UniProt functional annotation for Q63ZY3



	UniProt functional annotation for Q63ZY3

UniProt code: Q63ZY3.

Organism: Homo sapiens (Human).

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

Function: Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3 (PubMed:17476305). Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria (PubMed:22371500). Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis (PubMed:22371500). Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081). Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway (PubMed:17996375, PubMed:25961457). May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney (PubMed:25961457). Through the Rho signaling pathway may also regulate cell proliferation (By similarity). {ECO:0000250|UniProtKB:Q8BX02, ECO:0000269|PubMed:17476305, ECO:0000269|PubMed:17996375, ECO:0000269|PubMed:22371500, ECO:0000269|PubMed:24671081, ECO:0000269|PubMed:25961457}.

Subunit: Interacts (non-phosphorylated form) with NCOA1; NCOA2 AND NCOA3 (PubMed:17476305). Interacts with AIFM1 (PubMed:22371500). Interacts with ARHGDIA; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (PubMed:25961457). Interacts (via ANK repeats 1-5) with KIF21A (via residues 1146-1167) (PubMed:29183992). {ECO:0000269|PubMed:17476305, ECO:0000269|PubMed:22371500, ECO:0000269|PubMed:25961457, ECO:0000269|PubMed:29183992}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:17476305, ECO:0000269|PubMed:17996375, ECO:0000269|PubMed:22371500, ECO:0000269|PubMed:25961457}. Mitochondrion {ECO:0000269|PubMed:22371500}.

Tissue specificity: Strongly expressed in cervix, colon, heart, kidney and lung. Expressed in kidney glomerular podocytes and mesangial cells (at protein level). {ECO:0000269|PubMed:17996375, ECO:0000269|PubMed:20720434}.

Ptm: Phosphorylated by casein kinase II upon estrogen stimulation (PubMed:17476305). Phosphorylation induces the release by KANK2 of NCOA1 and its translocation to the nucleus where NCOA1 can activate gene transcription (PubMed:17476305). {ECO:0000269|PubMed:17476305}.

Disease: Palmoplantar keratoderma and woolly hair (PPKWH) [MIM:616099]: A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe. {ECO:0000269|PubMed:24671081}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Nephrotic syndrome 16 (NPHS16) [MIM:617783]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS16 inheritance is autosomal recessive. {ECO:0000269|PubMed:25961457}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=BAA92081.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA96042.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14531.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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:		Involved in transcription regulation by sequestering in the cytoplasm nuclear receptor coactivators such as NCOA1, NCOA2 and NCOA3 (PubMed:17476305). Involved in regulation of caspase-independent apoptosis by sequestering the proapoptotic factor AIFM1 in mitochondria (PubMed:22371500). Pro-apoptotic stimuli can induce its proteasomal degradation allowing the translocation of AIFM1 to the nucleus to induce apoptosis (PubMed:22371500). Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081). Involved in actin stress fibers formation through its interaction with ARHGDIA and the regulation of the Rho signaling pathway (PubMed:17996375, PubMed:25961457). May thereby play a role in cell adhesion and migration, regulating for instance podocytes migration during development of the kidney (PubMed:25961457). Through the Rho signaling pathway may also regulate cell proliferation (By similarity). {ECO:0000250\|UniProtKB:Q8BX02, ECO:0000269\|PubMed:17476305, ECO:0000269\|PubMed:17996375, ECO:0000269\|PubMed:22371500, ECO:0000269\|PubMed:24671081, ECO:0000269\|PubMed:25961457}.


Subunit:		Interacts (non-phosphorylated form) with NCOA1; NCOA2 AND NCOA3 (PubMed:17476305). Interacts with AIFM1 (PubMed:22371500). Interacts with ARHGDIA; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (PubMed:25961457). Interacts (via ANK repeats 1-5) with KIF21A (via residues 1146-1167) (PubMed:29183992). {ECO:0000269\|PubMed:17476305, ECO:0000269\|PubMed:22371500, ECO:0000269\|PubMed:25961457, ECO:0000269\|PubMed:29183992}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:17476305, ECO:0000269\|PubMed:17996375, ECO:0000269\|PubMed:22371500, ECO:0000269\|PubMed:25961457}. Mitochondrion {ECO:0000269\|PubMed:22371500}.
Tissue specificity:		Strongly expressed in cervix, colon, heart, kidney and lung. Expressed in kidney glomerular podocytes and mesangial cells (at protein level). {ECO:0000269\|PubMed:17996375, ECO:0000269\|PubMed:20720434}.
Ptm:		Phosphorylated by casein kinase II upon estrogen stimulation (PubMed:17476305). Phosphorylation induces the release by KANK2 of NCOA1 and its translocation to the nucleus where NCOA1 can activate gene transcription (PubMed:17476305). {ECO:0000269\|PubMed:17476305}.
Disease:		Palmoplantar keratoderma and woolly hair (PPKWH) [MIM:616099]: A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe. {ECO:0000269\|PubMed:24671081}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Nephrotic syndrome 16 (NPHS16) [MIM:617783]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS16 inheritance is autosomal recessive. {ECO:0000269\|PubMed:25961457}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=BAA92081.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAA96042.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; Sequence=BAB14531.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};