Gene/Proteome Database (LMPD)

LMPD ID
LMP012626
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
eukaryotic translation initiation factor 2 alpha kinase 3
Gene Symbol
Synonyms
PEK;
Alternate Names
eukaryotic translation initiation factor 2-alpha kinase 3; pancreatic eIF2-alpha kinase; PRKR-like endoplasmic reticulum kinase;
Chromosome
4
Map Location
4q32
EC Number
2.7.11.1
Summary
kinase that phosphorylates eukaryotic initiation factor 2alpha; has an important role in translational control [RGD, Feb 2006]
Orthologs

Proteins

eukaryotic translation initiation factor 2-alpha kinase 3 precursor
Refseq ID NP_113787
Protein GI 13928816
UniProt ID Q9Z1Z1
mRNA ID NM_031599
Length 1108
MERATQPRPRALLLLFLLLGCAAGISAVARARSLLAPTSDTAFGLGAAAAPTSAARVPAVATAEVTVEDAEALPAASGEQESRATESDDDVELRPRGRSLVIISTLDGRIAALDAENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGDLFQWDRDRESMEAVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKLRYICSALGCRRWDSDEMEEEEDILLLQRTQKTVRAVGPRSGSEKWNFSVGHFELRYIPDMETRAGFIESTFKLGGNKEDSKIISDVEEQDVDTVIKVSVADWKVMAFSKKGGRLEWEYQFCTPIASAWLVRDGKVIPISLFDDTSYTANEEVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRVSEKFPTRPKALESVNGESAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKYSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDSPHYSKNIRKKDPILLLHWWKEIFGTILLCIVATTFIVRRLFHPQPHRQRKESETQCQTESKYDSVSADNSDNSWNDIKHSGYVSRYLTDFEPIQCMGRGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLETPPEKWQEEMDEIWLKDESTDWPLSSPSPMDAPSVKIRQMDPFSTKEQIEVIAPSPERSRSFSVGISCGRTSSSESQFSPLEFSGTDCGDNSDSEDAAHNLQDSCLTDCDMEDGTVDGDDEGHSFELCPSEASPYTRSREGTSSSIVFEDSGCDNASSKEDPRMNRLHNGHHYVNKLTEFKHSSSRSSSEATLSTSPTRPTTLSLDFTRNTVDRLQPSSPKVYLYIQMQLCRKENLKDWMNRRCSMEDREHRVCLHIFLQIAEAVQFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPMPAYATHTGQVGTKLYMSPEQIHGNNYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPQEHMMVQDMLSPSPMERPEATDIIENAVFENLEFPGKTVLRQRSRSLSSSGTKHSRQPSSTFSPLPGN
sig_peptide: 1..27 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2883 peptide sequence: MERATQPRPRALLLLFLLLGCAAGISA mat_peptide: 28..1108 product: Eukaryotic translation initiation factor 2-alpha kinase 3 experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q9Z1Z1.1) calculated_mol_wt: 121906 peptide sequence: VARARSLLAPTSDTAFGLGAAAAPTSAARVPAVATAEVTVEDAEALPAASGEQESRATESDDDVELRPRGRSLVIISTLDGRIAALDAENHGKKQWDLDVGSGSLVSSSLSKPEVFGNKMIIPSLDGDLFQWDRDRESMEAVPFTVESLLESSYKFGDDVVLVGGKSLTTYGLSAYSGKLRYICSALGCRRWDSDEMEEEEDILLLQRTQKTVRAVGPRSGSEKWNFSVGHFELRYIPDMETRAGFIESTFKLGGNKEDSKIISDVEEQDVDTVIKVSVADWKVMAFSKKGGRLEWEYQFCTPIASAWLVRDGKVIPISLFDDTSYTANEEVLEDEEDIVEAARGATENSVYLGMYRGQLYLQSSVRVSEKFPTRPKALESVNGESAIIPLPTIKWKPLIHSPSRTPVLVGSDEFDKCLSNDKYSHEEYSNGALSILQYPYDNGYYLPYYKRERNKRSTQITVRFLDSPHYSKNIRKKDPILLLHWWKEIFGTILLCIVATTFIVRRLFHPQPHRQRKESETQCQTESKYDSVSADNSDNSWNDIKHSGYVSRYLTDFEPIQCMGRGGFGVVFEAKNKVDDCNYAIKRIRLPNRELAREKVMREVKALAKLEHPGIVRYFNAWLETPPEKWQEEMDEIWLKDESTDWPLSSPSPMDAPSVKIRQMDPFSTKEQIEVIAPSPERSRSFSVGISCGRTSSSESQFSPLEFSGTDCGDNSDSEDAAHNLQDSCLTDCDMEDGTVDGDDEGHSFELCPSEASPYTRSREGTSSSIVFEDSGCDNASSKEDPRMNRLHNGHHYVNKLTEFKHSSSRSSSEATLSTSPTRPTTLSLDFTRNTVDRLQPSSPKVYLYIQMQLCRKENLKDWMNRRCSMEDREHRVCLHIFLQIAEAVQFLHSKGLMHRDLKPSNIFFTMDDVVKVGDFGLVTAMDQDEEEQTVLTPMPAYATHTGQVGTKLYMSPEQIHGNNYSHKVDIFSLGLILFELLYPFSTQMERVRTLTDVRNLKFPPLFTQKYPQEHMMVQDMLSPSPMERPEATDIIENAVFENLEFPGKTVLRQRSRSLSSSGTKHSRQPSSTFSPLPGN

Gene Information

Entrez Gene ID
Gene Name
eukaryotic translation initiation factor 2 alpha kinase 3
Gene Symbol
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005623 IDA:RGD C cell
GO:0005789 IEA:Ensembl C endoplasmic reticulum membrane
GO:0016021 IEA:UniProtKB-KW C integral component of membrane
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0004694 ISS:UniProtKB F eukaryotic translation initiation factor 2alpha kinase activity
GO:0004674 IDA:RGD F protein serine/threonine kinase activity
GO:0006983 ISS:UniProtKB P ER overload response
GO:0032933 IEA:Ensembl P SREBP signaling pathway
GO:0006919 IEA:Ensembl P activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0030282 IEA:Ensembl P bone mineralization
GO:0019722 IEA:Ensembl P calcium-mediated signaling
GO:0002063 IEA:Ensembl P chondrocyte development
GO:0031018 ISS:UniProtKB P endocrine pancreas development
GO:0007029 IEA:Ensembl P endoplasmic reticulum organization
GO:0030968 ISS:UniProtKB P endoplasmic reticulum unfolded protein response
GO:0045444 IEA:Ensembl P fat cell differentiation
GO:0048009 IEA:Ensembl P insulin-like growth factor receptor signaling pathway
GO:0070059 IEA:Ensembl P intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0007595 IEA:Ensembl P lactation
GO:0043066 IEA:Ensembl P negative regulation of apoptotic process
GO:0010629 IEA:Ensembl P negative regulation of gene expression
GO:0031642 IEA:Ensembl P negative regulation of myelination
GO:0032055 IDA:RGD P negative regulation of translation in response to stress
GO:0032057 TAS:RGD P negative regulation of translational initiation in response to stress
GO:0001503 ISS:UniProtKB P ossification
GO:0032092 IEA:Ensembl P positive regulation of protein binding
GO:0009967 IEA:Ensembl P positive regulation of signal transduction
GO:0046777 ISS:UniProtKB P protein autophosphorylation
GO:0051260 ISS:UniProtKB P protein homooligomerization
GO:0006468 IDA:RGD P protein phosphorylation
GO:0019217 IEA:Ensembl P regulation of fatty acid metabolic process
GO:0006412 IEA:Ensembl P translation

KEGG Pathway Links

KEGG Pathway ID Description
ko05010 Alzheimer's disease
rno05010 Alzheimer's disease
ko05169 Epstein-Barr virus infection
rno05169 Epstein-Barr virus infection
ko05160 Hepatitis C
rno05160 Hepatitis C
ko05168 Herpes simplex infection
rno05168 Herpes simplex infection
ko05164 Influenza A
rno05164 Influenza A
ko05162 Measles
rno05162 Measles
ko04932 Non-alcoholic fatty liver disease (NAFLD)
rno04932 Non-alcoholic fatty liver disease (NAFLD)
ko04141 Protein processing in endoplasmic reticulum
rno04141 Protein processing in endoplasmic reticulum

REACTOME Pathway Links

REACTOME Pathway ID Description
5953345 Metabolism of proteins
5954164 PERK regulates gene expression
5954163 Unfolded Protein Response (UPR)

Domain Information

InterPro Annotations

Accession Description
IPR000719 Protein kinase domain
IPR011009 Protein kinase-like domain
IPR011047 Quinonprotein alcohol dehydrogenase-like superfamily
IPR027295 Quinonprotein_ADH-like_fam
IPR008271 Serine/threonine-protein kinase, active site

UniProt Annotations

Entry Information

Gene Name
eukaryotic translation initiation factor 2 alpha kinase 3
Protein Entry
E2AK3_RAT
UniProt ID
Species
Rat

Comments

Comment Type Description
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Domain The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.
Enzyme Regulation Perturbation in protein folding in the endoplasmic reticulum (ER) promotes reversible dissociation from HSPA5/BIP and oligomerization, resulting in transautophosphorylation and kinase activity induction.
Function Phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2 (EIF2), leading to its inactivation and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1). Involved in control of mitochondrial morphology and function (By similarity)
Induction By ER stress.
Ptm ADP-ribosylated by PARP16 upon ER stress, which increases kinase activity
Ptm Autophosphorylated. Phosphorylated at Tyr-611 following endoplasmic reticulum stress, leading to activate its tyrosine- protein kinase activity. Dephosphorylated by PTPN1/TP1B, leading to inactivate its enzyme activity (By similarity)
Ptm N-glycosylated
Similarity Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. GCN2 subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
Similarity Contains 1 protein kinase domain
Subcellular Location Endoplasmic reticulum membrane; Single-pass type I membrane protein.
Subunit Interacts with DNAJC3 and MFN2 (By similarity). Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER- stressed cells
Tissue Specificity Ubiquitous.

Identical and Related Proteins

Unique RefSeq proteins for LMP012626 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
13928816 RefSeq NP_113787 1108 eukaryotic translation initiation factor 2-alpha kinase 3 precursor

Identical Sequences to LMP012626 proteins

Reference Database Accession Length Protein Name
GI:13928816 GenBank AAC83801.1 1108 pancreatic eukaryotic initiation factor 2 alpha-subunit kinase [Rattus norvegicus]
GI:13928816 GenBank EDL90978.1 1108 eukaryotic translation initiation factor 2 alpha kinase 3, isoform CRA_a [Rattus norvegicus]
GI:13928816 SwissProt Q9Z1Z1.1 1108 RecName: Full=Eukaryotic translation initiation factor 2-alpha kinase 3; AltName: Full=PRKR-like endoplasmic reticulum kinase; AltName: Full=Pancreatic eIF2-alpha kinase; Flags: Precursor [Rattus norvegicus]

Related Sequences to LMP012626 proteins

Reference Database Accession Length Protein Name
GI:13928816 GenBank AAC83801.1 1108 pancreatic eukaryotic initiation factor 2 alpha-subunit kinase [Rattus norvegicus]
GI:13928816 GenBank EDL90978.1 1108 eukaryotic translation initiation factor 2 alpha kinase 3, isoform CRA_a [Rattus norvegicus]
GI:13928816 SwissProt Q9Z1Z1.1 1108 RecName: Full=Eukaryotic translation initiation factor 2-alpha kinase 3; AltName: Full=PRKR-like endoplasmic reticulum kinase; AltName: Full=Pancreatic eIF2-alpha kinase; Flags: Precursor [Rattus norvegicus]