UniProt functional annotation for P41148



	UniProt functional annotation for P41148

UniProt code: P41148.

Organism: Canis lupus familiaris (Dog) (Canis familiaris).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.

Function: Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD) (By similarity). Has ATPase activity (PubMed:17936703). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum- Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (By similarity). {ECO:0000250|UniProtKB:P08113, ECO:0000250|UniProtKB:P14625, ECO:0000269|PubMed:17936703}.

Biophysicochemical properties: Kinetic parameters: KM=10 uM for ATP {ECO:0000269|PubMed:17936703};

Subunit: Homodimer; disulfide-linked. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with AIMP1; regulates its retention in the endoplasmic reticulum. Interacts with OS9 (By similarity). Interacts with CNPY3; this interaction is disrupted in the presence of ATP. Interacts with several TLRs, including TLR4 and TLR9, but not with TLR3 (By similarity). Interacts with MZB1 in a calcium- dependent manner (By similarity). Interacts with METTL23 (By similarity). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P14625}.

Subcellular location: Endoplasmic reticulum lumen {ECO:0000250|UniProtKB:P08113}. Sarcoplasmic reticulum lumen {ECO:0000269|PubMed:8119936}. Melanosome {ECO:0000250|UniProtKB:P14625}.

Tissue specificity: Detected in heart muscle (at protein level). {ECO:0000269|PubMed:8119936}.

Ptm: Phosphorylated by CK2. {ECO:0000269|PubMed:8119936}.

Similarity: Belongs to the heat shock protein 90 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Canis lupus familiaris (Dog) (Canis familiaris).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.



Function:		Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD) (By similarity). Has ATPase activity (PubMed:17936703). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum- Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (By similarity). {ECO:0000250\|UniProtKB:P08113, ECO:0000250\|UniProtKB:P14625, ECO:0000269\|PubMed:17936703}.


Biophysicochemical properties:		Kinetic parameters: KM=10 uM for ATP {ECO:0000269\|PubMed:17936703};
Subunit:		Homodimer; disulfide-linked. Component of an EIF2 complex at least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. Interacts with AIMP1; regulates its retention in the endoplasmic reticulum. Interacts with OS9 (By similarity). Interacts with CNPY3; this interaction is disrupted in the presence of ATP. Interacts with several TLRs, including TLR4 and TLR9, but not with TLR3 (By similarity). Interacts with MZB1 in a calcium- dependent manner (By similarity). Interacts with METTL23 (By similarity). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (By similarity). {ECO:0000250, ECO:0000250\|UniProtKB:P14625}.
Subcellular location:		Endoplasmic reticulum lumen {ECO:0000250\|UniProtKB:P08113}. Sarcoplasmic reticulum lumen {ECO:0000269\|PubMed:8119936}. Melanosome {ECO:0000250\|UniProtKB:P14625}.
Tissue specificity:		Detected in heart muscle (at protein level). {ECO:0000269\|PubMed:8119936}.
Ptm:		Phosphorylated by CK2. {ECO:0000269\|PubMed:8119936}.
Similarity:		Belongs to the heat shock protein 90 family. {ECO:0000305}.