UniProt functional annotation for Q13217



	UniProt functional annotation for Q13217

UniProt code: Q13217.

Organism: Homo sapiens (Human).

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

Function: Involved in the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Acts as a negative regulator of the EIF2AK4/GCN2 kinase activity by preventing the phosphorylation of eIF- 2-alpha at 'Ser-52' and hence attenuating general protein synthesis under ER stress, hypothermic and amino acid starving stress conditions (By similarity). Co-chaperone of HSPA8/HSC70, it stimulates its ATPase activity. May inhibit both the autophosphorylation of EIF2AK2/PKR and the ability of EIF2AK2 to catalyze phosphorylation of the EIF2A. May inhibit EIF2AK3/PERK activity. {ECO:0000250|UniProtKB:Q27968, ECO:0000250|UniProtKB:Q91YW3, ECO:0000269|PubMed:12601012, ECO:0000269|PubMed:8576172, ECO:0000269|PubMed:9447982, ECO:0000269|PubMed:9920933}.

Subunit: Interacts with EIF2AK4/GCN2; this interaction occurs under endoplasmic reticulum (ER) stress, hypothermic and amino acid starving stress conditions and inhibits EIF2AK4/GCN2 kinase activity. Interacts with EIF2AK3 (By similarity). Interacts with EIF2AK2 (PubMed:8576172). Forms a trimeric complex with DNAJB1 and HSPA8 (PubMed:9920933). Interacts with THAP12 (PubMed:9447982). {ECO:0000250|UniProtKB:Q91YW3, ECO:0000269|PubMed:8576172, ECO:0000269|PubMed:9447982, ECO:0000269|PubMed:9920933}.

Subcellular location: Endoplasmic reticulum {ECO:0000250}.

Tissue specificity: Widely expressed with high level in the pancreas and testis. Also expressed in cell lines with different levels. {ECO:0000269|PubMed:8666242}.

Induction: Up-regulated during an endoplasmic reticulum stress via ATF6. Activated in response to infection by influenza virus through the dissociation of DNAJB1. Down-regulated by DNAJB1 and THAP12. {ECO:0000269|PubMed:12601012, ECO:0000269|PubMed:9447982, ECO:0000269|PubMed:9920933}.

Domain: The J domain mediates interaction with HSPA8.

Domain: Binding to misfolded proteins is mediated by a hydrophobic patch forming a large groove within the first two TPR repeats. {ECO:0000250}.

Disease: Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus (ACPHD) [MIM:616192]: A disease characterized by juvenile-onset diabetes and neurodegeneration, resulting in ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. {ECO:0000269|PubMed:25466870}. Note=The disease is caused by variants affecting the gene represented in this entry.

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:		Involved in the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Acts as a negative regulator of the EIF2AK4/GCN2 kinase activity by preventing the phosphorylation of eIF- 2-alpha at 'Ser-52' and hence attenuating general protein synthesis under ER stress, hypothermic and amino acid starving stress conditions (By similarity). Co-chaperone of HSPA8/HSC70, it stimulates its ATPase activity. May inhibit both the autophosphorylation of EIF2AK2/PKR and the ability of EIF2AK2 to catalyze phosphorylation of the EIF2A. May inhibit EIF2AK3/PERK activity. {ECO:0000250\|UniProtKB:Q27968, ECO:0000250\|UniProtKB:Q91YW3, ECO:0000269\|PubMed:12601012, ECO:0000269\|PubMed:8576172, ECO:0000269\|PubMed:9447982, ECO:0000269\|PubMed:9920933}.


Subunit:		Interacts with EIF2AK4/GCN2; this interaction occurs under endoplasmic reticulum (ER) stress, hypothermic and amino acid starving stress conditions and inhibits EIF2AK4/GCN2 kinase activity. Interacts with EIF2AK3 (By similarity). Interacts with EIF2AK2 (PubMed:8576172). Forms a trimeric complex with DNAJB1 and HSPA8 (PubMed:9920933). Interacts with THAP12 (PubMed:9447982). {ECO:0000250\|UniProtKB:Q91YW3, ECO:0000269\|PubMed:8576172, ECO:0000269\|PubMed:9447982, ECO:0000269\|PubMed:9920933}.
Subcellular location:		Endoplasmic reticulum {ECO:0000250}.
Tissue specificity:		Widely expressed with high level in the pancreas and testis. Also expressed in cell lines with different levels. {ECO:0000269\|PubMed:8666242}.
Induction:		Up-regulated during an endoplasmic reticulum stress via ATF6. Activated in response to infection by influenza virus through the dissociation of DNAJB1. Down-regulated by DNAJB1 and THAP12. {ECO:0000269\|PubMed:12601012, ECO:0000269\|PubMed:9447982, ECO:0000269\|PubMed:9920933}.
Domain:		The J domain mediates interaction with HSPA8.
Domain:		Binding to misfolded proteins is mediated by a hydrophobic patch forming a large groove within the first two TPR repeats. {ECO:0000250}.
Disease:		Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus (ACPHD) [MIM:616192]: A disease characterized by juvenile-onset diabetes and neurodegeneration, resulting in ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. {ECO:0000269\|PubMed:25466870}. Note=The disease is caused by variants affecting the gene represented in this entry.