UniProt functional annotation for Q15650



	UniProt functional annotation for Q15650

UniProt code: Q15650.

Organism: Homo sapiens (Human).

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

Function: Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription. May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions. Plays a role in thyroid hormone receptor and estrogen receptor transactivation (PubMed:10454579, PubMed:25219498). Also involved in androgen receptor transactivation (By similarity). Plays a pivotal role in the transactivation of NF-kappa-B, SRF and AP1. Acts as a mediator of transrepression between nuclear receptor and either AP1 or NF-kappa-B (PubMed:12077347). May play a role in the development of neuromuscular junction (PubMed:26924529). May play a role in late myogenic differentiation (By similarity). {ECO:0000250|UniProtKB:Q9QXN3, ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:26924529}.

Subunit: Interacts with the thyroid hormone receptor/TR (via the ligand-binding domain); this interaction requires the presence of thyroid hormone (PubMed:10454579). Interacts with the androgen receptor/AR; in an androgen, testosterone and dihydrotestosterone- dependent manner (PubMed:12390891). Interacts with ESR1 (estrogen ligand-bound); competes with UFSP2 (PubMed:10454579, PubMed:25219498). Interacts with UFSP2; competes with ligand-bound ESR1 (PubMed:25219498). Interacts with DDRGK1 and UFL1; the interaction with DDRGK1 is direct (PubMed:25219498). Interacts with NCOA1 (PubMed:25219498). Interacts with EP300 (PubMed:25219498). Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3 (PubMed:12077347). Interacts with NEK6 (PubMed:20873783). Interacts with CSRP1 (PubMed:26924529). Interacts with ZCCHC4 (PubMed:31799605). {ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:12390891, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:26924529, ECO:0000269|PubMed:31799605}.

Subcellular location: Nucleus {ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:12077347, ECO:0000269|PubMed:20873783, ECO:0000269|PubMed:26924529}. Cytoplasm, cytosol {ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:20873783}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:20873783}. Note=Cytoplasmic under conditions of serum deprivation (PubMed:10454579). Colocalizes with NEK6 in the centrosome (PubMed:20873783). {ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:20873783}.

Domain: The C4-type zinc finger mediates a competitive interaction with UFSP2 and ligand-bound nuclear receptors. It also mediates interaction with the transcriptional coactivators and the basal transcription machinery. {ECO:0000269|PubMed:10454579, ECO:0000269|PubMed:12390891, ECO:0000269|PubMed:25219498}.

Ptm: Phosphorylated by NEK6. {ECO:0000269|PubMed:20873783}.

Ptm: Polyufmylated by the UFM1-conjugating system composed of the enzymes UBA5, UFC1 and UFL1. Deufmylated by the protease UFSP2. Ufmylation of TRIP4 is promoted by ligand-bound nuclear receptors that compete with UFSP2 for interaction with TRIP4. Nuclear receptors- induced ufmylation promotes the recruitment of additional transcriptional coactivators like EP300 and NCOA1 and therefore the assembly of a coactivator complex facilitating nuclear receptor- mediated transcription. {ECO:0000269|PubMed:25219498}.

Disease: Spinal muscular atrophy with congenital bone fractures 1 (SMABF1) [MIM:616866]: An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures. {ECO:0000269|PubMed:26924529}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Muscular dystrophy, congenital, Davignon-Chauveau type (MDCDC) [MIM:617066]: An autosomal recessive, severe congenital muscular dystrophy characterized by neonatal onset of muscle weakness predominantly involving axial muscles, life-threatening respiratory failure, skin abnormalities and joint hyperlaxity without contractures. Muscle biopsies show multi-minicores, caps and dystrophic lesions. {ECO:0000269|PubMed:27008887}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=AAC41738.1; Type=Frameshift; 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:		Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription. May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions. Plays a role in thyroid hormone receptor and estrogen receptor transactivation (PubMed:10454579, PubMed:25219498). Also involved in androgen receptor transactivation (By similarity). Plays a pivotal role in the transactivation of NF-kappa-B, SRF and AP1. Acts as a mediator of transrepression between nuclear receptor and either AP1 or NF-kappa-B (PubMed:12077347). May play a role in the development of neuromuscular junction (PubMed:26924529). May play a role in late myogenic differentiation (By similarity). {ECO:0000250\|UniProtKB:Q9QXN3, ECO:0000269\|PubMed:10454579, ECO:0000269\|PubMed:12077347, ECO:0000269\|PubMed:25219498, ECO:0000269\|PubMed:26924529}.


Subunit:		Interacts with the thyroid hormone receptor/TR (via the ligand-binding domain); this interaction requires the presence of thyroid hormone (PubMed:10454579). Interacts with the androgen receptor/AR; in an androgen, testosterone and dihydrotestosterone- dependent manner (PubMed:12390891). Interacts with ESR1 (estrogen ligand-bound); competes with UFSP2 (PubMed:10454579, PubMed:25219498). Interacts with UFSP2; competes with ligand-bound ESR1 (PubMed:25219498). Interacts with DDRGK1 and UFL1; the interaction with DDRGK1 is direct (PubMed:25219498). Interacts with NCOA1 (PubMed:25219498). Interacts with EP300 (PubMed:25219498). Part of the ASC-1 complex, that contains TRIP4, ASCC1, ASCC2 and ASCC3 (PubMed:12077347). Interacts with NEK6 (PubMed:20873783). Interacts with CSRP1 (PubMed:26924529). Interacts with ZCCHC4 (PubMed:31799605). {ECO:0000269\|PubMed:10454579, ECO:0000269\|PubMed:12077347, ECO:0000269\|PubMed:12390891, ECO:0000269\|PubMed:20873783, ECO:0000269\|PubMed:25219498, ECO:0000269\|PubMed:26924529, ECO:0000269\|PubMed:31799605}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:10454579, ECO:0000269\|PubMed:12077347, ECO:0000269\|PubMed:20873783, ECO:0000269\|PubMed:26924529}. Cytoplasm, cytosol {ECO:0000269\|PubMed:10454579, ECO:0000269\|PubMed:20873783}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:20873783}. Note=Cytoplasmic under conditions of serum deprivation (PubMed:10454579). Colocalizes with NEK6 in the centrosome (PubMed:20873783). {ECO:0000269\|PubMed:10454579, ECO:0000269\|PubMed:20873783}.
Domain:		The C4-type zinc finger mediates a competitive interaction with UFSP2 and ligand-bound nuclear receptors. It also mediates interaction with the transcriptional coactivators and the basal transcription machinery. {ECO:0000269\|PubMed:10454579, ECO:0000269\|PubMed:12390891, ECO:0000269\|PubMed:25219498}.
Ptm:		Phosphorylated by NEK6. {ECO:0000269\|PubMed:20873783}.
Ptm:		Polyufmylated by the UFM1-conjugating system composed of the enzymes UBA5, UFC1 and UFL1. Deufmylated by the protease UFSP2. Ufmylation of TRIP4 is promoted by ligand-bound nuclear receptors that compete with UFSP2 for interaction with TRIP4. Nuclear receptors- induced ufmylation promotes the recruitment of additional transcriptional coactivators like EP300 and NCOA1 and therefore the assembly of a coactivator complex facilitating nuclear receptor- mediated transcription. {ECO:0000269\|PubMed:25219498}.
Disease:		Spinal muscular atrophy with congenital bone fractures 1 (SMABF1) [MIM:616866]: An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures. {ECO:0000269\|PubMed:26924529}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Muscular dystrophy, congenital, Davignon-Chauveau type (MDCDC) [MIM:617066]: An autosomal recessive, severe congenital muscular dystrophy characterized by neonatal onset of muscle weakness predominantly involving axial muscles, life-threatening respiratory failure, skin abnormalities and joint hyperlaxity without contractures. Muscle biopsies show multi-minicores, caps and dystrophic lesions. {ECO:0000269\|PubMed:27008887}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=AAC41738.1; Type=Frameshift; Evidence={ECO:0000305};