TTI2_HUMAN
ID TTI2_HUMAN Reviewed; 508 AA.
AC Q6NXR4; D3DSV7; Q96IM2; Q9H5N4;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=TELO2-interacting protein 2;
GN Name=TTI2; Synonyms=C8orf41;
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], AND VARIANT GLY-63.
RC TISSUE=Colon;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-63.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-63.
RC TISSUE=Skin, and 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 [5]
RP FUNCTION, AND INTERACTION WITH TELO2 AND TTI1.
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 [6]
RP FUNCTION, AND INTERACTION WITH TTI1 AND TELO2.
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 [7]
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 [8]
RP INTERACTION WITH WAC.
RX PubMed=26812014; DOI=10.1016/j.devcel.2015.12.019;
RA David-Morrison G., Xu Z., Rui Y.N., Charng W.L., Jaiswal M., Yamamoto S.,
RA Xiong B., Zhang K., Sandoval H., Duraine L., Zuo Z., Zhang S., Bellen H.J.;
RT "WAC regulates mTOR activity by acting as an adaptor for the TTT and
RT Pontin/Reptin complexes.";
RL Dev. Cell 36:139-151(2016).
RN [9]
RP VARIANT MRT39 ASN-436.
RX PubMed=23956177; DOI=10.1002/humu.22399;
RA Langouet M., Saadi A., Rieunier G., Moutton S., Siquier-Pernet K.,
RA Fernet M., Nitschke P., Munnich A., Stern M.H., Chaouch M., Colleaux L.;
RT "Mutation in TTI2 reveals a role for triple T complex in human brain
RT development.";
RL Hum. Mutat. 34:1472-1476(2013).
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.
CC {ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:20810650}.
CC -!- SUBUNIT: Component of the TTT complex composed of TELO2, TTI1 and TTI2.
CC Interacts with TELO2 and TTI1 (PubMed:20801936, PubMed:20810650).
CC Interacts with WAC; WAC positively regulates MTOR activity by promoting
CC the assembly of the TTT complex and the RUVBL complex composed of
CC RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the
CC dimerization of the mTORC1 complex and its subsequent activation
CC (PubMed:26812014). {ECO:0000269|PubMed:20801936,
CC ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:26812014}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal recessive 39
CC (MRT39) [MIM:615541]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRT39
CC affected individuals show delayed psychomotor development, severe
CC speech delay, short stature, kyphoscoliosis, and dysmorphic facial
CC features. Behavioral abnormalities include hyperactivity, aggression,
CC and stereotypic movements. {ECO:0000269|PubMed:23956177}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the TTI2 family. {ECO:0000305}.
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DR EMBL; AK026916; BAB15590.1; -; mRNA.
DR EMBL; AC091144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63397.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63398.1; -; Genomic_DNA.
DR EMBL; BC007387; AAH07387.1; -; mRNA.
DR EMBL; BC066935; AAH66935.1; -; mRNA.
DR CCDS; CCDS6090.1; -.
DR RefSeq; NP_001095871.1; NM_001102401.2.
DR RefSeq; NP_001252510.1; NM_001265581.1.
DR RefSeq; NP_079391.2; NM_025115.3.
DR PDB; 7OLE; EM; 3.41 A; J=1-508.
DR PDBsum; 7OLE; -.
DR AlphaFoldDB; Q6NXR4; -.
DR BioGRID; 123164; 64.
DR ComplexPortal; CPX-6148; TTT complex.
DR IntAct; Q6NXR4; 17.
DR MINT; Q6NXR4; -.
DR STRING; 9606.ENSP00000478396; -.
DR GlyGen; Q6NXR4; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q6NXR4; -.
DR PhosphoSitePlus; Q6NXR4; -.
DR BioMuta; TTI2; -.
DR DMDM; 74736990; -.
DR EPD; Q6NXR4; -.
DR jPOST; Q6NXR4; -.
DR MassIVE; Q6NXR4; -.
DR MaxQB; Q6NXR4; -.
DR PaxDb; Q6NXR4; -.
DR PeptideAtlas; Q6NXR4; -.
DR PRIDE; Q6NXR4; -.
DR ProteomicsDB; 66765; -.
DR Antibodypedia; 10728; 52 antibodies from 17 providers.
DR DNASU; 80185; -.
DR Ensembl; ENST00000360742.9; ENSP00000353971.5; ENSG00000129696.13.
DR Ensembl; ENST00000431156.7; ENSP00000411169.3; ENSG00000129696.13.
DR Ensembl; ENST00000613904.1; ENSP00000478396.1; ENSG00000129696.13.
DR GeneID; 80185; -.
DR KEGG; hsa:80185; -.
DR MANE-Select; ENST00000431156.7; ENSP00000411169.3; NM_001102401.4; NP_001095871.1.
DR UCSC; uc003xjl.6; human.
DR CTD; 80185; -.
DR DisGeNET; 80185; -.
DR GeneCards; TTI2; -.
DR HGNC; HGNC:26262; TTI2.
DR HPA; ENSG00000129696; Low tissue specificity.
DR MalaCards; TTI2; -.
DR MIM; 614426; gene.
DR MIM; 615541; phenotype.
DR neXtProt; NX_Q6NXR4; -.
DR OpenTargets; ENSG00000129696; -.
DR Orphanet; 391307; Severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome.
DR PharmGKB; PA142672360; -.
DR VEuPathDB; HostDB:ENSG00000129696; -.
DR eggNOG; ENOG502QVMM; Eukaryota.
DR GeneTree; ENSGT00390000003878; -.
DR HOGENOM; CLU_047507_0_0_1; -.
DR InParanoid; Q6NXR4; -.
DR OMA; WDVHTDQ; -.
DR OrthoDB; 1298755at2759; -.
DR PhylomeDB; Q6NXR4; -.
DR TreeFam; TF328871; -.
DR PathwayCommons; Q6NXR4; -.
DR SignaLink; Q6NXR4; -.
DR BioGRID-ORCS; 80185; 631 hits in 1099 CRISPR screens.
DR ChiTaRS; TTI2; human.
DR GenomeRNAi; 80185; -.
DR Pharos; Q6NXR4; Tdark.
DR PRO; PR:Q6NXR4; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6NXR4; protein.
DR Bgee; ENSG00000129696; Expressed in ventricular zone and 140 other tissues.
DR ExpressionAtlas; Q6NXR4; baseline and differential.
DR Genevisible; Q6NXR4; HS.
DR GO; GO:0070209; C:ASTRA complex; IBA:GO_Central.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0110078; C:TTT complex; IPI:ComplexPortal.
DR GO; GO:2000003; P:positive regulation of DNA damage checkpoint; IC:ComplexPortal.
DR GO; GO:0050821; P:protein stabilization; IC:ComplexPortal.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR018870; Tti2.
DR PANTHER; PTHR32226; PTHR32226; 1.
DR Pfam; PF10521; Tti2; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Intellectual disability; Reference proteome.
FT CHAIN 1..508
FT /note="TELO2-interacting protein 2"
FT /id="PRO_0000279414"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 63
FT /note="E -> G (in dbSNP:rs2304748)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_030886"
FT VARIANT 425
FT /note="L -> R (in dbSNP:rs3736497)"
FT /id="VAR_030887"
FT VARIANT 436
FT /note="I -> N (in MRT39; impaired TTT complex formation;
FT dbSNP:rs398122367)"
FT /evidence="ECO:0000269|PubMed:23956177"
FT /id="VAR_070671"
FT CONFLICT 468
FT /note="C -> R (in Ref. 1; BAB15590)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 508 AA; 56915 MW; 6BF98826997034F7 CRC64;
MELDSALEAP SQEDSNLSEE LSHSAFGQAF SKILHCLARP EARRGNVKDA VLKDLGDLIE
ATEFDRLFEG TGARLRGMPE TLGQVAKALE KYAAPSKEEE GGGDGHSEAA EKAAQVGLLF
LKLLGKVETA KNSLVGPAWQ TGLHHLAGPV YIFAITHSLE QPWTTPRSRE VAREVLTSLL
QVTECGSVAG FLHGENEDEK GRLSVILGLL KPDLYKESWK NNPAIKHVFS WTLQQVTRPW
LSQHLERVLP ASLVISDDYQ TENKILGVHC LHHIVLNVPA ADLLQYNRAQ VLYHAISNHL
YTPEHHLIQA VLLCLLDLFP ILEKTLHWKG DGARPTTHCD EVLRLILTHM EPEHRLLLRR
TYARNLPAFV NRLGILTVRH LKRLERVIIG YLEVYDGPEE EARLKILETL KLLMQHTWPR
VSCRLVVLLK ALLKLICDVA RDPNLTPESV KSALLQEATD CLILLDRCSQ GRVKGLLAKI
PQSCEDRKVV NYIRKVQQVS EGAPYNGT
