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protein coding gene - tsc1 (SPAC22F3.13) - Rheb GAP, hamartin Tsc1

Gene summary

Standard name
tsc1
Systematic ID
SPAC22F3.13
Product
Rheb GAP, hamartin Tsc1
Organism
Schizosaccharomyces pombe (fission yeast)
UniProt ID
Q09778
ORFeome ID
39/39A02
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome I: 673984..678259 reverse strand

Annotation

Disease association

MONDO:0011818 - isolated focal cortical dysplasia type II

References:

MONDO:0011705 - lymphangioleiomyomatosis

References:

MONDO:0001734 - tuberous sclerosis

References:

MONDO:0008612 - tuberous sclerosis 1

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

References:

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

References:

GO:1905626 - positive regulation of L-methionine import across plasma membrane

References:

GO:0006457 - protein folding

References:

GO cellular component

GO:0005737 - cytoplasm

References:

GO:0033596 - TSC1-TSC2 complex

References:

GO molecular function

GO:0005096 - GTPase activator activity

References:

GO:0044183 - protein folding chaperone

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Modification

MOD:00046 - O-phospho-L-serine

References:

MOD:00047 - O-phospho-L-threonine

References:

MOD:01149 - sumoylated lysine

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Multi-locus phenotype

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

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:0001117 - decreased RNA level during vegetative growth

References:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

References:

Genotypes:

FYPO:0000761 - increased conjugation frequency

References:

Genotypes:

FYPO:0002020 - increased RNA level during nitrogen starvation

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Genotypes:

FYPO:0002061 - inviable vegetative cell population

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Genotypes:

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

References:

Genotypes:

FYPO:0002672 - normal growth on rapamycin

References:

Genotypes:

FYPO:0000099 - sensitive to canavanine

References:

Genotypes:

FYPO:0000111 - sensitive to rapamycin

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Genotypes:

FYPO:0001234 - slow vegetative cell population growth

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Genotypes:

FYPO:0001492 - viable elongated vegetative cell

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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

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Single locus phenotype

FYPO:0003209 - abolished protein localization to cell tip, with protein mislocalized to cytoplasm

References:

Genotypes:

FYPO:0001141 - abolished transcriptional response to pheromone

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:0009053 - decreased cell population growth on glutamate nitrogen source

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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

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Genotypes:

FYPO:0002749 - decreased cellular asparagine level

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Genotypes:

FYPO:0001561 - decreased cellular citrulline level

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Genotypes:

FYPO:0001727 - decreased cellular glutamine level

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Genotypes:

FYPO:0001562 - decreased cellular histidine level

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Genotypes:

FYPO:0001560 - decreased cellular threonine level

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Genotypes:

FYPO:0000303 - decreased conjugation frequency

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Genotypes:

FYPO:0001140 - decreased leucine import

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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:0003938 - increased cell population growth during glucose starvation

References:

Genotypes:

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

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Genotypes:

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

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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

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Genotypes:

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

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Genotypes:

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

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Genotypes:

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

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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

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Genotypes:

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

References:

Genotypes:

FYPO:0002020 - increased RNA level during nitrogen starvation

References:

Genotypes:

FYPO:0000825 - increased RNA level during vegetative growth

References:

Genotypes:

FYPO:0004557 - increased vegetative cell population growth

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Genotypes:

FYPO:0000333 - mitotic G1/S phase transition delay

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Genotypes:

FYPO:0001725 - normal cellular aspartate level

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Genotypes:

FYPO:0001637 - normal cellular glycine level

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Genotypes:

FYPO:0001640 - normal cellular leucine level

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Genotypes:

FYPO:0002747 - normal cellular lysine level

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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

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Genotypes:

FYPO:0001357 - normal vegetative cell population growth

References:

Genotypes:

FYPO:0009030 - resistance to amitrole

References:

Genotypes:

FYPO:0009031 - resistance to bleomycin

References:

Genotypes:

FYPO:0009032 - resistance to bortezomib

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Genotypes:

FYPO:0000067 - resistance to brefeldin A

References:

Genotypes:

FYPO:0000763 - resistance to cadmium

References:

Genotypes:

FYPO:0000073 - resistance to caffeine

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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

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Genotypes:

FYPO:0009035 - resistance to formamide

References:

Genotypes:

FYPO:0002578 - resistance to hydroxyurea

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Genotypes:

FYPO:0009070 - resistance to itraconazole

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Genotypes:

FYPO:0001583 - resistance to lithium

References:

Genotypes:

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

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Genotypes:

FYPO:0000725 - resistance to methyl methanesulfonate

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Genotypes:

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

References:

Genotypes:

FYPO:0002767 - resistance to terbinafine

References:

Genotypes:

FYPO:0005193 - resistance to torin1

References:

Genotypes:

FYPO:0007808 - resistance to valproic acid

References:

Genotypes:

FYPO:0000830 - resistance to vanadate

References:

Genotypes:

FYPO:0000096 - sensitive to cadmium

References:

Genotypes:

FYPO:0000842 - sensitive to ethanol during vegetative growth

References:

Genotypes:

FYPO:0001719 - sensitive to lithium

References:

Genotypes:

FYPO:0001214 - sensitive to potassium chloride

References:

Genotypes:

FYPO:0000111 - sensitive to rapamycin

References:

Genotypes:

FYPO:0002617 - sensitive to sodium butyrate

References:

Genotypes:

FYPO:0000797 - sensitive to tert-butyl hydroperoxide

References:

Genotypes:

FYPO:0002546 - sensitive to trichostatin A

References:

Genotypes:

FYPO:0000115 - sensitive to valproic acid

References:

Genotypes:

FYPO:0000022 - shmoo with long tip

References:

Genotypes:

FYPO:0000280 - sterile

References:

Genotypes:

FYPO:0002060 - viable vegetative cell population

References:

Genotypes:

FYPO:0002177 - viable vegetative cell with normal cell morphology

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
PF04388Hamartin_NHamartin_NPfam
SSF48371ARM-type_foldSUPERFAMILY
PTHR15154HamartinPANTHER
CoilCOILS
mobidb-lite-Disorderdisorder_predictionMobiDB-Disorder
mobidb-lite-Polardisorder_predictionMobiDB-Polar

Orthologs

References / Literature

PMID:29996109 - Quantitative Phosphoproteomics Reveals the Signaling Dynamics of Cell-Cycle Kinases in the Fission Yeast Schizosaccharomyces pombe.
Swaffer MP et al. Cell Rep 2018 Jul 10;24(2):503-514
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: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: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: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: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:22681890 - Hierarchical modularity and the evolution of genetic interactomes across species.
Ryan CJ et al. Mol Cell 2012 Jun 08;46(5):691-704
GO_REF:0000033 - Annotation inferences using phylogenetic trees
PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs
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: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: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:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
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
GO_REF:0000051 - S. pombe keyword mapping
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:26537787 - Targeting of SUMO substrates to a Cdc48-Ufd1-Npl4 segregase and STUbL pathway in fission yeast.
Køhler JB et al. Nat Commun 2015 Nov 05;6:8827
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: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
GO_REF:0000108 - Automatic assignment of GO terms using logical inference, based on on inter-ontology links.
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: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: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
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: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:11751918 - The fission yeast ES2 homologue, Bis1, interacts with the Ish1 stress-responsive nuclear envelope protein.
Taricani L et al. J Biol Chem 2002 Mar 22;277(12):10562-72
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: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
PB_REF:0000003 - Disease Association Curation
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: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:22160596 - Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.
Cherkasova V et al. Mol Biol Cell 2012 Feb;23(3):480-91
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:25639242 - Nitrogen regulates AMPK to control TORC1 signaling.
Davie E et al. Curr Biol 2015 Feb 16;25(4):445-54
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: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: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:23857276 - Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations.
Sun W et al. Nat Commun 2013;4:2135
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: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: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:34296454 - The TOR-dependent phosphoproteome and regulation of cellular protein synthesis.
Mak T et al. EMBO J 2021 Aug 16;40(16):e107911
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: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: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