TELO2_HUMAN
ID TELO2_HUMAN Reviewed; 837 AA.
AC Q9Y4R8; D3DU73; O75168; Q7LDV4; Q9BR21;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Telomere length regulation protein TEL2 homolog;
DE AltName: Full=Protein clk-2 homolog;
DE Short=hCLK2;
GN Name=TELO2; Synonyms=KIAA0683;
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 [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-146.
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-146.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11157797; DOI=10.1093/hmg/10.4.339;
RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C.,
RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.;
RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of
RT the short arm of human chromosome 16.";
RL Hum. Mol. Genet. 10:339-352(2001).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-146.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-146.
RC TISSUE=Placenta;
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 [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12670948; DOI=10.1074/jbc.m300286200;
RA Jiang N., Benard C.Y., Kebir H., Shoubridge E.A., Hekimi S.;
RT "Human CLK2 links cell cycle progression, apoptosis, and telomere length
RT regulation.";
RL J. Biol. Chem. 278:21678-21684(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
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 [11]
RP FUNCTION, AND INTERACTION WITH TTI1 AND TTI2.
RX PubMed=20810650; DOI=10.1101/gad.1934210;
RA Hurov K.E., Cotta-Ramusino C., Elledge S.J.;
RT "A genetic screen identifies the Triple T complex required for DNA damage
RT signaling and ATM and ATR stability.";
RL Genes Dev. 24:1939-1950(2010).
RN [12]
RP INTERACTION WITH ATM; ATR; MTOR; PRKDC; RUVBL2; TTI1 AND TTI2.
RX PubMed=20801936; DOI=10.1101/gad.1956410;
RA Takai H., Xie Y., de Lange T., Pavletich N.P.;
RT "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and
RT ATR complexes.";
RL Genes Dev. 24:2019-2030(2010).
RN [13]
RP INTERACTION WITH TTI1; MTOR; ATM; ATR; PRKDC; SMG1 AND TRRAP.
RX PubMed=20427287; DOI=10.1074/jbc.m110.121699;
RA Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K.,
RA Iemura S., Natsume T., Mizushima N.;
RT "Tti1 and Tel2 are critical factors in mammalian target of rapamycin
RT complex assembly.";
RL J. Biol. Chem. 285:20109-20116(2010).
RN [14]
RP INTERACTION WITH PIH1D1.
RX PubMed=20864032; DOI=10.1016/j.molcel.2010.08.037;
RA Horejsi Z., Takai H., Adelman C.A., Collis S.J., Flynn H., Maslen S.,
RA Skehel J.M., de Lange T., Boulton S.J.;
RT "CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for
RT mTOR and SMG1 stability.";
RL Mol. Cell 39:839-850(2010).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-836, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP HYDROXYLATION AT PRO-374; PRO-419 AND PRO-422 BY PHD3.
RX PubMed=22797300; DOI=10.1172/jci62374;
RA Xie L., Pi X., Mishra A., Fong G., Peng J., Patterson C.;
RT "PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response.";
RL J. Clin. Invest. 122:2827-2836(2012).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-836, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [21]
RP IDENTIFICATION IN THE MTORC1 COMPLEX, IDENTIFICATION IN THE MTORC2 COMPLEX,
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-485; SER-487 AND SER-491,
RP UBIQUITINATION, AND MUTAGENESIS OF SER-485.
RX PubMed=23263282; DOI=10.1038/ncb2651;
RA Fernandez-Saiz V., Targosz B.S., Lemeer S., Eichner R., Langer C.,
RA Bullinger L., Reiter C., Slotta-Huspenina J., Schroeder S., Knorn A.M.,
RA Kurutz J., Peschel C., Pagano M., Kuster B., Bassermann F.;
RT "SCF(Fbxo9) and CK2 direct the cellular response to growth factor
RT withdrawal via Tel2/Tti1 degradation and promote survival in multiple
RT myeloma.";
RL Nat. Cell Biol. 15:72-81(2013).
RN [22]
RP INVOLVEMENT IN YHFS, VARIANTS YHFS LEU-260; PHE-367; HIS-609; VAL-720 AND
RP MET-766, AND CHARACTERIZATION OF VARIANTS YHFS PHE-367; VAL-720 AND
RP MET-766.
RX PubMed=27132593; DOI=10.1016/j.ajhg.2016.03.014;
RA You J., Sobreira N.L., Gable D.L., Jurgens J., Grange D.K., Belnap N.,
RA Siniard A., Szelinger S., Schrauwen I., Richholt R.F., Vallee S.E.,
RA Dinulos M.B., Valle D., Armanios M., Hoover-Fong J.;
RT "A syndromic intellectual disability disorder caused by variants in TELO2,
RT a gene encoding a component of the TTT complex.";
RL Am. J. Hum. Genet. 98:909-918(2016).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 489-498 IN COMPLEX WITH PIH1D1,
RP AND INTERACTION WITH PIH1D1.
RX PubMed=24656813; DOI=10.1016/j.celrep.2014.03.013;
RA Horejsi Z., Stach L., Flower T.G., Joshi D., Flynn H., Skehel J.M.,
RA O'Reilly N.J., Ogrodowicz R.W., Smerdon S.J., Boulton S.J.;
RT "Phosphorylation-dependent PIH1D1 interactions define substrate specificity
RT of the R2TP cochaperone complex.";
RL Cell Rep. 7:19-26(2014).
CC -!- FUNCTION: Regulator of the DNA damage response (DDR). Part of the TTT
CC complex that is required to stabilize protein levels of the
CC phosphatidylinositol 3-kinase-related protein kinase (PIKK) family
CC proteins. The TTT complex is involved in the cellular resistance to DNA
CC damage stresses, like ionizing radiation (IR), ultraviolet (UV) and
CC mitomycin C (MMC). Together with the TTT complex and HSP90 may
CC participate in the proper folding of newly synthesized PIKKs. Promotes
CC assembly, stabilizes and maintains the activity of mTORC1 and mTORC2
CC complexes, which regulate cell growth and survival in response to
CC nutrient and hormonal signals. May be involved in telomere length
CC regulation. {ECO:0000269|PubMed:12670948, ECO:0000269|PubMed:20810650}.
CC -!- SUBUNIT: Component of the TTT complex composed of TELO2, TTI1 and TTI2.
CC Interacts with ATM, ATR, MTOR, PRKDC, RUVBL2, TTI1, TTI2, SMG1 and
CC TRRAP. Component of the mTORC1 and mTORC2 complexes. Interacts
CC (phosphorylated form) with PIH1D1 which mediates interaction of TELO2
CC with the R2TP complex composed of RUVBL1, RUVBL2, PIH1D1, and RPAP3
CC (PubMed:20864032, PubMed:24656813). {ECO:0000269|PubMed:20427287,
CC ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650,
CC ECO:0000269|PubMed:20864032, ECO:0000269|PubMed:23263282,
CC ECO:0000269|PubMed:24656813}.
CC -!- INTERACTION:
CC Q9Y4R8; Q13315: ATM; NbExp=4; IntAct=EBI-1043674, EBI-495465;
CC Q9Y4R8; P54252: ATXN3; NbExp=3; IntAct=EBI-1043674, EBI-946046;
CC Q9Y4R8; Q9UK97: FBXO9; NbExp=5; IntAct=EBI-1043674, EBI-2869927;
CC Q9Y4R8; Q9NWS0: PIH1D1; NbExp=14; IntAct=EBI-1043674, EBI-357318;
CC Q9Y4R8; O43156: TTI1; NbExp=7; IntAct=EBI-1043674, EBI-1055680;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane. Nucleus. Chromosome,
CC telomere {ECO:0000305}.
CC -!- PTM: Hydroxylation by PHD3 is required for a proper interaction with
CC ATR, and activation of the ATR/CHK1/p53 pathway following DNA damage.
CC {ECO:0000269|PubMed:22797300}.
CC -!- PTM: Phosphorylated at Ser-485 by CK2 following growth factor
CC deprivation, leading to its subsequent ubiquitination by the SCF(FBXO9)
CC complex. Phosphorylation by CK2 only takes place when TELO2 is bound to
CC mTORC1, not mTORC2; leading to selective ubiquitination of mTORC1-
CC associated protein. {ECO:0000269|PubMed:23263282}.
CC -!- PTM: Ubiquitinated by the SCF(FBXO9) complex following phosphorylation
CC by CK2 in response to growth factor deprivation, leading to its
CC degradation by the proteasome. Only mTORC1-associated protein is
CC ubiquitinated and degraded, leading to selective inactivation of mTORC1
CC to restrain cell growth and protein translation, while mTORC2 is
CC activated due to the relief of feedback inhibition by mTORC1.
CC {ECO:0000269|PubMed:23263282}.
CC -!- DISEASE: You-Hoover-Fong syndrome (YHFS) [MIM:616954]: A syndrome
CC characterized by severe global developmental delay, intellectual
CC disability, dysmorphic facial features, microcephaly, abnormal
CC movements, congenital heart disease comprising developmental
CC abnormalities of the great vessels, and abnormal auditory and visual
CC function. The transmission pattern is consistent with autosomal
CC recessive inheritance. {ECO:0000269|PubMed:27132593}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Cells overexpressing TELO2 are hypersensitive to
CC hydroxyurea (HU) and undergo apoptotic death in response to treatment
CC with HU.
CC -!- SIMILARITY: Belongs to the TEL2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31658.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB014583; BAA31658.3; ALT_INIT; mRNA.
DR EMBL; AL080126; CAB45724.1; -; mRNA.
DR EMBL; AL137394; CAB70722.1; -; mRNA.
DR EMBL; AE006467; AAK61284.1; -; Genomic_DNA.
DR EMBL; AL031705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471112; EAW85647.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85649.1; -; Genomic_DNA.
DR EMBL; CH471112; EAW85650.1; -; Genomic_DNA.
DR EMBL; BC017188; AAH17188.1; -; mRNA.
DR CCDS; CCDS32363.1; -.
DR PIR; T12514; T12514.
DR RefSeq; NP_057195.2; NM_016111.3.
DR RefSeq; XP_016879403.1; XM_017023914.1.
DR PDB; 4PSI; X-ray; 2.45 A; D/E=489-498.
DR PDB; 7OLE; EM; 3.41 A; K=1-455.
DR PDBsum; 4PSI; -.
DR PDBsum; 7OLE; -.
DR AlphaFoldDB; Q9Y4R8; -.
DR SMR; Q9Y4R8; -.
DR BioGRID; 115223; 147.
DR ComplexPortal; CPX-6148; TTT complex.
DR DIP; DIP-40568N; -.
DR IntAct; Q9Y4R8; 61.
DR MINT; Q9Y4R8; -.
DR STRING; 9606.ENSP00000262319; -.
DR GlyGen; Q9Y4R8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y4R8; -.
DR PhosphoSitePlus; Q9Y4R8; -.
DR BioMuta; TELO2; -.
DR DMDM; 166987394; -.
DR EPD; Q9Y4R8; -.
DR jPOST; Q9Y4R8; -.
DR MassIVE; Q9Y4R8; -.
DR MaxQB; Q9Y4R8; -.
DR PaxDb; Q9Y4R8; -.
DR PeptideAtlas; Q9Y4R8; -.
DR PRIDE; Q9Y4R8; -.
DR ProteomicsDB; 86248; -.
DR Antibodypedia; 23134; 125 antibodies from 21 providers.
DR DNASU; 9894; -.
DR Ensembl; ENST00000262319.11; ENSP00000262319.6; ENSG00000100726.15.
DR GeneID; 9894; -.
DR KEGG; hsa:9894; -.
DR MANE-Select; ENST00000262319.11; ENSP00000262319.6; NM_016111.4; NP_057195.2.
DR UCSC; uc002cly.4; human.
DR CTD; 9894; -.
DR DisGeNET; 9894; -.
DR GeneCards; TELO2; -.
DR HGNC; HGNC:29099; TELO2.
DR HPA; ENSG00000100726; Low tissue specificity.
DR MalaCards; TELO2; -.
DR MIM; 611140; gene.
DR MIM; 616954; phenotype.
DR neXtProt; NX_Q9Y4R8; -.
DR OpenTargets; ENSG00000100726; -.
DR Orphanet; 488642; TELO2-related intellectual disability-neurodevelopmental disorder.
DR PharmGKB; PA162405604; -.
DR VEuPathDB; HostDB:ENSG00000100726; -.
DR eggNOG; KOG4346; Eukaryota.
DR GeneTree; ENSGT00390000006698; -.
DR HOGENOM; CLU_008764_1_0_1; -.
DR InParanoid; Q9Y4R8; -.
DR OMA; MAMTCLQ; -.
DR OrthoDB; 355610at2759; -.
DR PhylomeDB; Q9Y4R8; -.
DR TreeFam; TF313925; -.
DR PathwayCommons; Q9Y4R8; -.
DR SignaLink; Q9Y4R8; -.
DR SIGNOR; Q9Y4R8; -.
DR BioGRID-ORCS; 9894; 576 hits in 1087 CRISPR screens.
DR ChiTaRS; TELO2; human.
DR GeneWiki; TELO2; -.
DR GenomeRNAi; 9894; -.
DR Pharos; Q9Y4R8; Tbio.
DR PRO; PR:Q9Y4R8; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9Y4R8; protein.
DR Bgee; ENSG00000100726; Expressed in right uterine tube and 153 other tissues.
DR ExpressionAtlas; Q9Y4R8; baseline and differential.
DR Genevisible; Q9Y4R8; HS.
DR GO; GO:0070209; C:ASTRA complex; IBA:GO_Central.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0034399; C:nuclear periphery; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0031931; C:TORC1 complex; IDA:UniProtKB.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0110078; C:TTT complex; IPI:ComplexPortal.
DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB.
DR GO; GO:0060090; F:molecular adaptor activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI.
DR GO; GO:0042162; F:telomeric DNA binding; IBA:GO_Central.
DR GO; GO:2000003; P:positive regulation of DNA damage checkpoint; IC:ComplexPortal.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IMP:UniProtKB.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:UniProtKB.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IBA:GO_Central.
DR Gene3D; 1.25.40.720; -; 2.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR038528; TEL2_C_sf.
DR InterPro; IPR019337; Telomere_length_regulation_dom.
DR Pfam; PF10193; Telomere_reg-2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromosome; Cytoplasm; Disease variant;
KW Hydroxylation; Intellectual disability; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Telomere; Ubl conjugation.
FT CHAIN 1..837
FT /note="Telomere length regulation protein TEL2 homolog"
FT /id="PRO_0000318515"
FT REGION 444..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 627..651
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 490
FT /note="Interaction with PIH1D1"
FT /evidence="ECO:0000250|UniProtKB:Q9DC40"
FT SITE 491
FT /note="Interaction with PIH1D1"
FT /evidence="ECO:0000250|UniProtKB:Q9DC40"
FT SITE 492
FT /note="Interaction with PIH1D1"
FT /evidence="ECO:0000250|UniProtKB:Q9DC40"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 374
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:22797300"
FT MOD_RES 419
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:22797300"
FT MOD_RES 422
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:22797300"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9DC40"
FT MOD_RES 485
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:23263282"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23263282"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23263282"
FT MOD_RES 688
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 836
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT VARIANT 7
FT /note="E -> G (in dbSNP:rs2667661)"
FT /id="VAR_038752"
FT VARIANT 7
FT /note="E -> Q (in dbSNP:rs2667660)"
FT /id="VAR_061839"
FT VARIANT 146
FT /note="Q -> R (in dbSNP:rs2235624)"
FT /evidence="ECO:0000269|PubMed:11230166,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|Ref.6"
FT /id="VAR_038753"
FT VARIANT 260
FT /note="P -> L (in YHFS; dbSNP:rs369656775)"
FT /evidence="ECO:0000269|PubMed:27132593"
FT /id="VAR_077025"
FT VARIANT 367
FT /note="C -> F (in YHFS; dbSNP:rs202020308)"
FT /evidence="ECO:0000269|PubMed:27132593"
FT /id="VAR_077026"
FT VARIANT 511
FT /note="A -> V (in dbSNP:rs58099766)"
FT /id="VAR_061840"
FT VARIANT 609
FT /note="R -> H (in YHFS; dbSNP:rs754162070)"
FT /evidence="ECO:0000269|PubMed:27132593"
FT /id="VAR_077027"
FT VARIANT 674
FT /note="Q -> R (in dbSNP:rs2248128)"
FT /id="VAR_038754"
FT VARIANT 720
FT /note="D -> V (in YHFS; dbSNP:rs878853271)"
FT /evidence="ECO:0000269|PubMed:27132593"
FT /id="VAR_077028"
FT VARIANT 766
FT /note="V -> M (in YHFS; dbSNP:rs371675497)"
FT /evidence="ECO:0000269|PubMed:27132593"
FT /id="VAR_077029"
FT MUTAGEN 485
FT /note="S->A: Abolishes phosphorylation by CK2 in response
FT to growth factor deprivation and subsequent ubiquitination
FT and degradation."
FT /evidence="ECO:0000269|PubMed:23263282"
FT CONFLICT 7
FT /note="E -> R (in Ref. 1; BAA31658)"
FT /evidence="ECO:0000305"
FT HELIX 12..21
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 25..37
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 60..68
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 70..77
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 111..122
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 126..156
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 168..173
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 181..200
FT /evidence="ECO:0007829|PDB:7OLE"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 209..224
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 227..243
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 247..255
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 260..274
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 276..287
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 294..305
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 311..327
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 331..343
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 355..369
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 375..395
FT /evidence="ECO:0007829|PDB:7OLE"
FT HELIX 400..413
FT /evidence="ECO:0007829|PDB:7OLE"
SQ SEQUENCE 837 AA; 91747 MW; 76CB619C73C1F1A7 CRC64;
MEPAPSEVRL AVREAIHALS SSEDGGHIFC TLESLKRYLG EMEPPALPRE KEEFASAHFS
PVLRCLASRL SPAWLELLPH GRLEELWASF FLEGPADQAF LVLMETIEGA AGPSFRLMKM
ARLLARFLRE GRLAVLMEAQ CRQQTQPGFI LLRETLLGKV VALPDHLGNR LQQENLAEFF
PQNYFRLLGE EVVRVLQAVV DSLQGGLDSS VSFVSQVLGK ACVHGRQQEI LGVLVPRLAA
LTQGSYLHQR VCWRLVEQVP DRAMEAVLTG LVEAALGPEV LSRLLGNLVV KNKKAQFVMT
QKLLFLQSRL TTPMLQSLLG HLAMDSQRRP LLLQVLKELL ETWGSSSAIR HTPLPQQRHV
SKAVLICLAQ LGEPELRDSR DELLASMMAG VKCRLDSSLP PVRRLGMIVA EVVSARIHPE
GPPLKFQYEE DELSLELLAL ASPQPAGDGA SEAGTSLVPA TAEPPAETPA EIVDGGVPQA
QLAGSDSDLD SDDEFVPYDM SGDRELKSSK APAYVRDCVE ALTTSEDIER WEAALRALEG
LVYRSPTATR EVSVELAKVL LHLEEKTCVV GFAGLRQRAL VAVTVTDPAP VADYLTSQFY
ALNYSLRQRM DILDVLTLAA QELSRPGCLG RTPQPGSPSP NTPCLPEAAV SQPGSAVASD
WRVVVEERIR SKTQRLSKGG PRQGPAGSPS RFNSVAGHFF FPLLQRFDRP LVTFDLLGED
QLVLGRLAHT LGALMCLAVN TTVAVAMGKA LLEFVWALRF HIDAYVRQGL LSAVSSVLLS
LPAARLLEDL MDELLEARSW LADVAEKDPD EDCRTLALRA LLLLQRLKNR LLPPASP
