UniProt functional annotation for P62942



	UniProt functional annotation for P62942

UniProt code: P62942.

Organism: Homo sapiens (Human).

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

Function: Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. {ECO:0000269|PubMed:16720724, ECO:0000269|PubMed:1696686, ECO:0000269|PubMed:1701173, ECO:0000269|PubMed:9233797}.

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:1696686, ECO:0000269|PubMed:1701173};

Activity regulation: Inhibited by both FK506 and rapamycin.

Subunit: Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation (PubMed:9233797). Interacts with ACVR1B and SMAD7 (PubMed:16720724). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Interacts directly with RYR2 and RYR3 (PubMed:10358090, PubMed:22100703). Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner (PubMed:8955134). Interacts directly with RYR1 (By similarity). {ECO:0000250|UniProtKB:P26883, ECO:0000250|UniProtKB:P62943, ECO:0000269|PubMed:10025408, ECO:0000269|PubMed:10358090, ECO:0000269|PubMed:16720724, ECO:0000269|PubMed:22100703, ECO:0000269|PubMed:8955134, ECO:0000269|PubMed:9233797}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:1701173}. Sarcoplasmic reticulum membrane {ECO:0000250|UniProtKB:P62943}; Peripheral membrane protein {ECO:0000250|UniProtKB:P62943}; Cytoplasmic side {ECO:0000250|UniProtKB:P62943}.

Similarity: Belongs to the FKBP-type PPIase family. FKBP1 subfamily. {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:		Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. {ECO:0000269\|PubMed:16720724, ECO:0000269\|PubMed:1696686, ECO:0000269\|PubMed:1701173, ECO:0000269\|PubMed:9233797}.


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:1696686, ECO:0000269\|PubMed:1701173};
Activity regulation:		Inhibited by both FK506 and rapamycin.
Subunit:		Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation (PubMed:9233797). Interacts with ACVR1B and SMAD7 (PubMed:16720724). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Interacts directly with RYR2 and RYR3 (PubMed:10358090, PubMed:22100703). Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner (PubMed:8955134). Interacts directly with RYR1 (By similarity). {ECO:0000250\|UniProtKB:P26883, ECO:0000250\|UniProtKB:P62943, ECO:0000269\|PubMed:10025408, ECO:0000269\|PubMed:10358090, ECO:0000269\|PubMed:16720724, ECO:0000269\|PubMed:22100703, ECO:0000269\|PubMed:8955134, ECO:0000269\|PubMed:9233797}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:1701173}. Sarcoplasmic reticulum membrane {ECO:0000250\|UniProtKB:P62943}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P62943}; Cytoplasmic side {ECO:0000250\|UniProtKB:P62943}.
Similarity:		Belongs to the FKBP-type PPIase family. FKBP1 subfamily. {ECO:0000305}.