GCN1_MOUSE
ID GCN1_MOUSE Reviewed; 2671 AA.
AC E9PVA8; B2RWW6;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=eIF-2-alpha kinase activator GCN1 {ECO:0000305};
DE AltName: Full=GCN1 eIF-2-alpha kinase activator homolog {ECO:0000250|UniProtKB:Q92616};
DE AltName: Full=GCN1-like protein 1 {ECO:0000312|MGI:MGI:2444248};
DE AltName: Full=General control of amino-acid synthesis 1-like protein 1 {ECO:0000312|MGI:MGI:2444248};
DE AltName: Full=Translational activator GCN1 {ECO:0000305};
GN Name=Gcn1 {ECO:0000250|UniProtKB:Q92616};
GN Synonyms=Gcn1l1 {ECO:0000312|MGI:MGI:2444248};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|Proteomes:UP000000589};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI50736.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, INTERACTION WITH IMPACT, AND TISSUE SPECIFICITY.
RX PubMed=15937339; DOI=10.1074/jbc.m408571200;
RA Pereira C.M., Sattlegger E., Jiang H.-Y., Longo B.M., Jaqueta C.B.,
RA Hinnebusch A.G., Wek R.C., Mello L.E.A.M., Castilho B.A.;
RT "IMPACT, a protein preferentially expressed in the mouse brain, binds GCN1
RT and inhibits GCN2 activation.";
RL J. Biol. Chem. 280:28316-28323(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP INTERACTION WITH IMPACT.
RX PubMed=22404850; DOI=10.1111/j.1742-4658.2012.08553.x;
RA Waller T., Lee S.J., Sattlegger E.;
RT "Evidence that Yih1 resides in a complex with ribosomes.";
RL FEBS J. 279:1761-1776(2012).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=23447528; DOI=10.1074/jbc.m113.461970;
RA Roffe M., Hajj G.N., Azevedo H.F., Alves V.S., Castilho B.A.;
RT "IMPACT is a developmentally regulated protein in neurons that opposes the
RT eukaryotic initiation factor 2alpha kinase GCN2 in the modulation of
RT neurite outgrowth.";
RL J. Biol. Chem. 288:10860-10869(2013).
RN [7]
RP FUNCTION, AND INTERACTION WITH EIF2AK4.
RX PubMed=24333428; DOI=10.1016/j.bbrc.2013.12.021;
RA Cambiaghi T.D., Pereira C.M., Shanmugam R., Bolech M., Wek R.C.,
RA Sattlegger E., Castilho B.A.;
RT "Evolutionarily conserved IMPACT impairs various stress responses that
RT require GCN1 for activating the eIF2 kinase GCN2.";
RL Biochem. Biophys. Res. Commun. 443:592-597(2014).
CC -!- FUNCTION: Acts as a positive activator of the GCN2 protein kinase
CC activity in response to amino acid starvation (PubMed:15937339). Forms
CC a complex with EIF2AK4/GCN2 on translating ribosomes; during this
CC process, GCN1 seems to act as a chaperone to facilitate delivery of
CC uncharged tRNAs that enter the A site of ribosomes to the tRNA-binding
CC domain of EIF2AK4/GCN2, and hence stimulating EIF2AK4/GCN2 kinase
CC activity (By similarity). Participates in the repression of global
CC protein synthesis and in gene-specific mRNA translation activation,
CC such as the transcriptional activator ATF4, by promoting the
CC EIF2AK4/GCN2-mediated phosphorylation of eukaryotic translation
CC initiation factor 2 (eIF-2-alpha/EIF2S1) on 'Ser-52', and hence
CC allowing ATF4-mediated reprogramming of amino acid biosynthetic gene
CC expression to alleviate nutrient depletion (PubMed:24333428).
CC {ECO:0000250|UniProtKB:P33892, ECO:0000269|PubMed:15937339,
CC ECO:0000269|PubMed:24333428}.
CC -!- SUBUNIT: Interacts with EIF2AK4/GCN2; this interaction stimulates the
CC EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a variety
CC of stress conditions, such as amino acid depletion, UV-C irradiation,
CC proteasome inhibitor treatment and glucose deprivation
CC (PubMed:24333428). Interacts with IMPACT; this prevents the interaction
CC of GCN1 with EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity
CC (PubMed:15937339, PubMed:22404850). {ECO:0000269|PubMed:15937339,
CC ECO:0000269|PubMed:22404850, ECO:0000269|PubMed:24333428}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:23447528}.
CC Note=Associates with ribosomes in undifferentiated neuroblastoma cells
CC and increases after neuronal differentiation (PubMed:23447528).
CC -!- TISSUE SPECIFICITY: Expressed in the hypothalamus, cortex and
CC hippocampus (PubMed:15937339). {ECO:0000269|PubMed:15937339}.
CC -!- SIMILARITY: Belongs to the GCN1 family. {ECO:0000305}.
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DR EMBL; AC159539; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC150735; AAI50736.1; -; mRNA.
DR CCDS; CCDS19595.1; -.
DR RefSeq; NP_766307.2; NM_172719.2.
DR AlphaFoldDB; E9PVA8; -.
DR IntAct; E9PVA8; 5.
DR MINT; E9PVA8; -.
DR STRING; 10090.ENSMUSP00000069432; -.
DR iPTMnet; E9PVA8; -.
DR PhosphoSitePlus; E9PVA8; -.
DR SwissPalm; E9PVA8; -.
DR jPOST; E9PVA8; -.
DR MaxQB; E9PVA8; -.
DR PaxDb; E9PVA8; -.
DR PeptideAtlas; E9PVA8; -.
DR PRIDE; E9PVA8; -.
DR ProteomicsDB; 267424; -.
DR Antibodypedia; 9618; 80 antibodies from 15 providers.
DR Ensembl; ENSMUST00000064454; ENSMUSP00000069432; ENSMUSG00000041638.
DR GeneID; 231659; -.
DR KEGG; mmu:231659; -.
DR UCSC; uc008zeg.1; mouse.
DR CTD; 10985; -.
DR MGI; MGI:2444248; Gcn1.
DR VEuPathDB; HostDB:ENSMUSG00000041638; -.
DR eggNOG; KOG1242; Eukaryota.
DR GeneTree; ENSGT00940000153612; -.
DR HOGENOM; CLU_000504_2_2_1; -.
DR InParanoid; E9PVA8; -.
DR OMA; DQWRSKK; -.
DR OrthoDB; 160593at2759; -.
DR PhylomeDB; E9PVA8; -.
DR TreeFam; TF105398; -.
DR BioGRID-ORCS; 231659; 21 hits in 77 CRISPR screens.
DR ChiTaRS; Gcn1l1; mouse.
DR PRO; PR:E9PVA8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; E9PVA8; protein.
DR Bgee; ENSMUSG00000041638; Expressed in retinal neural layer and 154 other tissues.
DR Genevisible; E9PVA8; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005844; C:polysome; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:InterPro.
DR GO; GO:0019887; F:protein kinase regulator activity; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; IEA:InterPro.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:UniProtKB.
DR GO; GO:1990253; P:cellular response to leucine starvation; IDA:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IEA:InterPro.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IDA:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IBA:GO_Central.
DR Gene3D; 1.25.10.10; -; 6.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR033173; Gcn1.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR034085; TOG.
DR PANTHER; PTHR23346:SF7; PTHR23346:SF7; 1.
DR SMART; SM00185; ARM; 5.
DR SMART; SM01349; TOG; 1.
DR SUPFAM; SSF48371; SSF48371; 4.
DR PROSITE; PS50077; HEAT_REPEAT; 3.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Coiled coil; Cytoplasm; Phosphoprotein;
KW Reference proteome; Repeat; Stress response; Translation regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q92616"
FT CHAIN 2..2671
FT /note="eIF-2-alpha kinase activator GCN1"
FT /id="PRO_0000435424"
FT REPEAT 140..178
FT /note="HEAT 1"
FT /evidence="ECO:0000255"
FT REPEAT 257..293
FT /note="HEAT 2"
FT /evidence="ECO:0000255"
FT REPEAT 294..331
FT /note="HEAT 3"
FT /evidence="ECO:0000255"
FT REPEAT 385..423
FT /note="HEAT 4"
FT /evidence="ECO:0000255"
FT REPEAT 425..459
FT /note="HEAT 5"
FT /evidence="ECO:0000255"
FT REPEAT 460..500
FT /note="HEAT 6"
FT /evidence="ECO:0000255"
FT REPEAT 560..597
FT /note="HEAT 7"
FT /evidence="ECO:0000255"
FT REPEAT 599..636
FT /note="HEAT 8"
FT /evidence="ECO:0000255"
FT REPEAT 700..732
FT /note="HEAT 9"
FT /evidence="ECO:0000255"
FT REPEAT 733..772
FT /note="HEAT 10"
FT /evidence="ECO:0000255"
FT REPEAT 879..918
FT /note="HEAT 11"
FT /evidence="ECO:0000255"
FT REPEAT 979..1016
FT /note="HEAT 12"
FT /evidence="ECO:0000255"
FT REPEAT 1035..1072
FT /note="HEAT 13"
FT /evidence="ECO:0000255"
FT REPEAT 1078..1115
FT /note="HEAT 14"
FT /evidence="ECO:0000255"
FT REPEAT 1155..1192
FT /note="HEAT 15"
FT /evidence="ECO:0000255"
FT REPEAT 1210..1250
FT /note="HEAT 16"
FT /evidence="ECO:0000255"
FT REPEAT 1251..1289
FT /note="HEAT 17"
FT /evidence="ECO:0000255"
FT REPEAT 1290..1332
FT /note="HEAT 18"
FT /evidence="ECO:0000255"
FT REPEAT 1335..1372
FT /note="HEAT 19"
FT /evidence="ECO:0000255"
FT REPEAT 1374..1410
FT /note="HEAT 20"
FT /evidence="ECO:0000255"
FT REPEAT 1413..1451
FT /note="HEAT 21"
FT /evidence="ECO:0000255"
FT REPEAT 1455..1492
FT /note="HEAT 22"
FT /evidence="ECO:0000255"
FT REPEAT 1493..1530
FT /note="HEAT 23"
FT /evidence="ECO:0000255"
FT REPEAT 1534..1571
FT /note="HEAT 24"
FT /evidence="ECO:0000255"
FT REPEAT 1573..1609
FT /note="HEAT 25"
FT /evidence="ECO:0000255"
FT REPEAT 1611..1648
FT /note="HEAT 26"
FT /evidence="ECO:0000255"
FT REPEAT 1653..1690
FT /note="HEAT 27"
FT /evidence="ECO:0000255"
FT REPEAT 1692..1729
FT /note="HEAT 28"
FT /evidence="ECO:0000255"
FT REPEAT 1731..1769
FT /note="HEAT 29"
FT /evidence="ECO:0000255"
FT REPEAT 1773..1810
FT /note="HEAT 30"
FT /evidence="ECO:0000255"
FT REPEAT 1812..1848
FT /note="HEAT 31"
FT /evidence="ECO:0000255"
FT REPEAT 1921..1958
FT /note="HEAT 32"
FT /evidence="ECO:0000255"
FT REPEAT 1959..1996
FT /note="HEAT 33"
FT /evidence="ECO:0000255"
FT REPEAT 2001..2038
FT /note="HEAT 34"
FT /evidence="ECO:0000255"
FT REPEAT 2039..2074
FT /note="HEAT 35"
FT /evidence="ECO:0000255"
FT REPEAT 2076..2108
FT /note="HEAT 36"
FT /evidence="ECO:0000255"
FT REPEAT 2111..2146
FT /note="HEAT 37"
FT /evidence="ECO:0000255"
FT REPEAT 2147..2184
FT /note="HEAT 38"
FT /evidence="ECO:0000255"
FT REPEAT 2188..2225
FT /note="HEAT 39"
FT /evidence="ECO:0000255"
FT REPEAT 2259..2296
FT /note="HEAT 40"
FT /evidence="ECO:0000255"
FT REPEAT 2301..2338
FT /note="HEAT 41"
FT /evidence="ECO:0000255"
FT REPEAT 2339..2380
FT /note="HEAT 42"
FT /evidence="ECO:0000255"
FT REPEAT 2382..2417
FT /note="HEAT 43"
FT /evidence="ECO:0000255"
FT REPEAT 2422..2459
FT /note="HEAT 44"
FT /evidence="ECO:0000255"
FT REPEAT 2546..2583
FT /note="HEAT 45"
FT /evidence="ECO:0000255"
FT REPEAT 2588..2625
FT /note="HEAT 46"
FT /evidence="ECO:0000255"
FT REPEAT 2627..2661
FT /note="HEAT 47"
FT /evidence="ECO:0000255"
FT COILED 804..865
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q92616"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92616"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92616"
FT MOD_RES 2276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92616"
FT CONFLICT 466
FT /note="L -> V (in Ref. 2; AAI50736)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="D -> E (in Ref. 2; AAI50736)"
FT /evidence="ECO:0000305"
FT CONFLICT 1477
FT /note="E -> K (in Ref. 2; AAI50736)"
FT /evidence="ECO:0000305"
FT CONFLICT 2544
FT /note="S -> G (in Ref. 2; AAI50736)"
FT /evidence="ECO:0000305"
FT CONFLICT 2583
FT /note="P -> H (in Ref. 2; AAI50736)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2671 AA; 293021 MW; 77B317C0797DC5A7 CRC64;
MAADTQVSET LKRFAVKVTT ASVKERREIL SELGRCIAGK DLPEGAVKGL CKLFCLTLHR
YRDAASRRAL QAAIQQLAEA QPEATAKNLL HSLQSSGVGS KACVPSKSSG SAALLALTWT
CLLVRIVFPL KAKRQGDIWN KLVEVQCLLL LEVLGGSHKH AVDGAVKKLT KLWKENPGLV
EQYFSAILSL EPSQNYAAML GLLVQFCTNH KEMDAVSQHK STLLEFYVKN ILMSKAKPPK
YLLDNCAPLL RFMSHSEFKD LILPTIQKSL LRSPENVIET ISSLLASVTL DLSQYALDIV
KGLANQLKSN SPRLMDEAVL ALRNLARQCS DSSATEALTK HLFAILGGSE GKLTIIAQKM
SVLSGIGSLS HHVVSGPSGQ VLNGCVAELF IPFLQQEVHE GTLVHAVSIL ALWCNRFTTE
VPKKLTDWFK KVFSLKTSTS AVRHAYLQCM LASFRGDTLL QALDFLPLLM QTVEKAASQG
TQVPTVTEGV AAALLLSKLS VADAQAEAKL SGFWQLVVDE KRQTFTSEKF LLLASEDALC
TVLRLTERLF LDHPHRLTNS KVQQYYRVLV AVLLSRTWHV RRQAQQTVRK LLSSLGGVKL
ANGLLDELKT VLNSHKVLPL EALVTDAGEV TEMGKTYVPP RVLQEALCVI SGVPGLKGDI
PSTEQLAQEM LIISHHPSLV AVQSGLWPAL LTRMKIDPDA FITRHLDQII PRITTQSPLN
QSSMNAMGSL SVLSPDRVLP QLISTITASV QNPALCLVTR EEFSIMQTPA GELFDKSIIQ
SAQQDSIKKA NMKRENKAYS FKEQIIEMEL KEEIKKKKGI KEEVQLTSKQ KEMLQAQMDK
EAQIRRRLQE LDGELEAALG LLDAIMARNP CGLIQYIPVL VDAFLPLLKS PLAAPRVKGP
FLSLAACVMP PRLKTLGTLV SHVTLRLLKP ECALDKSWCQ EELPVAVRRA VSLLHTHTIP
SRVGKGEPDA APLSAPAFSL VFPMLKMVLT EMPYHSEEEE EQMAQILQIL TVHAQLRASP
DTPPERVDEN GPELLPRVAM LRLLTWVIGT GSPRLQVLAS DTLTALCASS SGEDGCAFAE
QEEVDVLLAA LQSPCASVRE TALRGLMELR LVLPSPDTDE KSGLSLLRRL WVIKFDKEDE
IRKLAERLWS TMGLDLQSDL CSLLIDDVIY HEAAVRQAGA EALSQAVARY QRQAAEVMGR
LMEIYQEKLY RPPPVLDALG RVISESPPDQ WEARCGLALA LNKLSQYLDS SQVKPLFQFF
VPDALNDRNP DVRKCMLDAA LATLNAHGKE NVNSLLPVFE EFLKDAPNDA SYDAVRQSVV
VLMGSLAKHL DKSDPKVKPI VAKLIAALST PSQQVQESVA SCLPPLVPAV KEDAGGMIQR
LMQQLLESDK YAERKGAAYG LAGLVKGLGI LSLKQQEMMA ALTDAIQDKK NFRRREGALF
AFEMLCTMLG KLFEPYVVHV LPHLLLCFGD GNQYVREAAD DCAKAVMSNL SAHGVKLVLP
SLLAALEEES WRTKAGSVEL LGAMAYCAPK QLSSCLPNIV PKLTEVLTDS HVKVQKAGQQ
ALRQIGSVIR NPEILAIAPV LLDALTDPSR KTQKCLQTLL DTKFVHFIDA PSLALIMPIV
QRAFQDRSTD TRKMAAQIIG NMYSLTDQKD LAPYLPSVTP GLKASLLDPV PEVRTVSAKA
LGAMVKGMGE SCFEDLLPWL METLTYEQSS VDRSGAAQGL AEVMAGLGVE KLEKLMPEIV
ATASKVDIAP HVRDGYIMMF NYLPITFGDK FTPYVGPIIP CILKALADEN EFVRDTALRA
GQRVISMYAE TAIALLLPQL EQGLFDDLWR IRFSSVQLLG DLLFHISGVT GKMTTETASE
DDNFGTAQSN KAIITALGVD RRNRVLAGLY MGRSDTQLVV RQASLHVWKI VVSNTPRTLR
EILPTLFGLL LGFLASTCAD KRTIAARTLG DLVRKLGEKI LPEIIPILEE GLRSQKSDER
QGVCIGLSEI MKSTSRDAVL FFSESLVPTA RKALCDPLEE VREAAAKTFE QLHSTIGHQA
LEDILPFLLK QLDDEEVSEF ALDGLKQVMA VKSRVVLPYL VPKLTTPPVN TRVLAFLSSV
AGDALTRHLG VILPAVMLAL KEKLGTPDEQ LEMANCQAVI LSVEDDTGHR IIIEDLLEAT
RSPEVGMRQA AAIILNMYCS RSKADYSSHL RSLVSGLIRL FNDSSPVVLE ESWDALNAIT
KKLDAGNQLA LIEELHKEIR FIGNECKGEH VPGFCLPKRG VTSILPVLRE GVLTGSPEQK
EEAAKGLGLV IRLTSADALR PSVVSITGPL IRILGDRFNW TVKAALLETL SLLLGKVGIA
LKPFLPQLQT TFTKALQDSN RGVRLKAADA LGKLISIHVK VDPLFTELLN GIRAVEDPGI
RDTMLQALRF VIQGAGSKVD AAIRKNLVSL LLSMLGHDED NTRISTAGCL GELCAFLTDE
ELNTVLQQCL LADVSGIDWM VRHGRSLALS VAVNVAPSRL CAGRYSNEVQ DMILSNAVAD
RIPIAMSGIR GMGFLMKYHI ETGSGQLPPR LSSLLIKCLQ NPCSDIRLVA EKMIWWANKE
PRPPLEPQTI KPILKALLDN TKDKNTVVRA YSDQAIVNLL KMRRGEELLQ SLSKILDVAS
LEALNECSRR SLRKLACQAD SVEQVDDTIL T
