UniProt functional annotation for P52952



	UniProt functional annotation for P52952

UniProt code: P52952.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Transcription factor required for the development of the heart and the spleen (PubMed:22560297). During heart development, acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity). Binds to the core DNA motif of NPPA promoter (PubMed:22849347, PubMed:26926761). Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression (PubMed:22560297). {ECO:0000250|UniProtKB:P42582, ECO:0000269|PubMed:22560297, ECO:0000269|PubMed:22849347, ECO:0000269|PubMed:26926761}.

Subunit: Homodimer (via the homeobox); binds DNA as homodimer (PubMed:22849347). Interacts (via the homeobox) with TBX5 (via the T- box); this complex binds DNA (PubMed:26926761). 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. Interacts with TBX18 (By similarity). Interacts with histone methyltransferase NSD2 (via HMG box) (By similarity). {ECO:0000250|UniProtKB:P42582, ECO:0000269|PubMed:22849347, ECO:0000269|PubMed:26926761}.

Subcellular location: Nucleus {ECO:0000305}.

Tissue specificity: Expressed only in the heart.

Domain: The homeobox domain binds to double-stranded DNA (PubMed:22849347). {ECO:0000269|PubMed:22849347}.

Disease: Atrial septal defect 7, with or without atrioventricular conduction defects (ASD7) [MIM:108900]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria, and atrioventricular conduction defects in some cases. {ECO:0000269|PubMed:10587520, ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:15342699, ECO:0000269|PubMed:15810002, ECO:0000269|PubMed:9651244}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Tetralogy of Fallot (TOF) [MIM:187500]: 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. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. {ECO:0000269|PubMed:10587520, ECO:0000269|PubMed:11714651, ECO:0000269|PubMed:14607454}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: 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. {ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:17891434}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Hypothyroidism, congenital, non-goitrous, 5 (CHNG5) [MIM:225250]: A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. CHNG5 presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. {ECO:0000269|PubMed:16418214}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Ventricular septal defect 3 (VSD3) [MIM:614432]: A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. {ECO:0000269|PubMed:21110066, ECO:0000269|PubMed:21165553}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Hypoplastic left heart syndrome 2 (HLHS2) [MIM:614435]: A syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged. {ECO:0000269|PubMed:14607454, ECO:0000269|PubMed:15810002}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the NK-2 homeobox family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Transcription factor required for the development of the heart and the spleen (PubMed:22560297). During heart development, acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity). Binds to the core DNA motif of NPPA promoter (PubMed:22849347, PubMed:26926761). Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression (PubMed:22560297). {ECO:0000250\|UniProtKB:P42582, ECO:0000269\|PubMed:22560297, ECO:0000269\|PubMed:22849347, ECO:0000269\|PubMed:26926761}.


Subunit:		Homodimer (via the homeobox); binds DNA as homodimer (PubMed:22849347). Interacts (via the homeobox) with TBX5 (via the T- box); this complex binds DNA (PubMed:26926761). 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. Interacts with TBX18 (By similarity). Interacts with histone methyltransferase NSD2 (via HMG box) (By similarity). {ECO:0000250\|UniProtKB:P42582, ECO:0000269\|PubMed:22849347, ECO:0000269\|PubMed:26926761}.
Subcellular location:		Nucleus {ECO:0000305}.
Tissue specificity:		Expressed only in the heart.
Domain:		The homeobox domain binds to double-stranded DNA (PubMed:22849347). {ECO:0000269\|PubMed:22849347}.
Disease:		Atrial septal defect 7, with or without atrioventricular conduction defects (ASD7) [MIM:108900]: A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria, and atrioventricular conduction defects in some cases. {ECO:0000269\|PubMed:10587520, ECO:0000269\|PubMed:14607454, ECO:0000269\|PubMed:15342699, ECO:0000269\|PubMed:15810002, ECO:0000269\|PubMed:9651244}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Tetralogy of Fallot (TOF) [MIM:187500]: 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. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. {ECO:0000269\|PubMed:10587520, ECO:0000269\|PubMed:11714651, ECO:0000269\|PubMed:14607454}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		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. {ECO:0000269\|PubMed:14607454, ECO:0000269\|PubMed:17891434}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Hypothyroidism, congenital, non-goitrous, 5 (CHNG5) [MIM:225250]: A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. CHNG5 presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. {ECO:0000269\|PubMed:16418214}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Ventricular septal defect 3 (VSD3) [MIM:614432]: A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. {ECO:0000269\|PubMed:21110066, ECO:0000269\|PubMed:21165553}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Hypoplastic left heart syndrome 2 (HLHS2) [MIM:614435]: A syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged. {ECO:0000269\|PubMed:14607454, ECO:0000269\|PubMed:15810002}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the NK-2 homeobox family. {ECO:0000305}.