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Protein Page:
PERK (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
PERK a transmembrane protein kinase of the PEK family resident in the endoplasmic reticulum (ER) membrane and is linked to insulin processing.. Couples ER stress to translation inhibition. Stress induces autophosphorylation of its kinase domain and increases its activity. Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (eIF2alpha), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. A critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin d1. Forms dimers with BiP in resting cells. Oligomerizes in ER-stressed cells. LOF mutations cause Wolcott-Rallison syndrome (WRS), characterized by insulin-dependent diabetes in early infancy and, later, multiple system abnormalities. Neuronal death in Alzheimer?s and Parkinson?s diseases is thought to be due to ER stress and has been weakly linked to PEK. Note: This description may include information from UniProtKB.
Protein type: Membrane protein, integral; Protein kinase, Other; Kinase, protein; EC 2.7.11.1; Translation; Protein kinase, Ser/Thr (non-receptor); Other group; PEK family; PEK subfamily
Chromosomal Location of Human Ortholog: 2p12
Cellular Component: cytoplasm; endoplasmic reticulum; endoplasmic reticulum membrane; membrane
Molecular Function: enzyme binding; eukaryotic translation initiation factor 2alpha kinase activity; identical protein binding; protein binding; protein homodimerization activity; protein kinase activity; protein phosphatase binding; protein serine/threonine kinase activity
Biological Process: angiogenesis; bone mineralization; calcium-mediated signaling; caspase activation; cellular response to amino acid starvation; cellular response to glucose starvation; chondrocyte development; endocrine pancreas development; endoplasmic reticulum organization and biogenesis; ER overload response; insulin secretion; insulin-like growth factor receptor signaling pathway; negative regulation of myelination; negative regulation of translation; negative regulation of translation initiation in response to stress; ossification; peptidyl-serine phosphorylation; positive regulation of transcription from RNA polymerase I promoter; protein amino acid autophosphorylation; protein amino acid phosphorylation; protein homooligomerization; skeletal development; unfolded protein response
Disease: Epiphyseal Dysplasia, Multiple, With Early-onset Diabetes Mellitus
Reference #:  Q9NZJ5 (UniProtKB)
Alt. Names/Synonyms: DKFZp781H1925; E2AK3; EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3; Eukaryotic translation initiation factor 2-alpha kinase 3; heme-regulated EIF2-alpha kinase; HRI; HsPEK; Pancreatic eIF2-alpha kinase; PEK; PERK; PRKR-like endoplasmic reticulum kinase; WRS
Gene Symbols: EIF2AK3
Molecular weight: 125,216 Da
Basal Isoelectric point: 5.27  Predict pI for various phosphorylation states
CST Pathways:  Translation: eIF2
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

PERK

Protein Structure Not Found.
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Download ChimeraX Script


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Sites Implicated In
enzymatic activity, induced: T982‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment



 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 T177‑p SMETVPFtVESLLES
0 2 Y268‑p VGHFELRyIPDMETR
0 1 T441‑p LIHSPSRtPVLVGsD
0 1 S447‑p RtPVLVGsDEFDKCL
0 1 S455‑p DEFDKCLsNDKFSHE
0 1 Y464‑p DKFSHEEySNGALSI
0 1 Y474‑p GALSILQyPYDNGyy
0 1 Y480‑p QyPYDNGyyLPyyKR
0 2 Y481‑p yPYDNGyyLPyyKRE
0 1 Y484‑p DNGyyLPyyKRERNK
0 2 Y485‑p NGyyLPyyKRERNKR
0 1 S493 KRERNKRSTQITVRF
0 1 T494 RERNKRSTQITVRFL
0 1 T497 NKRSTQITVRFLDNP
0 19 S555‑p PHRQRKEsEtQCQtE
0 2 T557‑p RQRKEsEtQCQtENK
0 2 T561‑p EsEtQCQtENKYDsV
1 0 Y565 QCQtENKYDsVSGEA
0 1 S567‑p QtENKYDsVSGEAND
1 0 Y585‑p NDIKNSGyISRYLTD
4 0 Y619‑p NKVDDCNyAIkRIRL
0 1 K622‑ub DDCNyAIkRIRLPNR
0 1 K669‑ub PPEKWQEkMDEIWLK
0 1 S688‑p DWPLSSPsPMDAPsV
0 1 S694‑p PsPMDAPsVKIRRMD
0 4 T705‑p RRMDPFAtKEHIEII
0 12 S715‑p HIEIIAPsPQRsRSF
0 3 S719‑p IAPsPQRsRSFSVGI
2 1 T802‑p YVRSRERtssSIVFE
0 1 S803‑p VRSRERtssSIVFED
0 2 S804‑p RSRERtssSIVFEDS
0 1 S844‑p LTAFKPTssKSSSEA
0 2 S845‑p TAFKPTssKSSSEAT
0 1 S854‑p SSSEATLsIsPPRPT
0 1 S856‑p SEATLsIsPPRPTTL
10 0 T982‑p MPAYARHtGQVGTKL
0 4 S1092 KTVLRQRSRsLsSSG
1 12 S1094‑p VLRQRSRsLsSSGTK
0 6 S1096‑p RQRSRsLsSSGTKHS
0 8 N1107 TKHSRQSNNsHsPLP
0 1 S1109‑p HSRQSNNsHsPLPSN
0 2 H1110 SRQSNNsHsPLPSN_
0 1 S1111‑p RQSNNsHsPLPSN__
  mouse

 
T173 SMEAVPFTVESLLES
Y264 VGHFELRYIPDMETR
T437 LIHSPSRTPVLVGSD
S443 RTPVLVGSDEFDKCL
S451 DEFDKCLSNDKYSHE
Y460 DKYSHEEYSNGALSI
Y470 GALSILQYPYDNGYY
Y476 QYPYDNGYYLPYYKR
Y477 YPYDNGYYLPYYKRE
Y480 DNGYYLPYYKRERNK
Y481 NGYYLPYYKRERNKR
S489‑p KRERNKRstQItVRF
T490‑p RERNKRstQItVRFL
T493‑p NKRstQItVRFLDSP
S551‑p PHRQRKEsETQCQTE
T553 RQRKEsETQCQTESK
T557 EsETQCQTESKyDSV
Y561‑p QCQTESKyDSVSADV
S563 QTESKyDSVSADVSD
Y581 NDMKYSGYVSRYLTD
Y615‑p NKVDDCNyAIKRIRL
K618 DDCNyAIKRIRLPNR
E665 PPEKWQEEMDEIWLK
S684 DWPLSSPSPMDAPSV
S690 PSPMDAPSVKIRRMD
T701 RRMDPFSTKEQIEVI
S711‑p QIEVIAPsPERSRSF
S715 IAPsPERSRSFSVGI
T799‑p YTRSREGtSSSIVFE
S800 TRSREGtSSSIVFED
S801 RSREGtSSSIVFEDS
S841 LTDLKCSSSRSSSEA
S842 TDLKCSSSRSSSEAT
S852 SSEATTLSTSPTRPT
S854 EATTLSTSPTRPTTL
T980‑p MPAYATHtGQVGTKL
S1090‑p KTVLRQRsRsMsSSG
S1092‑p VLRQRsRsMsSSGTK
S1094‑p RQRsRsMsSSGTKHS
S1105‑p TKHSRQPsCSySPLP
S1107 HSRQPsCSySPLPGN
Y1108‑p SRQPsCSySPLPGN_
S1109 RQPsCSySPLPGN__
3179 : Phospho-PERK (Thr980) (16F8) Rabbit mAb
  rat

 
T172 SMEAVPFTVESLLES
Y263 VGHFELRYIPDMETR
T433 LIHSPSRTPVLVGSD
S439 RTPVLVGSDEFDKCL
S447 DEFDKCLSNDKYSHE
Y456 DKYSHEEYSNGALSI
Y466 GALSILQYPYDNGYY
Y472 QYPYDNGYYLPYYKR
Y473 YPYDNGYYLPYYKRE
Y476 DNGYYLPYYKRERNK
Y477 NGYYLPYYKRERNKR
S485 KRERNKRSTQITVRF
T486 RERNKRSTQITVRFL
T489 NKRSTQITVRFLDSP
S547 PHRQRKESETQCQTE
T549 RQRKESETQCQTESK
T553 ESETQCQTESKYDSV
Y557 QCQTESKYDSVSADN
S559 QTESKYDSVSADNSD
Y577 NDIKHSGYVSRYLTD
Y611 NKVDDCNYAIKRIRL
K614 DDCNYAIKRIRLPNR
E661 PPEKWQEEMDEIWLK
S680 DWPLSSPSPMDAPSV
S686 PSPMDAPSVKIRQMD
T697 RQMDPFSTKEQIEVI
S707 QIEVIAPSPERSRSF
S711 IAPSPERSRSFSVGI
T794 YTRSREGTSSSIVFE
S795 TRSREGTSSSIVFED
S796 RSREGTSSSIVFEDS
S836 LTEFKHSSSRSSSEA
S837 TEFKHSSSRSSSEAT
S846 SSSEATLSTSPTRPT
S848 SEATLSTSPTRPTTL
T974‑p MPAYATHtGQVGTKL
S1084 KTVLRQRSRSLSSSG
S1086 VLRQRSRSLSSSGTK
S1088 RQRSRSLSSSGTKHS
S1099 TKHSRQPSSTFSPLP
T1101 HSRQPSSTFSPLPGN
F1102 SRQPSSTFSPLPGN_
S1103 RQPSSTFSPLPGN__
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