DNAJC3: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''DnaJ homolog subfamily C member 3''' is a [[protein]] that in humans is encoded by the ''DNAJC3'' [[gene]].<ref name="pmid7511204">{{cite journal | vauthors = Lee TG, Tang N, Thompson S, Miller J, Katze MG | title = The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins | journal = Molecular and Cellular Biology | volume = 14 | issue = 4 | pages = 2331–42 | date = Apr 1994 | pmid = 7511204 | pmc = 358600 | doi = 10.1128/mcb.14.4.2331 }}</ref><ref name="pmid8824806">{{cite journal | vauthors = Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC | title = Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q | journal = Genomics | volume = 31 | issue = 2 | pages = 230–3 | date = Jan 1996 | pmid = 8824806 | pmc = | doi = 10.1006/geno.1996.0036 }}</ref><ref name="entrez"/>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = DnaJ (Hsp40) homolog, subfamily C, member 3
| HGNCid = 9439
| Symbol = DNAJC3
| AltSymbols =; P58; HP58; P58IPK; PRKRI
| OMIM = 601184
| ECnumber = 
| Homologene = 2486
| MGIid = 107373
| Function = {{GNF_GO|id=GO:0004860 |text = protein kinase inhibitor activity}} {{GNF_GO|id=GO:0005488 |text = binding}} {{GNF_GO|id=GO:0031072 |text = heat shock protein binding}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0006457 |text = protein folding}} {{GNF_GO|id=GO:0006952 |text = defense response}} {{GNF_GO|id=GO:0006986 |text = response to unfolded protein}} {{GNF_GO|id=GO:0009615 |text = response to virus}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5611
    | Hs_Ensembl = ENSG00000102580
    | Hs_RefseqProtein = NP_006251
    | Hs_RefseqmRNA = NM_006260
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 13
    | Hs_GenLoc_start = 95125276
    | Hs_GenLoc_end = 95245243
    | Hs_Uniprot = Q13217
    | Mm_EntrezGene = 19107
    | Mm_Ensembl = ENSMUSG00000022136
    | Mm_RefseqmRNA = NM_008929
    | Mm_RefseqProtein = NP_032955
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 14
    | Mm_GenLoc_start = 118073171
    | Mm_GenLoc_end = 118113365
    | Mm_Uniprot = Q3UFV9
  }}
}}
'''DnaJ (Hsp40) homolog, subfamily C, member 3''', also known as '''DNAJC3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DNAJC3 DnaJ (Hsp40) homolog, subfamily C, member 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5611| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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).<ref name="entrez">{{cite web | title = Entrez Gene: DNAJC3 DnaJ (Hsp40) homolog, subfamily C, member 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5611| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = 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).<ref name="entrez">{{cite web | title = Entrez Gene: DNAJC3 DnaJ (Hsp40) homolog, subfamily C, member 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5611| accessdate = }}</ref>
}}


==References==
== Clinical significance ==
{{reflist|2}}
 
==Further reading==
The DNAJC3 protein is an important apoptotic constituent. During a normal [[embryologic]] processes, or during cell injury (such as ischemia-reperfusion injury during [[heart attacks]] and [[strokes]]) or during developments and processes in [[cancer]], an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the [[DNA]] and [[Cell nucleus|nucleus]]. This is followed by fragmentation into apoptotic bodies that are quickly removed by [[phagocytes]], thereby preventing an [[inflammation|inflammatory]] response.<ref>{{cite journal | vauthors = Kerr JF, Wyllie AH, Currie AR | title = Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics | journal = British Journal of Cancer | volume = 26 | issue = 4 | pages = 239–57 | date = Aug 1972 | pmid = 4561027 | doi=10.1038/bjc.1972.33 | pmc=2008650}}</ref> It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite [[mitosis]] in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of [[necrosis]] is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many [[physiological]] and [[pathological]] processes. It plays an important role during [[embryonal]] development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
 
Moreover, an important role for DNAJC3 has been attributed to diabetes mellitus as well as multi system neurodegeneration.<ref name="Synofzik M 2014">{{cite journal | vauthors = Synofzik M, Haack TB, Kopajtich R, Gorza M, Rapaport D, Greiner M, Schönfeld C, Freiberg C, Schorr S, Holl RW, Gonzalez MA, Fritsche A, Fallier-Becker P, Zimmermann R, Strom TM, Meitinger T, Züchner S, Schüle R, Schöls L, Prokisch H | title = Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration | journal = American Journal of Human Genetics | volume = 95 | issue = 6 | pages = 689–97 | date = Dec 2014 | pmid = 25466870 | doi = 10.1016/j.ajhg.2014.10.013 | pmc=4259973}}</ref><ref name="ReferenceA">{{cite journal | vauthors = Lin Y, Sun Z | title = In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes | journal = Diabetes | volume = 64 | issue = 4 | pages = 1444–58 | date = Apr 2015 | pmid = 25377875 | doi = 10.2337/db14-0632 | pmc=4375073}}</ref> [[Diabetes mellitus]] and neurodegeneration are common diseases for which shared genetic factors are still only partly known. It was shown that loss of the [[Binding immunoglobulin protein|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.<ref name="Synofzik M 2014"/> Notably, the DNAJC3 protein is also considered as an important marker for stress in the [[endoplasmatic reticulum]].
<ref name="ReferenceA"/>
 
== Interactions ==
 
DNAJC3 has been shown to [[Protein-protein interaction|interact]] with:
* [[Protein kinase R|EIF2AK2]],<ref name = pmid8576172>{{cite journal | vauthors = Polyak SJ, Tang N, Wambach M, Barber GN, Katze MG | title = The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity | journal = The Journal of Biological Chemistry | volume = 271 | issue = 3 | pages = 1702–7 | date = Jan 1996 | pmid = 8576172 | doi = 10.1074/jbc.271.3.1702 }}</ref><ref name = pmid9447982>{{cite journal | vauthors = Gale M, Blakely CM, Hopkins DA, Melville MW, Wambach M, Romano PR, Katze MG | title = Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK | journal = Molecular and Cellular Biology | volume = 18 | issue = 2 | pages = 859–71 | date = Feb 1998 | pmid = 9447982 | pmc = 108797 | doi =  10.1128/mcb.18.2.859}}</ref>
* [[EIF2AK3]],<ref name = pmid12446838>{{cite journal | vauthors = Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG | title = Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 25 | pages = 15920–5 | date = Dec 2002 | pmid = 12446838 | pmc = 138540 | doi = 10.1073/pnas.252341799 }}</ref> and
* [[PRKRIR]].<ref name = pmid9447982/>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Polyak SJ, Tang N, Wambach M, Barber GN, Katze MG | title = The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity | journal = The Journal of Biological Chemistry | volume = 271 | issue = 3 | pages = 1702–7 | date = Jan 1996 | pmid = 8576172 | doi = 10.1074/jbc.271.3.1702 }}
| citations =
* {{cite journal | vauthors = Korth MJ, Lyons CN, Wambach M, Katze MG | title = Cloning, expression, and cellular localization of the oncogenic 58-kDa inhibitor of the RNA-activated human and mouse protein kinase | journal = Gene | volume = 170 | issue = 2 | pages = 181–8 | date = May 1996 | pmid = 8666242 | doi = 10.1016/0378-1119(95)00883-7 }}
*{{cite journal | author=Lee TG, Tang N, Thompson S, ''et al.'' |title=The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins. |journal=Mol. Cell. Biol. |volume=14 |issue= 4 |pages= 2331-42 |year= 1994 |pmid= 7511204 |doi=  }}
* {{cite journal | vauthors = Korth MJ, Edelhoff S, Disteche CM, Katze MG | title = Chromosomal assignment of the gene encoding the human 58-kDa inhibitor (PRKRI) of the interferon-induced dsRNA-activated protein kinase to chromosome 13q32 | journal = Genomics | volume = 31 | issue = 2 | pages = 238–9 | date = Jan 1996 | pmid = 8824808 | doi = 10.1006/geno.1996.0038 }}
*{{cite journal  | author=Polyak SJ, Tang N, Wambach M, ''et al.'' |title=The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity. |journal=J. Biol. Chem. |volume=271 |issue= 3 |pages= 1702-7 |year= 1996 |pmid= 8576172 |doi= }}
* {{cite journal | vauthors = Gale M, Blakely CM, Hopkins DA, Melville MW, Wambach M, Romano PR, Katze MG | title = Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK | journal = Molecular and Cellular Biology | volume = 18 | issue = 2 | pages = 859–71 | date = Feb 1998 | pmid = 9447982 | pmc = 108797 | doi =  10.1128/mcb.18.2.859}}
*{{cite journal | author=Korth MJ, Lyons CN, Wambach M, Katze MG |title=Cloning, expression, and cellular localization of the oncogenic 58-kDa inhibitor of the RNA-activated human and mouse protein kinase. |journal=Gene |volume=170 |issue= 2 |pages= 181-8 |year= 1996 |pmid= 8666242 |doi=  }}
* {{cite journal | vauthors = Melville MW, Tan SL, Wambach M, Song J, Morimoto RI, Katze MG | title = The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity | journal = The Journal of Biological Chemistry | volume = 274 | issue = 6 | pages = 3797–803 | date = Feb 1999 | pmid = 9920933 | doi = 10.1074/jbc.274.6.3797 }}
*{{cite journal  | author=Scherer SW, Duvoisin RM, Kuhn R, ''et al.'' |title=Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. |journal=Genomics |volume=31 |issue= 2 |pages= 230-3 |year= 1997 |pmid= 8824806 |doi= 10.1006/geno.1996.0036 }}
* {{cite journal | vauthors = Ohtsuka K, Hata M | title = Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature | journal = Cell Stress & Chaperones | volume = 5 | issue = 2 | pages = 98–112 | date = Apr 2000 | pmid = 11147971 | pmc = 312896 | doi = 10.1379/1466-1268(2000)005<0098:MHDHCO>2.0.CO;2 }}
*{{cite journal | author=Korth MJ, Edelhoff S, Disteche CM, Katze MG |title=Chromosomal assignment of the gene encoding the human 58-kDa inhibitor (PRKRI) of the interferon-induced dsRNA-activated protein kinase to chromosome 13q32. |journal=Genomics |volume=31 |issue= 2 |pages= 238-9 |year= 1997 |pmid= 8824808 |doi= 10.1006/geno.1996.0038 }}
* {{cite journal | vauthors = Horng T, Barton GM, Medzhitov R | title = TIRAP: an adapter molecule in the Toll signaling pathway | journal = Nature Immunology | volume = 2 | issue = 9 | pages = 835–41 | date = Sep 2001 | pmid = 11526399 | doi = 10.1038/ni0901-835 }}
*{{cite journal | author=Gale M, Blakely CM, Hopkins DA, ''et al.'' |title=Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK. |journal=Mol. Cell. Biol. |volume=18 |issue= 2 |pages= 859-71 |year= 1998 |pmid= 9447982 |doi=  }}
* {{cite journal | vauthors = Yan W, Gale MJ, Tan SL, Katze MG | title = Inactivation of the PKR protein kinase and stimulation of mRNA translation by the cellular co-chaperone P58(IPK) does not require J domain function | journal = Biochemistry | volume = 41 | issue = 15 | pages = 4938–45 | date = Apr 2002 | pmid = 11939789 | doi = 10.1021/bi0121499 }}
*{{cite journal | author=Melville MW, Tan SL, Wambach M, ''et al.'' |title=The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity. |journal=J. Biol. Chem. |volume=274 |issue= 6 |pages= 3797-803 |year= 1999 |pmid= 9920933 |doi= }}
* {{cite journal | vauthors = Ladiges W, Morton J, Hopkins H, Wilson R, Filley G, Ware C, Gale M | title = Expression of human PKR protein kinase in transgenic mice | journal = Journal of Interferon & Cytokine Research | volume = 22 | issue = 3 | pages = 329–34 | date = Mar 2002 | pmid = 12034040 | doi = 10.1089/107999002753675758 }}
*{{cite journal | author=Ohtsuka K, Hata M |title=Mammalian HSP40/DNAJ homologs: cloning of novel cDNAs and a proposal for their classification and nomenclature. |journal=Cell Stress Chaperones |volume=5 |issue= 2 |pages= 98-112 |year= 2001 |pmid= 11147971 |doi= }}
* {{cite journal | vauthors = Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG | title = Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 25 | pages = 15920–5 | date = Dec 2002 | pmid = 12446838 | pmc = 138540 | doi = 10.1073/pnas.252341799 }}
*{{cite journal | author=Horng T, Barton GM, Medzhitov R |title=TIRAP: an adapter molecule in the Toll signaling pathway. |journal=Nat. Immunol. |volume=2 |issue= 9 |pages= 835-41 |year= 2001 |pmid= 11526399 |doi= 10.1038/ni0901-835 }}
* {{cite journal | vauthors = van Huizen R, Martindale JL, Gorospe M, Holbrook NJ | title = P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling | journal = The Journal of Biological Chemistry | volume = 278 | issue = 18 | pages = 15558–64 | date = May 2003 | pmid = 12601012 | doi = 10.1074/jbc.M212074200 }}
*{{cite journal | author=Yan W, Gale MJ, Tan SL, Katze MG |title=Inactivation of the PKR protein kinase and stimulation of mRNA translation by the cellular co-chaperone P58(IPK) does not require J domain function. |journal=Biochemistry |volume=41 |issue= 15 |pages= 4938-45 |year= 2002 |pmid= 11939789 |doi= }}
*{{cite journal | author=Ladiges W, Morton J, Hopkins H, ''et al.'' |title=Expression of human PKR protein kinase in transgenic mice. |journal=J. Interferon Cytokine Res. |volume=22 |issue= 3 |pages= 329-34 |year= 2003 |pmid= 12034040 |doi= 10.1089/107999002753675758 }}
*{{cite journal | author=Yan W, Frank CL, Korth MJ, ''et al.'' |title=Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 25 |pages= 15920-5 |year= 2003 |pmid= 12446838 |doi= 10.1073/pnas.252341799 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal | author=van Huizen R, Martindale JL, Gorospe M, Holbrook NJ |title=P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling. |journal=J. Biol. Chem. |volume=278 |issue= 18 |pages= 15558-64 |year= 2003 |pmid= 12601012 |doi= 10.1074/jbc.M212074200 }}
*{{cite journal  | author=Dunham A, Matthews LH, Burton J, ''et al.'' |title=The DNA sequence and analysis of human chromosome 13. |journal=Nature |volume=428 |issue= 6982 |pages= 522-8 |year= 2004 |pmid= 15057823 |doi= 10.1038/nature02379 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{Chaperones}}
{{WikiDoc Sources}}
 
[[Category:Heat shock proteins]]

Latest revision as of 18:38, 30 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

DnaJ homolog subfamily C member 3 is a protein that in humans is encoded by the DNAJC3 gene.[1][2][3]

Function

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).[3]

Clinical significance

The DNAJC3 protein is an important apoptotic constituent. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[4] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.

Moreover, an important role for DNAJC3 has been attributed to diabetes mellitus as well as multi system neurodegeneration.[5][6] 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.[5] Notably, the DNAJC3 protein is also considered as an important marker for stress in the endoplasmatic reticulum. [6]

Interactions

DNAJC3 has been shown to interact with:

References

  1. ↑ Lee TG, Tang N, Thompson S, Miller J, Katze MG (Apr 1994). "The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of proteins". Molecular and Cellular Biology. 14 (4): 2331–42. doi:10.1128/mcb.14.4.2331. PMC 358600. PMID 7511204.
  2. ↑ Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC (Jan 1996). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics. 31 (2): 230–3. doi:10.1006/geno.1996.0036. PMID 8824806.
  3. ↑ 3.0 3.1 "Entrez Gene: DNAJC3 DnaJ (Hsp40) homolog, subfamily C, member 3".
  4. ↑ Kerr JF, Wyllie AH, Currie AR (Aug 1972). "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics". British Journal of Cancer. 26 (4): 239–57. doi:10.1038/bjc.1972.33. PMC 2008650. PMID 4561027.
  5. ↑ 5.0 5.1 Synofzik M, Haack TB, Kopajtich R, Gorza M, Rapaport D, Greiner M, Schönfeld C, Freiberg C, Schorr S, Holl RW, Gonzalez MA, Fritsche A, Fallier-Becker P, Zimmermann R, Strom TM, Meitinger T, Züchner S, Schüle R, Schöls L, Prokisch H (Dec 2014). "Absence of BiP co-chaperone DNAJC3 causes diabetes mellitus and multisystemic neurodegeneration". American Journal of Human Genetics. 95 (6): 689–97. doi:10.1016/j.ajhg.2014.10.013. PMC 4259973. PMID 25466870.
  6. ↑ 6.0 6.1 Lin Y, Sun Z (Apr 2015). "In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes". Diabetes. 64 (4): 1444–58. doi:10.2337/db14-0632. PMC 4375073. PMID 25377875.
  7. ↑ Polyak SJ, Tang N, Wambach M, Barber GN, Katze MG (Jan 1996). "The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity". The Journal of Biological Chemistry. 271 (3): 1702–7. doi:10.1074/jbc.271.3.1702. PMID 8576172.
  8. ↑ 8.0 8.1 Gale M, Blakely CM, Hopkins DA, Melville MW, Wambach M, Romano PR, Katze MG (Feb 1998). "Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK". Molecular and Cellular Biology. 18 (2): 859–71. doi:10.1128/mcb.18.2.859. PMC 108797. PMID 9447982.
  9. ↑ Yan W, Frank CL, Korth MJ, Sopher BL, Novoa I, Ron D, Katze MG (Dec 2002). "Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK". Proceedings of the National Academy of Sciences of the United States of America. 99 (25): 15920–5. doi:10.1073/pnas.252341799. PMC 138540. PMID 12446838.

Further reading

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