Q13217 (DNJC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DnaJ homolog subfamily C member 3

Alternative name(s):
Endoplasmic reticulum DnaJ protein 6
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 names

Name:	DNAJC3
Synonyms:	P58IPK, PRKRI

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	504 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the unfolded protein response (UPR) during ER stress. 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. Ref.5 Ref.6 Ref.7 Ref.8
Subunit structure	Interacts with EIF2AK3 By similarity and EIF2AK2. Forms a trimeric complex with DNAJB1 and HSPA8. Interacts with PRKRIR/P52RIPK. Ref.5 Ref.6 Ref.7
Subcellular location	Endoplasmic reticulum By similarity.
Tissue specificity	Widely expressed with high level in the pancreas and testis. Also expressed in cell lines with different levels. Ref.1
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 PRKRIR/P52RIPK. Ref.6 Ref.7 Ref.8
Domain	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 similarities	Contains 1 J domain. Contains 9 TPR repeats.

Ontologies

Keywords
Biological process	Antiviral defense Unfolded protein response
Cellular component	Endoplasmic reticulum
Domain	Repeat Signal TPR repeat
Molecular function	Chaperone
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of signaling protein activity involved in unfolded protein response Traceable author statement. Source: Reactome defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW proteolysis involved in cellular protein catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum Sec complex Inferred from electronic annotation. Source: Compara endoplasmic reticulum lumen Traceable author statement. Source: Reactome
Molecular_function	protein kinase inhibitor activity Traceable author statement PubMed 7511204. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Potential

Chain

32 – 504

473

DnaJ homolog subfamily C member 3

PRO_0000071045

Regions

Repeat

37 – 70

34

TPR 1

Repeat

72 – 104

33

TPR 2

Repeat

105 – 138

34

TPR 3

Repeat

154 – 187

34

TPR 4

Repeat

189 – 221

33

TPR 5

Repeat

222 – 255

34

TPR 6

Repeat

268 – 301

34

TPR 7

Repeat

306 – 339

34

TPR 8

Repeat

340 – 373

34

TPR 9

Domain

394 – 462

69

J

Region

375 – 393

19

Flexible linker

Amino acid modifications

Disulfide bond

248 ↔ 258

Ref.10

Disulfide bond

313 ↔ 329

Ref.10

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

504

Helix Strand Turn

Details...

Helix

35 – 49

15

Helix

53 – 66

14

Helix

71 – 83

13

Helix

87 – 100

14

Turn

101 – 103

3

Helix

105 – 117

13

Helix

121 – 132

12

Helix

138 – 167

30

Helix

170 – 183

14

Helix

188 – 200

13

Helix

204 – 207

4

Helix

208 – 218

11

Helix

222 – 234

13

Helix

238 – 251

14

Helix

256 – 281

26

Helix

284 – 297

14

Helix

302 – 317

16

Turn

318 – 320

3

Helix

322 – 335

14

Helix

340 – 352

13

Helix

356 – 367

12

Beta strand

370 – 372

3

Helix

374 – 391

18

Helix

396 – 398

3

Helix

409 – 420

12

Helix

423 – 425

3

Helix

429 – 448

20

Helix

451 – 454

4

Sequences

	Sequence		Length	Mass (Da)
	Q13217 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: E720A1E7F618B912	FASTA	504	57,580
	10 20 30 40 50 60 MVAPGSVTSR LGSVFPFLLV LVDLQYEGAE CGVNADVEKH LELGKKLLAA GQLADALSQF 70 80 90 100 110 120 HAAVDGDPDN YIAYYRRATV FLAMGKSKAA LPDLTKVIQL KMDFTAARLQ RGHLLLKQGK 130 140 150 160 170 180 LDEAEDDFKK VLKSNPSENE EKEAQSQLIK SDEMQRLRSQ ALNAFGSGDY TAAIAFLDKI 190 200 210 220 230 240 LEVCVWDAEL RELRAECFIK EGEPRKAISD LKAASKLKND NTEAFYKIST LYYQLGDHEL 250 260 270 280 290 300 SLSEVRECLK LDQDHKRCFA HYKQVKKLNK LIESAEELIR DGRYTDATSK YESVMKTEPS 310 320 330 340 350 360 IAEYTVRSKE RICHCFSKDE KPVEAIRVCS EVLQMEPDNV NALKDRAEAY LIEEMYDEAI 370 380 390 400 410 420 QDYETAQEHN ENDQQIREGL EKAQRLLKQS QKRDYYKILG VKRNAKKQEI IKAYRKLALQ 430 440 450 460 470 480 WHPDNFQNEE EKKKAEKKFI DIAAAKEVLS DPEMRKKFDD GEDPLDAESQ QGGGGNPFHR 490 500 SWNSWQGFNP FSSGGPFRFK FHFN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression, and cellular localization of the oncogenic 58-kDa inhibitor of the RNA-activated human and mouse protein kinase." Korth M.J., Lyons C.N., Wambach M., Katze M.G. Gene 170:181-188(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Leukocyte.
[5]	"The P58 cellular inhibitor complexes with the interferon-induced, double-stranded RNA-dependent protein kinase, PKR, to regulate its autophosphorylation and activity." Polyak S.J., Tang N., Wambach M., Barber G.N., Katze M.G. J. Biol. Chem. 271:1702-1707(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH EIF2AK2.
[6]	"Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK." Gale M.J. Jr., Blakely C.M., Hopkins D.A., Melville M.W., Wambach M., Romano P.R., Katze M.G. Mol. Cell. Biol. 18:859-871(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PRKRIR, INDUCTION.
[7]	"The cellular inhibitor of the PKR protein kinase, P58(IPK), is an influenza virus-activated co-chaperone that modulates heat shock protein 70 activity." Melville M.W., Tan S.-L., Wambach M., Song J., Morimoto R.I., Katze M.G. J. Biol. Chem. 274:3797-3803(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DNAJB1 AND HSPA8, INDUCTION.
[8]	"P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling." van Huizen R., Martindale J.L., Gorospe M., Holbrook N.J. J. Biol. Chem. 278:15558-15564(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"The crystal structure of the human co-chaperone P58(IPK)." Svard M., Biterova E.I., Bourhis J.M., Guy J.E. PLoS ONE 6:E22337-E22337(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 35-461, DISULFIDE BONDS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U28424 mRNA. Translation: AAC50502.1.
AY795482 Genomic DNA. Translation: AAV40838.1.
AL138955 Genomic DNA. Translation: CAH70090.1.
BC047936 mRNA. Translation: AAH47936.2.

IPI

IPI00006713.

PIR

JC4775.

RefSeq

NP_006251.1. NM_006260.4.

UniGene

Hs.59214.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Y4T	X-ray	3.00	A/B/C	35-461	[»]
2Y4U	X-ray	3.20	A	35-461	[»]

ProteinModelPortal

Q13217.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13217. 1 interaction.

STRING

9606.ENSP00000365991.

PTM databases

PhosphoSite

Q13217.

Polymorphism databases

DMDM

73620807.

Proteomic databases

PaxDb

Q13217.

PeptideAtlas

Q13217.

PRIDE

Q13217.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000376795; ENSP00000365991; ENSG00000102580.

GeneID

5611.

KEGG

hsa:5611.

UCSC

uc001vmq.3. human.

Organism-specific databases

CTD

5611.

GeneCards

GC13P096329.

HGNC

HGNC:9439. DNAJC3.

HPA

HPA039336.
HPA041326.

MIM

601184. gene.

neXtProt

NX_Q13217.

PharmGKB

PA27420.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0484.

HOGENOM

HOG000193351.

HOVERGEN

HBG053820.

InParanoid

Q13217.

KO

K09523.

OMA

SIVEYTV.

OrthoDB

EOG44TP7Q.

PhylomeDB

Q13217.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

Q13217.

Bgee

Q13217.

CleanEx

HS_DNAJC3.

Genevestigator

Q13217.

GermOnline

ENSG00000102580. Homo sapiens.

Family and domain databases

Gene3D

1.10.287.110. 1 hit.
1.25.40.10. 3 hits.

InterPro

IPR001623. DnaJ_domain.
IPR026901. DNAJC3.
IPR001440. TPR-1.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical.
IPR019734. TPR_repeat.
[Graphical view]

PANTHER

PTHR24078:SF1. PTHR24078:SF1. 1 hit.

Pfam

PF00226. DnaJ. 1 hit.
PF00515. TPR_1. 2 hits.
[Graphical view]

PRINTS

PR00625. JDOMAIN.

SMART

SM00271. DnaJ. 1 hit.
SM00028. TPR. 7 hits.
[Graphical view]

PROSITE

PS00636. DNAJ_1. False negative.
PS50076. DNAJ_2. 1 hit.
PS50005. TPR. 8 hits.
PS50293. TPR_REGION. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

DNAJC3. human.

GenomeRNAi

5611.

NextBio

21810.

SOURCE

Search...

Entry information

Entry name

DNJC3_HUMAN

Accession

Primary (citable) accession number: Q13217
Secondary accession number(s): Q86WT9, Q8N4N2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.