databases

DMDM

12644474.

Proteomic databases

PRIDE

Q99593.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000310346; ENSP00000309913; ENSG00000089225.
ENST00000405440; ENSP00000384152; ENSG00000089225.

GeneID

6910.

KEGG

hsa:6910.

UCSC

uc001tvo.1. human.
uc001tvr.1. human.

Organism-specific databases

CTD

6910.

GeneCards

GC12M114791.

H-InvDB

HIX0011026.

HGNC

HGNC:11604. TBX5.

HPA

HPA008786.

MIM

142900. phenotype.
601620. gene.

neXtProt

NX_Q99593.

Orphanet

392. Holt-Oram syndrome.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12223.

GeneTree

ENSGT00600000084211.

HOGENOM

HBG713452.

HOVERGEN

HBG007310.

InParanoid

Q99593.

OMA

PFYRSSY.

OrthoDB

EOG42Z4PW.

PhylomeDB

Q99593.

Gene expression databases

ArrayExpress

Q99593.

Bgee

Q99593.

CleanEx

HS_TBX5.

Genevestigator

Q99593.

GermOnline

ENSG00000089225. Homo sapiens.

Family and domain databases

InterPro

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

Gene3D

G3DSA:2.60.40.820. TF_T-box. 1 hit.

KO

K10179.

PANTHER

PTHR11267. TF_T-box. 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

NextBio

27023.

SOURCE

Search...

Entry information

Entry name

TBX5_HUMAN

Accession

Primary (citable) accession number: Q99593
Secondary accession number(s): O15301, Q9Y4I2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 121 of the entry and version 2 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.