TIM_CAEEL
ID TIM_CAEEL Reviewed; 1353 AA.
AC G5EDN3;
DT 04-MAR-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Protein timeless homolog {ECO:0000250|UniProtKB:Q9R1X4};
GN Name=tim-1 {ECO:0000312|WormBase:Y75B8A.22};
GN Synonyms=csg-5 {ECO:0000312|WormBase:Y75B8A.22};
GN ORFNames=Y75B8A.22 {ECO:0000312|WormBase:Y75B8A.22};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:AAF13189.1};
RN [1] {ECO:0000312|EMBL:AAF13189.1}
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAF13189.1};
RX PubMed=10550049; DOI=10.1126/science.286.5442.1141;
RA Jeon M., Gardner H.F., Miller E.A., Deshler J., Rougvie A.E.;
RT "Similarity of the C. elegans developmental timing protein LIN-42 to
RT circadian rhythm proteins.";
RL Science 286:1141-1146(1999).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION
RP PHENOTYPE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12827206; DOI=10.1038/nature01697;
RA Chan R.C., Chan A., Jeon M., Wu T.F., Pasqualone D., Rougvie A.E.,
RA Meyer B.J.;
RT "Chromosome cohesion is regulated by a clock gene paralogue TIM-1.";
RL Nature 423:1002-1009(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15691769; DOI=10.1016/j.devcel.2004.12.006;
RA Banerjee D., Kwok A., Lin S.-Y., Slack F.J.;
RT "Developmental timing in C. elegans is regulated by kin-20 and tim-1,
RT homologs of core circadian clock genes.";
RL Dev. Cell 8:287-295(2005).
CC -!- FUNCTION: Plays an important role in chromosome cohesion during both
CC mitosis and meiosis (PubMed:12827206). In prophase of meiosis, it is
CC involved in the formation of the synaptonemal complex (SC) and
CC specifically, in the diplotene and diakinesis phases of prophase, it
CC stabilizes the association of homologous chromosomes during synapsis
CC and sister chromatid cohesion (PubMed:12827206). It regulates cohesin
CC subunits to promote meiotic chromosome cohesion and localizes non-SMC
CC (structural maintenance of chromosome) cohesin subunits to chromatin
CC prior to or during pre-meiotic S phase (PubMed:12827206). Implicated in
CC influencing either the stability or loading of meiotic-specific cohesin
CC subunit, rec8 (PubMed:12827206). Controls cell cycle exit and cell
CC fusion to prevent the premature differentiation into adult cells
CC (PubMed:15691769). Specifically, regulates hypodermal seam cell
CC identity (PubMed:15691769). {ECO:0000269|PubMed:12827206,
CC ECO:0000269|PubMed:15691769}.
CC -!- SUBUNIT: Associates with the cohesin complex (PubMed:12827206).
CC Interacts with smc-1, smc-3, scc-1 and scc-3 (PubMed:12827206).
CC {ECO:0000269|PubMed:12827206}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10550049,
CC ECO:0000269|PubMed:12827206}.
CC -!- DEVELOPMENTAL STAGE: Expression is increased during late postembryonic
CC development (PubMed:10550049). In embryos, there is diffuse nuclear
CC expression at interphase, but this reduces by the metaphase-anaphase
CC transition (PubMed:12827206). There is diffuse expression in pre-
CC meiotic germline nuclei as the nuclei enter meiotic prophase and later
CC in the diplotene and diakinesis phases of prophase (PubMed:12827206).
CC {ECO:0000269|PubMed:10550049, ECO:0000269|PubMed:12827206}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown is embryonic lethal
CC (PubMed:12827206). In germline cells, aberrant segregation of
CC chromosomes is observed during both mitosis and meiosis, resulting in
CC aneuploidy (PubMed:12827206). There is a weaker mitosis phenotype in
CC somatic tissues (PubMed:12827206). Weak seam cell differentiation
CC capacity during the L4 larval development stage, including 30%
CC increased seam cell fusion and reduced cell cycle exit
CC (PubMed:15691769). RNAi-mediated knockdown increases the survival rate
CC and partially restores alae formation of let-7 n2853 mutants at 20
CC dgrees Celsius (PubMed:15691769). {ECO:0000269|PubMed:12827206,
CC ECO:0000269|PubMed:15691769}.
CC -!- SIMILARITY: Belongs to the timeless family. {ECO:0000305}.
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DR EMBL; AF183401; AAF13189.1; -; mRNA.
DR EMBL; BX284603; CAA22106.3; -; Genomic_DNA.
DR PIR; T27404; T27404.
DR RefSeq; NP_499594.2; NM_067193.5.
DR AlphaFoldDB; G5EDN3; -.
DR STRING; 6239.Y75B8A.22.2; -.
DR EPD; G5EDN3; -.
DR PaxDb; G5EDN3; -.
DR PeptideAtlas; G5EDN3; -.
DR PRIDE; G5EDN3; -.
DR EnsemblMetazoa; Y75B8A.22.1; Y75B8A.22.1; WBGene00006571.
DR EnsemblMetazoa; Y75B8A.22.2; Y75B8A.22.2; WBGene00006571.
DR GeneID; 176652; -.
DR KEGG; cel:CELE_Y75B8A.22; -.
DR CTD; 176652; -.
DR WormBase; Y75B8A.22; CE23033; WBGene00006571; tim-1.
DR eggNOG; KOG1974; Eukaryota.
DR GeneTree; ENSGT00390000015124; -.
DR HOGENOM; CLU_003493_2_0_1; -.
DR InParanoid; G5EDN3; -.
DR OMA; QGPEECG; -.
DR OrthoDB; 839367at2759; -.
DR PhylomeDB; G5EDN3; -.
DR PRO; PR:G5EDN3; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00006571; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0031298; C:replication fork protection complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IBA:GO_Central.
DR GO; GO:0000076; P:DNA replication checkpoint signaling; IBA:GO_Central.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0051177; P:meiotic sister chromatid cohesion; IMP:WormBase.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IMP:WormBase.
DR GO; GO:0007063; P:regulation of sister chromatid cohesion; IMP:WormBase.
DR GO; GO:0043111; P:replication fork arrest; IBA:GO_Central.
DR GO; GO:0048478; P:replication fork protection; IBA:GO_Central.
DR InterPro; IPR044998; Timeless.
DR InterPro; IPR006906; Timeless_N.
DR PANTHER; PTHR22940; PTHR22940; 1.
DR Pfam; PF04821; TIMELESS; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cell division; Developmental protein; Meiosis; Mitosis;
KW Nucleus; Reference proteome.
FT CHAIN 1..1353
FT /note="Protein timeless homolog"
FT /id="PRO_0000432381"
FT REGION 798..825
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1150..1291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1306..1335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 802..825
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1150..1184
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1185..1204
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1205..1239
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1272..1291
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1353 AA; 157011 MW; 6A0F730A7912A3EE CRC64;
MNVLVQGAVH ALGYYEDGKY SREPDCYESI RDLIRYLRED GDDHTARIEC GRHNLVEQDL
VPMVKCEDLT DDEFDIAIRL MVNLCQPAIS TMRGKPPADR DQWKMYWELE ENLRRAKTAF
SDAHFFTAIK KRIDNYFIDT EYEDRDERLR LVVERIVLLI KYVFSINPDT SEGRRTRIED
SSHDRVIIAF LESGIDKTLM HIANQPREKE FHVTILDIFA LILKEQTAED LATKSEEVST
AEQKKTEEEF RKIIENHVVK ETQKRKSFSR FGGSYTIKGL KGISANSSQV VFKPIQNVEK
HNFLDDRKAK KRAPRNRRPF EIDTNSHFAS SEVRGMLRDM VIRIIETCFN RLMKSSKTTV
FVQVQKTSQI NYFFLIKFVL RFVRLSRQDH LLERISECIG VEAFHENNVQ LTEYVENATT
LKGVEAKSHG LKAQYALGAY NELVLLHRYI YEHAKEENER KFAKRALEHI VNVEEYRELP
IFIIKKFSSS VLSNNFLREL VLTTHHYMKL VERFVKTGAL KKVTKKVKVR KATKKSKMSE
EDVRSEFDGM SKKDLDRLWE ESKGLVLQIL KKEVPEMRGM NPIDSQLDVP VDAQQKFAKL
SIQRSLRSRG FPAAVGLYHA SRALWPESFK RGLTDFQDSP GEEDQLQELE QLLKADMKKV
AKDLKKAESC KTCDEDPAYK KYDKMDATAL QSLWEQSTDT LARILSHELP ESESTSPVNW
QLDITPDVQQ KFAMLAIQRA LRARDLPAAV GLYHTSRKLW PGDEAIFGAP GIGVEEEIAE
LKAILEADLH EVAREMKVAE DRAEDPDEED PAEPYDSEQE EEEEVPAWKV EEIDFQFDSY
VCKFSNVDVL KWYVFLLNDF SKNSTELNQA LVKMLHRIAF DLKLPIKLYQ VSLFQVFSKV
NEHFTHLSKD LRKSSRLYEL YQFGFHLLKK FFSKFTGDLA IEALFWKGPR ECFEIENGYG
SWVKSREADI RVWTEDLEIE LRNLYEEYRT METRDGIDVL DFIEHNLSRA RSRKKVAKKL
IEFGFDLLGA KWKNSDKARM DSVLPIGDIQ KWYDEWKEAG ARGDLVNVLQ EKLNEDLGME
ISRKKILKQL AHMDILYEKP KKEKPLPQWD TGLIEELKKL KEQYDDIPDA LNMLGVNIVR
YVMKRLSEKK PTRQVERHLE SLGATIPERS KKSEKNGKKF DDFLNDDDDD SENDVGGGSE
DDEEEEIVMK SKRIIPDSED EEEHIEQEEA QKKLEKVAEK PNTLMGMIAG RKRKLAQLES
DSSDESDDDD SAEKEEKKLP AAEDDSDLEE DAVIYKRSYV DALLTGGSIA GNGITETRRD
TSEEREDDDD EDPFTKKLTF KRRIVMSDNE DEA
