E2AK3_HUMAN » Eukaryotic translation initiation factor 2-alpha kinase 3

E2AK3_HUMAN » Eukaryotic translation initiation factor 2-alpha kinase 3
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Topology in Endoplasmic reticulum membrane
Topologylumenal side
cytoplasmic side
E2AK3_HUMAN » Eukaryotic translation initiation factor 2-alpha kinase 3 » PRKR-like endoplasmic reticulum kinase;Pancreatic eIF2-alpha kinase;HsPEK;
Hydrophobic Thickness 26.4 ± 2.4 Å
Tilt Angle 1 ± 0°
ΔGtransfer -35.5 kcal/mol
ΔGfold -10.7 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 520-541 (514-541)
Pathways

Alzheimer's disease (KEGG)

Epstein-Barr virus infection (KEGG)

Hepatitis C (KEGG)

Herpes simplex infection (KEGG)

Influenza A (KEGG)

Measles (KEGG)

Protein processing in endoplasmic reticulum (KEGG)

PDB 4x7h (575-1094), 4x7j (575-1094), 4x7k (575-1094), 4x7l (575-1094), 4x7n (575-1094), 4x7o (575-1094), 4g31 (588-1093), 4g34 (588-1093), 4m7i (588-1093)
OPM none
Complexes none
Interactions

PLS4, Complex: E2AK3:PLS4, PubMed

Domains

AA: 593-678, PDBID: 4G31, Subunit A, Seq Identity:100%, Protein kinase domain

AA: 865-1077, PDBID: 4G31, Subunit A, Seq Identity:100%, Protein kinase domain

UniProt annotation for E2AK3_HUMAN » Eukaryotic translation initiation factor 2-alpha kinase 3
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).

CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.

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.

SUBUNIT: Forms dimers with HSPA5/BIP in resting cells. Oligomerizes in ER-stressed cells. Interacts with DNAJC3 and MFN2 (By similarity).

TISSUE SPECIFICITY: Ubiquitous. A high level expression is seen in secretory tissues.

INDUCTION: By endoplasmic reticulum stress.

DOMAIN: The lumenal domain senses perturbations in protein folding in the ER, probably through reversible interaction with HSPA5/BIP.

DISEASE: Wolcott-Rallison syndrome (WRS) OMIM: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities. mutations affecting the gene represented in this entry.

UniProt features for E2AK3_HUMAN » Eukaryotic translation initiation factor 2-alpha kinase 3
SIGNAL 1 29 Potential.
CHAIN 30 1116 Eukaryotic translation initiation factor 2-alpha kinase 3.
DOMAIN 593 1077 Protein kinase.
ACT_SITE 937 937 Proton acceptor (By similarity).
Amino Acid Sequence for E2AK3_HUMAN » Eukaryotic translation initiation factor 2-alpha kinase 3
MERAISPGLL VRALLLLLLL GLAARTVAAG RARGLPAPTA EAAFGLGAAA APTSATRVPA AGAVAAAEVT VEDAEALPAA AGEQEPRGPE PDDETELRPR GRSLVIISTL DGRIAALDPE NHGKKQWDLD VGSGSLVSSS LSKPEVFGNK MIIPSLDGAL FQWDRDRESM ETVPFTVESL LESSYKFGDD VVLVGGKSLT TYGLSAYSGK VRYICSALGC RQWDSDEMEQ EEDILLLQRT QKTVRAVGPR SGNEKWNFSV GHFELRYIPD METRAGFIES TFKPNENTEE SKIISDVEEQ EAAIMDIVIK VSVADWKVMA FSKKGGHLEW EYQFCTPIAS AWLLKDGKVI PISLFDDTSY TSNDDVLEDE EDIVEAARGA TENSVYLGMY RGQLYLQSSV RISEKFPSSP KALESVTNEN AIIPLPTIKW KPLIHSPSRT PVLVGSDEFD KCLSNDKFSH EEYSNGALSI LQYPYDNGYY LPYYKRERNK RSTQITVRFL DNPHYNKNIR KKDPVLLLHW WKEIVATILF CIIATTFIVR RLFHPHPHRQ RKESETQCQT ENKYDSVSGE ANDSSWNDIK NSGYISRYLT DFEPIQCLGR GGFGVVFEAK NKVDDCNYAI KRIRLPNREL AREKVMREVK ALAKLEHPGI VRYFNAWLEA PPEKWQEKMD EIWLKDESTD WPLSSPSPMD APSVKIRRMD PFSTKEHIEI IAPSPQRSRS FSVGISCDQT SSSESQFSPL EFSGMDHEDI SESVDAAYNL QDSCLTDCDV EDGTMDGNDE GHSFELCPSE ASPYVRSRER TSSSIVFEDS GCDNASSKEE PKTNRLHIGN HCANKLTAFK PTSSKSSSEA TLSISPPRPT TLSLDLTKNT TEKLQPSSPK VYLYIQMQLC RKENLKDWMN GRCTIEERER SVCLHIFLQI AEAVEFLHSK GLMHRDLKPS NIFFTMDDVV KVGDFGLVTA MDQDEEEQTV LTPMPAYARH TGQVGTKLYM SPEQIHGNSY SHKVDIFSLG LILFELLYPF STQMERVRTL TDVRNLKFPP LFTQKYPCEY VMVQDMLSPS PMERPEAINI IENAVFEDLD FPGKTVLRQR SRSLSSSGTK HSRQSNNSHS PLPSN