UniProt functional annotation for Q13451



	UniProt functional annotation for Q13451

UniProt code: Q13451.

Organism: Homo sapiens (Human).

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

Function: Immunophilin protein with PPIase and co-chaperone activities (PubMed:11350175). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded (PubMed:12538866). Acts as a regulator of Akt/AKT1 activity by promoting the interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). {ECO:0000269|PubMed:11350175, ECO:0000269|PubMed:12538866, ECO:0000269|PubMed:28147277}.

Catalytic activity: Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269|PubMed:11350175};

Activity regulation: Inhibited by both FK506 and rapamycin. {ECO:0000250|UniProtKB:Q64378}.

Subunit: Part of a heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding dissociates from the complex and FKBP4 takes its place (By similarity). Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP (PubMed:7693698). Interacts with NR3C1 (By similarity). Interacts with Akt/AKT1 and PHLPP1; enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). {ECO:0000250|UniProtKB:Q64378, ECO:0000269|PubMed:28147277, ECO:0000269|PubMed:7693698}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:Q64378}. Nucleus {ECO:0000250|UniProtKB:Q64378}.

Tissue specificity: Widely expressed, enriched in testis compared to other tissues.

Induction: By androgen.

Ptm: Acetylation impairs ability to promote interaction between Akt/AKT1 and PHLPP1 (PubMed:28147277). Deacetylation by SIRT7 promotes interaction between Akt/AKT1 and PHLPP1, leading to suppress Akt/AKT1 activation (PubMed:28147277). {ECO:0000269|PubMed:28147277}.

Sequence caution: Sequence=BAD93130.1; 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:		Immunophilin protein with PPIase and co-chaperone activities (PubMed:11350175). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded (PubMed:12538866). Acts as a regulator of Akt/AKT1 activity by promoting the interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). {ECO:0000269\|PubMed:11350175, ECO:0000269\|PubMed:12538866, ECO:0000269\|PubMed:28147277}.


Catalytic activity:		Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269\|PubMed:11350175};
Activity regulation:		Inhibited by both FK506 and rapamycin. {ECO:0000250\|UniProtKB:Q64378}.
Subunit:		Part of a heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B and steroid receptors. Upon ligand binding dissociates from the complex and FKBP4 takes its place (By similarity). Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP (PubMed:7693698). Interacts with NR3C1 (By similarity). Interacts with Akt/AKT1 and PHLPP1; enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). {ECO:0000250\|UniProtKB:Q64378, ECO:0000269\|PubMed:28147277, ECO:0000269\|PubMed:7693698}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:Q64378}. Nucleus {ECO:0000250\|UniProtKB:Q64378}.
Tissue specificity:		Widely expressed, enriched in testis compared to other tissues.
Induction:		By androgen.
Ptm:		Acetylation impairs ability to promote interaction between Akt/AKT1 and PHLPP1 (PubMed:28147277). Deacetylation by SIRT7 promotes interaction between Akt/AKT1 and PHLPP1, leading to suppress Akt/AKT1 activation (PubMed:28147277). {ECO:0000269\|PubMed:28147277}.
Sequence caution:		Sequence=BAD93130.1; Type=Frameshift; Evidence={ECO:0000305};