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 12-APR-2017, entry version 52. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; 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., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the 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 RT project: 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 RT GCN1 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, RC Pancreas, 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 RT 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 RT the eukaryotic initiation factor 2alpha kinase GCN2 in the modulation RT of 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). CC Forms a complex with EIF2AK4/GCN2 on translating ribosomes; during CC this process, GCN1 seems to act as a chaperone to facilitate CC delivery of uncharged tRNAs that enter the A site of ribosomes to CC the tRNA-binding domain of EIF2AK4/GCN2, and hence stimulating CC EIF2AK4/GCN2 kinase activity (By similarity). Participates in the CC repression of global protein synthesis and in gene-specific mRNA CC translation activation, such as the transcriptional activator CC ATF4, by promoting the EIF2AK4/GCN2-mediated phosphorylation of CC eukaryotic translation initiation factor 2 (eIF-2-alpha/EIF2S1) on CC 'Ser-52', and hence allowing ATF4-mediated reprogramming of amino CC acid biosynthetic gene expression to alleviate nutrient depletion CC (PubMed:24333428). {ECO:0000250|UniProtKB:P33892, CC ECO:0000269|PubMed:15937339, ECO:0000269|PubMed:24333428}. CC -!- SUBUNIT: Interacts with EIF2AK4/GCN2; this interaction stimulates CC the EIF2AK4/GCN2 kinase activity and is impaired by IMPACT upon a CC variety of stress conditions, such as amino acid depletion, UV-C CC irradiation, proteasome inhibitor treatment and glucose CC deprivation (PubMed:24333428). Interacts with IMPACT; this CC prevents the interaction of GCN1 with EIF2AK4/GCN2 and inhibits CC EIF2AK4/GCN2 kinase activity (PubMed:15937339, PubMed:22404850). CC {ECO:0000269|PubMed:15937339, ECO:0000269|PubMed:22404850, CC ECO:0000269|PubMed:24333428}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:23447528}. CC Note=Associates with ribosomes in undifferentiated neuroblastoma CC cells and increases after neuronal differentiation CC (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 UniGene; Mm.153014; -. DR IntAct; E9PVA8; 3. DR STRING; 10090.ENSMUSP00000069432; -. DR iPTMnet; E9PVA8; -. DR PhosphoSitePlus; E9PVA8; -. DR MaxQB; E9PVA8; -. DR PaxDb; E9PVA8; -. DR PeptideAtlas; E9PVA8; -. DR PRIDE; E9PVA8; -. DR Ensembl; ENSMUST00000064454; ENSMUSP00000069432; ENSMUSG00000041638. DR GeneID; 231659; -. DR KEGG; mmu:231659; -. DR UCSC; uc008zeg.1; mouse. DR CTD; 231659; -. DR MGI; MGI:2444248; Gcn1l1. DR eggNOG; KOG1242; Eukaryota. DR eggNOG; ENOG410XPSD; LUCA. DR GeneTree; ENSGT00390000011675; -. DR HOGENOM; HOG000213714; -. DR HOVERGEN; HBG081550; -. DR InParanoid; E9PVA8; -. DR OMA; SCKSGPL; -. DR OrthoDB; EOG091G008Q; -. DR TreeFam; TF105398; -. DR ChiTaRS; Gcn1l1; mouse. DR PRO; PR:E9PVA8; -. DR Proteomes; UP000000589; Chromosome 5. DR Bgee; ENSMUSG00000041638; -. DR Genevisible; E9PVA8; MM. DR GO; GO:0005913; C:cell-cell adherens junction; ISO:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0016020; C:membrane; ISO:MGI. DR GO; GO:0005844; C:polysome; IDA:UniProtKB. DR GO; GO:0098641; F:cadherin binding involved in cell-cell adhesion; ISO:MGI. DR GO; GO:0019887; F:protein kinase regulator activity; IEA:InterPro. DR GO; GO:0043022; F:ribosome binding; IEA:InterPro. DR GO; GO:0003723; F:RNA binding; ISO:MGI. 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; -; 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:SF20; PTHR23346:SF20; 1. DR SMART; SM00185; ARM; 5. DR SMART; SM01349; TOG; 1. DR SUPFAM; SSF48371; SSF48371; 8. DR PROSITE; PS50077; HEAT_REPEAT; 3. PE 1: Evidence at protein level; KW Acetylation; Activator; Coiled coil; Complete proteome; Cytoplasm; KW Phosphoprotein; Reference proteome; Repeat; Stress response; KW Translation regulation. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:Q92616}. FT CHAIN 2 2671 eIF-2-alpha kinase activator GCN1. FT /FTId=PRO_0000435424. FT REPEAT 140 178 HEAT 1. {ECO:0000255}. FT REPEAT 257 293 HEAT 2. {ECO:0000255}. FT REPEAT 294 331 HEAT 3. {ECO:0000255}. FT REPEAT 385 423 HEAT 4. {ECO:0000255}. FT REPEAT 425 459 HEAT 5. {ECO:0000255}. FT REPEAT 460 500 HEAT 6. {ECO:0000255}. FT REPEAT 560 597 HEAT 7. {ECO:0000255}. FT REPEAT 599 636 HEAT 8. {ECO:0000255}. FT REPEAT 700 732 HEAT 9. {ECO:0000255}. FT REPEAT 733 772 HEAT 10. {ECO:0000255}. FT REPEAT 879 918 HEAT 11. {ECO:0000255}. FT REPEAT 979 1016 HEAT 12. {ECO:0000255}. FT REPEAT 1035 1072 HEAT 13. {ECO:0000255}. FT REPEAT 1078 1115 HEAT 14. {ECO:0000255}. FT REPEAT 1155 1192 HEAT 15. {ECO:0000255}. FT REPEAT 1210 1250 HEAT 16. {ECO:0000255}. FT REPEAT 1251 1289 HEAT 17. {ECO:0000255}. FT REPEAT 1290 1332 HEAT 18. {ECO:0000255}. FT REPEAT 1335 1372 HEAT 19. {ECO:0000255}. FT REPEAT 1374 1410 HEAT 20. {ECO:0000255}. FT REPEAT 1413 1451 HEAT 21. {ECO:0000255}. FT REPEAT 1455 1492 HEAT 22. {ECO:0000255}. FT REPEAT 1493 1530 HEAT 23. {ECO:0000255}. FT REPEAT 1534 1571 HEAT 24. {ECO:0000255}. FT REPEAT 1573 1609 HEAT 25. {ECO:0000255}. FT REPEAT 1611 1648 HEAT 26. {ECO:0000255}. FT REPEAT 1653 1690 HEAT 27. {ECO:0000255}. FT REPEAT 1692 1729 HEAT 28. {ECO:0000255}. FT REPEAT 1731 1769 HEAT 29. {ECO:0000255}. FT REPEAT 1773 1810 HEAT 30. {ECO:0000255}. FT REPEAT 1812 1848 HEAT 31. {ECO:0000255}. FT REPEAT 1921 1958 HEAT 32. {ECO:0000255}. FT REPEAT 1959 1996 HEAT 33. {ECO:0000255}. FT REPEAT 2001 2038 HEAT 34. {ECO:0000255}. FT REPEAT 2039 2074 HEAT 35. {ECO:0000255}. FT REPEAT 2076 2108 HEAT 36. {ECO:0000255}. FT REPEAT 2111 2146 HEAT 37. {ECO:0000255}. FT REPEAT 2147 2184 HEAT 38. {ECO:0000255}. FT REPEAT 2188 2225 HEAT 39. {ECO:0000255}. FT REPEAT 2259 2296 HEAT 40. {ECO:0000255}. FT REPEAT 2301 2338 HEAT 41. {ECO:0000255}. FT REPEAT 2339 2380 HEAT 42. {ECO:0000255}. FT REPEAT 2382 2417 HEAT 43. {ECO:0000255}. FT REPEAT 2422 2459 HEAT 44. {ECO:0000255}. FT REPEAT 2546 2583 HEAT 45. {ECO:0000255}. FT REPEAT 2588 2625 HEAT 46. {ECO:0000255}. FT REPEAT 2627 2661 HEAT 47. {ECO:0000255}. FT COILED 804 865 {ECO:0000255}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000250|UniProtKB:Q92616}. FT MOD_RES 729 729 Phosphoserine. FT {ECO:0000250|UniProtKB:Q92616}. FT MOD_RES 786 786 Phosphoserine. FT {ECO:0000250|UniProtKB:Q92616}. FT MOD_RES 2276 2276 Phosphoserine. FT {ECO:0000250|UniProtKB:Q92616}. FT CONFLICT 466 466 L -> V (in Ref. 2; AAI50736). FT {ECO:0000305}. FT CONFLICT 537 537 D -> E (in Ref. 2; AAI50736). FT {ECO:0000305}. FT CONFLICT 1477 1477 E -> K (in Ref. 2; AAI50736). FT {ECO:0000305}. FT CONFLICT 2544 2544 S -> G (in Ref. 2; AAI50736). FT {ECO:0000305}. FT CONFLICT 2583 2583 P -> H (in Ref. 2; AAI50736). FT {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 //