PomBase home

protein coding gene - tsc2 (SPAC630.13c) - Rheb GAP, tuberin Tsc2

Gene summary

Standard name
tsc2
Systematic ID
SPAC630.13c
Product
Rheb GAP, tuberin Tsc2
Organism
Schizosaccharomyces pombe (fission yeast)
UniProt ID
Q9UUG9
ORFeome ID
48/48F09
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome I: 369791..374131 reverse strand

Annotation

Disease association

MONDO:0009008 - heart defect - tongue hamartoma - polysyndactyly syndrome

References:

MONDO:0011818 - isolated focal cortical dysplasia type II

References:

MONDO:0011705 - lymphangioleiomyomatosis

References:

MONDO:0001734 - tuberous sclerosis

References:

MONDO:0013199 - tuberous sclerosis 2

References:

GO biological process

GO:2000134 - negative regulation of G1/S transition of mitotic cell cycle

References:

GO:1904262 - negative regulation of TORC1 signaling

References:

GO:0010508 - positive regulation of autophagy

References:

GO:1905589 - positive regulation of L-arginine import across plasma membrane

References:

GO:1905534 - positive regulation of L-leucine import across plasma membrane

References:

GO:0016239 - positive regulation of macroautophagy

References:

GO cellular component

GO:0005737 - cytoplasm

References:

GO:0005829 - cytosol

References:

GO:0005634 - nucleus

References:

GO:0033596 - TSC1-TSC2 complex

References:

GO molecular function

GO:0005096 - GTPase activator activity

References:

GO:0005515 - protein binding

References:

Modification

MOD:00046 - O-phospho-L-serine

References:

MOD:00047 - O-phospho-L-threonine

References:

Multi-locus phenotype

FYPO:0003252 - abolished cell population growth on proline nitrogen source

References:

Genotypes:

FYPO:0003255 - abolished proline import

References:

Genotypes:

FYPO:0002033 - abolished protein phosphorylation during vegetative growth

References:

Genotypes:

FYPO:0000082 - decreased cell population growth at high temperature

References:

Genotypes:

FYPO:0001407 - decreased cell population growth on glucose carbon source

References:

Genotypes:

FYPO:0000250 - decreased cell population growth on proline nitrogen source

References:

Genotypes:

FYPO:0001140 - decreased leucine import

References:

Genotypes:

FYPO:0001117 - decreased RNA level during vegetative growth

References:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

References:

Genotypes:

FYPO:0000747 - growth auxotrophic for adenine

References:

Genotypes:

FYPO:0000035 - growth auxotrophic for arginine

References:

Genotypes:

FYPO:0000761 - increased conjugation frequency

References:

Genotypes:

FYPO:0001038 - increased protein phosphorylation during vegetative growth

References:

Genotypes:

FYPO:0002020 - increased RNA level during nitrogen starvation

References:

Genotypes:

FYPO:0002061 - inviable vegetative cell population

References:

Genotypes:

FYPO:0001056 - normal arginine import

References:

Genotypes:

FYPO:0001000 - normal cell cycle arrest in mitotic G1 phase during nitrogen starvation

References:

Genotypes:

FYPO:0000243 - normal growth on proline nitrogen source

References:

Genotypes:

FYPO:0002672 - normal growth on rapamycin

References:

Genotypes:

FYPO:0001029 - resistance to canavanine

References:

Genotypes:

FYPO:0002578 - resistance to hydroxyurea

References:

Genotypes:

FYPO:0000084 - sensitive to 6-azauracil

References:

Genotypes:

FYPO:0000099 - sensitive to canavanine

References:

Genotypes:

FYPO:0001525 - sensitive to L-thialysine

References:

Genotypes:

FYPO:0000111 - sensitive to rapamycin

References:

Genotypes:

FYPO:0001234 - slow vegetative cell population growth

References:

Genotypes:

FYPO:0001492 - viable elongated vegetative cell

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

References:

Genotypes:

Qualitative gene expression

PomGeneEx:0000018 - protein level increased

References:

Quantitative gene expression

PBO:0006310 - protein level

References:

PBO:0011963 - RNA level

References:

Single locus phenotype

FYPO:0000152 - abnormal cellular response to nitrogen starvation

References:

Genotypes:

FYPO:0000121 - abnormal sporulation

References:

Genotypes:

FYPO:0007434 - attenuated change in cell size at division upon shift to poor nitrogen source

References:

Genotypes:

FYPO:0001592 - decreased arginine import

References:

Genotypes:

FYPO:0000709 - decreased cell population growth during nitrogen starvation

References:

Genotypes:

FYPO:0009053 - decreased cell population growth on glutamate nitrogen source

References:

Genotypes:

FYPO:0009091 - decreased cell population growth on lysine and proline nitrogen source

References:

Genotypes:

FYPO:0000250 - decreased cell population growth on proline nitrogen source

References:

Genotypes:

FYPO:0002748 - decreased cellular alanine level

References:

Genotypes:

FYPO:0001621 - decreased cellular arginine level

References:

Genotypes:

FYPO:0002749 - decreased cellular asparagine level

References:

Genotypes:

FYPO:0001561 - decreased cellular citrulline level

References:

Genotypes:

FYPO:0001727 - decreased cellular glutamine level

References:

Genotypes:

FYPO:0001562 - decreased cellular histidine level

References:

Genotypes:

FYPO:0001560 - decreased cellular threonine level

References:

Genotypes:

FYPO:0000303 - decreased conjugation frequency

References:

Genotypes:

FYPO:0001140 - decreased leucine import

References:

Genotypes:

FYPO:0000708 - decreased mating efficiency

References:

Genotypes:

FYPO:0003257 - decreased proline import

References:

Genotypes:

FYPO:0001586 - decreased protein localization to cell tip during vegetative growth

References:

Genotypes:

FYPO:0001152 - decreased RNA level during nitrogen starvation

References:

Genotypes:

FYPO:0001117 - decreased RNA level during vegetative growth

References:

Genotypes:

FYPO:0000712 - delayed onset of cell cycle arrest in mitotic G1 phase in response to nitrogen starvation

References:

Genotypes:

FYPO:0000998 - elongated cell during nitrogen starvation

References:

Genotypes:

FYPO:0006012 - elongated cell with abolished shmoo formation

References:

Genotypes:

FYPO:0004806 - incomplete cell wall disassembly at cell fusion site

References:

Genotypes:

FYPO:0003938 - increased cell population growth during glucose starvation

References:

Genotypes:

FYPO:0009077 - increased cell population growth on ethanol carbon source

References:

Genotypes:

FYPO:0005261 - increased cell population growth on galactose carbon source

References:

Genotypes:

FYPO:0009101 - increased cell population growth on glycerol and galactose carbon source

References:

Genotypes:

FYPO:0004167 - increased cell population growth on glycerol carbon source

References:

Genotypes:

FYPO:0009072 - increased cell population growth on lysine nitrogen source

References:

Genotypes:

FYPO:0009098 - increased cell population growth on mannitol carbon source

References:

Genotypes:

FYPO:0009096 - increased cell population growth on xylose carbon source

References:

Genotypes:

FYPO:0001728 - increased cellular serine level

References:

Genotypes:

FYPO:0006345 - increased duration of protein phosphorylation during nitrogen starvation

References:

Genotypes:

FYPO:0002743 - increased level of amino acid metabolism gene mRNA during vegetative growth

References:

Genotypes:

FYPO:0002742 - increased level of iron transport gene mRNA during vegetative growth

References:

Genotypes:

FYPO:0002681 - increased protein phosphorylation during nitrogen starvation

References:

Genotypes:

FYPO:0001038 - increased protein phosphorylation during vegetative growth

References:

Genotypes:

FYPO:0001571 - increased protein-protein interaction

References:

Genotypes:

FYPO:0003482 - increased punctate cytoplasmic protein localization

References:

Genotypes:

FYPO:0002020 - increased RNA level during nitrogen starvation

References:

Genotypes:

FYPO:0000825 - increased RNA level during vegetative growth

References:

Genotypes:

FYPO:0000127 - increased sensitivity to chemical during vegetative growth

References:

Genotypes:

FYPO:0004557 - increased vegetative cell population growth

References:

Genotypes:

FYPO:0000245 - loss of viability in stationary phase

References:

Genotypes:

FYPO:0000333 - mitotic G1/S phase transition delay

References:

Genotypes:

FYPO:0001725 - normal cellular aspartate level

References:

Genotypes:

FYPO:0001637 - normal cellular glycine level

References:

Genotypes:

FYPO:0001640 - normal cellular leucine level

References:

Genotypes:

FYPO:0002747 - normal cellular lysine level

References:

Genotypes:

FYPO:0002745 - normal cellular proline level

References:

Genotypes:

FYPO:0002746 - normal cellular valine level

References:

Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

References:

Genotypes:

FYPO:0002672 - normal growth on rapamycin

References:

Genotypes:

FYPO:0002620 - normal growth on trichostatin A

References:

Genotypes:

FYPO:0000644 - normal protein localization during vegetative growth

References:

Genotypes:

FYPO:0001317 - normal RNA level during vegetative growth

References:

Genotypes:

FYPO:0000783 - protein mislocalized to cytoplasm during vegetative growth

References:

Genotypes:

FYPO:0009030 - resistance to amitrole

References:

Genotypes:

FYPO:0009036 - resistance to benzamidine

References:

Genotypes:

FYPO:0009031 - resistance to bleomycin

References:

Genotypes:

FYPO:0009032 - resistance to bortezomib

References:

Genotypes:

FYPO:0000067 - resistance to brefeldin A

References:

Genotypes:

FYPO:0000763 - resistance to cadmium

References:

Genotypes:

FYPO:0000073 - resistance to caffeine

References:

Genotypes:

FYPO:0001029 - resistance to canavanine

References:

Genotypes:

FYPO:0000764 - resistance to cycloheximide

References:

Genotypes:

FYPO:0002693 - resistance to diamide

References:

Genotypes:

FYPO:0009038 - resistance to egtazic acid

References:

Genotypes:

FYPO:0001557 - resistance to ethionine

References:

Genotypes:

FYPO:0009034 - resistance to ethylenediaminetetraacetic acid

References:

Genotypes:

FYPO:0001524 - resistance to L-thialysine

References:

Genotypes:

FYPO:0009083 - resistance to lithium chloride and methyl methanesulfonate

References:

Genotypes:

FYPO:0009087 - resistance to magnesium chloride and sodium dodecyl sulfate

References:

Genotypes:

FYPO:0000725 - resistance to methyl methanesulfonate

References:

Genotypes:

FYPO:0009081 - resistance to potassium chloride and methyl methanesulfonate

References:

Genotypes:

FYPO:0009043 - resistance to potassium chloride and sodium dodecyl sulfate

References:

Genotypes:

FYPO:0002767 - resistance to terbinafine

References:

Genotypes:

FYPO:0003383 - resistance to tert-butyl hydroperoxide

References:

Genotypes:

FYPO:0000830 - resistance to vanadate

References:

Genotypes:

FYPO:0001996 - RNA absent from cell during nitrogen starvation

References:

Genotypes:

FYPO:0007921 - sensitive to benzamidine

References:

Genotypes:

FYPO:0000096 - sensitive to cadmium

References:

Genotypes:

FYPO:0009080 - sensitive to calcofluor and sodium dodecyl sulfate

References:

Genotypes:

FYPO:0000099 - sensitive to canavanine

References:

Genotypes:

FYPO:0005078 - sensitive to canavanine and rapamycin

References:

Genotypes:

FYPO:0000842 - sensitive to ethanol during vegetative growth

References:

Genotypes:

FYPO:0000111 - sensitive to rapamycin

References:

Genotypes:

FYPO:0002617 - sensitive to sodium butyrate

References:

Genotypes:

FYPO:0000115 - sensitive to valproic acid

References:

Genotypes:

FYPO:0000280 - sterile

References:

Genotypes:

FYPO:0000648 - viable small vegetative cell

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

References:

Genotypes:

FYPO:0001510 - viable vegetative cell, abnormal cell shape, normal cell size

References:

Genotypes:

Taxonomic conservation

PBO:0011065 - conserved in eukaryotes

PBO:0011071 - conserved in eukaryotes only

PBO:0011064 - conserved in fungi

PBO:0011069 - conserved in metazoa

PBO:0011070 - conserved in vertebrates

PBO:0000055 - no apparent S. cerevisiae ortholog

PBO:0006222 - predominantly single copy (one to one)

Protein features

IDNameInterPro nameDB name
PF03542TuberinTuberin-type_domainPFAM
PF02145Rap_GAPRap/Ran_GAP_domPFAM
PF11864DUF3384Tuberin_NPFAM
PS50085RAPGAPRap/Ran_GAP_domPROSITE_PROFILES
G3DSA:3.40.50.11210:FF:000007FUNFAM
SSF111347Rap/Ran-GAPRap/Ran-GAP_sfSUPERFAMILY
G3DSA:3.40.50.11210Rap/Ran-GAP_sfGENE3D
PTHR10063TUBERINTuberin/Ral-act_asuPANTHER

Orthologs

References / Literature

PMID:29259000 - Genes Important for Schizosaccharomyces pombe Meiosis Identified Through a Functional Genomics Screen.
Blyth J et al. Genetics 2018 Feb;208(2):589-603
PMID:22681890 - Hierarchical modularity and the evolution of genetic interactomes across species.
Ryan CJ et al. Mol Cell 2012 Jun 08;46(5):691-704
PMID:29343513 - Using genetic buffering relationships identified in fission yeast to reveal susceptibilities in cells lacking hamartin or tuberin function.
Rayhan A et al. Biol Open 2018 Jan 17;7(1)
PMID:33534698 - Tripartite suppression of fission yeast TORC1 signaling by the GATOR1-Sea3 complex, the TSC complex, and Gcn2 kinase.
Fukuda T et al. Elife 2021 Feb 03;10
PMID:17556368 - The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in amino acid homeostasis in Schizosaccharomyces pombe.
van Slegtenhorst M et al. J Biol Chem 2007 Aug 24;282(34):24583-90
PMID:37156397 - Identification of novel coenzyme Q 10 biosynthetic proteins Coq11 and Coq12 in Schizosaccharomyces pombe.
Nishida I et al. J Biol Chem 2023 Jun;299(6):104797
PMID:16115814 - Pas1, a G1 cyclin, regulates amino acid uptake and rescues a delay in G1 arrest in Tsc1 and Tsc2 mutants in Schizosaccharomyces pombe.
van Slegtenhorst M et al. Hum Mol Genet 2005 Oct 01;14(19):2851-8
PMID:18684775 - A genome-wide screen of genes involved in cadmium tolerance in Schizosaccharomyces pombe.
Kennedy PJ et al. Toxicol Sci 2008 Nov;106(1):124-39
PMID:23101633 - Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells.
Marguerat S et al. Cell 2012 Oct 26;151(3):671-83
PMID:39705284 - Proteomic and phosphoproteomic analyses reveal that TORC1 is reactivated by pheromone signaling during sexual reproduction in fission yeast.
Bérard M et al. PLoS Biol 2024 Dec 20;22(12):e3002963
PMID:30726745 - Fission Yeast NDR/LATS Kinase Orb6 Regulates Exocytosis via Phosphorylation of the Exocyst Complex.
Tay YD et al. Cell Rep 2019 Feb 05;26(6):1654-1667.e7
PMID:22976295 - Psk1, an AGC kinase family member in fission yeast, is directly phosphorylated and controlled by TORC1 and functions as S6 kinase.
Nakashima A et al. J Cell Sci 2012 Dec 01;125(Pt 23):5840-9
PMID:16262791 - Identification of novel single amino acid changes that result in hyperactivation of the unique GTPase, Rheb, in fission yeast.
Urano J et al. Mol Microbiol 2005 Nov;58(4):1074-86
PMID:25639242 - Nitrogen regulates AMPK to control TORC1 signaling.
Davie E et al. Curr Biol 2015 Feb 16;25(4):445-54
PMID:26173815 - Genome-wide screen of fission yeast mutants for sensitivity to 6-azauracil, an inhibitor of transcriptional elongation.
Zhou H et al. Yeast 2015 Oct;32(10):643-55
PMID:29199950 - Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases.
Chia KH et al. Elife 2017 Dec 04;6
PMID:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:33823663 - A TOR (target of rapamycin) and nutritional phosphoproteome of fission yeast reveals novel targets in networks conserved in humans.
Halova L et al. Open Biol 2021 Apr;11(4):200405
PMID:22992726 - The SAGA histone acetyltransferase complex regulates leucine uptake through the Agp3 permease in fission yeast.
Takahashi H et al. J Biol Chem 2012 Nov 02;287(45):38158-67
PMID:23697806 - A genome-wide resource of cell cycle and cell shape genes of fission yeast.
Hayles J et al. Open Biol 2013 May 22;3(5):130053
PMID:24876389 - Fission yeast arrestin-related trafficking adaptor, Arn1/Any1, is ubiquitinated by Pub1 E3 ligase and regulates endocytosis of Cat1 amino acid transporter.
Nakashima A et al. Biol Open 2014 May 29;3(6):542-52
PMID:34028542 - TORC2 inhibition of α-arrestin Aly3 mediates cell surface persistence of S. pombe Ght5 glucose transporter in low glucose.
Toyoda Y et al. J Cell Sci 2021 May 15;134(10)
PMID:37787768 - Broad functional profiling of fission yeast proteins using phenomics and machine learning.
Rodríguez-López M et al. Elife 2023 Oct 03;12
PMID:23813957 - The fission yeast β-arrestin-like protein Any1 is involved in TSC-Rheb signaling and the regulation of amino acid transporters.
Nakase Y et al. J Cell Sci 2013 Sep 01;126(Pt 17):3972-81
PMID:19620394 - Distinctive responses to nitrogen starvation in the dominant active mutants of the fission yeast Rheb GTPase.
Murai T et al. Genetics 2009 Oct;183(2):517-27
PMID:17261596 - Loss of the TOR kinase Tor2 mimics nitrogen starvation and activates the sexual development pathway in fission yeast.
Matsuo T et al. Mol Cell Biol 2007 Apr;27(8):3154-64
PMID:34250083 - Barcode sequencing and a high-throughput assay for chronological lifespan uncover ageing-associated genes in fission yeast.
Romila CA et al. Microb Cell 2021 Jul 05;8(7):146-160
GO_REF:0000033 - Annotation inferences using phylogenetic trees
PMID:20473289 - Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe.
Kim DU et al. Nat Biotechnol 2010 Jun;28(6):617-623
PMID:23934889 - TORC1 signaling is governed by two negative regulators in fission yeast.
Ma N et al. Genetics 2013 Oct;195(2):457-68
PMID:12618370 - Schizosaccharomyces pombe essential genes: a pilot study.
Decottignies A et al. Genome Res 2003 Mar;13(3):399-406
PMID:24344203 - Isp7 is a novel regulator of amino acid uptake in the TOR signaling pathway.
Laor D et al. Mol Cell Biol 2014 Mar;34(5):794-806
PMID:20144990 - Fission yeast TORC1 regulates phosphorylation of ribosomal S6 proteins in response to nutrients and its activity is inhibited by rapamycin.
Nakashima A et al. J Cell Sci 2010 Mar 01;123(Pt 5):777-86
PMID:28041796 - A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast.
Martín R et al. Curr Biol 2017 Jan 23;27(2):175-188
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
PMID:30814334 - Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling.
Forte GM et al. J Cell Sci 2019 Apr 03;132(7)
PMID:17121544 - Fission yeast Tor2 links nitrogen signals to cell proliferation and acts downstream of the Rheb GTPase.
Uritani M et al. Genes Cells 2006 Dec;11(12):1367-79
PMID:16624901 - A defect in protein farnesylation suppresses a loss of Schizosaccharomyces pombe tsc2+, a homolog of the human gene predisposing to tuberous sclerosis complex.
Nakase Y et al. Genetics 2006 Jun;173(2):569-78
PMID:18219492 - The Tsc/Rheb signaling pathway controls basic amino acid uptake via the Cat1 permease in fission yeast.
Aspuria PJ et al. Mol Genet Genomics 2008 May;279(5):441-50
PMID:25076038 - Large scale screening of genetic interaction with sgf73(+) in fission yeast.
Guo Y et al. Yi Chuan 2014 Jul;36(7):723-31
PMID:23861937 - Genome-wide screening for genes associated with valproic acid sensitivity in fission yeast.
Zhang L et al. PLoS One 2013;8(7):e68738
PMID:26447710 - Constitutive Tor2 Activity Promotes Retention of the Amino Acid Transporter Agp3 at Trans-Golgi/Endosomes in Fission Yeast.
Liu Q et al. PLoS One 2015;10(10):e0139045
PMID:39367033 - Quantitative proteomics and phosphoproteomics profiling of meiotic divisions in the fission yeast Schizosaccharomyces pombe.
Sivakova B et al. Sci Rep 2024 Oct 04;14(1):23105
PMID:30301783 - The RHEB-mTOR axis regulates expression of Tf2 transposons in fission yeast.
Nakase Y et al. J Cell Sci 2018 Nov 21;131(22)
PMID:17179073 - Opposite effects of tor1 and tor2 on nitrogen starvation responses in fission yeast.
Weisman R et al. Genetics 2007 Mar;175(3):1153-62
PMID:24463365 - Systematic screen for mutants resistant to TORC1 inhibition in fission yeast reveals genes involved in cellular ageing and growth.
Rallis C et al. Biol Open 2014 Feb 15;3(2):161-71
PMID:24763107 - Absolute proteome and phosphoproteome dynamics during the cell cycle of Schizosaccharomyces pombe (Fission Yeast).
Carpy A et al. Mol Cell Proteomics 2014 Aug;13(8):1925-36
PMID:16823372 - ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
Matsuyama A et al. Nat Biotechnol 2006 Jul;24(7):841-7
PMID:12136010 - Role of the Tsc1-Tsc2 complex in signaling and transport across the cell membrane in the fission yeast Schizosaccharomyces pombe.
Matsumoto S et al. Genetics 2002 Jul;161(3):1053-63
PMID:36793083 - The SAGA histone acetyltransferase module targets SMC5/6 to specific genes.
Mahrik L et al. Epigenetics Chromatin 2023 Feb 16;16(1):6
PMID:25814783 - Conservation of the Tsc/Rheb/TORC1/S6K/S6 Signaling in Fission Yeast.
Nakashima A et al. Enzymes 2010;28:167-187
PB_REF:0000003 - Disease Association Curation
PMID:21712547 - Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast.
Koch A et al. Sci Signal 2011 Jun 28;4(179):rs6
PMID:28410370 - A systematic screen for morphological abnormalities during fission yeast sexual reproduction identifies a mechanism of actin aster formation for cell fusion.
Dudin O et al. PLoS Genet 2017 Apr;13(4):e1006721
PMID:29079657 - TORC1 and TORC2 converge to regulate the SAGA co-activator in response to nutrient availability.
Laboucarié T et al. EMBO Rep 2017 Dec;18(12):2197-2218
PMID:14718525 - Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe.
van Slegtenhorst M et al. J Biol Chem 2004 Mar 26;279(13):12706-13
PMID:25720772 - Quantitative phosphoproteomics reveals pathways for coordination of cell growth and division by the conserved fission yeast kinase pom1.
Kettenbach AN et al. Mol Cell Proteomics 2015 May;14(5):1275-87