Reviewed,
UniProtKB/Swiss-Prot P52952 (NKX25_HUMAN)
Last modified
November 25, 2008.
Version 90.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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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 |
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| 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 | 324 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
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. |
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 promoterInferred 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.4Inferred from direct assay. Source: UniProtKB transcription repressor activityInferred from sequence or structural similarity. Source: UniProtKB |
| Complete GO annotation... | |
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 | 60 | Homeobox | ||||||
| Compositional bias | 42 – 108 | 67 | Ala/Pro-rich | ||||||
| Compositional bias | 208 – 282 | 75 | Ala/Pro-rich | ||||||
Natural variations | |||||||||
| Natural variant | 7 | 1 | L → P in ASD-AVCD; somatic mutation. | VAR_038212 | |||||
| Natural variant | 15 | 1 | K → I in ASD-AVCD. | VAR_038213 | |||||
| Natural variant | 19 | 1 | N → S in ASD-AVCD; somatic mutation. | VAR_038214 | |||||
| Natural variant | 21 | 1 | E → Q in TOF and ASD-AVCD. | VAR_038215 | |||||
| Natural variant | 22 | 1 | Q → P in ASD-AVCD. | VAR_038216 | |||||
| Natural variant | 25 | 1 | R → C in ASD-AVCD and TOF; uncertain pathological significance. | VAR_010116 | |||||
| Natural variant | 45 | 1 | S → P in ASD-AVCD; somatic mutation. | VAR_038217 | |||||
| Natural variant | 51 | 1 | F → L in ASD-AVCD; somatic mutation. | VAR_038218 | |||||
| Natural variant | 63 | 1 | A → V in ASD-AVCD. | VAR_038219 | |||||
| Natural variant | 69 | 1 | L → P in ASD-AVCD; somatic mutation. | VAR_038220 | |||||
| Natural variant | 77 | 1 | P → L in ASD-AVCD; somatic mutation. | VAR_038221 | |||||
| Natural variant | 114 | 1 | C → R in ASD-AVCD; somatic mutation. | VAR_038222 | |||||
| Natural variant | 114 | 1 | C → S in ASD-AVCD; somatic mutation. | VAR_038223 | |||||
| Natural variant | 118 | 1 | K → R in ASD-AVCD; somatic mutation. | VAR_038224 | |||||
| Natural variant | 124 | 1 | K → R in ASD-AVCD; somatic mutation. | VAR_038225 | |||||
| Natural variant | 126 | 1 | E → V in ASD-AVCD; somatic mutation. | VAR_038226 | |||||
| Natural variant | 127 | 1 | A → E in ASD-AVCD. | VAR_038227 | |||||
| Natural variant | 133 | 1 | P → S in ASD-AVCD; somatic mutation. | VAR_038228 | |||||
| Natural variant | 135 | 1 | A → T in ASD-AVCD; somatic mutation. | VAR_038229 | |||||
| Natural variant | 142 | 1 | R → C in ASD-AVCD. | VAR_038230 | |||||
| Natural variant | 144 | 1 | L → P in ASD-AVCD; somatic mutation. | VAR_038231 | |||||
| Natural variant | 178 | 1 | T → M in ASD-AVCD. | VAR_003752 | |||||
| Natural variant | 183 | 1 | K → E in ASD-AVCD; somatic mutation. | VAR_038232 | |||||
| Natural variant | 187 | 1 | Q → H in ASD-AVCD. | VAR_038233 | |||||
| Natural variant | 188 | 1 | N → K in ASD-AVCD. | VAR_010117 | |||||
| Natural variant | 189 | 1 | R → G in ASD-AVCD. | VAR_010118 | |||||
| Natural variant | 190 | 1 | R → C in ASD-AVCD. | VAR_038234 | |||||
| Natural variant | 191 | 1 | Y → C in ASD-AVCD. | VAR_010119 | |||||
| Natural variant | 192 | 1 | K → R in ASD-AVCD; somatic mutation. | VAR_038235 | |||||
| Natural variant | 192 | 1 | K → T in ASD-AVCD; somatic mutation. | VAR_038236 | |||||
| Natural variant | 194 | 1 | K → R in ASD-AVCD; somatic mutation. | VAR_038237 | |||||
| Natural variant | 205 | 1 | V → E in ASD-AVCD; somatic mutation. | VAR_038238 | |||||
| Natural variant | 216 | 1 | R → C in TOF and ASD-AVCD. | VAR_038239 | |||||
| Natural variant | 219 | 1 | A → V in ASD-AVCD and TOF; somatic mutation. | VAR_038240 | |||||
| Natural variant | 226 | 1 | D → N in ASD-AVCD; somatic mutation. | VAR_038241 | |||||
| Natural variant | 248 | 1 | Y → H in ASD-AVCD; somatic mutation. | VAR_038242 | |||||
| Natural variant | 275 | 1 | P → T in ASD-AVCD. | VAR_038243 | |||||
| Natural variant | 279 | 1 | S → F in ASD-AVCD; somatic mutation. | VAR_038244 | |||||
| Natural variant | 279 | 1 | S → P in ASD-AVCD; somatic mutation. | VAR_038245 | |||||
| Natural variant | 281 | 1 | A → V in ASD-AVCD; somatic mutation. | VAR_038246 | |||||
| Natural variant | 286 | 1 | A → V in ASD-AVCD; somatic mutation. | VAR_038247 | |||||
| Natural variant | 294 | 1 | N → H in ASD-AVCD; somatic mutation. | VAR_038248 | |||||
| Natural variant | 299 | 1 | D → G in ASD-AVCD; somatic mutation. | VAR_038249 | |||||
| Natural variant | 305 | 1 | S → G in ASD-AVCD; somatic mutation. | VAR_038250 | |||||
| Natural variant | 320 | 1 | G → S in ASD-AVCD; somatic mutation. | VAR_038251 | |||||
| Natural variant | 322 | 1 | R → Q in ASD-AVCD; somatic mutation. | VAR_038252 | |||||
| Natural variant | 323 | 1 | A → T in ASD-AVCD. | VAR_038253 | |||||
Sequences
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References
| « Hide '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. |
Web resources
| Atlas of Genetics and Cytogenetics in Oncology and Haematology |
| GeneDis Congenital heart disease website |
| GeneReviews |
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... |
Entry information
| Entry name | NKX25_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P52952 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |

Clusters with


