Q9Y4R8 (TELO2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Telomere length regulation protein TEL2 homolog

Alternative name(s):
Protein clk-2 homolog
Short name=hCLK2

Gene names

Name:	TELO2
Synonyms:	KIAA0683

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	837 AA.
Sequence status	Complete.
Protein existence	Evidence 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.12
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. Ref.12 Ref.13 Ref.14
Subcellular location	Cytoplasm. Membrane. Nucleus. Chromosome › telomere Probable Ref.8.
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.

Ontologies

Keywords
Cellular component	Chromosome Cytoplasm Membrane Nucleus Telomere
Coding sequence diversity	Polymorphism
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	chromosome, telomeric region Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from direct assay. Source: HPA membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction Ref.13. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATM	Q13315	4	EBI-1043674,EBI-495465
TTI1	O43156	6	EBI-1043674,EBI-1055680

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 837	837	Telomere length regulation protein TEL2 homolog		PRO_0000318515
Amino acid modifications
	Modified residue	637	1	Phosphoserine Ref.11
	Modified residue	642	1	Phosphothreonine Ref.11
	Modified residue	688	1	Phosphoserine Ref.9
	Modified residue	836	1	Phosphoserine Ref.9 Ref.10 Ref.11
Natural variations
	Natural variant	7	1	E → G. Corresponds to variant rs2667661 [ dbSNP | Ensembl ].		VAR_038752
	Natural variant	7	1	E → Q. Corresponds to variant rs2667660 [ dbSNP | Ensembl ].		VAR_061839
	Natural variant	146	1	Q → R. Ref.2 Ref.3 Ref.6 Ref.7 Corresponds to variant rs2235624 [ dbSNP | Ensembl ].		VAR_038753
	Natural variant	511	1	A → V. Corresponds to variant rs58099766 [ dbSNP | Ensembl ].		VAR_061840
	Natural variant	674	1	Q → R. Corresponds to variant rs2248128 [ dbSNP | Ensembl ].		VAR_038754
Experimental info
	Sequence conflict	7	1	E → R in BAA31658. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9Y4R8 [UniParc]. Last modified February 5, 2008. Version 2. Checksum: 76CB619C73C1F1A7	FASTA	837	91,747
	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

References

	« Hide 'large scale' referencesShow '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: 9734811] [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. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [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: 17974005] [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: 11157797] [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. , 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: 15616553] [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. , 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: 15489334] [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: 12670948] [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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-688 AND SER-836, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-836, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-637; THR-642 AND SER-836, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[12]	"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: 20810650] [Abstract] Cited for: FUNCTION, INTERACTION WITH TTI1 AND TTI2.
[13]	"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: 20801936] [Abstract] Cited for: INTERACTION WITH ATM; ATR; MTOR; PRKDC; RUVBL2; TTI1 AND TTI2.
[14]	"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: 20427287] [Abstract] Cited for: INTERACTION WITH TTI1; MTOR; ATM; ATR; PRKDC; SMG1 AND TRRAP.
[15]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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.
IPI	IPI00016868.
PIR	T12514.
RefSeq	NP_057195.2. NM_016111.3.
UniGene	Hs.271044.
3D structure databases
ProteinModelPortal	Q9Y4R8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y4R8. 16 interactions.
STRING	Q9Y4R8.
Polymorphism databases
DMDM	166987394.
Proteomic databases
PRIDE	Q9Y4R8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262319; ENSP00000262319; ENSG00000100726.
GeneID	9894.
KEGG	hsa:9894.
UCSC	uc002cly.1. human.
Organism-specific databases
CTD	9894.
GeneCards	GC16P001473.
H-InvDB	HIX0012685.
HGNC	HGNC:29099. TELO2.
HPA	HPA041348. HPA041473.
MIM	611140. gene.
neXtProt	NX_Q9Y4R8.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11806.
GeneTree	ENSGT00390000006698.
HOGENOM	HBG358250.
HOVERGEN	HBG108557.
InParanoid	Q9Y4R8.
OMA	RIHPEGP.
OrthoDB	EOG42JNQW.
PhylomeDB	Q9Y4R8.
Gene expression databases
ArrayExpress	Q9Y4R8.
Bgee	Q9Y4R8.
CleanEx	HS_TELO2.
Genevestigator	Q9Y4R8.
Family and domain databases
InterPro	IPR019337. Telomere_length_regulation_dom. [Graphical view]
KO	K11137.
Pfam	PF10193. Telomere_reg-2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	37303.
SOURCE	Search...

Entry information

Entry name

TELO2_HUMAN

Accession

Primary (citable) accession number: Q9Y4R8
Secondary accession number(s): D3DU73 , O75168, Q7LDV4, Q9BR21

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	February 5, 2008
Last modified:	January 25, 2012
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.