LIN35_CAEEL
ID LIN35_CAEEL Reviewed; 961 AA.
AC G5EDT1;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Retinoblastoma-like protein homolog lin-35 {ECO:0000305};
DE AltName: Full=Abnormal cell lineage protein 35 {ECO:0000312|WormBase:C32F10.2};
DE AltName: Full=Synthetic multivulva protein lin-35 {ECO:0000305};
GN Name=lin-35 {ECO:0000312|WormBase:C32F10.2};
GN ORFNames=C32F10.2 {ECO:0000312|WormBase:C32F10.2};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAD05570.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH LIN-53, SUBCELLULAR
RP LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=9875852; DOI=10.1016/s0092-8674(00)81722-5;
RA Lu X., Horvitz H.R.;
RT "lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway,
RT encode proteins similar to Rb and its binding protein RbAp48.";
RL Cell 95:981-991(1998).
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, AND DISRUPTION PHENOTYPE.
RX PubMed=11684669; DOI=10.1242/dev.128.21.4349;
RA Boxem M., van den Heuvel S.;
RT "lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1
RT progression in C. elegans.";
RL Development 128:4349-4359(2001).
RN [4] {ECO:0000305}
RP INTERACTION WITH DPL-1 AND EFL-1.
RX PubMed=11463372; DOI=10.1016/s1097-2765(01)00194-0;
RA Ceol C.J., Horvitz H.R.;
RT "dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in
RT C.elegans vulval development.";
RL Mol. Cell 7:461-473(2001).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=12062054; DOI=10.1016/s0960-9822(02)00844-8;
RA Boxem M., van den Heuvel S.;
RT "C. elegans class B synthetic multivulva genes act in G(1) regulation.";
RL Curr. Biol. 12:906-911(2002).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=11850412; DOI=10.1101/gad.952302;
RA Fay D.S., Keenan S., Han M.;
RT "fzr-1 and lin-35/Rb function redundantly to control cell proliferation in
RT C. elegans as revealed by a nonbiased synthetic screen.";
RL Genes Dev. 16:503-517(2002).
RN [7] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 151-TRP--ASP-961.
RX PubMed=12783801; DOI=10.1242/dev.00561;
RA Fay D.S., Large E., Han M., Darland M.;
RT "lin-35/Rb and ubc-18, an E2 ubiquitin-conjugating enzyme, function
RT redundantly to control pharyngeal morphogenesis in C. elegans.";
RL Development 130:3319-3330(2003).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=15315757; DOI=10.1016/j.cell.2004.07.026;
RA Reddy K.C., Villeneuve A.M.;
RT "C. elegans HIM-17 links chromatin modification and competence for
RT initiation of meiotic recombination.";
RL Cell 118:439-452(2004).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15196946; DOI=10.1016/j.ydbio.2004.03.022;
RA Fay D.S., Qiu X., Large E., Smith C.P., Mango S., Johanson B.L.;
RT "The coordinate regulation of pharyngeal development in C. elegans by lin-
RT 35/Rb, pha-1, and ubc-18.";
RL Dev. Biol. 271:11-25(2004).
RN [10] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15328017; DOI=10.1016/j.ydbio.2004.06.009;
RA Bender A.M., Wells O., Fay D.S.;
RT "lin-35/Rb and xnp-1/ATR-X function redundantly to control somatic gonad
RT development in C. elegans.";
RL Dev. Biol. 273:335-349(2004).
RN [11] {ECO:0000305}
RP FUNCTION.
RX PubMed=15238519; DOI=10.1534/genetics.103.026021;
RA Garbe D., Doto J.B., Sundaram M.V.;
RT "Caenorhabditis elegans lin-35/Rb, efl-1/E2F and other synthetic multivulva
RT genes negatively regulate the anaphase-promoting complex gene mat-3/APC8.";
RL Genetics 167:663-672(2004).
RN [12] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15280233; DOI=10.1534/genetics.103.024554;
RA Cui M., Fay D.S., Han M.;
RT "lin-35/Rb cooperates with the SWI/SNF complex to control Caenorhabditis
RT elegans larval development.";
RL Genetics 167:1177-1185(2004).
RN [13] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15649460; DOI=10.1016/j.ydbio.2004.10.014;
RA Cardoso C., Couillault C., Mignon-Ravix C., Millet A., Ewbank J.J.,
RA Fontes M., Pujol N.;
RT "XNP-1/ATR-X acts with RB, HP1 and the NuRD complex during larval
RT development in C. elegans.";
RL Dev. Biol. 278:49-59(2005).
RN [14] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=15621535; DOI=10.1016/j.devcel.2004.11.015;
RA Myers T.R., Greenwald I.;
RT "lin-35 Rb acts in the major hypodermis to oppose ras-mediated vulval
RT induction in C. elegans.";
RL Dev. Cell 8:117-123(2005).
RN [15] {ECO:0000305}
RP INTERACTION WITH LIN-8.
RX PubMed=16020796; DOI=10.1534/genetics.104.034173;
RA Davison E.M., Harrison M.M., Walhout A.J., Vidal M., Horvitz H.R.;
RT "lin-8, which antagonizes Caenorhabditis elegans Ras-mediated vulval
RT induction, encodes a novel nuclear protein that interacts with the LIN-35
RT Rb protein.";
RL Genetics 171:1017-1031(2005).
RN [16] {ECO:0000305}
RP FUNCTION.
RX PubMed=16287966; DOI=10.1073/pnas.0508989102;
RA Grishok A., Sharp P.A.;
RT "Negative regulation of nuclear divisions in Caenorhabditis elegans by
RT retinoblastoma and RNA interference-related genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17360-17365(2005).
RN [17] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16624904; DOI=10.1534/genetics.106.056465;
RA Ceol C.J., Stegmeier F., Harrison M.M., Horvitz H.R.;
RT "Identification and classification of genes that act antagonistically to
RT let-60 Ras signaling in Caenorhabditis elegans vulval development.";
RL Genetics 173:709-726(2006).
RN [18] {ECO:0000305}
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=16507136; DOI=10.1186/gb-2006-7-1-r4;
RA Lehner B., Calixto A., Crombie C., Tischler J., Fortunato A., Chalfie M.,
RA Fraser A.G.;
RT "Loss of LIN-35, the Caenorhabditis elegans ortholog of the tumor
RT suppressor p105Rb, results in enhanced RNA interference.";
RL Genome Biol. 7:R4.1-R4.10(2006).
RN [19] {ECO:0000305}
RP FUNCTION, AND IDENTIFICATION IN THE DRM COMPLEX.
RX PubMed=17075059; DOI=10.1073/pnas.0608461103;
RA Harrison M.M., Ceol C.J., Lu X., Horvitz H.R.;
RT "Some C. elegans class B synthetic multivulva proteins encode a conserved
RT LIN-35 Rb-containing complex distinct from a NuRD-like complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16782-16787(2006).
RN [20] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17417969; DOI=10.1186/1471-213x-7-30;
RA Ceron J., Rual J.F., Chandra A., Dupuy D., Vidal M., van den Heuvel S.;
RT "Large-scale RNAi screens identify novel genes that interact with the C.
RT elegans retinoblastoma pathway as well as splicing-related components with
RT synMuv B activity.";
RL BMC Dev. Biol. 7:30-30(2007).
RN [21] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17466069; DOI=10.1186/1471-213x-7-38;
RA Ouellet J., Roy R.;
RT "The lin-35/Rb and RNAi pathways cooperate to regulate a key cell cycle
RT transition in C. elegans.";
RL BMC Dev. Biol. 7:38-38(2007).
RN [22] {ECO:0000305}
RP FUNCTION.
RX PubMed=17881492; DOI=10.1242/dev.004606;
RA Schertel C., Conradt B.;
RT "C. elegans orthologs of components of the RB tumor suppressor complex have
RT distinct pro-apoptotic functions.";
RL Development 134:3691-3701(2007).
RN [23] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17070797; DOI=10.1016/j.ydbio.2006.09.051;
RA Bender A.M., Kirienko N.V., Olson S.K., Esko J.D., Fay D.S.;
RT "lin-35/Rb and the CoREST ortholog spr-1 coordinately regulate vulval
RT morphogenesis and gonad development in C. elegans.";
RL Dev. Biol. 302:448-462(2007).
RN [24] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17237514; DOI=10.1534/genetics.106.068148;
RA Reddien P.W., Andersen E.C., Huang M.C., Horvitz H.R.;
RT "DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein
RT to promote programmed cell death in Caenorhabditis elegans.";
RL Genetics 175:1719-1733(2007).
RN [25] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18437219; DOI=10.1371/journal.pgen.1000059;
RA Kirienko N.V., McEnerney J.D., Fay D.S.;
RT "Coordinated regulation of intestinal functions in C. elegans by LIN-35/Rb
RT and SLR-2.";
RL PLoS Genet. 4:E1000059-E1000059(2008).
RN [26] {ECO:0000305}
RP FUNCTION.
RX PubMed=19521497; DOI=10.1371/journal.pgen.1000510;
RA Mani K., Fay D.S.;
RT "A mechanistic basis for the coordinated regulation of pharyngeal
RT morphogenesis in Caenorhabditis elegans by LIN-35/Rb and UBC-18-ARI-1.";
RL PLoS Genet. 5:E1000510-E1000510(2009).
RN [27] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22542970; DOI=10.1534/genetics.112.140152;
RA Polley S.R., Fay D.S.;
RT "A network of genes antagonistic to the LIN-35 retinoblastoma protein of
RT Caenorhabditis elegans.";
RL Genetics 191:1367-1380(2012).
RN [28] {ECO:0000305}
RP FUNCTION.
RX PubMed=23664972; DOI=10.1016/j.cub.2013.04.046;
RA Cui M., Cohen M.L., Teng C., Han M.;
RT "The tumor suppressor Rb critically regulates starvation-induced stress
RT response in C. elegans.";
RL Curr. Biol. 23:975-980(2013).
RN [29] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23347407; DOI=10.1186/gb-2013-14-1-r5;
RA Kudron M., Niu W., Lu Z., Wang G., Gerstein M., Snyder M., Reinke V.;
RT "Tissue-specific direct targets of Caenorhabditis elegans Rb/E2F dictate
RT distinct somatic and germline programs.";
RL Genome Biol. 14:R5.1-R5.17(2013).
RN [30] {ECO:0000305}
RP FUNCTION.
RX PubMed=24214340; DOI=10.1534/genetics.113.158485;
RA Polley S.R., Kuzmanov A., Kuang J., Karpel J., Lazetic V., Karina E.I.,
RA Veo B.L., Fay D.S.;
RT "Implicating SCF complexes in organogenesis in Caenorhabditis elegans.";
RL Genetics 196:211-223(2014).
RN [31] {ECO:0000305}
RP FUNCTION.
RX PubMed=24752899; DOI=10.1128/mcb.01532-13;
RA Lascarez-Lagunas L.I., Silva-Garcia C.G., Dinkova T.D., Navarro R.E.;
RT "LIN-35/Rb causes starvation-induced germ cell apoptosis via CED-9/Bcl2
RT downregulation in Caenorhabditis elegans.";
RL Mol. Cell. Biol. 34:2499-2516(2014).
RN [32] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24715729; DOI=10.1073/pnas.1321698111;
RA Kozlowski L., Garvis S., Bedet C., Palladino F.;
RT "The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER
RT homeostasis through the UPR and hormesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:5956-5961(2014).
RN [33] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26100681; DOI=10.1534/g3.115.019257;
RA Kelly A.L., Senter-Zapata M.J., Campbell A.C., Lust H.E., Theriault M.E.,
RA Andralojc K.M., Updike D.L.;
RT "A forward genetic screen for suppressors of somatic P granules in
RT Caenorhabditis elegans.";
RL G3 (Bethesda) 5:2209-2215(2015).
RN [34] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-714 AND THR-719, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=25562820; DOI=10.1038/ncomms6906;
RA The I., Ruijtenberg S., Bouchet B.P., Cristobal A., Prinsen M.B.,
RA van Mourik T., Koreth J., Xu H., Heck A.J., Akhmanova A., Cuppen E.,
RA Boxem M., Munoz J., van den Heuvel S.;
RT "Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and
RT human cancer cells.";
RL Nat. Commun. 6:5906-5906(2015).
RN [35] {ECO:0000305}
RP FUNCTION.
RX PubMed=27104746; DOI=10.1080/15384101.2016.1146839;
RA Lee Y.U., Son M., Kim J., Shim Y.H., Kawasaki I.;
RT "CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression
RT of intestinal divisions.";
RL Cell Cycle 15:654-666(2016).
RN [36]
RP DISRUPTION PHENOTYPE.
RX PubMed=27650246; DOI=10.1038/srep33884;
RA Al-Amin M., Min H., Shim Y.H., Kawasaki I.;
RT "Somatically expressed germ-granule components, PGL-1 and PGL-3, repress
RT programmed cell death in C. elegans.";
RL Sci. Rep. 6:33884-33884(2016).
CC -!- FUNCTION: Key regulator of cell division which acts as a
CC transcriptional repressor and negatively regulates cell cycle
CC progression in its active unphosphorylated form, but allows cell cycle
CC progression when phosphorylated (PubMed:11684669, PubMed:12062054,
CC PubMed:16287966, PubMed:17466069, PubMed:25562820). When
CC unphosphorylated and in its active form, interacts with E2F
CC transcription factors such as efl-1 to repress their transcriptional
CC activity and negatively regulate the progression through the G1 phase
CC of the cell cycle during postembryonic development (PubMed:11684669,
CC PubMed:12062054, PubMed:15238519, PubMed:17466069, PubMed:25562820).
CC May furthermore act with cell cycle regulator cki-1 to negatively
CC regulate cell cycle progression (PubMed:11684669). Acts redundantly
CC with lin-53, fzr-1 and lin-23 to control cell cycle progression by
CC regulating the expression of G1 phase cyclins (PubMed:11850412,
CC PubMed:25562820). In particular, negatively regulates the expression of
CC the cyclin E homolog cye-1, which is essential for the G1/S phase
CC transition (PubMed:16287966, PubMed:17466069). Regulates cell division
CC in the intestinal lineage, repressing the expression of genes such as
CC cdc-25.2, which are required for intestinal cells to transition from
CC the karyokinesis cell cycle (also known as nuclear division) to
CC endoreplication, a specific growth pathway in the intestinal epithelium
CC required for feeding and gut development in growing larvae during the
CC L1 stage molt (PubMed:17466069, PubMed:27104746). Its role as a
CC transcriptional repressor in the regulation of intestinal cell division
CC during postembryonic development is most likely in complex with an E2F
CC cell cycle regulatory transcription factor efl-1 and its binding
CC partner the synthetic multivulva class B protein dpl-1
CC (PubMed:17466069). Synthetic multivulva (synMuv) class B protein
CC (PubMed:9875852, PubMed:11850412). SynMuv proteins are required to
CC repress the induction of vulval development by Ras signaling and
CC probably act by forming the multiprotein DRM complex that represses
CC transcription (PubMed:9875852, PubMed:17075059). Together with synMuv
CC class B protein lin-53, and redundantly with synMuv class A protein
CC lin-15A, represses transcription to control vulval development, most
CC likely through antagonization of the Ras-signaling pathway in the major
CC hypodermal syncytium hyp7 (PubMed:9875852, PubMed:15621535,
CC PubMed:16624904, PubMed:26100681). Acts redundantly with the
CC transcriptional corepressor spr-1 and the zinc finger protein zfp-2 to
CC play a role in vulval morphogenesis, promote germline proliferation and
CC somatic gonad development (PubMed:17417969, PubMed:17070797). Acts
CC redundantly with ubc-18 in the regulation of pharyngeal morphogenesis
CC during embryonic develpment by negatively regulating the expression of
CC proteins such as sup-35 (PubMed:12783801, PubMed:19521497,
CC PubMed:24214340). Functions with the SWI/SNF complex and proteins such
CC as pha-1 to regulate larval development (PubMed:15196946,
CC PubMed:15280233). Functions redundantly with xnp-1 to regulate somatic
CC gonad development (PubMed:15328017, PubMed:15649460). Acts redundantly
CC with slr-2 to regulate the expression of intestinal genes required for
CC nutrient utilization (PubMed:18437219, PubMed:22542970). Regulates
CC transcription in response to starvation (PubMed:23664972). Furthermore,
CC in response to starvation, promotes germ cell programmed cell death by
CC negatively regulating the expression of the anti-apoptotic protein ced-
CC 9 (PubMed:17881492, PubMed:24752899). Conversely, in conjunction with
CC mcd-1, efl-1 and the synthetic multivulva class B proteins dpl-1, lin-
CC 37 and lin-52, may also regulate transcription to promote programmed
CC cell death independently of ced-1, ced-8 and ced-9 cell death pathways
CC (PubMed:17237514). Directly involved in heterochromatin formation by
CC maintaining overall chromatin structure and, in particular, that of
CC constitutive heterochromatin by stabilizing histone methylation
CC (PubMed:23347407). In particular, negatively regulates the expression
CC of mes-4, a histone methyltransferase that controls the expression of
CC germline specific genes (PubMed:23347407). May play a role in double
CC strand break formation during meiosis (PubMed:15315757). May suppress
CC sensitivity to RNAi (PubMed:16507136, PubMed:17417969). May play a role
CC in the response to endoplasmic reticulum (ER) stress (PubMed:24715729).
CC {ECO:0000269|PubMed:11684669, ECO:0000269|PubMed:11850412,
CC ECO:0000269|PubMed:12062054, ECO:0000269|PubMed:12783801,
CC ECO:0000269|PubMed:15196946, ECO:0000269|PubMed:15280233,
CC ECO:0000269|PubMed:15328017, ECO:0000269|PubMed:15621535,
CC ECO:0000269|PubMed:15649460, ECO:0000269|PubMed:16287966,
CC ECO:0000269|PubMed:16624904, ECO:0000269|PubMed:17070797,
CC ECO:0000269|PubMed:17075059, ECO:0000269|PubMed:17237514,
CC ECO:0000269|PubMed:17417969, ECO:0000269|PubMed:17466069,
CC ECO:0000269|PubMed:17881492, ECO:0000269|PubMed:18437219,
CC ECO:0000269|PubMed:19521497, ECO:0000269|PubMed:22542970,
CC ECO:0000269|PubMed:23347407, ECO:0000269|PubMed:23664972,
CC ECO:0000269|PubMed:24214340, ECO:0000269|PubMed:24752899,
CC ECO:0000269|PubMed:25562820, ECO:0000269|PubMed:26100681,
CC ECO:0000269|PubMed:27104746, ECO:0000269|PubMed:9875852,
CC ECO:0000305|PubMed:15315757, ECO:0000305|PubMed:16507136,
CC ECO:0000305|PubMed:24715729}.
CC -!- SUBUNIT: Component of the DRM complex, at least composed of lin-9, lin-
CC 35, lin-37, lin-52, lin-53, lin-54, dpl-1 and efl-1 (PubMed:17075059).
CC Interacts with lin-53 (PubMed:9875852). Interacts (via C-terminus) with
CC dpl-1 (via C-terminus) and efl-1 (via C-terminus) (PubMed:11463372).
CC Interacts (via C-terminus) with lin-8 (PubMed:16020796).
CC {ECO:0000269|PubMed:11463372, ECO:0000269|PubMed:16020796,
CC ECO:0000269|PubMed:17075059, ECO:0000269|PubMed:9875852}.
CC -!- INTERACTION:
CC G5EDT1; Q22703: dpl-1; NbExp=2; IntAct=EBI-321470, EBI-324825;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15621535,
CC ECO:0000269|PubMed:23347407, ECO:0000269|PubMed:25562820,
CC ECO:0000269|PubMed:9875852}. Note=Expressed in dividing cells, but
CC decreased expression after cell cycle exit.
CC {ECO:0000269|PubMed:25562820}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos and newly hatched L1 larvae
CC (PubMed:9875852). In older larvae and adults expressed in P(3-8).p
CC vulval precursor cells and its descendents (PubMed:9875852). Expressed
CC in the major hypodermal syncytium hyp7 during the L3 stage of larval
CC development (PubMed:15621535). {ECO:0000269|PubMed:15621535,
CC ECO:0000269|PubMed:9875852}.
CC -!- PTM: Phosphorylated by the cyclin dependent kinase cdk-4.
CC Phosphorylation inhibits the transcriptional repressor activity of lin-
CC 35 and allows for progression through the G1 phase of the cell cycle
CC during postembryonic development. {ECO:0000269|PubMed:25562820}.
CC -!- DISRUPTION PHENOTYPE: Viable, but with a reduced fertility and brood
CC size (PubMed:11684669, PubMed:15328017, PubMed:15280233,
CC PubMed:17417969). Low penetrance defects including reduced integrity of
CC the proximal gonad, a low percentage of endomitotic oocytes, distal tip
CC cell migration defects and abnormalities in vulval morphology
CC (PubMed:17417969). Some studies demonstrate aberrant intestinal nuclear
CC divisions, with increased intestinal nuclei in growing larvae
CC (PubMed:17466069). In addition there is increased sensitivity to RNA-
CC induced gene silencing by RNAi (PubMed:16507136, PubMed:17417969).
CC RNAi-mediated knockdown results in increased survival in response to ER
CC stress inducer tunicamycin as compared to wild-type animals
CC (PubMed:24715729). RNAi-mediated knockdown results in larval arrest at
CC 25 degrees Celsius in an xpn-1 mutant background (PubMed:15649460).
CC RNAi-mediated knockdown in a ced-1 mutant background results in reduced
CC somatic cell apoptosis (PubMed:27650246). Double knockout with the
CC synthetic multivulva class B protein lin-15A results in a multiple
CC vulva (Muv) phenotype (PubMed:16624904, PubMed:26100681). Double
CC knockout with either cdk-4 or cyd-1 rescues the cell cycle progression
CC defect in the single cdk-4 and cyd-1 mutants (PubMed:11684669,
CC PubMed:25562820). Double knockout with xnp-1 results in 43% embryonic
CC lethality (PubMed:15328017). Surviving animals develop slowly, are
CC small, sterile and display male and female gonad developmental defects
CC characterized by shorter gonadal arms, fewer germ cells, an everted
CC vulva phenotype, and failed formation of sheath and spermathecal cells
CC (PubMed:15328017). Double knockout with spr-1 or zfp-2 results in
CC defects in growth, vulval morphogenesis, somatic gonad development and
CC fertility (PubMed:17417969, PubMed:17070797). Double knockout with the
CC programmed cell death regulator mcd-1 results in 100% lethality during
CC the L1 stage of larval development (PubMed:17237514). Programmed cell
CC death defect in a ced-3 n2427 mutant background (PubMed:17237514).
CC Knockout with RNAi-mediated knockdown of psa-1, ham-3, swsn-2.2, swsn-3
CC or swsn-6 (components of the SWI/SNF complex) results in larval arrest
CC during larval development (PubMed:15280233). Knockout with RNAi-
CC mediated knockdown of pha-1 (developmental protein), snfc-5 or swsn-8
CC (additional SWI/SNF complex components) results in sterility and/or a
CC protruding vulva phenotype (PubMed:15196946, PubMed:15280233). Double
CC knockout with slr-2 results in early larval arrest due to mis-
CC regulation of intestinal specific gene expression, which results in
CC starvation-induced growth arrest (PubMed:18437219, PubMed:22542970).
CC {ECO:0000269|PubMed:11684669, ECO:0000269|PubMed:15196946,
CC ECO:0000269|PubMed:15280233, ECO:0000269|PubMed:15328017,
CC ECO:0000269|PubMed:15649460, ECO:0000269|PubMed:16507136,
CC ECO:0000269|PubMed:16624904, ECO:0000269|PubMed:17070797,
CC ECO:0000269|PubMed:17237514, ECO:0000269|PubMed:17417969,
CC ECO:0000269|PubMed:17466069, ECO:0000269|PubMed:18437219,
CC ECO:0000269|PubMed:22542970, ECO:0000269|PubMed:24715729,
CC ECO:0000269|PubMed:25562820, ECO:0000269|PubMed:26100681,
CC ECO:0000269|PubMed:27650246}.
CC -!- SIMILARITY: Belongs to the retinoblastoma protein (RB) family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF116529; AAD05570.1; -; mRNA.
DR EMBL; BX284601; CCD61908.1; -; Genomic_DNA.
DR PIR; T34024; T34024.
DR RefSeq; NP_491686.1; NM_059285.3.
DR AlphaFoldDB; G5EDT1; -.
DR SMR; G5EDT1; -.
DR ComplexPortal; CPX-1100; DRM complex.
DR ComplexPortal; CPX-1138; RB1-E2F1-TFDP1 transcription repressor complex.
DR ComplexPortal; CPX-1146; RB1-E2F2-TFDP1 transcription repressor complex.
DR IntAct; G5EDT1; 9.
DR MINT; G5EDT1; -.
DR STRING; 6239.C32F10.2; -.
DR iPTMnet; G5EDT1; -.
DR EPD; G5EDT1; -.
DR PaxDb; G5EDT1; -.
DR PeptideAtlas; G5EDT1; -.
DR EnsemblMetazoa; C32F10.2.1; C32F10.2.1; WBGene00003020.
DR GeneID; 172249; -.
DR KEGG; cel:CELE_C32F10.2; -.
DR CTD; 172249; -.
DR WormBase; C32F10.2; CE24823; WBGene00003020; lin-35.
DR eggNOG; KOG1010; Eukaryota.
DR GeneTree; ENSGT00950000183202; -.
DR HOGENOM; CLU_312900_0_0_1; -.
DR InParanoid; G5EDT1; -.
DR OMA; DYIRFGW; -.
DR OrthoDB; 113612at2759; -.
DR PhylomeDB; G5EDT1; -.
DR Reactome; R-CEL-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1.
DR Reactome; R-CEL-1538133; G0 and Early G1.
DR Reactome; R-CEL-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-CEL-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-CEL-69200; Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes.
DR Reactome; R-CEL-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-CEL-69231; Cyclin D associated events in G1.
DR Reactome; R-CEL-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR PRO; PR:G5EDT1; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00003020; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0070176; C:DRM complex; IDA:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0035189; C:Rb-E2F complex; IDA:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IGI:WormBase.
DR GO; GO:0008406; P:gonad development; IGI:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IGI:UniProtKB.
DR GO; GO:0032876; P:negative regulation of DNA endoreduplication; IGI:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:ComplexPortal.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IGI:WormBase.
DR GO; GO:1903507; P:negative regulation of nucleic acid-templated transcription; IC:ComplexPortal.
DR GO; GO:0016479; P:negative regulation of transcription by RNA polymerase I; ISS:WormBase.
DR GO; GO:0040027; P:negative regulation of vulval development; IDA:ComplexPortal.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IGI:WormBase.
DR GO; GO:1902806; P:regulation of cell cycle G1/S phase transition; IGI:UniProtKB.
DR GO; GO:0051302; P:regulation of cell division; IGI:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:InterPro.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR InterPro; IPR036915; Cyclin-like_sf.
DR InterPro; IPR002720; RB_A.
DR InterPro; IPR002719; RB_B.
DR InterPro; IPR028309; RB_fam.
DR InterPro; IPR024599; RB_N.
DR PANTHER; PTHR13742; PTHR13742; 1.
DR Pfam; PF11934; DUF3452; 1.
DR Pfam; PF01858; RB_A; 1.
DR Pfam; PF01857; RB_B; 1.
DR SMART; SM01367; DUF3452; 1.
DR SMART; SM01368; RB_A; 1.
DR SUPFAM; SSF47954; SSF47954; 2.
PE 1: Evidence at protein level;
KW Cell cycle; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..961
FT /note="Retinoblastoma-like protein homolog lin-35"
FT /evidence="ECO:0000305"
FT /id="PRO_0000441023"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..79
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 714
FT /note="Phosphoserine; by CDK4"
FT /evidence="ECO:0000269|PubMed:25562820"
FT MOD_RES 719
FT /note="Phosphothreonine; by CDK4"
FT /evidence="ECO:0000269|PubMed:25562820"
FT MUTAGEN 151..961
FT /note="Missing: In n745; on a ubc-18 mutant background, 4%
FT of larvae display a Pun (pharyngeal unattached) phenotype,
FT whereby the pharynx fails to elongate and form an
FT attachment to the anterior alimentary opening or buccal
FT cavity."
FT /evidence="ECO:0000269|PubMed:12783801"
SQ SEQUENCE 961 AA; 110903 MW; 712475505E527DF1 CRC64;
MPKRAADEPG TSTTDPFHEQ SPFDAVLAGT ETTDTICEEP PAKRIDLDIK QEFNGGVQSG
GLIKNESELT QMTIKQETEG NINEARREEE DEEQDEDSRT SMPPALGEDD DYEEDDADSF
IDKTNTPPPS QSFLEGCRAA NLPNDIVTGA WETYNHAVQR VSLEGSESAW QLSAIYYYLL
SKGIKRRGKT IRILIQPFPV SILTIANSFD ISVAEMLDKT ARFVEIIHSR KIRRYQEYIR
RIQEGLAVSC VIFKKFCRIF CKIFEEIKVG SENCPSSHEL FTVLWTSFLV MKSRMTVDDL
ISNYQLLFSI LDQVYTEMCS MKEGIVHHLN QKFVEDLLEN DCTIIRALCT QFGGSVLDAR
HFSDHTFKKM EKTGIPSTWN FQEFRDLIMN VPKTAYENYL LQRGSIDERI FIPSVEDFSK
IFQSPDTYSV ADILKVSYSG RRFRDAEFLT KISNNHCLEK LALGGKVASE KLVTQSKEQP
RVPCVEYNLE LGNYPDDLES NNQSLYNRLT KIIGSWKLEN SKLEEVCGTM SDSPMATILL
KSDEMTNKFE RTLSAELGET INENIPKYHY NVRKELELVF LIFMEKIIVA ELKKKVREED
LLNVIRREEF LDSVFCFCVE LILVSNGYDR PFPWSAELCG VHPFMFHKVI DLMITHEKQL
SRQMVQHFSR IEETVIEYFS WKSDSPLWPM VVRCPFAHFQ EFGEDWADKL NSYSPIKFTP
IKKPDDLRDE LGRPIVPQNQ TSRTLRIFLK RTYFTAARRL QDLTDRVSMG ARAKSQCWSL
FDYLLRNDTL IFMDRHLDQI LLCCVFVIMK INESSMLFTE IMAQYRRQSA NSLLVYRSVT
VFQEQLNPEN PQAVNTKETI LERLEGPQKE KTTVDIIKYY NIEFRDRIKY IIGQIDSASD
EDLMEMPVAT ESGLMPVRVY LTHKLSIQTL PKTKHGESKQ ERAIANLEKS GITIAMERSG
D
