Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

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

Gene

PRKRA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • poly(A) RNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • cellular response to oxidative stress Source: Ensembl
  • gene silencing by RNA Source: Reactome
  • immune response Source: ProtInc
  • middle ear morphogenesis Source: Ensembl
  • negative regulation of cell proliferation Source: ProtInc
  • outer ear morphogenesis Source: Ensembl
  • positive regulation of intrinsic apoptotic signaling pathway Source: Ensembl
  • pre-miRNA processing Source: BHF-UCL
  • production of miRNAs involved in gene silencing by miRNA Source: BHF-UCL
  • production of siRNA involved in RNA interference Source: UniProtKB
  • protein phosphorylation Source: Ensembl
  • response to virus Source: ProtInc
  • skeletal system morphogenesis Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

RNA-mediated gene silencing

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180228-MONOMER.
ReactomeiR-HSA-203927. MicroRNA (miRNA) biogenesis.
R-HSA-426486. Small interfering RNA (siRNA) biogenesis.

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

HGNCiHGNC:9438. PRKRA.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • nucleoplasm Source: HPA
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

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 rs121434410dbSNPEnsembl.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.

PTM databases

iPTMnetiO75569.
PhosphoSitePlusiO75569.

Expressioni

Gene expression databases

BgeeiENSG00000180228.
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).By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself5EBI-713955,EBI-713955
ADARB1P78563-44EBI-713955,EBI-12002366
AGO2Q9UKV85EBI-713955,EBI-528269
DDX58O957862EBI-713955,EBI-995350
DICER1Q9UPY37EBI-713955,EBI-395506
EIF2AK2P195254EBI-713955,EBI-640775
LYARQ9NX584EBI-713955,EBI-713507
NKRFO152263EBI-713955,EBI-766011
NSP034963EBI-713955,EBI-2547442From a different organism.
PAQ670203EBI-713955,EBI-11514477From a different organism.
TARBP2Q156339EBI-713955,EBI-978581
VP35Q051272EBI-713955,EBI-6148294From a different organism.
ZMAT3Q9HA383EBI-713955,EBI-2548480

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi114143. 56 interactors.
DIPiDIP-41809N.
IntActiO75569. 42 interactors.
MINTiMINT-5003897.
STRINGi9606.ENSP00000318176.

Structurei

Secondary structure

1313
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 45Combined sources11
Beta strandi51 – 58Combined sources8
Beta strandi60 – 63Combined sources4
Beta strandi65 – 72Combined sources8
Beta strandi75 – 79Combined sources5
Helixi86 – 101Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DIXNMR-A33-103[»]
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
Contains 3 DRBM (double-stranded RNA-binding) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3732. Eukaryota.
ENOG410XSCK. LUCA.
GeneTreeiENSGT00830000128290.
HOGENOMiHOG000231919.
HOVERGENiHBG001700.
InParanoidiO75569.
OMAiNTDYIQM.
OrthoDBiEOG091G0I2L.
PhylomeDBiO75569.
TreeFamiTF315953.

Family and domain databases

Gene3Di3.30.160.20. 3 hits.
InterProiIPR014720. dsRBD_dom.
IPR033363. PRKRA.
IPR032478. Staufen_C.
[Graphical view]
PANTHERiPTHR10910:SF8. PTHR10910:SF8. 1 hit.
PfamiPF00035. dsrm. 2 hits.
PF16482. Staufen_C. 1 hit.
[Graphical view]
SMARTiSM00358. DSRM. 3 hits.
[Graphical view]
PROSITEiPS50137. DS_RBD. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

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

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 rs121434410dbSNPEnsembl.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

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. 56 interactors.
DIPiDIP-41809N.
IntActiO75569. 42 interactors.
MINTiMINT-5003897.
STRINGi9606.ENSP00000318176.

PTM databases

iPTMnetiO75569.
PhosphoSitePlusiO75569.

Polymorphism and mutation databases

BioMutaiPRKRA.

Proteomic databases

EPDiO75569.
MaxQBiO75569.
PaxDbiO75569.
PeptideAtlasiO75569.
PRIDEiO75569.

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.
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.
GeneTreeiENSGT00830000128290.
HOGENOMiHOG000231919.
HOVERGENiHBG001700.
InParanoidiO75569.
OMAiNTDYIQM.
OrthoDBiEOG091G0I2L.
PhylomeDBiO75569.
TreeFamiTF315953.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000180228-MONOMER.
ReactomeiR-HSA-203927. MicroRNA (miRNA) biogenesis.
R-HSA-426486. Small interfering RNA (siRNA) biogenesis.

Miscellaneous databases

EvolutionaryTraceiO75569.
GeneWikiiPRKRA.
GenomeRNAii8575.
PROiO75569.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180228.
CleanExiHS_PRKRA.
HS_RAX.
ExpressionAtlasiO75569. baseline and differential.
GenevisibleiO75569. HS.

Family and domain databases

Gene3Di3.30.160.20. 3 hits.
InterProiIPR014720. dsRBD_dom.
IPR033363. PRKRA.
IPR032478. Staufen_C.
[Graphical view]
PANTHERiPTHR10910:SF8. PTHR10910:SF8. 1 hit.
PfamiPF00035. dsrm. 2 hits.
PF16482. Staufen_C. 1 hit.
[Graphical view]
SMARTiSM00358. DSRM. 3 hits.
[Graphical view]
PROSITEiPS50137. DS_RBD. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPRKRA_HUMAN
AccessioniPrimary (citable) accession number: O75569
Secondary accession number(s): A8K3I6
, Q53G24, Q6X7T5, Q8NDK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: November 1, 1998
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 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.