ID RBL2_HUMAN Reviewed; 1139 AA. AC Q08999; B7Z913; Q15073; Q16084; Q8NE70; Q92812; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 27-MAR-2024, entry version 211. DE RecName: Full=Retinoblastoma-like protein 2; DE AltName: Full=130 kDa retinoblastoma-associated protein; DE Short=p130; DE AltName: Full=Retinoblastoma-related protein 2; DE Short=RBR-2; DE AltName: Full=pRb2; GN Name=RBL2; Synonyms=RB2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Spleen; RX PubMed=8253383; DOI=10.1101/gad.7.12a.2366; RA Li Y., Graham C., Lacy S., Duncan A.M.V., Whyte P.; RT "The adenovirus E1A-associated 130-kD protein is encoded by a member of the RT retinoblastoma gene family and physically interacts with cyclins A and E."; RL Genes Dev. 7:2366-2377(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8253384; DOI=10.1101/gad.7.12a.2378; RA Hannon G.J., Demetrick D., Beach D.; RT "Isolation of the Rb-related p130 through its interaction with CDK2 and RT cyclins."; RL Genes Dev. 7:2378-2391(1993). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 58-1139 (ISOFORM 1). RX PubMed=8361765; RA Mayol X., Grana X., Baldi A., Sang N., Hu Q., Giordano A.; RT "Cloning of a new member of the retinoblastoma gene family (pRb2) which RT binds to the E1A transforming domain."; RL Oncogene 8:2561-2566(1993). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-80. RC TISSUE=Placenta; RX PubMed=8643454; DOI=10.1073/pnas.93.10.4629; RA Baldi A., Boccia V., Claudio P.P., de Luca A., Giordano A.; RT "Genomic structure of the human retinoblastoma-related Rb2/p130 gene."; RL Proc. Natl. Acad. Sci. U.S.A. 93:4629-4632(1996). RN [8] RP PHOSPHORYLATION AT SER-639; SER-952; SER-966; SER-971; SER-972; SER-973; RP THR-974; SER-981; SER-982 AND THR-986, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=11042701; DOI=10.1038/sj.onc.1203893; RA Canhoto A.J., Chestukhin A., Litovchick L., DeCaprio J.A.; RT "Phosphorylation of the retinoblastoma-related protein p130 in growth- RT arrested cells."; RL Oncogene 19:5116-5122(2000). RN [9] RP INTERACTION WITH AATF. RX PubMed=12450794; DOI=10.1016/s1535-6108(02)00182-4; RA Bruno T., De Angelis R., De Nicola F., Barbato C., Di Padova M., Corbi N., RA Libri V., Benassi B., Mattei E., Chersi A., Soddu S., Floridi A., RA Passananti C., Fanciulli M.; RT "Che-1 affects cell growth by interfering with the recruitment of HDAC1 by RT Rb."; RL Cancer Cell 2:387-399(2002). RN [10] RP PHOSPHORYLATION AT SER-672. RX PubMed=12435635; DOI=10.1101/gad.1011202; RA Tedesco D., Lukas J., Reed S.I.; RT "The pRb-related protein p130 is regulated by phosphorylation-dependent RT proteolysis via the protein-ubiquitin ligase SCF(Skp2)."; RL Genes Dev. 16:2946-2957(2002). RN [11] RP INTERACTION WITH RINT1. RX PubMed=16600870; DOI=10.1016/j.molcel.2006.02.016; RA Kong L.-J., Meloni A.R., Nevins J.R.; RT "The Rb-related p130 protein controls telomere lengthening through an RT interaction with a Rad50-interacting protein, RINT-1."; RL Mol. Cell 22:63-71(2006). RN [12] RP IDENTIFICATION IN THE DREAM COMPLEX. RX PubMed=17671431; DOI=10.4161/cc.6.15.4512; RA Schmit F., Korenjak M., Mannefeld M., Schmitt K., Franke C., von Eyss B., RA Gagrica S., Haenel F., Brehm A., Gaubatz S.; RT "LINC, a human complex that is related to pRB-containing complexes in RT invertebrates regulates the expression of G2/M genes."; RL Cell Cycle 6:1903-1913(2007). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662; SER-672 AND SER-1035, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [16] RP INTERACTION WITH JC VIRUS SMALL T ANTIGEN (MICROBIAL INFECTION). RX PubMed=20485545; DOI=10.1371/journal.pone.0010606; RA Bollag B., Hofstetter C.A., Reviriego-Mendoza M.M., Frisque R.J.; RT "JC virus small T antigen binds phosphatase PP2A and Rb family proteins and RT is required for efficient viral DNA replication activity."; RL PLoS ONE 5:e10606-e10606(2010). RN [17] RP INTERACTION WITH PML. RX PubMed=22002537; DOI=10.1038/emboj.2011.370; RA Martin N., Benhamed M., Nacerddine K., Demarque M.D., van Lohuizen M., RA Dejean A., Bischof O.; RT "Physical and functional interaction between PML and TBX2 in the RT establishment of cellular senescence."; RL EMBO J. 31:95-109(2012). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413; SER-662; SER-688; RP SER-1068; SER-1080 AND SER-1112, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP VARIANT PHE-99. RX PubMed=23033978; DOI=10.1056/nejmoa1206524; RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., RA Veltman J.A., Vissers L.E.; RT "Diagnostic exome sequencing in persons with severe intellectual RT disability."; RL N. Engl. J. Med. 367:1921-1929(2012). RN [21] RP VARIANT BRUWAG 186-ARG--HIS-1139 DEL, AND INVOLVEMENT IN BRUWAG. RX PubMed=32105419; DOI=10.1002/acn3.50992; RA Brunet T., Radivojkov-Blagojevic M., Lichtner P., Kraus V., Meitinger T., RA Wagner M.; RT "Biallelic loss-of-function variants in RBL2 in siblings with a RT neurodevelopmental disorder."; RL Ann. Clin. Transl. Neurol. 7:390-396(2020). RN [22] RP INVOLVEMENT IN BRUWAG. RX PubMed=33980986; DOI=10.1038/s10038-021-00931-z; RA Samra N., Toubiana S., Yttervik H., Tzur-Gilat A., Morani I., Itzkovich C., RA Giladi L., Abu Jabal K., Cao J.Z., Godley L.A., Mory A., Baris Feldman H., RA Tveten K., Selig S., Weiss K.; RT "RBL2 bi-allelic truncating variants cause severe motor and cognitive RT impairment without evidence for abnormalities in DNA methylation or RT telomeric function."; RL J. Hum. Genet. 66:1101-1112(2021). RN [23] {ECO:0007744|PDB:4XI9, ECO:0007744|PDB:5C1D} RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 416-423 IN COMPLEX WITH OGT, AND RP GLYCOSYLATION AT SER-420. RX PubMed=26237509; DOI=10.1038/nsmb.3063; RA Pathak S., Alonso J., Schimpl M., Rafie K., Blair D.E., Borodkin V.S., RA Albarbarawi O., van Aalten D.M.F.; RT "The active site of O-GlcNAc transferase imposes constraints on substrate RT sequence."; RL Nat. Struct. Mol. Biol. 22:744-750(2015). CC -!- FUNCTION: Key regulator of entry into cell division. Directly involved CC in heterochromatin formation by maintaining overall chromatin structure CC and, in particular, that of constitutive heterochromatin by stabilizing CC histone methylation. Recruits and targets histone methyltransferases CC KMT5B and KMT5C, leading to epigenetic transcriptional repression. CC Controls histone H4 'Lys-20' trimethylation. Probably acts as a CC transcription repressor by recruiting chromatin-modifying enzymes to CC promoters. Potent inhibitor of E2F-mediated trans-activation, CC associates preferentially with E2F5. Binds to cyclins A and E. Binds to CC and may be involved in the transforming capacity of the adenovirus E1A CC protein. May act as a tumor suppressor. CC -!- SUBUNIT: Interacts with AATF. Interacts with KMT5B, KMT5C and USP4 (By CC similarity). Component of the DREAM complex (also named LINC complex) CC at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, CC MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in CC quiescent cells where it represses cell cycle-dependent genes. It CC dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a CC subcomplex that binds to MYBL2. Interacts with RINT1. Interacts with CC PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and CC isoform PML-5). Interacts with RBBP9 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:O55081, ECO:0000269|PubMed:12450794, CC ECO:0000269|PubMed:16600870, ECO:0000269|PubMed:17671431, CC ECO:0000269|PubMed:22002537}. CC -!- SUBUNIT: (Microbial infection) Interacts with JC virus small t antigen. CC {ECO:0000269|PubMed:20485545}. CC -!- INTERACTION: CC Q08999; Q13574-2: DGKZ; NbExp=2; IntAct=EBI-971439, EBI-715527; CC Q08999; Q16254: E2F4; NbExp=7; IntAct=EBI-971439, EBI-448943; CC Q08999; Q6MZP7: LIN54; NbExp=10; IntAct=EBI-971439, EBI-1389411; CC Q08999; P67775: PPP2CA; NbExp=2; IntAct=EBI-971439, EBI-712311; CC Q08999; I6L8A6: RBBP8; NbExp=3; IntAct=EBI-971439, EBI-11525639; CC Q08999; Q99708-2: RBBP8; NbExp=3; IntAct=EBI-971439, EBI-10203615; CC Q08999; P24610: Pax3; Xeno; NbExp=3; IntAct=EBI-971439, EBI-1208116; CC Q08999; Q923E4: Sirt1; Xeno; NbExp=2; IntAct=EBI-971439, EBI-1802585; CC Q08999; Q61412: Vsx2; Xeno; NbExp=4; IntAct=EBI-971439, EBI-1208174; CC Q08999; P03255; Xeno; NbExp=2; IntAct=EBI-971439, EBI-2603114; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q08999-1; Sequence=Displayed; CC Name=2; CC IsoId=Q08999-2; Sequence=VSP_054328, VSP_054329; CC -!- DEVELOPMENTAL STAGE: G0-restricted expression. CC -!- PTM: During G0 and early G1 phase of the cell cycle, phosphorylated on CC Ser-639 and on 5 sites within the domain B. Phosphorylation on Ser-672 CC in G1 leads to its ubiquitin-dependent proteolysis. CC {ECO:0000269|PubMed:11042701, ECO:0000269|PubMed:12435635}. CC -!- DISEASE: Brunet-Wagner neurodevelopmental syndrome (BRUWAG) CC [MIM:619690]: An autosomal recessive disorder characterized by severe CC developmental delay, intellectual disability, poor or absent speech, CC infantile hypotonia, inability to walk, behavioral abnormalities, and CC dysmorphic features. {ECO:0000269|PubMed:32105419, CC ECO:0000269|PubMed:33980986}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the retinoblastoma protein (RB) family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/443/RBL2"; 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; X76061; CAA53661.1; -; mRNA. DR EMBL; S67171; AAB29227.1; -; mRNA. DR EMBL; AK304283; BAH14149.1; -; mRNA. DR EMBL; AC007342; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC034490; AAH34490.1; -; mRNA. DR EMBL; X74594; CAA52671.1; -; mRNA. DR EMBL; U53220; AAC50479.1; -; Genomic_DNA. DR CCDS; CCDS10748.1; -. [Q08999-1] DR PIR; A49370; A49370. DR RefSeq; NP_001310537.1; NM_001323608.1. [Q08999-1] DR RefSeq; NP_005602.3; NM_005611.3. [Q08999-1] DR PDB; 4XI9; X-ray; 3.10 A; E/F/G/H=416-422. DR PDB; 5C1D; X-ray; 2.05 A; C=416-422. DR PDBsum; 4XI9; -. DR PDBsum; 5C1D; -. DR AlphaFoldDB; Q08999; -. DR SMR; Q08999; -. DR BioGRID; 111869; 80. DR ComplexPortal; CPX-7461; DREAM transcriptional repressor complex, RBL2 variant. DR CORUM; Q08999; -. DR DIP; DIP-425N; -. DR ELM; Q08999; -. DR IntAct; Q08999; 51. DR MINT; Q08999; -. DR STRING; 9606.ENSP00000262133; -. DR GlyCosmos; Q08999; 1 site, 1 glycan. DR GlyGen; Q08999; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q08999; -. DR PhosphoSitePlus; Q08999; -. DR BioMuta; RBL2; -. DR DMDM; 116242746; -. DR EPD; Q08999; -. DR jPOST; Q08999; -. DR MassIVE; Q08999; -. DR MaxQB; Q08999; -. DR PaxDb; 9606-ENSP00000262133; -. DR PeptideAtlas; Q08999; -. DR ProteomicsDB; 58652; -. [Q08999-1] DR ProteomicsDB; 6997; -. DR Pumba; Q08999; -. DR Antibodypedia; 4299; 532 antibodies from 39 providers. DR DNASU; 5934; -. DR Ensembl; ENST00000262133.11; ENSP00000262133.6; ENSG00000103479.17. [Q08999-1] DR GeneID; 5934; -. DR KEGG; hsa:5934; -. DR MANE-Select; ENST00000262133.11; ENSP00000262133.6; NM_005611.4; NP_005602.3. DR UCSC; uc002ehi.5; human. [Q08999-1] DR AGR; HGNC:9894; -. DR CTD; 5934; -. DR DisGeNET; 5934; -. DR GeneCards; RBL2; -. DR HGNC; HGNC:9894; RBL2. DR HPA; ENSG00000103479; Low tissue specificity. DR MalaCards; RBL2; -. DR MIM; 180203; gene. DR MIM; 619690; phenotype. DR neXtProt; NX_Q08999; -. DR OpenTargets; ENSG00000103479; -. DR PharmGKB; PA34258; -. DR VEuPathDB; HostDB:ENSG00000103479; -. DR eggNOG; KOG1010; Eukaryota. DR GeneTree; ENSGT00950000183202; -. DR HOGENOM; CLU_008943_0_0_1; -. DR InParanoid; Q08999; -. DR OMA; MHWLACA; -. DR OrthoDB; 519973at2759; -. DR PhylomeDB; Q08999; -. DR TreeFam; TF105568; -. DR PathwayCommons; Q08999; -. DR Reactome; R-HSA-1362277; Transcription of E2F targets under negative control by DREAM complex. DR Reactome; R-HSA-1362300; Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1. DR Reactome; R-HSA-1538133; G0 and Early G1. DR Reactome; R-HSA-6804114; TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest. DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-HSA-69205; G1/S-Specific Transcription. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-HSA-9617828; FOXO-mediated transcription of cell cycle genes. DR SignaLink; Q08999; -. DR SIGNOR; Q08999; -. DR BioGRID-ORCS; 5934; 15 hits in 1157 CRISPR screens. DR ChiTaRS; RBL2; human. DR GeneWiki; Retinoblastoma-like_protein_2; -. DR GenomeRNAi; 5934; -. DR Pharos; Q08999; Tbio. DR PRO; PR:Q08999; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q08999; Protein. DR Bgee; ENSG00000103479; Expressed in germinal epithelium of ovary and 205 other cell types or tissues. DR ExpressionAtlas; Q08999; baseline and differential. DR GO; GO:0000785; C:chromatin; IBA:GO_Central. DR GO; GO:0005694; C:chromosome; IDA:HPA. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central. DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI. 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:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IBA:GO_Central. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI. DR GO; GO:0043550; P:regulation of lipid kinase activity; IDA:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:InterPro. DR CDD; cd20606; CYCLIN_RBL2; 1. DR CDD; cd00043; CYCLIN_SF; 1. DR Gene3D; 1.10.472.140; -; 1. DR Gene3D; 1.10.472.10; Cyclin-like; 3. DR IDEAL; IID00663; -. DR InterPro; IPR013763; Cyclin-like_dom. DR InterPro; IPR036915; Cyclin-like_sf. DR InterPro; IPR002720; RB_A. DR InterPro; IPR002719; RB_B. DR InterPro; IPR015030; RB_C. DR InterPro; IPR028309; RB_fam. DR InterPro; IPR024599; RB_N. DR PANTHER; PTHR13742; RETINOBLASTOMA-ASSOCIATED PROTEIN RB -RELATED; 1. DR PANTHER; PTHR13742:SF8; RETINOBLASTOMA-LIKE PROTEIN 2; 1. DR Pfam; PF11934; DUF3452; 1. DR Pfam; PF01858; RB_A; 1. DR Pfam; PF01857; RB_B; 1. DR SMART; SM00385; CYCLIN; 2. DR SMART; SM01367; DUF3452; 1. DR SMART; SM01368; RB_A; 1. DR SMART; SM01369; Rb_C; 1. DR SUPFAM; SSF47954; Cyclin-like; 3. DR Genevisible; Q08999; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Chromatin regulator; KW Disease variant; DNA-binding; Glycoprotein; Host-virus interaction; KW Intellectual disability; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; Transcription; Transcription regulation; Tumor suppressor. FT CHAIN 1..1139 FT /note="Retinoblastoma-like protein 2" FT /id="PRO_0000167841" FT REGION 1..45 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 417..1024 FT /note="Pocket; binds E1A" FT REGION 417..616 FT /note="Domain A" FT REGION 617..827 FT /note="Spacer" FT REGION 654..678 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 810..832 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 828..1024 FT /note="Domain B" FT REGION 933..999 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..19 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 20..34 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 657..678 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 413 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 417 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q64700" FT MOD_RES 639 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11042701" FT MOD_RES 642 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q64700" FT MOD_RES 662 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 672 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12435635, FT ECO:0007744|PubMed:19690332" FT MOD_RES 688 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 948 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64700" FT MOD_RES 952 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11042701" FT MOD_RES 966 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11042701" FT MOD_RES 971 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11042701" FT MOD_RES 972 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11042701" FT MOD_RES 973 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11042701" FT MOD_RES 974 FT /note="Phosphothreonine" FT /evidence="ECO:0000305|PubMed:11042701" FT MOD_RES 981 FT /note="Phosphoserine" FT /evidence="ECO:0000305|PubMed:11042701" FT MOD_RES 982 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11042701" FT MOD_RES 986 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:11042701" FT MOD_RES 1035 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1068 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1080 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1112 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 420 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:26237509" FT VAR_SEQ 1..216 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054328" FT VAR_SEQ 638..1042 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054329" FT VARIANT 99 FT /note="V -> F" FT /evidence="ECO:0000269|PubMed:23033978" FT /id="VAR_069377" FT VARIANT 186..1139 FT /note="Missing (in BRUWAG)" FT /evidence="ECO:0000269|PubMed:32105419" FT /id="VAR_086722" FT VARIANT 210 FT /note="Y -> C (in dbSNP:rs17800727)" FT /id="VAR_028437" FT CONFLICT 37 FT /note="P -> S (in Ref. 1; CAA53661 and 7; AAC50479)" FT /evidence="ECO:0000305" FT CONFLICT 64 FT /note="A -> P (in Ref. 1 and 7)" FT /evidence="ECO:0000305" FT CONFLICT 206 FT /note="V -> M (in Ref. 6; CAA52671)" FT /evidence="ECO:0000305" FT CONFLICT 1093 FT /note="R -> H (in Ref. 5; AAH34490)" FT /evidence="ECO:0000305" SQ SEQUENCE 1139 AA; 128367 MW; D129032FB1F383D4 CRC64; MPSGGDQSPP PPPPPPAAAA SDEEEEDDGE AEDAAPPAES PTPQIQQRFD ELCSRLNMDE AARAEAWDSY RSMSESYTLE GNDLHWLACA LYVACRKSVP TVSKGTVEGN YVSLTRILKC SEQSLIEFFN KMKKWEDMAN LPPHFRERTE RLERNFTVSA VIFKKYEPIF QDIFKYPQEE QPRQQRGRKQ RRQPCTVSEI FHFCWVLFIY AKGNFPMISD DLVNSYHLLL CALDLVYGNA LQCSNRKELV NPNFKGLSED FHAKDSKPSS DPPCIIEKLC SLHDGLVLEA KGIKEHFWKP YIRKLYEKKL LKGKEENLTG FLEPGNFGES FKAINKAYEE YVLSVGNLDE RIFLGEDAEE EIGTLSRCLN AGSGTETAER VQMKNILQQH FDKSKALRIS TPLTGVRYIK ENSPCVTPVS TATHSLSRLH TMLTGLRNAP SEKLEQILRT CSRDPTQAIA NRLKEMFEIY SQHFQPDEDF SNCAKEIASK HFRFAEMLYY KVLESVIEQE QKRLGDMDLS GILEQDAFHR SLLACCLEVV TFSYKPPGNF PFITEIFDVP LYHFYKVIEV FIRAEDGLCR EVVKHLNQIE EQILDHLAWK PESPLWEKIR DNENRVPTCE EVMPPQNLER ADEICIAGSP LTPRRVTEVR ADTGGLGRSI TSPTTLYDRY SSPPASTTRR RLFVENDSPS DGGTPGRMPP QPLVNAVPVQ NVSGETVSVT PVPGQTLVTM ATATVTANNG QTVTIPVQGI ANENGGITFF PVQVNVGGQA QAVTGSIQPL SAQALAGSLS SQQVTGTTLQ VPGQVAIQQI SPGGQQQKQG QSVTSSSNRP RKTSSLSLFF RKVYHLAAVR LRDLCAKLDI SDELRKKIWT CFEFSIIQCP ELMMDRHLDQ LLMCAIYVMA KVTKEDKSFQ NIMRCYRTQP QARSQVYRSV LIKGKRKRRN SGSSDSRSHQ NSPTELNKDR TSRDSSPVMR SSSTLPVPQP SSAPPTPTRL TGANSDMEEE ERGDLIQFYN NIYIKQIKTF AMKYSQANMD APPLSPYPFV RTGSPRRIQL SQNHPVYISP HKNETMLSPR EKIFYYFSNS PSKRLREINS MIRTGETPTK KRGILLEDGS ESPAKRICPE NHSALLRRLQ DVANDRGSH //