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protein coding gene - spd1 (SPAC29B12.03) - ribonucleotide reductase (RNR) inhibitor

Gene summary

Standard name
spd1
Systematic ID
SPAC29B12.03
Product
ribonucleotide reductase (RNR) inhibitor
Organism
Schizosaccharomyces pombe (fission yeast)
UniProt ID
Q10585
ORFeome ID
02/02F08
Characterisation status
biological role published
Feature type
mRNA gene
Genomic location
chromosome I: 5412443..5413219 forward strand

Annotation

Comment

PBO:0002967 - degradation is promoted by two separate CSN-dependent mechanisms

References:

GO biological process

GO:0006240 - dCDP biosynthetic process

References:

GO cellular component

GO:0005737 - cytoplasm

References:

GO:0005829 - cytosol

References:

GO:0005634 - nucleus

References:

GO molecular function

GO:0005515 - protein binding

References:

GO:0044877 - protein-containing complex binding

References:

GO:0043495 - protein-membrane adaptor activity

References:

GO:1990846 - ribonucleoside-diphosphate reductase inhibitor activity

References:

Modification

MOD:01148 - ubiquitinylated lysine

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Multi-locus phenotype

FYPO:0002553 - abnormal double-strand break processing

References:

Genotypes:

FYPO:0003486 - abolished protein localization to double-strand break site

References:

Genotypes:

FYPO:0004188 - abolished protein localization to nucleus during cellular response to hydroxyurea

References:

Genotypes:

FYPO:0002779 - abolished protein localization to nucleus, with protein mislocalized to cytoplasm, during vegetative growth

References:

Genotypes:

FYPO:0000705 - abolished protein-protein interaction

References:

Genotypes:

FYPO:0003411 - decreased chromatin silencing at centromere inner repeat

References:

Genotypes:

FYPO:0003412 - decreased chromatin silencing at centromere outer repeat

References:

Genotypes:

FYPO:0002827 - decreased chromatin silencing at silent mating-type cassette

References:

Genotypes:

FYPO:0004604 - decreased chromatin silencing at subtelomere

References:

Genotypes:

FYPO:0003912 - decreased double-strand break repair via homologous recombination

References:

Genotypes:

FYPO:0005608 - decreased histone H2B-K119 ubiquitination at double-strand break site during vegetative growth

References:

Genotypes:

FYPO:0000888 - decreased histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

References:

Genotypes:

FYPO:0004137 - decreased histone H3-K9 dimethylation at subtelomeric heterochromatin during vegetative growth

References:

Genotypes:

FYPO:0004545 - decreased proteasomal ubiquitin-dependent protein degradation

References:

Genotypes:

FYPO:0000846 - decreased protein degradation during vegetative growth

References:

Genotypes:

FYPO:0002474 - decreased protein localization to double-strand break site

References:

Genotypes:

FYPO:0005609 - decreased spatial extent of histone H2B-K119 ubiquitination at double-strand break site during vegetative growth

References:

Genotypes:

FYPO:0005610 - decreased spatial extent of protein localization to double-strand break site

References:

Genotypes:

FYPO:0001355 - decreased vegetative cell population growth

References:

Genotypes:

FYPO:0005606 - delayed onset of protein localization to double-strand break site

References:

Genotypes:

FYPO:0005752 - increased cellular dNTP level

References:

Genotypes:

FYPO:0003584 - increased double-strand break repair via nonhomologous end joining

References:

Genotypes:

FYPO:0005604 - increased duration of Rad52 focus presence during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0005605 - increased duration of Ssb1 focus presence during cellular response to ionizing radiation

References:

Genotypes:

FYPO:0005611 - increased H4-K20 dimethylation at double-strand break site during vegetative growth

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Genotypes:

FYPO:0004066 - increased protein localization to chromatin at protein coding gene

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Genotypes:

FYPO:0002475 - increased protein localization to double-strand break site

References:

Genotypes:

FYPO:0004377 - increased protein localization to heterochromatin at silent mating-type cassette

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Genotypes:

FYPO:0004380 - increased protein localization to pericentric heterochromatin during vegetative growth

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Genotypes:

FYPO:0003010 - increased protein localization to subtelomeric heterochromatin during vegetative growth

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Genotypes:

FYPO:0006995 - normal chromatin silencing at centromere inner repeat

References:

Genotypes:

FYPO:0001532 - normal duration of mitotic S phase

References:

Genotypes:

FYPO:0000969 - normal growth during cellular response to UV

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Genotypes:

FYPO:0001690 - normal growth on camptothecin

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Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

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Genotypes:

FYPO:0000963 - normal growth on hydroxyurea

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Genotypes:

FYPO:0000957 - normal growth on methyl methanesulfonate

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Genotypes:

FYPO:0005751 - normal growth on Zeocin

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Genotypes:

FYPO:0004743 - normal histone H3-K9 dimethylation at centromere outer repeat during vegetative growth

References:

Genotypes:

FYPO:0002358 - normal histone H3-K9 dimethylation at silent mating-type cassette during vegetative growth

References:

Genotypes:

FYPO:0006429 - normal histone H3-K9 dimethylation at subtelomeric heterochromatin during vegetative growth

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Genotypes:

FYPO:0000833 - normal protein level during vegetative growth

References:

Genotypes:

FYPO:0002554 - normal protein localization to double-strand break site

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Genotypes:

FYPO:0004378 - normal protein localization to heterochromatin at silent mating-type cassette

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Genotypes:

FYPO:0000590 - normal sporulation

References:

Genotypes:

FYPO:0001357 - normal vegetative cell population growth

References:

Genotypes:

FYPO:0000085 - sensitive to camptothecin

References:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

References:

Genotypes:

FYPO:0000089 - sensitive to methyl methanesulfonate

References:

Genotypes:

FYPO:0000268 - sensitive to UV during vegetative growth

References:

Genotypes:

FYPO:0005750 - sensitive to Zeocin

References:

Genotypes:

FYPO:0001234 - slow vegetative cell population growth

References:

Genotypes:

FYPO:0001492 - viable elongated vegetative cell

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Genotypes:

Qualitative gene expression

PomGeneEx:0000019 - protein level decreased

References:

PomGeneEx:0000021 - protein present

References:

PomGeneEx:0000011 - RNA level increased

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Quantitative gene expression

PBO:0006310 - protein level

References:

PBO:0011963 - RNA level

References:

Single locus phenotype

FYPO:0000444 - abnormal mitotic cell cycle arrest with replicated DNA

References:

Genotypes:

FYPO:0001430 - abnormal mitotic cell cycle arrest with unreplicated DNA

References:

Genotypes:

FYPO:0002779 - abolished protein localization to nucleus, with protein mislocalized to cytoplasm, during vegetative growth

References:

Genotypes:

FYPO:0001122 - elongated vegetative cell

References:

Genotypes:

FYPO:0005752 - increased cellular dNTP level

References:

Genotypes:

FYPO:0000614 - increased duration of mitotic S phase

References:

Genotypes:

FYPO:0001974 - increased number of cells with 1C DNA content

References:

Genotypes:

FYPO:0006995 - normal chromatin silencing at centromere inner repeat

References:

Genotypes:

FYPO:0004742 - normal chromatin silencing at centromere outer repeat

References:

Genotypes:

FYPO:0002336 - normal chromatin silencing at silent mating-type cassette

References:

Genotypes:

FYPO:0003555 - normal chromatin silencing at subtelomere

References:

Genotypes:

FYPO:0001532 - normal duration of mitotic S phase

References:

Genotypes:

FYPO:0001690 - normal growth on camptothecin

References:

Genotypes:

FYPO:0001164 - normal growth on glucose carbon source

References:

Genotypes:

FYPO:0000963 - normal growth on hydroxyurea

References:

Genotypes:

FYPO:0000957 - normal growth on methyl methanesulfonate

References:

Genotypes:

FYPO:0005751 - normal growth on Zeocin

References:

Genotypes:

FYPO:0010035 - normal nuclear pore clustering during cellular response to hydroxyurea

References:

Genotypes:

FYPO:0001357 - normal vegetative cell population growth

References:

Genotypes:

FYPO:0009031 - resistance to bleomycin

References:

Genotypes:

FYPO:0000067 - resistance to brefeldin A

References:

Genotypes:

FYPO:0000764 - resistance to cycloheximide

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Genotypes:

FYPO:0002693 - resistance to diamide

References:

Genotypes:

FYPO:0009038 - resistance to egtazic acid

References:

Genotypes:

FYPO:0001453 - resistance to ethanol

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Genotypes:

FYPO:0001583 - resistance to lithium

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Genotypes:

FYPO:0009085 - resistance to lithium chloride and sodium dodecyl sulfate

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Genotypes:

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

References:

Genotypes:

FYPO:0003383 - resistance to tert-butyl hydroperoxide

References:

Genotypes:

FYPO:0006680 - sensitive to bisphenol A

References:

Genotypes:

FYPO:0000096 - sensitive to cadmium

References:

Genotypes:

FYPO:0000085 - sensitive to camptothecin

References:

Genotypes:

FYPO:0000088 - sensitive to hydroxyurea

References:

Genotypes:

FYPO:0001457 - sensitive to tunicamycin

References:

Genotypes:

FYPO:0001492 - viable elongated vegetative cell

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:0011064 - conserved in fungi

PBO:0011063 - conserved in fungi only

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

Protein features

IDNameInterPro nameDB name
PF08591RNR_inhibRNR_inhibitorPFAM
PTHR28081DAMAGE-REGULATED IMPORT FACILITATOR 1-RELATEDRNR_inhibitorPANTHER
mobidb-lite-Disorderdisorder_predictionMOBIDB-Disorder
mobidb-lite-Polardisorder_predictionMOBIDB-Polar

Orthologs

References / Literature

PMID:30154212 - Nutritional cell cycle reprogramming reveals that inhibition of Cdk1 is required for proper MBF-dependent transcription.
Rubio A et al. J Cell Sci 2018 Sep 20;131(18)
PMID:33313903 - Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.
Rubio A et al. Nucleic Acids Res 2021 Jan 11;49(1):383-399
PMID:16317005 - The Schizosaccharomyces pombe replication inhibitor Spd1 regulates ribonucleotide reductase activity and dNTPs by binding to the large Cdc22 subunit.
Håkansson P et al. J Biol Chem 2006 Jan 20;281(3):1778-83
PMID:27098497 - CRL4(Wdr70) regulates H2B monoubiquitination and facilitates Exo1-dependent resection.
Zeng M et al. Nat Commun 2016 Apr 21;7:11364
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:21183410 - Schizosaccharomyces pombe Mms1 channels repair of perturbed replication into Rhp51 independent homologous recombination.
Vejrup-Hansen R et al. DNA Repair (Amst) 2011 Mar 07;10(3):283-95
PMID:32692737 - CRL4Cdt2 ubiquitin ligase regulates Dna2 and Rad16 (XPF) nucleases by targeting Pxd1 for degradation.
Zhang JM et al. PLoS Genet 2020 Jul;16(7):e1008933
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:21123655 - Break-induced ATR and Ddb1-Cul4(Cdt)² ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast.
Moss J et al. Genes Dev 2010 Dec 01;24(23):2705-16
PMID:41259369 - Hydroxyurea induces an oxidative stress response that triggers ER expansion and cytoplasmic protein aggregation.
Sánchez-Molina A et al. PLoS Biol 2025 Nov 19;23(11):e3003493
PMID:23986475 - Spd1 accumulation causes genome instability independently of ribonucleotide reductase activity but functions to protect the genome when deoxynucleotide pools are elevated.
Fleck O et al. J Cell Sci 2013 Nov 01;126(Pt 21):4985-94
PMID:21215368 - The Cul4-Ddb1(Cdt)² ubiquitin ligase inhibits invasion of a boundary-associated antisilencing factor into heterochromatin.
Braun S et al. Cell 2011 Jan 07;144(1):41-54
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:24623809 - The DNA damage checkpoint pathway promotes extensive resection and nucleotide synthesis to facilitate homologous recombination repair and genome stability in fission yeast.
Blaikley EJ et al. Nucleic Acids Res 2014 May;42(9):5644-56
PMID:27558664 - Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.
Guo L et al. G3 (Bethesda) 2016 Oct 13;6(10):3317-3333
PMID:12695334 - Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and -independent mechanisms.
Liu C et al. Genes Dev 2003 May 01;17(9):1130-40
PMID:26771498 - A Proteome-wide Fission Yeast Interactome Reveals Network Evolution Principles from Yeasts to Human.
Vo TV et al. Cell 2016 Jan 14;164(1-2):310-323
PMID:22464192 - Ribonucleotide reductase activity is coupled to DNA synthesis via proliferating cell nuclear antigen.
Salguero I et al. Curr Biol 2012 Apr 24;22(8):720-6
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:26918805 - Consequences of abnormal CDK activity in S phase.
Anda S et al. Cell Cycle 2016;15(7):963-73
PMID:28281664 - Genetic interactions and functional analyses of the fission yeast gsk3 and amk2 single and double mutants defective in TORC1-dependent processes.
Rallis C et al. Sci Rep 2017 Mar 10;7:44257
PMID:28903048 - Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription.
Pai CC et al. Cell Rep 2017 Sep 12;20(11):2693-2705
PMID:15805471 - Ddb1 controls genome stability and meiosis in fission yeast.
Holmberg C et al. Genes Dev 2005 Apr 01;19(7):853-62
PMID:16252005 - Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase.
Liu C et al. EMBO J 2005 Nov 16;24(22):3940-51
PMID:23231582 - Genome-wide characterization of the phosphate starvation response in Schizosaccharomyces pombe.
Carter-O'Connell I et al. BMC Genomics 2012 Dec 12;13:697
PMID:24652833 - Spd2 assists Spd1 in the modulation of ribonucleotide reductase architecture but does not regulate deoxynucleotide pools.
Vejrup-Hansen R et al. J Cell Sci 2014 Jun 01;127(Pt 11):2460-70
PMID:25795664 - Genetic Interaction Landscape Reveals Critical Requirements for Schizosaccharomyces pombe Brc1 in DNA Damage Response Mutants.
Sánchez A et al. G3 (Bethesda) 2015 Mar 19;5(5):953-62
PMID:28441348 - Deoxynucleoside Salvage in Fission Yeast Allows Rescue of Ribonucleotide Reductase Deficiency but Not Spd1-Mediated Inhibition of Replication.
Fleck O et al. Genes (Basel) 2017 Apr 25;8(5)
PMID:30647105 - Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress.
Alhoch B et al. G3 (Bethesda) 2019 Mar 07;9(3):639-650
PMID:14701809 - Ddb1 is required for the proteolysis of the Schizosaccharomyces pombe replication inhibitor Spd1 during S phase and after DNA damage.
Bondar T et al. J Biol Chem 2004 Mar 12;279(11):9937-43
PMID:20537132 - Global fitness profiling of fission yeast deletion strains by barcode sequencing.
Han TX et al. Genome Biol 2010;11(6):R60
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:37970674 - SUMOylation regulates Lem2 function in centromere clustering and silencing.
Strachan J et al. J Cell Sci 2023 Dec 01;136(23)
PMID:8887552 - A novel S phase inhibitor in fission yeast.
Woollard A et al. EMBO J 1996 Sep 02;15(17):4603-12
PMID:29432178 - General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4.
Duncan CDS et al. Proc Natl Acad Sci U S A 2018 Feb 20;115(8):E1829-E1838
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:35974206 - A context-dependent and disordered ubiquitin-binding motif.
Dreier JE et al. Cell Mol Life Sci 2022 Aug 16;79(9):484
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:21511999 - Comparative functional genomics of the fission yeasts.
Rhind N et al. Science 2011 May 20;332(6032):930-6
PMID:26518661 - The Paf1 complex factors Leo1 and Paf1 promote local histone turnover to modulate chromatin states in fission yeast.
Sadeghi L et al. EMBO Rep 2015 Dec;16(12):1673-87
PMID:38261971 - Checkpoint activation by Spd1: a competition-based system relying on tandem disordered PCNA binding motifs.
Olsen JG et al. Nucleic Acids Res 2024 Jan 23;
PMID:26890608 - A functional genome-wide genetic screening identifies new pathways controlling the G1/S transcriptional wave.
Gaspa L et al. Cell Cycle 2016;15(5):720-9
PMID:27984744 - Survival in Quiescence Requires the Euchromatic Deployment of Clr4/SUV39H by Argonaute-Associated Small RNAs.
Joh RI et al. Mol Cell 2016 Dec 15;64(6):1088-1101
PMID:16407242 - An evolutionarily conserved function of proliferating cell nuclear antigen for Cdt1 degradation by the Cul4-Ddb1 ubiquitin ligase in response to DNA damage.
Hu J et al. J Biol Chem 2006 Feb 17;281(7):3753-6
PMID:24634168 - Proteome-wide search for PP2A substrates in fission yeast.
Bernal M et al. Proteomics 2014 Jun;14(11):1367-80
PMID:11069778 - The Spd1p S phase inhibitor can activate the DNA replication checkpoint pathway in fission yeast.
Borgne A et al. J Cell Sci 2000 Dec;113 Pt 23:4341-50