Reviewed, UniProtKB/Swiss-Prot Q13217 (DNJC3_HUMAN)

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
    Protein kinase inhibitor p58

Gene names

Name:	DNAJC3
Synonyms:	P58IPK, PRKRI

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
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.
Sequence similarities	Contains 1 J domain. Contains 9 TPR repeats.

Ontologies

Keywords
Biological process	Antiviral defense Unfolded protein response
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal TPR repeat
Molecular function	Chaperone
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	response to unfolded protein Inferred from electronic annotation. Source: UniProtKB-KW response to virus Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	heat shock protein binding Inferred from electronic annotation. Source: InterPro protein kinase inhibitor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13217-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q13217-2)

The sequence of this isoform differs from the canonical sequence as follows:
     132-234: LKSNPSENEE...FYKISTLYYQ → VFPVPSLLGL...FIFKPIVYLS
     235-504: Missing.

Note: No experimental confirmation available.

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
Natural variations
	Alternative sequence	132 – 234	103	LKSNP…TLYYQ → VFPVPSLLGLQRSLLDDLYL LFWFFLMKKVTFRCLSSAIS ECLPQSLNLMKFNLLISFLL LWTVRLVSCLRSIHYAVGSK TFLISSKSFMVLCFIFKPIV YLS in isoform 2.		VSP_015148
	Alternative sequence	235 – 504	270	Missing in isoform 2.		VSP_015149

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [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
	Isoform 2. Checksum: A0362017BCBD0C14	FASTA	234	26,181
	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 VVFPVPSLLG LQRSLLDDLY LLFWFFLMKK VTFRCLSSAI SECLPQSLNL 190 200 210 220 230 MKFNLLISFL LLWTVRLVSC LRSIHYAVGS KTFLISSKSF MVLCFIFKPI VYLS

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: 8666242] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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: 15057823] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Blood.
[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: 8576172] [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: 9447982] [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: 9920933] [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: 12601012] [Abstract] Cited for: FUNCTION, INDUCTION.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U28424 mRNA. Translation: AAC50502.1. AY795482 Genomic DNA. Translation: AAV40838.1. AL138955 Genomic DNA. Translation: CAH70090.1. BC033823 mRNA. Translation: AAH33823.1. BC047936 mRNA. Translation: AAH47936.2.
IPI	IPI00006713. IPI00166730.
PIR	JC4775.
RefSeq	NP_006251.1.
UniGene	Hs.656476
3D structure databases
HSSP	HSSP built from PDB template 1HDJ based on UniProtKB P25685.
ModBase	Search...
Proteomic databases
PeptideAtlas	Q13217.
PRIDE	Q13217.
Genome annotation databases
Ensembl	ENSG00000102580. Homo sapiens. [Contig view]
GeneID	5611.
KEGG	hsa:5611.
UCSC	uc001vmp.1. human. uc001vmq.1. human.
Organism-specific databases
GeneCards	GC13P095127.
H-InvDB	HIX0037309.
HGNC	HGNC:9439. DNAJC3.
MIM	601184. gene.
PharmGKB	PA27420.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q13217.
HOVERGEN	Q13217.
OMA	Q13217. ISSKSFM.
Gene expression databases
ArrayExpress	Q13217.
Bgee	Q13217.
CleanEx	HS_DNAJC3.
GermOnline	ENSG00000102580. Homo sapiens.
Family and domain databases
InterPro	IPR001623. DnaJ_N. IPR018253. Heat_shock_DnaJ_CS. IPR015609. Hsp40/DnaJ_Rel. IPR001440. TPR-1. IPR011990. TPR-like_helical. IPR013026. TPR_region. IPR019734. TPR_repeat. [Graphical view]
Gene3D	G3DSA:1.10.287.110. DnaJ_N. 1 hit. G3DSA:1.25.40.10. TPR-like_helical. 1 hit.
PANTHER	PTHR11821. Hsp40/DnaJ_Rel. 1 hit.
Pfam	PF00226. DnaJ. 1 hit. PF00515. TPR_1. 6 hits. [Graphical view]
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 Resources
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:	July 7, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)