UniProt functional annotation for O60481



	UniProt functional annotation for O60481

UniProt code: O60481.

Organism: Homo sapiens (Human).

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

Function: Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC- 3'. {ECO:0000269|PubMed:17764085}.

Subunit: Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity (By similarity). Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity. {ECO:0000250, ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:18716025}.

Subcellular location: Nucleus. Cytoplasm {ECO:0000250}. Note=Localizes in the cytoplasm in presence of MDFIC overexpression (By similarity). Translocation to the nucleus requires KPNA1 or KPNA6. {ECO:0000250}.

Domain: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation. {ECO:0000250}.

Disease: Heterotaxy, visceral, 1, X-linked (HTX1) [MIM:306955]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left- right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. {ECO:0000269|PubMed:14681828, ECO:0000269|PubMed:17295247, ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:18716025, ECO:0000269|PubMed:24123890, ECO:0000269|PubMed:9354794}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: VACTERL association X-linked with or without hydrocephalus (VACTERLX) [MIM:314390]: A syndrome characterized by a non-random association of congenital defects. Affected individuals manifest vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) such as urethral atresia with hydronephrosis, and limb anomalies (L) such as hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb. Some patients may have hydrocephalus. Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement. {ECO:0000269|PubMed:20452998, ECO:0000269|PubMed:24123890}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Congenital heart defects, multiple types, 1, X-linked (CHTD1) [MIM:306955]: A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. {ECO:0000269|PubMed:14681828, ECO:0000269|PubMed:17764085, ECO:0000269|PubMed:24123890}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the GLI C2H2-type zinc-finger protein 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:		Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC- 3'. {ECO:0000269\|PubMed:17764085}.


Subunit:		Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity (By similarity). Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity. {ECO:0000250, ECO:0000269\|PubMed:17764085, ECO:0000269\|PubMed:18716025}.
Subcellular location:		Nucleus. Cytoplasm {ECO:0000250}. Note=Localizes in the cytoplasm in presence of MDFIC overexpression (By similarity). Translocation to the nucleus requires KPNA1 or KPNA6. {ECO:0000250}.
Domain:		The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation. {ECO:0000250}.
Disease:		Heterotaxy, visceral, 1, X-linked (HTX1) [MIM:306955]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left- right axis and with respect to one another. It can be associated with a variety of congenital defects including cardiac malformations. {ECO:0000269\|PubMed:14681828, ECO:0000269\|PubMed:17295247, ECO:0000269\|PubMed:17764085, ECO:0000269\|PubMed:18716025, ECO:0000269\|PubMed:24123890, ECO:0000269\|PubMed:9354794}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		VACTERL association X-linked with or without hydrocephalus (VACTERLX) [MIM:314390]: A syndrome characterized by a non-random association of congenital defects. Affected individuals manifest vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheoesophageal fistula (TE), renal anomalies (R) such as urethral atresia with hydronephrosis, and limb anomalies (L) such as hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb. Some patients may have hydrocephalus. Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement. {ECO:0000269\|PubMed:20452998, ECO:0000269\|PubMed:24123890}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Congenital heart defects, multiple types, 1, X-linked (CHTD1) [MIM:306955]: A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, and patent ductus arteriosus. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. {ECO:0000269\|PubMed:14681828, ECO:0000269\|PubMed:17764085, ECO:0000269\|PubMed:24123890}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the GLI C2H2-type zinc-finger protein family. {ECO:0000305}.