Q91YW3 (DNJC3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DnaJ homolog subfamily C member 3

Alternative name(s):
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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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.3 Ref.4
Subunit structure	Interacts with EIF2AK2. Forms a trimeric complex with DNAJB1 and HSPA8. Interacts with PRKRIR/P52RIPK By similarity. Interacts with EIF2AK3. Ref.3
Subcellular location	Endoplasmic reticulum Ref.3.
Tissue specificity	Widely expressed, with high level in the liver. Ref.1
Induction	Up-regulated during an endoplasmic reticulum stress. Ref.3
Domain	The J domain mediates interaction with HSPA8 By similarity. Binding to misfolded proteins is mediated by a hydrophobic patch forming a large groove within the first two TPR repeats.
Sequence similarities	Contains 1 J domain. Contains 9 TPR repeats.

Ontologies

Keywords
Biological process	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	endoplasmic reticulum unfolded protein response Inferred by curator PubMed 18923430. Source: BHF-UCL proteolysis involved in cellular protein catabolic process Inferred from direct assay PubMed 18923430. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement PubMed 18923430. Source: BHF-UCL endoplasmic reticulum lumen Inferred from direct assay PubMed 18923430. Source: BHF-UCL
Molecular_function	misfolded protein binding Inferred from direct assay PubMed 18923430. Source: BHF-UCL protein kinase inhibitor activity Inferred from sequence or structural similarity Ref.1. Source: MGI
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_0000071046

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

188 – 221

34

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 By similarity

Amino acid modifications

Disulfide bond

248 ↔ 258

By similarity

Disulfide bond

313 ↔ 329

By similarity

Experimental info

Mutagenesis

48

1

L → D: Reduces binding affinity for misfolded proteins by 40%. Ref.4

Mutagenesis

71

1

Y → A: Reduces binding affinity for misfolded proteins by 40%. Ref.4

Mutagenesis

75

1

Y → H: Reduces binding affinity for misfolded proteins by 40%. Ref.4

Mutagenesis

104

1

F → A: Reduces binding affinity for misfolded proteins by 40%. Ref.4

Mutagenesis

186

1

W → A: Doesn't affect binding of misfolded proteins. Ref.4

Sequence conflict

89 – 91

3

AAL → RRV in AAC52592. Ref.1

Sequence conflict

134

1

S → C in AAC52592. Ref.1

Sequence conflict

405

1

A → T in AAC52592. Ref.1

Secondary structure

1

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504

Helix Strand Turn

Details...

Helix

36 – 49

14

Helix

53 – 66

14

Helix

71 – 84

14

Helix

87 – 100

14

Helix

105 – 118

14

Helix

121 – 132

12

Helix

138 – 166

29

Helix

170 – 183

14

Helix

188 – 200

13

Helix

204 – 215

12

Helix

222 – 235

14

Helix

238 – 251

14

Helix

256 – 280

25

Helix

284 – 297

14

Helix

302 – 318

17

Helix

322 – 335

14

Helix

340 – 352

13

Helix

356 – 367

12

Helix

374 – 391

18

Sequences

	Sequence		Length	Mass (Da)
	Q91YW3 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 510C27782C6EDF66	FASTA	504	57,464
	10 20 30 40 50 60 MVAPGSVGSR LGAVFPFLLV LVDLQYEGAE CGVNADVEKH LELGKKLLAA GQLADALSQF 70 80 90 100 110 120 HAAVDGDPDN YIAYYRRATV FLAMGKSKAA LPDLTKVIAL KMDFTAARLQ RGHLLLKQGK 130 140 150 160 170 180 LDEAEDDFKK VLKSNPSEQE EKEAESQLVK ADEMQRLRSQ ALDAFDGADY TAAITFLDKI 190 200 210 220 230 240 LEVCVWDAEL RELRAECFIK EGEPRKAISD LKAASKLKSD NTEAFYKIST LYYQLGDHEL 250 260 270 280 290 300 SLSEVRECLK LDQDHKRCFA HYKQVKKLNK LIESAEELIR DGRYTDATSK YESVMKTEPS 310 320 330 340 350 360 VAEYTVRSKE RICHCFSKDE KPVEAIRICS EVLQMEPDNV NALKDRAEAY LIEEMYDEAI 370 380 390 400 410 420 QDYEAAQEHN 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]	"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]. Strain: Czech II. Tissue: Mammary tumor.
[3]	"Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK." Yan W., Frank C.L., Korth M.J., Sopher B.L., Novoa I., Ron D., Katze M.G. Proc. Natl. Acad. Sci. U.S.A. 99:15920-15925(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH EIF2AK3, INDUCTION.
[4]	"Crystal structure of P58(IPK) TPR fragment reveals the mechanism for its molecular chaperone activity in UPR." Tao J., Petrova K., Ron D., Sha B. J. Mol. Biol. 397:1307-1315(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 35-393, FUNCTION, MUTAGENESIS OF LEU-48; TYR-71; TYR-75; PHE-104 AND TRP-186.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U28423 mRNA. Translation: AAC52592.1.
BC013766 mRNA. Translation: AAH13766.1.

IPI

IPI00459033.

RefSeq

NP_032955.2. NM_008929.3.

UniGene

Mm.12616.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3IEG	X-ray	2.51	A/B	35-393	[»]

ProteinModelPortal

Q91YW3.

SMR

Q91YW3. Positions 35-455.

ModBase

Search...

PTM databases

PhosphoSite

Q91YW3.

2D gel databases

REPRODUCTION-2DPAGE

Q91YW3.

Proteomic databases

PaxDb

Q91YW3.

PRIDE

Q91YW3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000022734; ENSMUSP00000022734; ENSMUSG00000022136.

GeneID

100037258.

KEGG

mmu:100037258.

Organism-specific databases

CTD

5611.

MGI

MGI:107373. Dnajc3.

Phylogenomic databases

eggNOG

COG0484.

GeneTree

ENSGT00700000104458.

HOGENOM

HOG000193351.

HOVERGEN

HBG053820.

InParanoid

Q91YW3.

KO

K09523.

OMA

SIVEYTV.

OrthoDB

EOG44TP7Q.

Gene expression databases

ArrayExpress

Q91YW3.

Bgee

Q91YW3.

Genevestigator

Q91YW3.

GermOnline

ENSMUSG00000022136. Mus musculus.
ENSMUSG00000075474. Mus musculus.

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

EvolutionaryTrace

Q91YW3.

NextBio

444137.

SOURCE

Search...

Entry information

Entry name

DNJC3_MOUSE

Accession

Primary (citable) accession number: Q91YW3
Secondary accession number(s): Q60873

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 16, 2005
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program