UniProt functional annotation for Q60739



	UniProt functional annotation for Q60739

UniProt code: Q60739.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Co-chaperone for HSP70 and HSC70 chaperone proteins (PubMed:9873016). Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate- binding domain (SBD) of HSPA8/HSC70. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli (By similarity). {ECO:0000250|UniProtKB:Q99933, ECO:0000269|PubMed:9873016}.

Subunit: Homodimer. Forms a heteromeric complex with HSP70/HSC70. Binds to the ATPase domain of HSP/HSC70 chaperones. Interacts with NR3C1. Interacts with the N-terminal region of STK19. Interacts with PPP1R15A. Interacts with BCL2 in an ATP-dependent manner. Interacts with SIAH1, HSPA8 (via NBD), HSPA1A (via NBD) and HSPA1B (via NBD) (By similarity). Interacts with SIAH2 (PubMed:11257006). {ECO:0000250|UniProtKB:Q99933, ECO:0000269|PubMed:11257006}.

Subcellular location: [Isoform 1]: Nucleus.

Subcellular location: [Isoform 2]: Cytoplasm.

Tissue specificity: Isoform 2 is expressed in the heart, lung, kidney and spinal cord. Isoform 1 and isoform 2 are expressed in hematopoietic cell lines. The levels of isoform 2 are relatively constant in all the cell lines examined while the levels of isoform 1 are more variable (at protein level). Isoform 1 is expressed in the lung and kidney. Isoform 2 is expressed in various tissues, with highest levels in testis and stomach. {ECO:0000269|PubMed:9396724, ECO:0000269|PubMed:9679980}.

Ptm: Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. {ECO:0000305|PubMed:11257006}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Co-chaperone for HSP70 and HSC70 chaperone proteins (PubMed:9873016). Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate- binding domain (SBD) of HSPA8/HSC70. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli (By similarity). {ECO:0000250\|UniProtKB:Q99933, ECO:0000269\|PubMed:9873016}.


Subunit:		Homodimer. Forms a heteromeric complex with HSP70/HSC70. Binds to the ATPase domain of HSP/HSC70 chaperones. Interacts with NR3C1. Interacts with the N-terminal region of STK19. Interacts with PPP1R15A. Interacts with BCL2 in an ATP-dependent manner. Interacts with SIAH1, HSPA8 (via NBD), HSPA1A (via NBD) and HSPA1B (via NBD) (By similarity). Interacts with SIAH2 (PubMed:11257006). {ECO:0000250\|UniProtKB:Q99933, ECO:0000269\|PubMed:11257006}.
Subcellular location:		[Isoform 1]: Nucleus.
Subcellular location:		[Isoform 2]: Cytoplasm.
Tissue specificity:		Isoform 2 is expressed in the heart, lung, kidney and spinal cord. Isoform 1 and isoform 2 are expressed in hematopoietic cell lines. The levels of isoform 2 are relatively constant in all the cell lines examined while the levels of isoform 1 are more variable (at protein level). Isoform 1 is expressed in the lung and kidney. Isoform 2 is expressed in various tissues, with highest levels in testis and stomach. {ECO:0000269\|PubMed:9396724, ECO:0000269\|PubMed:9679980}.
Ptm:		Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation. {ECO:0000305\|PubMed:11257006}.