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Protein

DnaJ homolog subfamily C member 3

Gene

DNAJC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity4 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chaperone, Repressor

Keywords - Biological processi

Antiviral defense, Stress response, Translation regulation, Unfolded protein response

Enzyme and pathway databases

ReactomeiR-HSA-192823. Viral mRNA Translation.
R-HSA-381038. XBP1(S) activates chaperone genes.
R-HSA-6798695. Neutrophil degranulation.
SIGNORiQ13217.

Names & Taxonomyi

Protein namesi
Recommended name:
DnaJ homolog subfamily C member 3
Alternative name(s):
Endoplasmic reticulum DNA J domain-containing protein 6
Short name:
ER-resident protein ERdj6
Short name:
ERdj6
Interferon-induced, double-stranded RNA-activated protein kinase inhibitor
Protein kinase inhibitor of 58 kDa
Short name:
Protein kinase inhibitor p58
Gene namesi
Name:DNAJC3
Synonyms:P58IPK, PRKRI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:9439. DNAJC3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytosol Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • endoplasmic reticulum Sec complex Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular vesicle Source: UniProtKB
  • membrane Source: UniProtKB
  • smooth endoplasmic reticulum Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus (ACPHD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by juvenile-onset diabetes and neurodegeneration, resulting in ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy.
See also OMIM:616192

Keywords - Diseasei

Deafness, Diabetes mellitus, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi5611.
MalaCardsiDNAJC3.
MIMi616192. phenotype.
OpenTargetsiENSG00000102580.
PharmGKBiPA27420.

Polymorphism and mutation databases

BioMutaiDNAJC3.
DMDMi73620807.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000007104532 – 504DnaJ homolog subfamily C member 3Add BLAST473

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi248 ↔ 2581 Publication
Modified residuei274Phosphoserine; by FAM20C1 Publication1
Disulfide bondi313 ↔ 3291 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiQ13217.
MaxQBiQ13217.
PaxDbiQ13217.
PeptideAtlasiQ13217.
PRIDEiQ13217.

PTM databases

iPTMnetiQ13217.
PhosphoSitePlusiQ13217.

Expressioni

Tissue specificityi

Widely expressed with high level in the pancreas and testis. Also expressed in cell lines with different levels.1 Publication

Inductioni

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 THAP12.3 Publications

Gene expression databases

BgeeiENSG00000102580.
CleanExiHS_DNAJC3.
ExpressionAtlasiQ13217. baseline and differential.
GenevisibleiQ13217. HS.

Organism-specific databases

HPAiHPA039336.
HPA041326.

Interactioni

Subunit structurei

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).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111597. 17 interactors.
IntActiQ13217. 3 interactors.
MINTiMINT-1531270.
STRINGi9606.ENSP00000365991.

Structurei

Secondary structure

1504
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 49Combined sources15
Helixi53 – 66Combined sources14
Helixi71 – 83Combined sources13
Helixi87 – 100Combined sources14
Turni101 – 103Combined sources3
Helixi105 – 117Combined sources13
Helixi121 – 132Combined sources12
Helixi138 – 167Combined sources30
Helixi170 – 183Combined sources14
Helixi188 – 200Combined sources13
Helixi204 – 207Combined sources4
Helixi208 – 218Combined sources11
Helixi222 – 234Combined sources13
Helixi238 – 251Combined sources14
Helixi256 – 281Combined sources26
Helixi284 – 297Combined sources14
Helixi302 – 317Combined sources16
Turni318 – 320Combined sources3
Helixi322 – 335Combined sources14
Helixi340 – 352Combined sources13
Helixi356 – 367Combined sources12
Beta strandi370 – 372Combined sources3
Helixi374 – 391Combined sources18
Helixi396 – 398Combined sources3
Helixi409 – 420Combined sources12
Helixi423 – 425Combined sources3
Helixi429 – 448Combined sources20
Helixi451 – 454Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y4TX-ray3.00A/B/C35-461[»]
2Y4UX-ray3.20A35-461[»]
ProteinModelPortaliQ13217.
SMRiQ13217.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati37 – 70TPR 1Add BLAST34
Repeati72 – 104TPR 2Add BLAST33
Repeati105 – 138TPR 3Add BLAST34
Repeati154 – 187TPR 4Add BLAST34
Repeati189 – 221TPR 5Add BLAST33
Repeati222 – 255TPR 6Add BLAST34
Repeati268 – 301TPR 7Add BLAST34
Repeati306 – 339TPR 8Add BLAST34
Repeati340 – 373TPR 9Add BLAST34
Domaini394 – 462JPROSITE-ProRule annotationAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni375 – 393Flexible linkerAdd BLAST19

Domaini

The J domain mediates interaction with HSPA8.
Binding to misfolded proteins is mediated by a hydrophobic patch forming a large groove within the first two TPR repeats.By similarity

Sequence similaritiesi

Contains 1 J domain.PROSITE-ProRule annotation
Contains 9 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, TPR repeat

Phylogenomic databases

eggNOGiKOG0624. Eukaryota.
COG0484. LUCA.
GeneTreeiENSGT00760000118947.
HOGENOMiHOG000193351.
HOVERGENiHBG053820.
InParanoidiQ13217.
KOiK09523.
OMAiLCFPFYK.
OrthoDBiEOG091G0783.
PhylomeDBiQ13217.
TreeFamiTF105162.

Family and domain databases

CDDicd06257. DnaJ. 1 hit.
Gene3Di1.10.287.110. 1 hit.
1.25.40.10. 3 hits.
InterProiIPR001623. DnaJ_domain.
IPR026901. DNAJC3.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR018704. TPR_21.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR24078:SF318. PTHR24078:SF318. 1 hit.
PfamiPF00226. DnaJ. 1 hit.
PF09976. TPR_21. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
PRINTSiPR00625. JDOMAIN.
SMARTiSM00271. DnaJ. 1 hit.
SM00028. TPR. 7 hits.
[Graphical view]
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF48452. SSF48452. 2 hits.
PROSITEiPS50076. DNAJ_2. 1 hit.
PS50005. TPR. 8 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q13217-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVAPGSVTSR LGSVFPFLLV LVDLQYEGAE CGVNADVEKH LELGKKLLAA
60 70 80 90 100
GQLADALSQF HAAVDGDPDN YIAYYRRATV FLAMGKSKAA LPDLTKVIQL
110 120 130 140 150
KMDFTAARLQ RGHLLLKQGK LDEAEDDFKK VLKSNPSENE EKEAQSQLIK
160 170 180 190 200
SDEMQRLRSQ ALNAFGSGDY TAAIAFLDKI LEVCVWDAEL RELRAECFIK
210 220 230 240 250
EGEPRKAISD LKAASKLKND NTEAFYKIST LYYQLGDHEL SLSEVRECLK
260 270 280 290 300
LDQDHKRCFA HYKQVKKLNK LIESAEELIR DGRYTDATSK YESVMKTEPS
310 320 330 340 350
IAEYTVRSKE RICHCFSKDE KPVEAIRVCS EVLQMEPDNV NALKDRAEAY
360 370 380 390 400
LIEEMYDEAI QDYETAQEHN ENDQQIREGL EKAQRLLKQS QKRDYYKILG
410 420 430 440 450
VKRNAKKQEI IKAYRKLALQ WHPDNFQNEE EKKKAEKKFI DIAAAKEVLS
460 470 480 490 500
DPEMRKKFDD GEDPLDAESQ QGGGGNPFHR SWNSWQGFNP FSSGGPFRFK

FHFN
Length:504
Mass (Da):57,580
Last modified:November 1, 1996 - v1
Checksum:iE720A1E7F618B912
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28424 mRNA. Translation: AAC50502.1.
AY795482 Genomic DNA. Translation: AAV40838.1.
AL138955 Genomic DNA. Translation: CAH70090.1.
BC047936 mRNA. Translation: AAH47936.2.
CCDSiCCDS9479.1.
PIRiJC4775.
RefSeqiNP_006251.1. NM_006260.4.
UniGeneiHs.59214.

Genome annotation databases

EnsembliENST00000602402; ENSP00000473631; ENSG00000102580.
GeneIDi5611.
KEGGihsa:5611.
UCSCiuc001vmq.3. human.

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28424 mRNA. Translation: AAC50502.1.
AY795482 Genomic DNA. Translation: AAV40838.1.
AL138955 Genomic DNA. Translation: CAH70090.1.
BC047936 mRNA. Translation: AAH47936.2.
CCDSiCCDS9479.1.
PIRiJC4775.
RefSeqiNP_006251.1. NM_006260.4.
UniGeneiHs.59214.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Y4TX-ray3.00A/B/C35-461[»]
2Y4UX-ray3.20A35-461[»]
ProteinModelPortaliQ13217.
SMRiQ13217.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111597. 17 interactors.
IntActiQ13217. 3 interactors.
MINTiMINT-1531270.
STRINGi9606.ENSP00000365991.

PTM databases

iPTMnetiQ13217.
PhosphoSitePlusiQ13217.

Polymorphism and mutation databases

BioMutaiDNAJC3.
DMDMi73620807.

Proteomic databases

EPDiQ13217.
MaxQBiQ13217.
PaxDbiQ13217.
PeptideAtlasiQ13217.
PRIDEiQ13217.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000602402; ENSP00000473631; ENSG00000102580.
GeneIDi5611.
KEGGihsa:5611.
UCSCiuc001vmq.3. human.

Organism-specific databases

CTDi5611.
DisGeNETi5611.
GeneCardsiDNAJC3.
HGNCiHGNC:9439. DNAJC3.
HPAiHPA039336.
HPA041326.
MalaCardsiDNAJC3.
MIMi601184. gene.
616192. phenotype.
neXtProtiNX_Q13217.
OpenTargetsiENSG00000102580.
PharmGKBiPA27420.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0624. Eukaryota.
COG0484. LUCA.
GeneTreeiENSGT00760000118947.
HOGENOMiHOG000193351.
HOVERGENiHBG053820.
InParanoidiQ13217.
KOiK09523.
OMAiLCFPFYK.
OrthoDBiEOG091G0783.
PhylomeDBiQ13217.
TreeFamiTF105162.

Enzyme and pathway databases

ReactomeiR-HSA-192823. Viral mRNA Translation.
R-HSA-381038. XBP1(S) activates chaperone genes.
R-HSA-6798695. Neutrophil degranulation.
SIGNORiQ13217.

Miscellaneous databases

ChiTaRSiDNAJC3. human.
GeneWikiiDNAJC3.
GenomeRNAii5611.
PROiQ13217.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102580.
CleanExiHS_DNAJC3.
ExpressionAtlasiQ13217. baseline and differential.
GenevisibleiQ13217. HS.

Family and domain databases

CDDicd06257. DnaJ. 1 hit.
Gene3Di1.10.287.110. 1 hit.
1.25.40.10. 3 hits.
InterProiIPR001623. DnaJ_domain.
IPR026901. DNAJC3.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR018704. TPR_21.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR24078:SF318. PTHR24078:SF318. 1 hit.
PfamiPF00226. DnaJ. 1 hit.
PF09976. TPR_21. 1 hit.
PF13181. TPR_8. 1 hit.
[Graphical view]
PRINTSiPR00625. JDOMAIN.
SMARTiSM00271. DnaJ. 1 hit.
SM00028. TPR. 7 hits.
[Graphical view]
SUPFAMiSSF46565. SSF46565. 1 hit.
SSF48452. SSF48452. 2 hits.
PROSITEiPS50076. DNAJ_2. 1 hit.
PS50005. TPR. 8 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDNJC3_HUMAN
AccessioniPrimary (citable) accession number: Q13217
Secondary accession number(s): Q86WT9, Q8N4N2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2005
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.