GCN2_SCHPO
ID GCN2_SCHPO Reviewed; 1576 AA.
AC Q9HGN1; Q66T01; Q9HDW2;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=eIF-2-alpha kinase GCN2 {ECO:0000312|PomBase:SPBC36B7.09};
DE AltName: Full=Serine/threonine-protein kinase gcn2 {ECO:0000250|UniProtKB:P15442};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P15442};
DE AltName: Full=Serine/threonine-protein kinase ppk28;
GN Name=gcn2 {ECO:0000312|PomBase:SPBC36B7.09}; Synonyms=ppk28;
GN ORFNames=SPBC36B7.09, SPBP18G5.01;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=15611163; DOI=10.1534/genetics.104.031443;
RA Zhan K., Narasimhan J., Wek R.C.;
RT "Differential activation of eIF2 kinases in response to cellular stresses
RT in Schizosaccharomyces pombe.";
RL Genetics 168:1867-1875(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP IDENTIFICATION.
RX PubMed=15821139; DOI=10.1128/ec.4.4.799-813.2005;
RA Bimbo A., Jia Y., Poh S.L., Karuturi R.K.M., den Elzen N., Peng X.,
RA Zheng L., O'Connell M., Liu E.T., Balasubramanian M.K., Liu J.;
RT "Systematic deletion analysis of fission yeast protein kinases.";
RL Eukaryot. Cell 4:799-813(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29432178; DOI=10.1073/pnas.1713991115;
RA Duncan C.D.S., Rodriguez-Lopez M., Ruis P., Baehler J., Mata J.;
RT "General amino acid control in fission yeast is regulated by a nonconserved
RT transcription factor, with functions analogous to Gcn4/Atf4.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E1829-E1838(2018).
CC -!- FUNCTION: Metabolic-stress sensing protein kinase that phosphorylates
CC the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2-
CC alpha/tif211) on 'Ser-52' in response to low amino acid availability
CC (PubMed:15611163). Plays a role as an activator of the general amino
CC acid control (GAAC) pathway required for adapatation to amino acid
CC starvation (PubMed:15821139). Converts phosphorylated eIF-2-
CC alpha/tif211 either to a competitive inhibitor of translation
CC initiation factor eIF-2B, leading to a global protein synthesis
CC repression, and thus to a reduced overall utilization of amino acids,
CC or to a translational initiation activation of specific mRNAs, such as
CC the transcriptional activator fil1, and hence allowing fil1-mediated
CC reprogramming of amino acid biosynthetic gene expression to alleviate
CC nutrient depletion (PubMed:15821139). Binds uncharged tRNAs (By
CC similarity). {ECO:0000250|UniProtKB:P15442,
CC ECO:0000269|PubMed:15611163, ECO:0000269|PubMed:15821139}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P15442};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P15442};
CC -!- ACTIVITY REGULATION: The kinase activity is stimulated upon binding to
CC uncharged tRNAs. {ECO:0000250|UniProtKB:P15442}.
CC -!- SUBUNIT: Homodimer; homodimerization is important for kinase activation
CC by uncharged tRNAs. Interacts (via N-terminal RWD domain) with gcn1
CC (via N- and C-terminus); this interaction stimulates gcn2 kinase
CC activity in a gcn20-dependent manner in response to amino acid
CC starvation. Interacts (via N-terminus) with the gcn1-gcn20 complex on
CC translating ribosomes in amino acid-starved cells; gcn1 may bind near
CC the ribosomal A-site and promotes the transfer of uncharged tRNAs from
CC the A-site to the tRNA-binding domain in gcn2 for its subsequent kinase
CC activation, and hence allowing fil1 translational activation and
CC derepression of amino acid biosynthetic genes.
CC {ECO:0000250|UniProtKB:P15442}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P15442}.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:P15442}.
CC -!- DISRUPTION PHENOTYPE: Decreases translation of transcription factor
CC fil1 (PubMed:29432178). Decreases RNA level and translation of genes
CC involved the response to amino acid starvation (PubMed:29432178).
CC {ECO:0000269|PubMed:29432178}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. GCN2 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AY705913; AAU11313.1; -; mRNA.
DR EMBL; CU329671; CAC05730.1; -; Genomic_DNA.
DR RefSeq; NP_595991.2; NM_001021898.2.
DR AlphaFoldDB; Q9HGN1; -.
DR SMR; Q9HGN1; -.
DR BioGRID; 277028; 48.
DR STRING; 4896.SPBC36B7.09.1; -.
DR iPTMnet; Q9HGN1; -.
DR MaxQB; Q9HGN1; -.
DR PaxDb; Q9HGN1; -.
DR PRIDE; Q9HGN1; -.
DR EnsemblFungi; SPBC36B7.09.1; SPBC36B7.09.1:pep; SPBC36B7.09.
DR GeneID; 2540500; -.
DR KEGG; spo:SPBC36B7.09; -.
DR PomBase; SPBC36B7.09; gcn2.
DR VEuPathDB; FungiDB:SPBC36B7.09; -.
DR eggNOG; KOG1035; Eukaryota.
DR eggNOG; KOG1936; Eukaryota.
DR HOGENOM; CLU_001222_2_0_1; -.
DR InParanoid; Q9HGN1; -.
DR OMA; GSEMIYE; -.
DR PhylomeDB; Q9HGN1; -.
DR PRO; PR:Q9HGN1; -.
DR Proteomes; UP000002485; Chromosome II.
DR GO; GO:0005829; C:cytosol; ISO:PomBase.
DR GO; GO:0005524; F:ATP binding; ISM:PomBase.
DR GO; GO:0004694; F:eukaryotic translation initiation factor 2alpha kinase activity; IDA:PomBase.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0072755; P:cellular response to benomyl; ISS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:1990451; P:cellular stress response to acidic pH; ISS:UniProtKB.
DR GO; GO:0070314; P:G1 to G0 transition; IMP:PomBase.
DR GO; GO:0140469; P:GCN2-mediated signaling; IMP:PomBase.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IMP:PomBase.
DR GO; GO:1904689; P:negative regulation of cytoplasmic translational initiation; IDA:PomBase.
DR GO; GO:1990625; P:negative regulation of cytoplasmic translational initiation in response to stress; IMP:PomBase.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; IMP:PomBase.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:PomBase.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IEA:UniProt.
DR Gene3D; 3.10.110.10; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR016255; Gcn2.
DR InterPro; IPR041715; HisRS-like_core.
DR InterPro; IPR024435; HisRS-related_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR006575; RWD-domain.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF12745; HGTP_anticodon2; 1.
DR Pfam; PF00069; Pkinase; 3.
DR Pfam; PF05773; RWD; 1.
DR Pfam; PF13393; tRNA-synt_His; 1.
DR PIRSF; PIRSF000660; Ser/Thr_PK_GCN2; 1.
DR SMART; SM00591; RWD; 1.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF54495; SSF54495; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50908; RWD; 1.
PE 2: Evidence at transcript level;
KW Activator; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding;
KW Reference proteome; Repeat; RNA-binding; Serine/threonine-protein kinase;
KW Stress response; Transferase; Translation regulation; tRNA-binding.
FT CHAIN 1..1576
FT /note="eIF-2-alpha kinase GCN2"
FT /id="PRO_0000085962"
FT DOMAIN 16..127
FT /note="RWD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00179"
FT DOMAIN 235..511
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 556..928
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 180..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 673..714
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 772
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 562..570
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 585
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SQ SEQUENCE 1576 AA; 181193 MW; 97A97E1025C37087 CRC64;
MDAAKRLELC KEIQENEIEA LKAIFMDDFE ELKVRNAWNV TNGHVYCIHL CSRSANSKSI
AKLDLCIELG RSYPYVKPVI KLQNGENVLN SQIRFLLDKL DTKAKDLLGE EMIFELASIV
QDYLNDWQSD LSSQFASLEE ERAVQLKHDR ERAEVDLQLR LKREKDALFE EEQTLQNKIQ
DELQRRSYET PQSSSKKKTN SKETTSLETL PTSIYFDCSI SVRDCHDSLV TFNRVLPLYT
ISHSNLSTLT LVKPESKEIS LQDCVFLLRT VRISTPYWST EDGKREIQEL EYELESLKVI
RHDLLASIYE YQLERETRGY GWRLYVLQEY SPKFTLFSLL QTVLTLDVET VRAFSNNILE
GLAELHRLGI SHKSLHLDNV VLFHSGHRTF AKLMDFGFTR TLRDMNASHP FNINSQSITN
ILPEGLYPPE VSESSFAAAS RKTDIWCFGL LVLQMLCGAH VLNKFSSLKL IMTHVIPLLP
GSYQDLVRRC LMRDSRKRPS AIDLLSSHVI RLGTAVLPPV EQGTFSKSAR PSYGGQQDGI
IDLLYRKSVS RYETDFEELE FLGRGGFGEV VKVKNRIDGR FYAVKKLVLL SDDKENSRIL
REVMTLSRLH HEHVVRYYTA WVETEANDTV TEIISSDSES LSQSLNMAVD FRQSSSLPAD
KLSSLDIHFE DDYNSSADEE DPEASDISFQ YSNTSDKEGS SDKDSSIEEA SSVKTQENGL
NATLYIQMEY CEKLSLQDII RDKIPVDEMW RLFRQILEAL AYIHSRGMMH RDLKPGNIFL
DENRNVKLGD FGLATENENY QDNNDKWKNR QSADEDLTTG VGTALYVAPE LLSRRNGVRY
DAKVDMYSLG IILFEMCMTF STSMERIRII DTIRSPSISF PSTFPFSRAS HEFKVIHCLL
QHDPTKRPSS QELLESEAIP PKVGEEFIQE GLRLLSNPNT PYYLKLLKVL FGQVPDRHKD
FTYDFNLSEE SGVLSKVSDR GWDSLLACLV RDHVVKVFRR HGAKERESHI LFPKSSQYDK
DQASVSLLDK NGTLLQLPYD TVLPYARNVA RNAVEEEKTY LISDVFREAK GGGRPKAIKE
ISFDITTNSD NLDWYDAETI KALDEVLTEI PSLTESCILI NHADILSSIL DYLQVSKDKR
RMATHILGQI NQRLTLSQVR NQLRIESLVP STTLDDLSLF DFRENYEEGA SKLRKIFGKE
MPQKMRTALN YMERVVKLLR ALKISHQLYF MPLCVYNFEF YDGGLMFQAI NLAEKSELIC
AGGRYDKLVR FFDPPLMRTA RKKHVVGICF ALEKLVFSML RYIRFHNSKQ SSKHSPSPTL
KSVGPWAPRR VDVLVTSIGK DSILEKCSLL QELWALNIQA DIVLRGASSL EEIVTHYRSE
GINWVLVVRQ KNTQMEHSVK ARNILKNEDD EIRFDEVGMW LLGEINERKR NESMLQSKRI
LDSAQQDVAK FVDTSQSNLD VQLISLKDVN DRKYKWKHKQ NAMNKVYDLV QSAIRESSED
AIALAVDCDS EAMEKLRSTT TLDEESWKRL IESCPASQRE YMQRLQKKLV TLAEQDKKRV
WICSFRTNEI YLYGLK
