ID   A0A804HIT4_HUMAN        Unreviewed;       965 AA.
AC   A0A804HIT4;
DT   29-SEP-2021, integrated into UniProtKB/TrEMBL.
DT   29-SEP-2021, sequence version 1.
DT   29-MAY-2024, entry version 13.
DE   RecName: Full=PRKR-like endoplasmic reticulum kinase {ECO:0000256|ARBA:ARBA00041500};
GN   Name=EIF2AK3 {ECO:0000313|Ensembl:ENSP00000507214.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000507214.1, ECO:0000313|Proteomes:UP000005640};
RN   [1] {ECO:0000313|Ensembl:ENSP00000507214.1, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [2] {ECO:0000313|Ensembl:ENSP00000507214.1}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (FEB-2024) to UniProtKB.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000256|ARBA:ARBA00004115}; Single-pass type I membrane protein
CC       {ECO:0000256|ARBA:ARBA00004115}.
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DR   EMBL; AC062029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC104134; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; NP_001300844.1; NM_001313915.1.
DR   AlphaFoldDB; A0A804HIT4; -.
DR   SMR; A0A804HIT4; -.
DR   PeptideAtlas; A0A804HIT4; -.
DR   Ensembl; ENST00000682892.1; ENSP00000507214.1; ENSG00000172071.15.
DR   GeneID; 9451; -.
DR   CTD; 9451; -.
DR   DisGeNET; 9451; -.
DR   HGNC; HGNC:3255; EIF2AK3.
DR   GeneTree; ENSGT00940000158121; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000172071; Expressed in body of pancreas and 199 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IEA:TreeGrafter.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IEA:UniProt.
DR   GO; GO:0070887; P:cellular response to chemical stimulus; IEA:UniProt.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:UniProt.
DR   GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR   CDD; cd09768; Luminal_EIF2AK3; 1.
DR   CDD; cd14048; STKc_EIF2AK3_PERK; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR11042:SF166; EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE 3; 1.
DR   PANTHER; PTHR11042; EUKARYOTIC TRANSLATION INITIATION FACTOR 2-ALPHA KINASE EIF2-ALPHA KINASE -RELATED; 1.
DR   Pfam; PF00069; Pkinase; 2.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF50998; Quinoprotein alcohol dehydrogenase-like; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW   ProRule:PRU10141}; Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW   Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW   Membrane {ECO:0000256|ARBA:ARBA00022989};
KW   Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW   ProRule:PRU10141};
KW   Proteomics identification {ECO:0007829|EPD:A0A804HIT4,
KW   ECO:0007829|MaxQB:A0A804HIT4};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Stress response {ECO:0000256|ARBA:ARBA00023016};
KW   Translation regulation {ECO:0000256|ARBA:ARBA00022845};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989};
KW   Unfolded protein response {ECO:0000256|ARBA:ARBA00023230}.
FT   DOMAIN          442..926
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000259|PROSITE:PS50011"
FT   REGION          399..420
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          690..712
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          939..965
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         471
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
SQ   SEQUENCE   965 AA;  109916 MW;  F569903EAD5E681E CRC64;
     MIIPSLDGAL FQWDQDRESM 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 PFATKEHIEI 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
//