Contents

DNAJC3

Human protein and coding gene

DNAJC3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Y4T, 2Y4U
Identifiers
Aliases	DNAJC3, ERdj6, HP58, P58, P58IPK, PRKRI, ACPHD, DnaJ heat shock protein family (Hsp40) member C3, p58(IPK)
External IDs	OMIM: 601184; MGI: 107373; HomoloGene: 2486; GeneCards: DNAJC3; OMA:DNAJC3 - orthologs
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q32.1 Start 95,677,139 bp[1] End 95,794,988 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14|14 E4 Start 119,175,388 bp[2] End 119,219,109 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus epididymis caput epididymis oocyte epithelium of nasopharynx pericardium tail of epididymis secondary oocyte decidua pylorus palpebral conjunctiva Top expressed in lacrimal gland salivary gland parotid gland gastrula submandibular gland seminal vesicula secondary oocyte decidua renal corpuscle left lobe of liver More reference expression data BioGPS n/a
Gene ontology Molecular function chaperone binding misfolded protein binding protein kinase binding protein kinase inhibitor activity unfolded protein binding Cellular component cytoplasm extracellular vesicle endoplasmic reticulum lumen membrane smooth endoplasmic reticulum endoplasmic reticulum Sec complex extracellular exosome endoplasmic reticulum cytosol extracellular region azurophil granule lumen Biological process negative regulation of apoptotic process response to unfolded protein IRE1-mediated unfolded protein response defense response to virus proteolysis involved in cellular protein catabolic process regulation of translation cellular response to cold negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation positive regulation of translation initiation in response to endoplasmic reticulum stress negative regulation of protein kinase activity neutrophil degranulation post-translational protein modification protein folding in endoplasmic reticulum response to endoplasmic reticulum stress Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5611 100037258 Ensembl ENSG00000102580 ENSMUSG00000022136 UniProt Q13217 Q91YW3 RefSeq (mRNA) NM_006260 NM_008929 RefSeq (protein) NP_006251 NP_032955 Location (UCSC) Chr 13: 95.68 – 95.79 Mb Chr 14: 119.18 – 119.22 Mb PubMed search [3] [4]
Wikidata
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DnaJ homolog subfamily C member 3 is a protein that in humans is encoded by the DNAJC3 gene.^[5][6][7]

The protein encoded by this gene contains multiple tetratricopeptide repeat (TPR) motifs as well as the highly conserved J domain found in DNAJ chaperone family members. It is a member of the tetratricopeptide repeat family of proteins and acts as an inhibitor of the interferon-induced, dsRNA-activated protein kinase (PKR).^[7]

An important role for DNAJC3 has been attributed to diabetes mellitus as well as multi system neurodegeneration.^[8][9] Diabetes mellitus and neurodegeneration are common diseases for which shared genetic factors are still only partly known. It was shown that loss of the BiP (immunoglobulin heavy-chain binding protein) co-chaperone DNAJC3 leads to diabetes mellitus and widespread neurodegeneration. Accordingly, three siblings were investigated with juvenile-onset diabetes and central and peripheral neurodegeneration, including ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. Subsequently, exome sequencing identified a homozygous stop mutation in DNAJC3. Further screening of a diabetes database with 226,194 individuals yielded eight phenotypically similar individuals and one family carrying a homozygous DNAJC3 deletion. DNAJC3 was absent in fibroblasts from all affected subjects in both families. To delineate the phenotypic and mutational spectrum and the genetic variability of DNAJC3, 8,603 exomes were further analyzed, including 506 from families affected by diabetes, ataxia, upper-motor-neuron damage, peripheral neuropathy, or hearing loss. This analysis revealed only one further loss-of-function allele in DNAJC3 and no further associations in subjects with only a subset of the features of the main phenotype.^[8] Notably, the DNAJC3 protein is also considered as an important marker for stress in the endoplasmatic reticulum. ^[9]

DNAJC3 has been shown to interact with:

• EIF2AK2,^[10][11]
• EIF2AK3,^[12] and
• PRKRIR.^[11]