Annotation Priorities
- Processes relevant to the most , (especially anything related to cell cycle regulation, cancer, broadly conserved)
- Have large percentage of functionally characterised genes (for example mitochondrion organization has 40 published genes/294, so is low priority compared to cytokinesis 136/139)
- Are mature enough to be able to construct pathways/networks
- New gene characterizations -These should be sent out for community curation, but followed up
- phenotype screens see canto
- Process priorities : chromosome segregation, DNA metabolism, cytokinesis, regulation of mitotic cell cycle, any signaling pathway, chromatin organization, , cytokinesis, establishment or maintenance of cell polarity, protein modification by small protein conjugation or removal
- kinases, phosphatases, GTPAses, ubiquitin ligases, protein methylases (anything with direct substrate to improve networks)
HIGHEST priority genes/complexes/papers
mus81 | PMID:15805465 | Mus81-T239A disrupts the ability of Cds1 to bind and phosphorylate Mus81 and causes hyper-recombination upon hydroxyurea-induced replication arrest
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cdc2 | PMID:8557037 | mcs6 substrate cdc2
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cdc2 | PMID:6526270 | uniprot has this paper for allele cdc2-4w C67F (we have 'unspecified')
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Clp1 | PMID:18378776 | Clp1 in turn dephosphorylates the essential F-BAR scaffold protein Cdc15, CR assembly
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plo1 | ????? | mid is a substrate
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Sid2 | Chen et al. 2008 | phosphorylates the nonessential Cdc14 phosphatase Clp1 to foster Clp1’s cytoplasmic retention
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Mre1 complex | PMID:21008122 and papers cited within | In humans and both yeasts, DSBs are initially detected and processed by the 1Xrs2 (MRN) nucleolytic protein complex in association with the Tel1ATM checkpoint kinase and the Ctp1CtIP/Sae2 DNA-end processing factor;...implies tel1 /rad50/nbs1 should be annotated to GO:0000729 The functions of ATM and ATR orthologs are intimately tied to the detection and nucleolytic processing of DSBs. ATMTel1 localizes at DSBs by interacting with (MRN) protein complex, which directly binds DNA ends (12, 20, 24, 50, 52). use these papers to annotate the missing connection between tel1 and the mre11 complex
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crb2 | PMID:14739927 | Finally, we show direct interaction between Rad3 and Crb2, which is inhibitory to Rad3 activity (direct enzyme regulator substrate)
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crb2 | PMID:21098122 | There are two pathways that lead to Crb2 localization at sites of DNA damage (10). One pathway requires two inde- pendent histone modifications: (i) phosphorylation of the C- terminal tail of histone H2A
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Tel1 | PMID:21098122 | Tel1 phosphorylation of histone H2A at DSBs depends on its interaction with the Nbs1 subunit of MRN complex (52). (add tel1 targets as histones)
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crb2 | ???? | Find physical interaction with Rad9
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All histones | ???? | These are often not annotated with their roles in cell cycle regulation and repair, and so they are excluded from the graphs (also need to have specific nucleosome terms, 'what do you call a normal nucleosome?l' and 'centromere specific'
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srw | PMID:9571240, PMID:9736616 PMID:10921878 | has no mitotic cell cycle regulation annotation
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fnx1 & 2 | PMID: 18503766 | This wouldn't normally be a priority, but I'm putting it in becasue the exisitng transport GO annotations look a bit of a mess (stretch) ... need to get detailed phenotypes and then decide what it is possible to infer sensibly
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Scf complex | ????? | -
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scp1 | ??? | Skp1 doesn't have ubiquitin ligase activity so these MF annotations should probably be on BP
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dsc2 | ??? | activation of sre2 TF? positive regulation of SREBP signaling pathway by transcription factor cleavage? for the Dsc subunits?(may be in one of the other dsc papers though....) chung paper?
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cul1 | ????? | -
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Pad1/Rpn11 and Mts3/Rpn12 are subunits of the lid subcomplex | in PMID: 16149916 Mutations in the genes encoding these two subunits were isolated in a screen for mutants that were both esistant to methyl 2-benzimidazolecarbamate, a microtubule in- hibitor, and Ts for cell-cycle progression [19,20]. Ts mutations in both genes cause arrest of the cells in mitosis, probably because of a failure to degrade cyclin B/Cdc13 and securin/Cut2. | -
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Process priorities
Chromosome segregation (Val, but feel free to do any genes or complexes that I haven't started)
process chromosome segregation: genes 207 of which 183 published esyN
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gene/complex | status | date
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fta1 Mis6-Sim4 complex | annotation complete | 6/1/2015
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fta2 Mis6-Sim4 complex | annotation complete | 6/1/2015
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fta3 Mis6-Sim4 complex | annotation complete | 6/1/2015
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fta4 Mis6-Sim4 complex | annotation complete | 15/1/2015
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fta6 Mis6-Sim4 complex | annotation complete | 15/1/2015
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fta7 Mis6-Sim4 complex | annotation complete except CC PMID: 24789708 | 20/1/2015
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mis6 Mis6-Sim4 complex | annotation complete except CC PMID:24789708 PMID25375240 | 20/1/2015
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mis15 Mis6-Sim4 complex | annotation complete | 6/1/2015
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mal2 Mis6-Sim4 complex | PMID: 12242294 + others | -
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sim4 Mis6-Sim4 complex | annotation complete | 20/1/2015
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sos7 NMS complex | annotation complete | 6/1/2014
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spc25 NMS complex/ Ndc80 complex | annotation complete needs annotation to ndc80 complex | 20/1/2015
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spc7 NMS complex | in progress IS THIS TURNING SAC SIGNALLING OFF? PMID: 17035632 | -
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ndc80 NMS complex/Ndc80 | annotation complete needs annotation to ndc80 complex | -
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mis12 NMS complex | to do PMID:15930132 check biorientation ann | -
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mis13 NMS complex | annotation complete | 20/1/2015
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mis14 NMS complex | annotation complete | 6/1/2014
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nnf1 NMS complex | to do PMID:17035632 | -
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mis16 CENP-A recruiting complex | complete except PMID:22771823 (out for CC) and scm3 papers | -
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mis18 CENP-A recruiting complex | complete except PMID:24789708 (out for CC) | -
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mis19 CENP-A recruiting complex | complete except PMID:25375240 (out for CC) | -
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mis20 CENP-A recruiting complex | annotation complete | 20/1/2015
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nuf2 Ndc80 complex | 2 plus PMID:23770679 (out for CC) needs annotation to ndc80 complex | -
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spc24 Ndc80 complex | annotation complete needs annotation to ndc80 complex | 20/1/2015
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dad1 DASH complex | to do PMID:16079914 PMID:16079915 | -
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csm1 monopolin complex | in progress PMID: 20935472 PMID:12689592 plus… | -
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mde4 monopolin complex | TODO ONLY PMID:19523829 PMID:20723757 PMID: 22264609 | -
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mis17 | annotation complete | 6/1/2015
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cnp20 | annotation complete | 6/1/2015
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dis1 | PMID:16920624 plus… | -
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ppe1 | to do PMID: 12773390 | -|
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scm3 | to do PMID: 19217403 PMID: 19217404 (also mis16) | -
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cnp1 | in progress | -
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mal3 | in progress | -
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dad1 | PMID:17352737 | -
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cnp3 | PMID:15791413 PMID: 24449889 autonomous | -
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sds22 phoshatase | PMID: 1846086 PMID: 15335873 PMID: 8374168 | -
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cnd1 condensin complex non-SMC subunit | PMID: 18362178 | -
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cnd2 condensin complex non-SMC subunit | PMID:21633354 | -
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cnd3 condensin complex non-SMC subunit | - | -
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hos2 | PMID:17352737 plus | -
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pcs1 | PMID:20935472 plus... | -
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ams12 | chen et al, cenp-a loading | -
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nsk1 | abnormal clustering of kinetochores to spindle pole bodies | -
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cut4/apc1 anaphase-promoting complex subunit, platform subcomplex | ??? | -
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apc4/cut5 anaphase-promoting complex subunit, platform subcomplex | ??? | -
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apc5/cut5 anaphase-promoting complex subunit, platform subcomplex TPR | ??? | -
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apc15 anaphase-promoting complex subunit, platform subcomplex | ??? | -
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apc8 anaphase-promoting complex TPR lobe subcomplex | ??? | -
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cut9/apc6 anaphase-promoting complex TPR lobe subcomplex | ??? | -
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apc3 anaphase-promoting complex TPR lobe subcomplex | ??? | -
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apc12 anaphase-promoting complex subunit TPR lobe accessory factor Hcn1 | ??? | -
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apc13 anaphase-promoting complex subunit TPR lobe accessory factor | ??? | -
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apc10 anaphase-promoting complex substrate recognition subunit Apc10 | ??? | -
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apc2 anaphase-promoting complex cullin family subunit | ??? | -
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apc11 anaphase-promoting complex ubiquitin protein-ligase E3 subunit | ??? | -
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apc14 anaphase-promoting complex (might be apc16 ortholog) | ??? | -
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other chromosome segregation
dis2 phosphatase | (PMID:14765108 - describes checkpoint termination Dis2 abrogates Chk1 phosphorylation and activation in vivo, ) PMID:2245912 PMID:8389306 PMID:8305731 PMID:7983142 PMID:7957097 PMID:9264466 PMID:9790575 PMID:10668632 PMID:11085271 PMID:16411888 PMID:17895368 PMID:19592249 PMID:21664573 (Out for CC PMID:21703453 PMID:21965289 PMID:23333317) (Iain Hagan PMID:25487150) | -
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dis1 | XMAP215/ TOG/Stu2-family homolog, binds microtubules and localizes to kinetochores (Nakaseko et al., 2001). Mutants in dis1 lack the chromosome alignment phase in metaphase and arrest with elongated spindles and segregated but unseparated chromosome pairs (Nabe- shima et al., 1998; Ohkura et al., 1988).dis1 mutants arrest with an activated spindle checkpoint and appear to ex- perience an increase in sister chromatid cosegregation (70%) at full restrictive temperature. Such cosegregation results when mono-oriented attachment of sister kineto- chores to microtubules from the same SPB is not corrected. Since dis1 mutants lack the phase of constant spindle length when chromosomes are properly aligned
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Notes and annotation questions on chromosome segregation
- read review PMID: 23512483
- is CENP-A containing nucleosome assembly part of kinetochore assembly? Although the outer repeats play an important role in sister centromere cohesion and possibly help to properly orient the multiple kinetochore microtubule attachment sites (Pidoux and Allshire, 2004
- Centromeres: getting a grip of chromosomes. Curr. Opin. Cell Biol. 12, 308–319., the central region is needed for the assembly of the kinetochore per se and the interaction with the mitotic spindle fibers
- what is the relationship between kinetochoe assembly, spindle elongation and chromosome segregation (currently disjoint)
- reannotate ndc80 and MIND subcomplexes annotate PAS complex
- ask expert to look at CENP_A assembly vs CENP-A assembly phenotype
- no substrates currently annotated for APC, look for motifs ABBA, KENm D-Box, C-BOX, F-box, 2BR, LRRL
- I think from humanUbc11 is the APC E2, has some substrates assigned (cdc13 direct, slp1 indirect), but sc imlies ubc4 and ubc1 (amybe all)
- possible substrates to annotate mitotic securin and cylin; late mitosis cdh1 , cytokinesis aurora, cyclins, cdc29; G1 geminin, cdc6, skp2,ubcH10(ubc11)
Cytokinesis but feel free to do any genes or complexes that I haven't started
process cytokinesis: 139 of which 136 published esyN
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gene/complex | status | date
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lsk1 | in progress | -
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mac1 | annotation complete | 22/1/2014
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lkh1 | chained 12565823 | -
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Notes and annotation questions on cytokinesis
- previously considered to be linear assembly mid1- rng2- others. But if you can ectopically localize rng2 you can get all of the others (any one of the 3 will work)
check should mid1 be ring assemlby or localization only?
check mid1 NOT assembly? positioning main target of mid1 is rng2 | rng3- myosin specific chaperone add to wiki with mohan paper details
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Regulation of mitotic cell cycle
process regulation of mitotic cell cycle: l genes 258 of which 231 published esyN
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gene/complex | status | date
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psk1 | annotation complete (except PMID: 22976295 out for CC) | 16/2/2015
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Notes and annotation questions on cell cycle regulation
- Only include gene products here not covered in chromosome segregation, cytokinesis or DNA metabolism
- genes which should be annotated to "signalling" based on the signalling components of the cell cycle regulation network
- Need to do cytokinesis checkpoint, G1 cell size control checkpoint, DNA damage checkpoint (ask experts to check specific checkpoint lists)
Misc other annotation complete
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gene/complex | status | date
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mcp60 | annotation complete | 16/2/2015
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