8.A.23.1.57
Translation initiation factor 2-alpha kinase 3, PERK, of 1116 aas and at least 2 TMSs, one at the N-terminus and one at about residue 530. There are also three smaller peaks of hydrophobicity near the C-terminus of the protein that could be TMSs. It is a metabolic-stress sensing protein kinase that phosphorylates the alpha
subunit of eukaryotic translation initiation factor 2
(EIF2S1/eIF-2-alpha) in response to various stress conditions. It is a key
activator of the integrated stress response (ISR) required for
adaptation to various stresses, such as the unfolded protein response (UPR)
and low amino acid availability. EIF2S1/eIF-2-alpha
phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a
global protein synthesis inhibitor, leading to a global attenuation of
cap-dependent translation, while concomitantly initiating the
preferential translation of ISR-specific mRNAs, such as the
transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and
QRICH1-mediated reprogramming (You et al. 2021). PERK/ATF3-reduced ER stress in a high potassium environment suppresses tumor ferroptosis (Pu et al. 2023).
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| Accession Number: | Q9NZJ5 |
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| Protein Name: | Eukaryotic translation initiation factor 2-alpha kinase 3 |
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| Length: | 1116 |
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| Molecular Weight: | 125216.00 |
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| Species: | Homo sapiens (Human) [9606] |
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| Number of TMSs: | 3 |
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| Location1 / Topology2 / Orientation3: |
Endoplasmic reticulum membrane1 / Single-pass type I membrane protein2 |
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| Substrate |
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1: MERAISPGLL VRALLLLLLL LGLAARTVAA GRARGLPAPT AEAAFGLGAA AAPTSATRVP
61: AAGAVAAAEV TVEDAEALPA AAGEQEPRGP EPDDETELRP RGRSLVIIST LDGRIAALDP
121: ENHGKKQWDL DVGSGSLVSS SLSKPEVFGN KMIIPSLDGA LFQWDQDRES METVPFTVES
181: LLESSYKFGD DVVLVGGKSL TTYGLSAYSG KVRYICSALG CRQWDSDEME QEEDILLLQR
241: TQKTVRAVGP RSGNEKWNFS VGHFELRYIP DMETRAGFIE STFKPNENTE ESKIISDVEE
301: QEAAIMDIVI KVSVADWKVM AFSKKGGHLE WEYQFCTPIA SAWLLKDGKV IPISLFDDTS
361: YTSNDDVLED EEDIVEAARG ATENSVYLGM YRGQLYLQSS VRISEKFPSS PKALESVTNE
421: NAIIPLPTIK WKPLIHSPSR TPVLVGSDEF DKCLSNDKFS HEEYSNGALS ILQYPYDNGY
481: YLPYYKRERN KRSTQITVRF LDNPHYNKNI RKKDPVLLLH WWKEIVATIL FCIIATTFIV
541: RRLFHPHPHR QRKESETQCQ TENKYDSVSG EANDSSWNDI KNSGYISRYL TDFEPIQCLG
601: RGGFGVVFEA KNKVDDCNYA IKRIRLPNRE LAREKVMREV KALAKLEHPG IVRYFNAWLE
661: APPEKWQEKM DEIWLKDEST DWPLSSPSPM DAPSVKIRRM DPFATKEHIE IIAPSPQRSR
721: SFSVGISCDQ TSSSESQFSP LEFSGMDHED ISESVDAAYN LQDSCLTDCD VEDGTMDGND
781: EGHSFELCPS EASPYVRSRE RTSSSIVFED SGCDNASSKE EPKTNRLHIG NHCANKLTAF
841: KPTSSKSSSE ATLSISPPRP TTLSLDLTKN TTEKLQPSSP KVYLYIQMQL CRKENLKDWM
901: NGRCTIEERE RSVCLHIFLQ IAEAVEFLHS KGLMHRDLKP SNIFFTMDDV VKVGDFGLVT
961: AMDQDEEEQT VLTPMPAYAR HTGQVGTKLY MSPEQIHGNS YSHKVDIFSL GLILFELLYP
1021: FSTQMERVRT LTDVRNLKFP PLFTQKYPCE YVMVQDMLSP SPMERPEAIN IIENAVFEDL
1081: DFPGKTVLRQ RSRSLSSSGT KHSRQSNNSH SPLPSN