Skip Header

Contribute Send feedback
Read comments (?) or add your own

Q9Y4R8 (TELO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Telomere length regulation protein TEL2 homolog
Alternative name(s):
Protein clk-2 homolog
Short name=hCLK2
Gene names
Name:TELO2
Synonyms:KIAA0683
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length837 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. The TTT complex is involved in the cellular resistance to DNA damage stresses, like ionizing radiation (IR), ultraviolet (UV) and mitomycin C (MMC). Together with the TTT complex and HSP90 may participate in the proper folding of newly synthesized PIKKs. Promotes assembly, stabilizes and maintains the activity of mTORC1 and mTORC2 complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. May be involved in telomere length regulation. Ref.8 Ref.10

Subunit structure

Component of the TTT complex composed of TELO2, TTI1 and TTI2. Interacts with ATM, ATR, MTOR, PRKDC, RUVBL2, TTI1, TTI2, SMG1 and TRRAP. Component of the mTORC1 and mTORC2 complexes. Ref.10 Ref.11 Ref.12 Ref.17

Subcellular location

Cytoplasm. Membrane. Nucleus. Chromosometelomere Probable Ref.8 Ref.17.

Post-translational modification

Hydroxylation by PHD3 is required for a proper interaction with ATR, and activation of the ATR/CHK1/p53 pathway following DNA damage.

Phosphorylated at Ser-485 by CK2 following growth factor deprivation, leading to its subsequent ubiquitination by the SCF(FBXO9) complex. Phosphorylation by CK2 only takes place when TELO2 is bound to mTORC1, not mTORC2; leading to selective ubiquitination of mTORC1-associated protein. Ref.17

Ubiquitinated by the SCF(FBXO9) complex following phosphorylation by CK2 in response to growth factor deprivation, leading to its degradation by the proteasome. Only mTORC1-associated protein is ubiquitinated and degraded, leading to selective inactivation of mTORC1 to restrain cell growth and protein translation, while mTORC2 is activated due to the relief of feedback inhibition by mTORC1. Ref.17

Miscellaneous

Cells overexpressing TELO2 are hypersensitive to hydroxyurea (HU) and undergo apoptotic death in response to treatment with HU.

Sequence similarities

Belongs to the TEL2 family.

Sequence caution

The sequence BAA31658.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 837837Telomere length regulation protein TEL2 homolog
PRO_0000318515

Amino acid modifications

Modified residue3741Hydroxyproline
Modified residue4191Hydroxyproline
Modified residue4221Hydroxyproline
Modified residue4561Phosphoserine By similarity
Modified residue4851Phosphoserine; by CK2 Ref.17
Modified residue4871Phosphoserine Ref.17
Modified residue4911Phosphoserine Ref.17
Modified residue6881Phosphoserine Ref.13
Modified residue8361Phosphoserine Ref.15

Natural variations

Natural variant71E → G.
Corresponds to variant rs2667661 [ dbSNP | Ensembl ].
VAR_038752
Natural variant71E → Q.
Corresponds to variant rs2667660 [ dbSNP | Ensembl ].
VAR_061839
Natural variant1461Q → R. Ref.2 Ref.3 Ref.6 Ref.7
Corresponds to variant rs2235624 [ dbSNP | Ensembl ].
VAR_038753
Natural variant5111A → V.
Corresponds to variant rs58099766 [ dbSNP | Ensembl ].
VAR_061840
Natural variant6741Q → R.
Corresponds to variant rs2248128 [ dbSNP | Ensembl ].
VAR_038754

Experimental info

Mutagenesis4851S → A: Abolishes phosphorylation by CK2 in response to growth factor deprivation and subsequent ubiquitination and degradation. Ref.17
Sequence conflict71E → R in BAA31658. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9Y4R8 [UniParc].

Last modified February 5, 2008. Version 2.
Checksum: 76CB619C73C1F1A7

FASTA83791,747
        10         20         30         40         50         60 
MEPAPSEVRL AVREAIHALS SSEDGGHIFC TLESLKRYLG EMEPPALPRE KEEFASAHFS 

        70         80         90        100        110        120 
PVLRCLASRL SPAWLELLPH GRLEELWASF FLEGPADQAF LVLMETIEGA AGPSFRLMKM 

       130        140        150        160        170        180 
ARLLARFLRE GRLAVLMEAQ CRQQTQPGFI LLRETLLGKV VALPDHLGNR LQQENLAEFF 

       190        200        210        220        230        240 
PQNYFRLLGE EVVRVLQAVV DSLQGGLDSS VSFVSQVLGK ACVHGRQQEI LGVLVPRLAA 

       250        260        270        280        290        300 
LTQGSYLHQR VCWRLVEQVP DRAMEAVLTG LVEAALGPEV LSRLLGNLVV KNKKAQFVMT 

       310        320        330        340        350        360 
QKLLFLQSRL TTPMLQSLLG HLAMDSQRRP LLLQVLKELL ETWGSSSAIR HTPLPQQRHV 

       370        380        390        400        410        420 
SKAVLICLAQ LGEPELRDSR DELLASMMAG VKCRLDSSLP PVRRLGMIVA EVVSARIHPE 

       430        440        450        460        470        480 
GPPLKFQYEE DELSLELLAL ASPQPAGDGA SEAGTSLVPA TAEPPAETPA EIVDGGVPQA 

       490        500        510        520        530        540 
QLAGSDSDLD SDDEFVPYDM SGDRELKSSK APAYVRDCVE ALTTSEDIER WEAALRALEG 

       550        560        570        580        590        600 
LVYRSPTATR EVSVELAKVL LHLEEKTCVV GFAGLRQRAL VAVTVTDPAP VADYLTSQFY 

       610        620        630        640        650        660 
ALNYSLRQRM DILDVLTLAA QELSRPGCLG RTPQPGSPSP NTPCLPEAAV SQPGSAVASD 

       670        680        690        700        710        720 
WRVVVEERIR SKTQRLSKGG PRQGPAGSPS RFNSVAGHFF FPLLQRFDRP LVTFDLLGED 

       730        740        750        760        770        780 
QLVLGRLAHT LGALMCLAVN TTVAVAMGKA LLEFVWALRF HIDAYVRQGL LSAVSSVLLS 

       790        800        810        820        830 
LPAARLLEDL MDELLEARSW LADVAEKDPD EDCRTLALRA LLLLQRLKNR LLPPASP 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[2]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-146.
Tissue: Testis.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-146.
Tissue: Testis.
[4]"Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16."
Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.
Hum. Mol. Genet. 10:339-352(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ARG-146.
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-146.
Tissue: Placenta.
[8]"Human CLK2 links cell cycle progression, apoptosis, and telomere length regulation."
Jiang N., Benard C.Y., Kebir H., Shoubridge E.A., Hekimi S.
J. Biol. Chem. 278:21678-21684(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability."
Hurov K.E., Cotta-Ramusino C., Elledge S.J.
Genes Dev. 24:1939-1950(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TTI1 AND TTI2.
[11]"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes."
Takai H., Xie Y., de Lange T., Pavletich N.P.
Genes Dev. 24:2019-2030(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATM; ATR; MTOR; PRKDC; RUVBL2; TTI1 AND TTI2.
[12]"Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly."
Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K., Iemura S., Natsume T., Mizushima N.
J. Biol. Chem. 285:20109-20116(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TTI1; MTOR; ATM; ATR; PRKDC; SMG1 AND TRRAP.
[13]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[14]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-836, MASS SPECTROMETRY.
[16]"PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response."
Xie L., Pi X., Mishra A., Fong G., Peng J., Patterson C.
J. Clin. Invest. 122:2827-2836(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: HYDROXYLATION AT PRO-374; PRO-419 AND PRO-422 BY PHD3.
[17]"SCF(Fbxo9) and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma."
Fernandez-Saiz V., Targosz B.S., Lemeer S., Eichner R., Langer C., Bullinger L., Reiter C., Slotta-Huspenina J., Schroeder S., Knorn A.M., Kurutz J., Peschel C., Pagano M., Kuster B., Bassermann F.
Nat. Cell Biol. 15:72-81(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE MTORC1 COMPLEX, IDENTIFICATION IN THE MTORC2 COMPLEX, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-485; SER-487 AND SER-491, UBIQUITINATION, MUTAGENESIS OF SER-485.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB014583 mRNA. Translation: BAA31658.3. Different initiation.
AL080126 mRNA. Translation: CAB45724.1.
AL137394 mRNA. Translation: CAB70722.1.
AE006467 Genomic DNA. Translation: AAK61284.1.
AL031705 Genomic DNA. Translation: CAC37283.1.
CH471112 Genomic DNA. Translation: EAW85647.1.
CH471112 Genomic DNA. Translation: EAW85649.1.
CH471112 Genomic DNA. Translation: EAW85650.1.
BC017188 mRNA. Translation: AAH17188.1.
IPIIPI00016868.
PIRT12514.
RefSeqNP_057195.2. NM_016111.3.
UniGeneHs.271044.

3D structure databases

ProteinModelPortalQ9Y4R8.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9Y4R8. 17 interactions.
STRING9606.ENSP00000262319.

PTM databases

PhosphoSiteQ9Y4R8.

Polymorphism databases

DMDM166987394.

Proteomic databases

PaxDbQ9Y4R8.
PRIDEQ9Y4R8.

Protocols and materials databases

DNASU9894.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262319; ENSP00000262319; ENSG00000100726.
GeneID9894.
KEGGhsa:9894.
UCSCuc002cly.3. human.

Organism-specific databases

CTD9894.
GeneCardsGC16P001543.
H-InvDBHIX0012685.
HGNCHGNC:29099. TELO2.
HPAHPA041348.
HPA041473.
MIM611140. gene.
neXtProtNX_Q9Y4R8.
PharmGKBPA162405604.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG327559.
HOGENOMHOG000154542.
HOVERGENHBG108557.
InParanoidQ9Y4R8.
KOK11137.
OMAHGRQKEI.
OrthoDBEOG42JNQW.

Gene expression databases

ArrayExpressQ9Y4R8.
BgeeQ9Y4R8.
CleanExHS_TELO2.
GenevestigatorQ9Y4R8.

Family and domain databases

InterProIPR019337. Telomere_length_regulation_dom.
[Graphical view]
PfamPF10193. Telomere_reg-2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTELO2. human.
GenomeRNAi9894.
NextBio37303.
SOURCESearch...

Entry information

Entry nameTELO2_HUMAN
AccessionPrimary (citable) accession number: Q9Y4R8
Secondary accession number(s): D3DU73 expand/collapse secondary AC list , O75168, Q7LDV4, Q9BR21
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: February 5, 2008
Last modified: May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families