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Protein Page:
PERK (mouse)

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: EC 2.7.11.1; Kinase, protein; Protein kinase, Ser/Thr (non-receptor); Translation; Membrane protein, integral; Protein kinase, Other; Other group; PEK family; PEK subfamily
Cellular Component: endoplasmic reticulum membrane; membrane; endoplasmic reticulum; cell; cytoplasm; integral to membrane; intracellular
Molecular Function: transferase activity; protein serine/threonine kinase activity; identical protein binding; protein binding; translation initiation factor activity; transferase activity, transferring phosphorus-containing groups; nucleotide binding; kinase activity; protein phosphatase binding; eukaryotic translation initiation factor 2alpha kinase activity; ATP binding; protein kinase activity
Biological Process: fat cell differentiation; lactation; positive regulation of protein binding; translation; protein amino acid autophosphorylation; protein amino acid phosphorylation; bone mineralization; regulation of translation; negative regulation of translation in response to stress; pancreas development; regulation of fatty acid metabolic process; translational initiation; response to stress; skeletal development; protein homooligomerization; ER overload response; endoplasmic reticulum organization and biogenesis; caspase activation; ossification; positive regulation of signal transduction; negative regulation of myelination; unfolded protein response; calcium-mediated signaling; chondrocyte development; SREBP-mediated signaling pathway; endocrine pancreas development; response to unfolded protein; insulin-like growth factor receptor signaling pathway; negative regulation of translation; phosphorylation; negative regulation of apoptosis
Reference #:  Q9Z2B5 (UniProtKB)
Alt. Names/Synonyms: AI427929; E2AK3; Eif2ak3; eukaryotic translation initiation factor 2 alpha kinase 3; Eukaryotic translation initiation factor 2-alpha kinase 3; Pancreatic eIF2-alpha kinase; Pek; Perk; PRKR-like endoplasmic reticulum kinase
Gene Symbols: Eif2ak3
Molecular weight: 124,682 Da
Basal Isoelectric point: 5.13  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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Sites Implicated In
apoptosis, induced: T799‑p
translation, altered: Y615‑p
enzymatic activity, induced: Y615‑p
enzymatic activity, inhibited: T799‑p

Modification Sites and Domains  

Modification Sites in Parent Protein, Orthologs, and Isoforms  
 

Show Multiple Sequence Alignment


 SS 

SS: 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.


 MS 

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


       mouse

 
0 2 Y264 VGHFELRYIPDMETR
0 2 Y477 YPYDNGYYLPYYKRE
0 2 Y481 NGYYLPYYKRERNKR
0 14 S551-p PHRQRKEsETQCQTE
0 2 T553 RQRKEsETQCQTESK
0 2 T557 EsETQCQTESKyDSV
1 0 Y561-p QCQTESKyDSVSADV
3 0 Y615-p NKVDDCNyAIKRIRL
0 3 T701 RRMDPFSTKEQIEVI
0 5 S711-p QIEVIAPsPERSRSF
0 1 S715 IAPsPERSRSFSVGI
1 1 T799-p YTRSREGtSSSIVFE
0 2 S801 RSREGtSSSIVFEDS
0 1 S842 TDLKCSSSRSSSEAT
7 0 T980-p MPAYATHtGQVGTKL
0 4 S1090-p KTVLRQRsRsMsSSG
1 12 S1092-p VLRQRsRsMsSSGTK
0 6 S1094-p RQRsRsMsSSGTKHS
0 8 S1105-p TKHSRQPsCSySPLP
0 2 Y1108-p SRQPsCSySPLPGN_
3179 : Phospho-PERK (Thr980) (16F8) Rabbit mAb
  human

 
Y268-p VGHFELRyIPDMETR
Y481-p YPYDNGYyLPYyKRE
Y485-p NGYyLPYyKRERNKR
S555-p PHRQRKEsEtQCQtE
T557-p RQRKEsEtQCQtENK
T561-p EsEtQCQtENKYDSV
Y565 QCQtENKYDSVSGEA
Y619 NKVDDCNYAIKRIRL
T705-p RRMDPFAtKEHIEII
S715-p HIEIIAPsPQRsRSF
S719-p IAPsPQRsRSFSVGI
T802-p YVRSRERtSsSIVFE
S804-p RSRERtSsSIVFEDS
S845-p TAFKPTSsKSSSEAT
T982-p MPAYARHtGQVGTKL
S1092 KTVLRQRSRsLsSSG
S1094-p VLRQRSRsLsSSGTK
S1096-p RQRSRsLsSSGTKHS
N1107 TKHSRQSNNSHSPLP
H1110 SRQSNNSHSPLPSN_
  rat

 
Y263 VGHFELRYIPDMETR
Y473 YPYDNGYYLPYYKRE
Y477 NGYYLPYYKRERNKR
S547 PHRQRKESETQCQTE
T549 RQRKESETQCQTESK
T553 ESETQCQTESKYDSV
Y557 QCQTESKYDSVSADN
Y611 NKVDDCNYAIKRIRL
T697 RQMDPFSTKEQIEVI
S707 QIEVIAPSPERSRSF
S711 IAPSPERSRSFSVGI
T794 YTRSREGTSSSIVFE
S796 RSREGTSSSIVFEDS
S837 TEFKHSSSRSSSEAT
T974 MPAYATHTGQVGTKL
S1084 KTVLRQRSRSLSSSG
S1086 VLRQRSRSLSSSGTK
S1088 RQRSRSLSSSGTKHS
S1099 TKHSRQPSSTFSPLP
F1102 SRQPSSTFSPLPGN_
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