TELO2_MOUSE
ID TELO2_MOUSE Reviewed; 840 AA.
AC Q9DC40; Q3U3J5; Q3UID7; Q3UP41; Q8BN03; Q8C1T3; Q91VQ3;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Telomere length regulation protein TEL2 homolog;
GN Name=Telo2; Synonyms=Kiaa0683;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney, Lung, Skin, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Brathwaite M., Waeltz P., Dudekula D., Nagaraja R.;
RT "Genomic sequence analysis in the mouse T-complex region.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [5]
RP MUTAGENESIS OF LEU-395; 395-LEU--MET-407; 395-LEU--LEU-424; MET-407;
RP 407-MET--LEU-424 AND LEU-424.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 488-496 IN COMPLEX WITH PIH1D1,
RP AND INTERACTION WITH PIH1D1.
RX PubMed=24794838; DOI=10.1016/j.str.2014.04.001;
RA Pal M., Morgan M., Phelps S.E., Roe S.M., Parry-Morris S., Downs J.A.,
RA Polier S., Pearl L.H., Prodromou C.;
RT "Structural basis for phosphorylation-dependent recruitment of Tel2 to
RT Hsp90 by Pih1.";
RL Structure 22:805-818(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 (By similarity). {ECO:0000250}.
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 (PubMed:24794838). Interaction with
CC PIH1D1 mediates interaction of TELO2 with the R2TP complex composed of
CC RUVBL1, RUVBL2, PIH1D1, and RPAP3 (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y4R8, ECO:0000269|PubMed:24794838}.
CC -!- INTERACTION:
CC Q9DC40; Q9CQJ2: Pih1d1; NbExp=3; IntAct=EBI-1571482, EBI-11658528;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Membrane {ECO:0000250}.
CC Nucleus {ECO:0000250}. Chromosome, telomere {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9DC40-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9DC40-2; Sequence=VSP_031207, VSP_031208, VSP_031209;
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:0000250}.
CC -!- PTM: Phosphorylated at Ser-486 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 (By similarity). {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the TEL2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE25556.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK004582; BAB23388.1; -; mRNA.
DR EMBL; AK045321; BAC32309.1; -; mRNA.
DR EMBL; AK028658; BAC26051.1; -; mRNA.
DR EMBL; AK143827; BAE25556.1; ALT_SEQ; mRNA.
DR EMBL; AK146963; BAE27569.1; -; mRNA.
DR EMBL; AK154727; BAE32791.1; -; mRNA.
DR EMBL; AY491413; AAS21644.1; -; Genomic_DNA.
DR EMBL; BC011077; AAH11077.1; -; mRNA.
DR CCDS; CCDS28507.1; -. [Q9DC40-1]
DR RefSeq; NP_001157133.1; NM_001163661.1. [Q9DC40-1]
DR RefSeq; NP_082156.2; NM_027880.2. [Q9DC40-1]
DR PDB; 4CKT; X-ray; 3.00 A; C/D=489-496.
DR PDB; 4CSE; X-ray; 3.30 A; C/D=488-496.
DR PDBsum; 4CKT; -.
DR PDBsum; 4CSE; -.
DR AlphaFoldDB; Q9DC40; -.
DR SMR; Q9DC40; -.
DR BioGRID; 214877; 5.
DR DIP; DIP-60997N; -.
DR IntAct; Q9DC40; 4.
DR MINT; Q9DC40; -.
DR STRING; 10090.ENSMUSP00000110835; -.
DR iPTMnet; Q9DC40; -.
DR PhosphoSitePlus; Q9DC40; -.
DR EPD; Q9DC40; -.
DR MaxQB; Q9DC40; -.
DR PaxDb; Q9DC40; -.
DR PeptideAtlas; Q9DC40; -.
DR PRIDE; Q9DC40; -.
DR ProteomicsDB; 262751; -. [Q9DC40-1]
DR ProteomicsDB; 262752; -. [Q9DC40-2]
DR Antibodypedia; 23134; 125 antibodies from 21 providers.
DR Ensembl; ENSMUST00000024987; ENSMUSP00000024987; ENSMUSG00000024170. [Q9DC40-1]
DR Ensembl; ENSMUST00000115181; ENSMUSP00000110835; ENSMUSG00000024170. [Q9DC40-1]
DR GeneID; 71718; -.
DR KEGG; mmu:71718; -.
DR UCSC; uc008azq.2; mouse. [Q9DC40-1]
DR CTD; 9894; -.
DR MGI; MGI:1918968; Telo2.
DR VEuPathDB; HostDB:ENSMUSG00000024170; -.
DR eggNOG; KOG4346; Eukaryota.
DR GeneTree; ENSGT00390000006698; -.
DR HOGENOM; CLU_008764_1_0_1; -.
DR InParanoid; Q9DC40; -.
DR OMA; MAMTCLQ; -.
DR OrthoDB; 355610at2759; -.
DR PhylomeDB; Q9DC40; -.
DR TreeFam; TF313925; -.
DR BioGRID-ORCS; 71718; 23 hits in 74 CRISPR screens.
DR ChiTaRS; Telo2; mouse.
DR PRO; PR:Q9DC40; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9DC40; protein.
DR Bgee; ENSMUSG00000024170; Expressed in molar tooth and 238 other tissues.
DR Genevisible; Q9DC40; MM.
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; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0034399; C:nuclear periphery; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0031931; C:TORC1 complex; ISS:UniProtKB.
DR GO; GO:0031932; C:TORC2 complex; ISS:UniProtKB.
DR GO; GO:0110078; C:TTT complex; ISO:MGI.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR GO; GO:0060090; F:molecular adaptor activity; IMP:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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:0071902; P:positive regulation of protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; ISO:MGI.
DR GO; GO:1904515; P:positive regulation of TORC2 signaling; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IBA:GO_Central.
DR Gene3D; 1.25.40.720; -; 2.
DR InterPro; IPR038528; TEL2_C_sf.
DR InterPro; IPR019337; Telomere_length_regulation_dom.
DR Pfam; PF10193; Telomere_reg-2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosome; Cytoplasm;
KW Hydroxylation; Membrane; Nucleus; Phosphoprotein; Reference proteome;
KW Telomere; Ubl conjugation.
FT CHAIN 1..840
FT /note="Telomere length regulation protein TEL2 homolog"
FT /id="PRO_0000318516"
FT REGION 443..497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 491
FT /note="Interaction with PIH1D1"
FT /evidence="ECO:0000269|PubMed:24794838"
FT SITE 492
FT /note="Interaction with PIH1D1"
FT /evidence="ECO:0000269|PubMed:24794838"
FT SITE 493
FT /note="Interaction with PIH1D1"
FT /evidence="ECO:0000269|PubMed:24794838"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4R8"
FT MOD_RES 374
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 419
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 422
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747"
FT MOD_RES 486
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4R8"
FT MOD_RES 488
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4R8"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4R8"
FT MOD_RES 837
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4R8"
FT VAR_SEQ 1..386
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031207"
FT VAR_SEQ 680..690
FT /note="GCPQRELSGVP -> VTGLCSDPMLS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031208"
FT VAR_SEQ 691..840
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_031209"
FT MUTAGEN 395
FT /note="L->Q: Does not inhibit interaction with TTI1 or
FT TTI2. Inhibits weakly interaction with TTI1 or TTI2; when
FT associated with E-407 or R-424. Inhibits interaction with
FT TTI1 or TTI2; when associated with E-407 and R-424."
FT /evidence="ECO:0000269|PubMed:20801936"
FT MUTAGEN 407
FT /note="M->E: Does not inhibit interaction with TTI1 or
FT TTI2. Inhibits weakly interaction with TTI1 or TTI2; when
FT associated with Q-395 or R-424. Inhibits interaction with
FT TTI1 or TTI2; when associated with Q-395 and R-424."
FT /evidence="ECO:0000269|PubMed:20801936"
FT MUTAGEN 424
FT /note="L->R: Does not inhibit interaction with TTI1 or
FT TTI2. Inhibits weakly interaction with TTI1 or TTI2; when
FT associated with Q-395 or E-407. Inhibits interaction with
FT TTI1 or TTI2; when associated with Q-395 and E-407."
FT /evidence="ECO:0000269|PubMed:20801936"
FT CONFLICT 18
FT /note="I -> T (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="A -> T (in Ref. 1; BAE32791)"
FT /evidence="ECO:0000305"
FT CONFLICT 205
FT /note="D -> G (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="V -> A (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="S -> P (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="S -> N (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 548
FT /note="T -> A (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 638..639
FT /note="PP -> SL (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="V -> M (in Ref. 2; AAS21644 and 3; AAH11077)"
FT /evidence="ECO:0000305"
FT CONFLICT 689
FT /note="V -> I (in Ref. 1; BAC26051)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="V -> M (in Ref. 1; BAB23388)"
FT /evidence="ECO:0000305"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:4CSE"
SQ SEQUENCE 840 AA; 93313 MW; C3ADB9DCE1724EAC CRC64;
MDPALSAVRL TVQEAIHILS SSEDAGHILS TLGTLKRYLG GTEDPVLPEE KEEFATVHFS
AVLRCLVSKL SPGWLELSPG GQLERLWESF FLDGPPDQAF LVLMEAIEST AGPSFRLMKM
AQLLDTFLST GRVAALMEEQ CRPQTKPSFP LFQETLLSKV VGLPDLLGNC LQRDNLTQFF
PQNYFPLLGQ EVVQALKAVV NFLQDGLDCS VSFVSRVLGK VCIQGRKREI LSVLVPQLTV
LTQDSCLWQR VCWRLVEQVP DRAVEAVLTG LVEAAPRPEV LSRLLGNLVV KNKKARFVVT
RKLLLLQYQH TTPMVQSLLG YLALDSQRRP LLIQVLKELL ETWGCSSAVR HTPLEQQCYI
SKAILVCLAH LGEPELQDIR DELLASMMAG VKCRLDSSLP PVRRLGMIVA EVISSRIHPE
GPLLKFQYED DEMSRELLAL ATPEPAGDCS SVSRGPSPAP VDTESPVEMP EKAVESDVPP
TQPQGSDSEL DSDDEFIPYD MSGDRELKSS KEPLYIRDCV EALTTSEDME RWEASLKGLE
GLVYRSPTAT REVSVELAKV LLHLEEKTCV AEFEQLRQSA LVAVTVTDPE QVAKYLTSQF
YGLNYSLRQR MDILDVLVLA AQALSRPKSL QRRSQHGPPV PGTMCSPALA VSQTGNVAAP
DWQVVVEERI RSKTRRFSKG CPQRELSGVP NEFSSVAGYF FFPLLQHFDR PLVTFDLLGD
DQLVLGRLTH TLASLMYLAV NTTVAVPMGK ALLEFVWALR FHVDIYVRRG LLSAVSSVLL
SVPTERLLGD LPDELLEARS WLADVAEKDV DEDCRELAVR ALLLLERLKD KLLSSSSPQP
