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Protein

Interferon-inducible double-stranded RNA-dependent protein kinase activator A

Gene

PRKRA

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

Functioni

Activates EIF2AK2/PKR in the absence of double-stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1. Promotes UBC9-p53/TP53 association and sumoylation and phosphorylation of p53/TP53 at 'Lys-386' at 'Ser-392' respectively and enhances its activity in a EIF2AK2/PKR-dependent manner (By similarity).By similarity6 Publications

GO - Molecular functioni

  • double-stranded RNA binding Source: BHF-UCL
  • enzyme activator activity Source: ProtInc
  • enzyme binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • pre-miRNA binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • RNA binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processHost-virus interaction, RNA-mediated gene silencing

Enzyme and pathway databases

ReactomeiR-HSA-203927 MicroRNA (miRNA) biogenesis
R-HSA-426486 Small interfering RNA (siRNA) biogenesis
SIGNORiO75569

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-inducible double-stranded RNA-dependent protein kinase activator A
Alternative name(s):
PKR-associated protein X
PKR-associating protein X
Protein activator of the interferon-induced protein kinase
Protein kinase, interferon-inducible double-stranded RNA-dependent activator
Gene namesi
Name:PRKRA
Synonyms:PACT, RAX
ORF Names:HSD-14, HSD14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000180228.12
HGNCiHGNC:9438 PRKRA
MIMi603424 gene
neXtProtiNX_O75569

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Dystonia 16 (DYT16)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.
See also OMIM:612067
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046213222P → L in DYT16. 1 PublicationCorresponds to variant dbSNP:rs121434410EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18S → A: No effect on apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi18S → D: Does not induce apoptosis. 1 Publication1
Mutagenesisi243Q → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi246S → A: Abrogates apoptosis induction under conditions of stress and binding to EIF2AK2. Prevents activation of EIF2AK2 in stressed cells; when associated with A-287. 1 Publication1
Mutagenesisi246S → D: Induces activation of EIF2AK2 and apoptosis in unstressed cells; when associated with D-287. 1 Publication1
Mutagenesisi260D → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi262D → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi265S → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi271Q → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi279S → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi287S → A: Abrogates apoptosis induction under conditions of stress. Prevents activation of EIF2AK2 in stressed cells; when associated with A-246. 1 Publication1
Mutagenesisi287S → D: Induces activation of EIF2AK2 and apoptosis in unstressed cells; when associated with D-246. 1 Publication1
Mutagenesisi288G → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi291C → A: Abrogates apoptosis induction under conditions of stress. 1 Publication1
Mutagenesisi298 – 299AA → KK: Abrogates interaction with DICER1 but does not affect interaction with AGO2. 1 Publication2

Keywords - Diseasei

Disease mutation, Dystonia, Parkinsonism

Organism-specific databases

DisGeNETi8575
MalaCardsiPRKRA
MIMi612067 phenotype
OpenTargetsiENSG00000180228
Orphaneti210571 Dystonia 16
PharmGKBiPA33780

Polymorphism and mutation databases

BioMutaiPRKRA

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002236091 – 313Interferon-inducible double-stranded RNA-dependent protein kinase activator AAdd BLAST313

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei18PhosphoserineCombined sources1
Modified residuei167PhosphoserineCombined sources1
Modified residuei246Phosphoserine1 Publication1
Modified residuei287Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated at Ser-246 in unstressed cells and at Ser-287 in stressed cells. Phosphorylation at Ser-246 appears to be a prerequisite for subsequent phosphorylation at Ser-287. Phosphorylation at Ser-246 and Ser-287 are necessary for activation of EIF2AK2/PKR under conditions of stress.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO75569
MaxQBiO75569
PaxDbiO75569
PeptideAtlasiO75569
PRIDEiO75569
ProteomicsDBi50088
50089 [O75569-2]
50090 [O75569-3]

PTM databases

iPTMnetiO75569
PhosphoSitePlusiO75569

Expressioni

Gene expression databases

BgeeiENSG00000180228 Expressed in 231 organ(s), highest expression level in sperm
CleanExiHS_PRKRA
HS_RAX
ExpressionAtlasiO75569 baseline and differential
GenevisibleiO75569 HS

Organism-specific databases

HPAiCAB004648
HPA034996
HPA034997

Interactioni

Subunit structurei

Homodimer. Interacts with EIF2AK2/PKR through its DRBM domains. Interacts with DICER1, AGO2 and TARBP2. Also able to interact with dsRNA. Interacts with UBC9 (By similarity). Forms a complex with UBC9 and p53/TP53 (By similarity). Interacts with DUS2L (via DRBM domain). Interacts with DDX58.By similarity8 Publications
(Microbial infection) Interacts with ebolavirus protein VP35; this interaction inhibits the interaction between DDX58 and PRKRA. In addition, this interaction disrupts the interaction between VP35 and the viral polymerase L. So the VP35-PRKRA interaction plays a critical role in determining the outcome of ebolavirus infection.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114143, 68 interactors
ComplexPortaliCPX-1072 RISC-loading complex, PRKRA variant
DIPiDIP-41809N
IntActiO75569, 48 interactors
MINTiO75569
STRINGi9606.ENSP00000318176

Structurei

Secondary structure

1313
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO75569
SMRiO75569
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75569

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini34 – 101DRBM 1PROSITE-ProRule annotationAdd BLAST68
Domaini126 – 194DRBM 2PROSITE-ProRule annotationAdd BLAST69
Domaini240 – 308DRBM 3PROSITE-ProRule annotationAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 103Sufficient for self-association and interaction with TARBP2Add BLAST103
Regioni102 – 195Sufficient for self-association and interaction with TARBP2Add BLAST94
Regioni195 – 313Sufficient for self-association and interaction with TARBP2Add BLAST119

Domaini

Self-association may occur via interactions between DRBM domains as follows: DRBM 1/DRBM 1, DRBM 1/DRBM 2, DRBM 2/DRBM 2 or DRBM 3/DRBM3.

Sequence similaritiesi

Belongs to the PRKRA family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3732 Eukaryota
ENOG410XSCK LUCA
GeneTreeiENSGT00900000141030
HOGENOMiHOG000231919
HOVERGENiHBG001700
InParanoidiO75569
OMAiVTVCHGT
OrthoDBiEOG091G0I2L
PhylomeDBiO75569
TreeFamiTF315953

Family and domain databases

CDDicd00048 DSRM, 3 hits
InterProiView protein in InterPro
IPR014720 dsRBD_dom
IPR033363 PRKRA
IPR032478 Staufen_C
PANTHERiPTHR10910:SF8 PTHR10910:SF8, 1 hit
PfamiView protein in Pfam
PF00035 dsrm, 2 hits
PF16482 Staufen_C, 1 hit
SMARTiView protein in SMART
SM00358 DSRM, 3 hits
PROSITEiView protein in PROSITE
PS50137 DS_RBD, 3 hits

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O75569-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MSQSRHRAEA PPLEREDSGT FSLGKMITAK PGKTPIQVLH EYGMKTKNIP
60 70 80 90 100
VYECERSDVQ IHVPTFTFRV TVGDITCTGE GTSKKLAKHR AAEAAINILK
110 120 130 140 150
ANASICFAVP DPLMPDPSKQ PKNQLNPIGS LQELAIHHGW RLPEYTLSQE
160 170 180 190 200
GGPAHKREYT TICRLESFME TGKGASKKQA KRNAAEKFLA KFSNISPENH
210 220 230 240 250
ISLTNVVGHS LGCTWHSLRN SPGEKINLLK RSLLSIPNTD YIQLLSEIAK
260 270 280 290 300
EQGFNITYLD IDELSANGQY QCLAELSTSP ITVCHGSGIS CGNAQSDAAH
310
NALQYLKIIA ERK
Length:313
Mass (Da):34,404
Last modified:November 1, 1998 - v1
Checksum:i9B01637E6194827E
GO
Isoform 2 (identifier: O75569-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: MSQSRHRAEAPPLEREDSGTF → MQSTPFCGFC

Note: No experimental confirmation available.
Show »
Length:302
Mass (Da):33,123
Checksum:i1A1002362E1095D5
GO
Isoform 3 (identifier: O75569-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: Missing.

Note: No experimental confirmation available.
Show »
Length:288
Mass (Da):31,635
Checksum:iE663866BAB6DF0BC
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
G5E9Q4G5E9Q4_HUMAN
Interferon-inducible double-strande...
PRKRA hCG_43233
105Annotation score:
F8WEG8F8WEG8_HUMAN
Interferon-inducible double-strande...
PRKRA
95Annotation score:
C9JMM3C9JMM3_HUMAN
Interferon-inducible double-strande...
PRKRA
108Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti282T → A in BAD96827 (Ref. 8) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046213222P → L in DYT16. 1 PublicationCorresponds to variant dbSNP:rs121434410EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0172821 – 25Missing in isoform 3. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_0172831 – 21MSQSR…DSGTF → MQSTPFCGFC in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072860 mRNA Translation: AAC25672.1
AF083033 mRNA Translation: AAD33099.1
AY251164 mRNA Translation: AAP20061.1
AL136615 mRNA Translation: CAB66550.1
AL833867 Transcribed RNA Translation: CAD38725.1
BT007243 mRNA Translation: AAP35907.1
AK290601 mRNA Translation: BAF83290.1
CR533525 mRNA Translation: CAG38556.1
AK223107 mRNA Translation: BAD96827.1
AC009948 Genomic DNA Translation: AAX88882.1
CH471058 Genomic DNA Translation: EAX11036.1
BC009470 mRNA Translation: AAH09470.1
CCDSiCCDS2279.1 [O75569-1]
CCDS46460.1 [O75569-2]
CCDS46461.1 [O75569-3]
RefSeqiNP_001132989.1, NM_001139517.1 [O75569-2]
NP_001132990.1, NM_001139518.1 [O75569-3]
NP_003681.1, NM_003690.4 [O75569-1]
UniGeneiHs.570274

Genome annotation databases

EnsembliENST00000325748; ENSP00000318176; ENSG00000180228 [O75569-1]
ENST00000432031; ENSP00000393883; ENSG00000180228 [O75569-2]
ENST00000487082; ENSP00000430604; ENSG00000180228 [O75569-3]
GeneIDi8575
KEGGihsa:8575
UCSCiuc002umd.4 human [O75569-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF072860 mRNA Translation: AAC25672.1
AF083033 mRNA Translation: AAD33099.1
AY251164 mRNA Translation: AAP20061.1
AL136615 mRNA Translation: CAB66550.1
AL833867 Transcribed RNA Translation: CAD38725.1
BT007243 mRNA Translation: AAP35907.1
AK290601 mRNA Translation: BAF83290.1
CR533525 mRNA Translation: CAG38556.1
AK223107 mRNA Translation: BAD96827.1
AC009948 Genomic DNA Translation: AAX88882.1
CH471058 Genomic DNA Translation: EAX11036.1
BC009470 mRNA Translation: AAH09470.1
CCDSiCCDS2279.1 [O75569-1]
CCDS46460.1 [O75569-2]
CCDS46461.1 [O75569-3]
RefSeqiNP_001132989.1, NM_001139517.1 [O75569-2]
NP_001132990.1, NM_001139518.1 [O75569-3]
NP_003681.1, NM_003690.4 [O75569-1]
UniGeneiHs.570274

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DIXNMR-A33-103[»]
ProteinModelPortaliO75569
SMRiO75569
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114143, 68 interactors
ComplexPortaliCPX-1072 RISC-loading complex, PRKRA variant
DIPiDIP-41809N
IntActiO75569, 48 interactors
MINTiO75569
STRINGi9606.ENSP00000318176

PTM databases

iPTMnetiO75569
PhosphoSitePlusiO75569

Polymorphism and mutation databases

BioMutaiPRKRA

Proteomic databases

EPDiO75569
MaxQBiO75569
PaxDbiO75569
PeptideAtlasiO75569
PRIDEiO75569
ProteomicsDBi50088
50089 [O75569-2]
50090 [O75569-3]

Protocols and materials databases

DNASUi8575
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000325748; ENSP00000318176; ENSG00000180228 [O75569-1]
ENST00000432031; ENSP00000393883; ENSG00000180228 [O75569-2]
ENST00000487082; ENSP00000430604; ENSG00000180228 [O75569-3]
GeneIDi8575
KEGGihsa:8575
UCSCiuc002umd.4 human [O75569-1]

Organism-specific databases

CTDi8575
DisGeNETi8575
EuPathDBiHostDB:ENSG00000180228.12
GeneCardsiPRKRA
HGNCiHGNC:9438 PRKRA
HPAiCAB004648
HPA034996
HPA034997
MalaCardsiPRKRA
MIMi603424 gene
612067 phenotype
neXtProtiNX_O75569
OpenTargetsiENSG00000180228
Orphaneti210571 Dystonia 16
PharmGKBiPA33780
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3732 Eukaryota
ENOG410XSCK LUCA
GeneTreeiENSGT00900000141030
HOGENOMiHOG000231919
HOVERGENiHBG001700
InParanoidiO75569
OMAiVTVCHGT
OrthoDBiEOG091G0I2L
PhylomeDBiO75569
TreeFamiTF315953

Enzyme and pathway databases

ReactomeiR-HSA-203927 MicroRNA (miRNA) biogenesis
R-HSA-426486 Small interfering RNA (siRNA) biogenesis
SIGNORiO75569

Miscellaneous databases

ChiTaRSiPRKRA human
EvolutionaryTraceiO75569
GeneWikiiPRKRA
GenomeRNAii8575
PROiPR:O75569
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180228 Expressed in 231 organ(s), highest expression level in sperm
CleanExiHS_PRKRA
HS_RAX
ExpressionAtlasiO75569 baseline and differential
GenevisibleiO75569 HS

Family and domain databases

CDDicd00048 DSRM, 3 hits
InterProiView protein in InterPro
IPR014720 dsRBD_dom
IPR033363 PRKRA
IPR032478 Staufen_C
PANTHERiPTHR10910:SF8 PTHR10910:SF8, 1 hit
PfamiView protein in Pfam
PF00035 dsrm, 2 hits
PF16482 Staufen_C, 1 hit
SMARTiView protein in SMART
SM00358 DSRM, 3 hits
PROSITEiView protein in PROSITE
PS50137 DS_RBD, 3 hits
ProtoNetiSearch...

Entry informationi

Entry nameiPRKRA_HUMAN
AccessioniPrimary (citable) accession number: O75569
Secondary accession number(s): A8K3I6
, Q53G24, Q6X7T5, Q8NDK4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: November 1, 1998
Last modified: November 7, 2018
This is version 172 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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