Homeobox protein Nkx-2.5 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot P52952 (NKX25_HUMAN)

Last modified November 25, 2008. Version 90. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Homeobox protein Nkx-2.5
Alternative name(s):
    Homeobox protein NK-2 homolog E
    Cardiac-specific homeobox
    Homeobox protein CSX

Gene names

Name:	NKX2-5
Synonyms:	CSX, NKX2.5, NKX2E

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	324 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4 By similarity.
Subunit structure	Interacts with HIPK1 and HIPK2, but not HIPK3. Interacts with the C-terminal zinc finger of GATA4 through its homeobox domain. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts with FBLIM1 By similarity.
Subcellular location	NucleusProbable.
Tissue specificity	Expressed only in the heart.
Involvement in disease	Defects in NKX2-5 are the cause of atrial septal defect with atrioventricular conduction defects (ASD-AVCD) [MIM:108900]. ASD-AVCD is a congenital heart malformation characterized by atrioventricular conduction defects and incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria. Defects in NKX2-5 are a cause of tetralogy of Fallot (TOF) [MIM:187500]. TOF is a congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. This condition results in a blue baby at birth due to inadequate oxygenation. Surgical correction is emergent.
Sequence similarities	Belongs to the NK-2 homeobox family. Contains 1 homeobox DNA-binding domain.

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Ontologies

Keywords
Cellular component	Nucleus
Disease	Atrial septal defect Disease mutation
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI
Cellular component	transcription factor complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Ref.4 Inferred from direct assay. Source: UniProtKB transcription repressor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
TBX5	Q99593-1	2	EBI-936601,EBI-304423

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 324

324

Homeobox protein Nkx-2.5

PRO_0000048937

Regions

DNA binding

138 – 197

Homeobox

Compositional bias

42 – 108

Ala/Pro-rich

Compositional bias

208 – 282

Ala/Pro-rich

Natural variations

Natural variant

L → P in ASD-AVCD; somatic mutation.

VAR_038212

Natural variant

K → I in ASD-AVCD.

VAR_038213

Natural variant

N → S in ASD-AVCD; somatic mutation.

VAR_038214

Natural variant

E → Q in TOF and ASD-AVCD.

VAR_038215

Natural variant

Q → P in ASD-AVCD.

VAR_038216

Natural variant

R → C in ASD-AVCD and TOF; uncertain pathological significance.

VAR_010116

Natural variant

S → P in ASD-AVCD; somatic mutation.

VAR_038217

Natural variant

F → L in ASD-AVCD; somatic mutation.

VAR_038218

Natural variant

A → V in ASD-AVCD.

VAR_038219

Natural variant

L → P in ASD-AVCD; somatic mutation.

VAR_038220

Natural variant

P → L in ASD-AVCD; somatic mutation.

VAR_038221

Natural variant

114

C → R in ASD-AVCD; somatic mutation.

VAR_038222

Natural variant

114

C → S in ASD-AVCD; somatic mutation.

VAR_038223

Natural variant

118

K → R in ASD-AVCD; somatic mutation.

VAR_038224

Natural variant

124

K → R in ASD-AVCD; somatic mutation.

VAR_038225

Natural variant

126

E → V in ASD-AVCD; somatic mutation.

VAR_038226

Natural variant

127

A → E in ASD-AVCD.

VAR_038227

Natural variant

133

P → S in ASD-AVCD; somatic mutation.

VAR_038228

Natural variant

135

A → T in ASD-AVCD; somatic mutation.

VAR_038229

Natural variant

142

R → C in ASD-AVCD.

VAR_038230

Natural variant

144

L → P in ASD-AVCD; somatic mutation.

VAR_038231

Natural variant

178

T → M in ASD-AVCD.

VAR_003752

Natural variant

183

K → E in ASD-AVCD; somatic mutation.

VAR_038232

Natural variant

187

Q → H in ASD-AVCD.

VAR_038233

Natural variant

188

N → K in ASD-AVCD.

VAR_010117

Natural variant

189

R → G in ASD-AVCD.

VAR_010118

Natural variant

190

R → C in ASD-AVCD.

VAR_038234

Natural variant

191

Y → C in ASD-AVCD.

VAR_010119

Natural variant

192

K → R in ASD-AVCD; somatic mutation.

VAR_038235

Natural variant

192

K → T in ASD-AVCD; somatic mutation.

VAR_038236

Natural variant

194

K → R in ASD-AVCD; somatic mutation.

VAR_038237

Natural variant

205

V → E in ASD-AVCD; somatic mutation.

VAR_038238

Natural variant

216

R → C in TOF and ASD-AVCD.

VAR_038239

Natural variant

219

A → V in ASD-AVCD and TOF; somatic mutation.

VAR_038240

Natural variant

226

D → N in ASD-AVCD; somatic mutation.

VAR_038241

Natural variant

248

Y → H in ASD-AVCD; somatic mutation.

VAR_038242

Natural variant

275

P → T in ASD-AVCD.

VAR_038243

Natural variant

279

S → F in ASD-AVCD; somatic mutation.

VAR_038244

Natural variant

279

S → P in ASD-AVCD; somatic mutation.

VAR_038245

Natural variant

281

A → V in ASD-AVCD; somatic mutation.

VAR_038246

Natural variant

286

A → V in ASD-AVCD; somatic mutation.

VAR_038247

Natural variant

294

N → H in ASD-AVCD; somatic mutation.

VAR_038248

Natural variant

299

D → G in ASD-AVCD; somatic mutation.

VAR_038249

Natural variant

305

S → G in ASD-AVCD; somatic mutation.

VAR_038250

Natural variant

320

G → S in ASD-AVCD; somatic mutation.

VAR_038251

Natural variant

322

R → Q in ASD-AVCD; somatic mutation.

VAR_038252

Natural variant

323

A → T in ASD-AVCD.

VAR_038253

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Sequences

Sequence

Length

Mass (Da)

Tools

P52952-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: ACCC9C2F9C292586
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FASTA

324

34,918

        10         20         30         40         50         60 
MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA FKPEAYAGPE 

        70         80         90        100        110        120 
AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP DPAKDPRAEK KELCALQKAV 

       130        140        150        160        170        180 
ELEKTEADNA ERPRARRRRK PRVLFSQAQV YELERRFKQQ RYLSAPERDQ LASVLKLTST 

       190        200        210        220        230        240 
QVKIWFQNRR YKCKRQRQDQ TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA 

       250        260        270        280        290        300 
YGVGLNPYGY NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL 

       310        320 
NAVQSPGIPQ SNSGVSTLHG IRAW

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning, chromosomal mapping, and characterization of the human cardiac-specific homeobox gene hCsx." Turbay D., Wechsler S.B., Blanchard K.M., Izumo S. Mol. Med. 2:86-96(1996) [PubMed: 8900537] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart.
[2]	"Human Nkx-2.5 gene." Tate G., Mitsuya T. Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal lung.
[3]	"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: Pancreas and Spleen.
[4]	"Congenital heart disease caused by mutations in the transcription factor NKX2-5." Schott J.-J., Benson D.W., Basson C.T., Pease W., Silberbach G.M., Moak J.P., Maron B.J., Seidman C.E., Seidman J.G. Science 281:108-111(1998) [PubMed: 9651244] [Abstract] Cited for: VARIANT ASD-AVCD MET-178.
[5]	"Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways." Benson D.W., Silberbach G.M., Kavanaugh-McHugh A., Cottrill C., Zhang Y., Riggs S., Smalls O., Johnson M.C., Watson M.S., Seidman J.G., Seidman C.E., Plowden J., Kugler J.D. J. Clin. Invest. 104:1567-1573(1999) [PubMed: 10587520] [Abstract] Cited for: VARIANT TOF CYS-25, VARIANTS ASD-AVCD LYS-188; GLY-189 AND CYS-191.
[6]	"NKX2.5 mutations in patients with tetralogy of fallot." Goldmuntz E., Geiger E., Benson D.W. Circulation 104:2565-2568(2001) [PubMed: 11714651] [Abstract] Cited for: VARIANTS TOF GLN-21; CYS-25; CYS-216 AND VAL-219.
[7]	"Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease." Reamon-Buettner S.M., Borlak J. J. Med. Genet. 41:684-690(2004) [PubMed: 15342699] [Abstract] Cited for: VARIANTS ASD-AVCD PRO-7; SER-19; CYS-25; PRO-45; LEU-51; PRO-69; LEU-77; SER-114; ARG-114; ARG-118; ARG-124; VAL-126; SER-133; THR-135; PRO-144; MET-178; GLU-183; THR-192; ARG-192; ARG-194; GLU-205; VAL-219; ASN-226; HIS-248; PRO-279; PHE-279; VAL-281; VAL-286; HIS-294; GLY-299; GLY-305; SER-320 AND GLN-322.
[8]	"Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect." Hirayama-Yamada K., Kamisago M., Akimoto K., Aotsuka H., Nakamura Y., Tomita H., Furutani M., Imamura S., Takao A., Nakazawa M., Matsuoka R. Am. J. Med. Genet. A 135:47-52(2005) [PubMed: 15810002] [Abstract] Cited for: VARIANTS ASD-AVCD ILE-15; GLN-21; PRO-22; CYS-25; VAL-63; GLU-127; CYS-142; MET-178; HIS-187; LYS-188; GLY-189; CYS-190; CYS-191; CYS-216; VAL-219; THR-275 AND THR-323.
+	Additional computationally mapped references.

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Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneDis

Congenital heart disease website

GeneReviews

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Cross-references

Sequence databases
	U34962 mRNA. Translation: AAC50470.1. AB021133 mRNA. Translation: BAA35181.1. BC025711 mRNA. Translation: AAH25711.1.
RefSeq	NP_004378.1.
UniGene	Hs.54473
3D structure databases
HSSP	HSSP built from PDB template 1FTT based on UniProtKB P23441.
SMR	P52952. Positions 138-203.
ModBase	Search...
Protein-protein interaction databases
IntAct	P52952.
PTM databases
PhosphoSite	P52952.
Genome annotation databases
Ensembl	ENSG00000183072. Homo sapiens. [Contig view]
GeneID	1482.
KEGG	hsa:1482.
Organism-specific databases
H-InvDB	HIX0005426.
HGNC	HGNC:2488. NKX2-5.
MIM	108900. phenotype. 187500. phenotype. 600584. gene.
Orphanet	1479. Atrial septal defect atrioventricular conduction. 871. Cardiac conduction defect, familial. 1478. Interauricular communication. 3303. Tetralogy of Fallot.
PharmGKB	PA24202.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P52952.
HOVERGEN	P52952.
Gene expression databases
ArrayExpress	P52952.
CleanEx	HS_NKX2-5.
GermOnline	ENSG00000183072. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00024. HOMEOBOX.
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	P52952.
NextBio	6089.
SOURCE	Search...

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Entry information

Entry name

NKX25_HUMAN

Accession

Primary (citable) accession number: P52952

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 25, 2008
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents