ID   TSC2_SCHPO              Reviewed;        1339 AA.
AC   Q9UUG9;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 130.
DE   RecName: Full=Tuberous sclerosis 2 protein homolog;
GN   Name=tsc2; ORFNames=SPAC630.13c;
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 [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   [2]
RP   FUNCTION, AND INTERACTION WITH TSC1.
RX   PubMed=12136010; DOI=10.1093/genetics/161.3.1053;
RA   Matsumoto S., Bandyopadhyay A., Kwiatkowski D.J., Maitra U., Matsumoto T.;
RT   "Role of the Tsc1-Tsc2 complex in signaling and transport across the cell
RT   membrane in the fission yeast Schizosaccharomyces pombe.";
RL   Genetics 161:1053-1063(2002).
RN   [3]
RP   FUNCTION, AND MUTAGENESIS OF ASN-1191.
RX   PubMed=14718525; DOI=10.1074/jbc.m313874200;
RA   van Slegtenhorst M., Carr E., Stoyanova R., Kruger W.D., Henske E.P.;
RT   "Tsc1+ and tsc2+ regulate arginine uptake and metabolism in
RT   Schizosaccharomyces pombe.";
RL   J. Biol. Chem. 279:12706-12713(2004).
RN   [4]
RP   FUNCTION.
RX   PubMed=16624901; DOI=10.1534/genetics.106.056895;
RA   Nakase Y., Fukuda K., Chikashige Y., Tsutsumi C., Morita D., Kawamoto S.,
RA   Ohnuki M., Hiraoka Y., Matsumoto T.;
RT   "A defect in protein farnesylation suppresses a loss of Schizosaccharomyces
RT   pombe tsc2+, a homolog of the human gene predisposing to tuberous sclerosis
RT   complex.";
RL   Genetics 173:569-578(2006).
RN   [5]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=16823372; DOI=10.1038/nbt1222;
RA   Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA   Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA   Yoshida M.;
RT   "ORFeome cloning and global analysis of protein localization in the fission
RT   yeast Schizosaccharomyces pombe.";
RL   Nat. Biotechnol. 24:841-847(2006).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1036, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=18257517; DOI=10.1021/pr7006335;
RA   Wilson-Grady J.T., Villen J., Gygi S.P.;
RT   "Phosphoproteome analysis of fission yeast.";
RL   J. Proteome Res. 7:1088-1097(2008).
CC   -!- FUNCTION: Together with tsc1, required for uptake of various amino
CC       acids from the environment and for proper conjugation. Involved in
CC       induction of gene expression of permeases and genes required for
CC       meiosis upon nitrogen starvation. May act as a GTPase-activating
CC       protein (GAP) for the small GTPase rhb1. {ECO:0000269|PubMed:12136010,
CC       ECO:0000269|PubMed:14718525, ECO:0000269|PubMed:16624901}.
CC   -!- SUBUNIT: Interacts with tsc1. {ECO:0000269|PubMed:12136010}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16823372}. Nucleus
CC       {ECO:0000269|PubMed:16823372}.
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DR   EMBL; CU329670; CAB52735.1; -; Genomic_DNA.
DR   PIR; T38991; T38991.
DR   RefSeq; NP_592909.1; NM_001018309.2.
DR   AlphaFoldDB; Q9UUG9; -.
DR   SMR; Q9UUG9; -.
DR   BioGRID; 279762; 111.
DR   STRING; 4896.SPAC630.13c.1; -.
DR   iPTMnet; Q9UUG9; -.
DR   MaxQB; Q9UUG9; -.
DR   PaxDb; Q9UUG9; -.
DR   PRIDE; Q9UUG9; -.
DR   EnsemblFungi; SPAC630.13c.1; SPAC630.13c.1:pep; SPAC630.13c.
DR   GeneID; 2543339; -.
DR   KEGG; spo:SPAC630.13c; -.
DR   PomBase; SPAC630.13c; tsc2.
DR   VEuPathDB; FungiDB:SPAC630.13c; -.
DR   eggNOG; KOG3687; Eukaryota.
DR   HOGENOM; CLU_003828_0_0_1; -.
DR   InParanoid; Q9UUG9; -.
DR   OMA; FDTFPSQ; -.
DR   PhylomeDB; Q9UUG9; -.
DR   Reactome; R-SPO-165181; Inhibition of TSC complex formation by PKB.
DR   Reactome; R-SPO-198323; AKT phosphorylates targets in the cytosol.
DR   Reactome; R-SPO-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR   Reactome; R-SPO-5628897; TP53 Regulates Metabolic Genes.
DR   PRO; PR:Q9UUG9; -.
DR   Proteomes; UP000002485; Chromosome I.
DR   GO; GO:0005737; C:cytoplasm; HDA:PomBase.
DR   GO; GO:0005829; C:cytosol; HDA:PomBase.
DR   GO; GO:0005634; C:nucleus; HDA:PomBase.
DR   GO; GO:0033596; C:TSC1-TSC2 complex; IPI:PomBase.
DR   GO; GO:0005096; F:GTPase activator activity; IMP:PomBase.
DR   GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:PomBase.
DR   GO; GO:0032007; P:negative regulation of TOR signaling; IBA:GO_Central.
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:0043547; P:positive regulation of GTPase activity; IEA:InterPro.
DR   GO; GO:1905589; P:positive regulation of L-arginine import across plasma membrane; IMP:PomBase.
DR   GO; GO:1905534; P:positive regulation of leucine import across plasma membrane; IMP:PomBase.
DR   GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; IEA:InterPro.
DR   Gene3D; 3.40.50.11210; -; 1.
DR   InterPro; IPR035974; Rap/Ran-GAP_sf.
DR   InterPro; IPR000331; Rap/Ran_GAP_dom.
DR   InterPro; IPR018515; Tuberin-type_domain.
DR   InterPro; IPR027107; Tuberin/Ral-act_asu.
DR   InterPro; IPR024584; Tuberin_N.
DR   PANTHER; PTHR10063; PTHR10063; 1.
DR   Pfam; PF11864; DUF3384; 1.
DR   Pfam; PF02145; Rap_GAP; 1.
DR   Pfam; PF03542; Tuberin; 1.
DR   SUPFAM; SSF111347; SSF111347; 1.
DR   PROSITE; PS50085; RAPGAP; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; GTPase activation; Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..1339
FT                   /note="Tuberous sclerosis 2 protein homolog"
FT                   /id="PRO_0000065657"
FT   DOMAIN          1109..1303
FT                   /note="Rap-GAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00165"
FT   MOD_RES         1036
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18257517"
FT   MUTAGEN         1191
FT                   /note="N->K: Decreased arginine uptake."
FT                   /evidence="ECO:0000269|PubMed:14718525"
SQ   SEQUENCE   1339 AA;  154813 MW;  B4D32AE6F0D100FE CRC64;
     MNNKSLLDLS SEPAIKDTDI LSYFDANLPF KKRHQIVRSI YHGLKYYIYS STSIIQVWQN
     IQDFISTKND NAAFRELVYN LMMRYVSTQK HLSIIERHTF FQTIEKDPFQ DIAELQLRLK
     SLSVLTDEGH KISGIENRVG PLLSAWFNQY LQWQSQATEL QGKDADSKLV HLLFFKSLFK
     FSTNLVKFQW FLVPEPQMLQ LVNSVVQICN HARLEDVVTE VLMFFDSMIR YSVIPKASLY
     DTVLILCSTY ISTYSYSKLA QSVIFNLISS PVSNLAFENV FNILQYNRSN VNAVRGAVRL
     MRFLMLQEVK NDAIASITLS SSIEFTEFPL GFNENVDFEI LGTVYLFLRT PSILNRLNFL
     DWHRILNILM YCSQYLPLKA STSKEAFSKT AAFANIYDRV LDFLDFEALI PLLQQFQVKL
     VFFLKDVLPV LKPKIRKKLL RLFETYNLIF PCNQYWVFNL EFLLGIYQCK TFDLEDRALL
     FKLVEDACSV ADENSAPILC SKFLFPVIES FSKESDDCVV SPVYNMLFFL SVNFQNPGLK
     DCIDHIFQQL ISDTSSVTVR RLATSTLIRL FYYYYDLRDA VPIQETLAKM LEILETPSFP
     FVSRMLCLQF FLRFRANGTS IYICENIDLN EPFKVLNVDS ELIPAVYPIS DSFVNSATVE
     KHIWERKEND LIKISNHSTE YGKDFVTFPT SSLLRFYRKS MATESNWTIL MFMITHLADQ
     ISNRSMFIGA LEEIYNLLDF MCDIVFERVS ISAEIPSNIR KANIMIPILQ NVQMLFVYHD
     QFSRAQEDEL VSVFFAGLQK WNEACHVSIH SLMLCCYELP VSIRKQLPAI LVTLSRLITK
     PDLSVHILEF LCSLARLPDL IANFTDADYR QIFAIALKYI QHRDFTKESK DSNDTESILK
     NSYSSYVLAL AYSVLQIWFL SLRLTERKKF VPWILRGLKL ASEGKPLEDL CLVQYDMMQQ
     FCYSNSDINN QTSTFVDSDV ESETWIRGNS LFTINVSVNS GFLEAVIRRP TGTTQYTFRN
     EASLQKFLWE ENLTSSKALT RGLLCTPSSF VSHFLDPHGI SLYNQPLLLP SNDDSVRRAI
     SVFDRIPVIE SLKAGLVYVG YQQRREADIL ANTNPSEDFL TFLNGLGTLF ELKTDQKVFA
     GGLDRENDID GAFAYCWKDK VTQMVFHCTT MMPTNIEHDP GCTLKKRHIG NDFVTIIFNE
     SGLEYDFDTI PSQFNFVNIV ITPESESIRR TGRQIKFYKV KALTKYDIDF SLFRRYKIVS
     SDALPAIVRD VTLNAAVFSH IYHRSAGDYV HIWAERLRQL KRLREKFQAS VLPEDYNLDE
     QTKTKLQNGT NFSDFTSYL