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 22-APR-2020, entry version 68. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 IntAct; E9PVA8; 3. 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 Antibodypedia; 9618; 73 antibodies. 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 eggNOG; KOG1242; Eukaryota. DR eggNOG; ENOG410XPSD; LUCA. DR GeneTree; ENSGT00940000153612; -. DR HOGENOM; CLU_000504_2_2_1; -. DR InParanoid; E9PVA8; -. DR OMA; DAKQGIC; -. DR OrthoDB; 160593at2759; -. DR TreeFam; TF105398; -. DR ChiTaRS; Gcn1l1; mouse. DR PRO; PR:E9PVA8; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; E9PVA8; protein. DR Bgee; ENSMUSG00000041638; Expressed in secondary oocyte and 156 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; IEA:InterPro. 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; IEA:UniProtKB-KW. DR Gene3D; 1.25.10.10; -; 5. 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 //