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Protein

TELO2-interacting protein 1 homolog

Gene

TTI1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Biological processi

  • regulation of TOR signaling Source: UniProtKB
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101407-MONOMER.
SIGNORiO43156.

Names & Taxonomyi

Protein namesi
Recommended name:
TELO2-interacting protein 1 homolog
Alternative name(s):
Protein SMG10
Gene namesi
Name:TTI1
Synonyms:KIAA0406, SMG10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:29029. TTI1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • TORC1 complex Source: UniProtKB
  • TORC2 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi828S → A: Abolishes phosphorylation by CK2 in response to growth factor deprivation and subsequent ubiquitination and degradation. 1 Publication1

Organism-specific databases

DisGeNETi9675.
OpenTargetsiENSG00000101407.
PharmGKBiPA165392722.

Polymorphism and mutation databases

BioMutaiTTI1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000507511 – 1089TELO2-interacting protein 1 homologAdd BLAST1089

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei459PhosphoserineCombined sources1
Modified residuei828Phosphoserine; by CK2Combined sources1 Publication1

Post-translational modificationi

Phosphorylated at Ser-828 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.1 Publication
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 mTORC1.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO43156.
MaxQBiO43156.
PaxDbiO43156.
PeptideAtlasiO43156.
PRIDEiO43156.

PTM databases

iPTMnetiO43156.
PhosphoSitePlusiO43156.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000101407.
CleanExiHS_KIAA0406.
ExpressionAtlasiO43156. baseline and differential.
GenevisibleiO43156. HS.

Organism-specific databases

HPAiCAB034230.

Interactioni

Subunit structurei

Component of the TTT complex composed of TELO2, TTI1 and TTI2. Interacts with ATM, ATR, MTOR, PRKDC, SMG1, TELO2, TRRAP AND TTI2. Component of the mTORC1 and mTORC2 complexes.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATMQ133155EBI-1055680,EBI-495465
ATRQ135352EBI-1055680,EBI-968983
TELO2Q9Y4R87EBI-1055680,EBI-1043674

Protein-protein interaction databases

BioGridi115030. 45 interactors.
DIPiDIP-50660N.
IntActiO43156. 21 interactors.
STRINGi9606.ENSP00000362546.

Structurei

3D structure databases

ProteinModelPortaliO43156.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi833 – 836Poly-Glu4

Sequence similaritiesi

Belongs to the tti1 family.Curated

Phylogenomic databases

eggNOGiKOG4524. Eukaryota.
ENOG410XSN6. LUCA.
GeneTreeiENSGT00390000009748.
HOGENOMiHOG000234009.
HOVERGENiHBG052183.
InParanoidiO43156.
KOiK20403.
OMAiEERRWNS.
OrthoDBiEOG091G06Y4.
PhylomeDBiO43156.
TreeFamiTF315296.

Family and domain databases

Gene3Di1.25.10.10. 4 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR016441. Tti1.
[Graphical view]
PIRSFiPIRSF005250. UCP005250. 1 hit.
SUPFAMiSSF48371. SSF48371. 5 hits.

Sequencei

Sequence statusi: Complete.

O43156-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVFDTPEEA FGVLRPVCVQ LTKTQTVENV EHLQTRLQAV SDSALQELQQ
60 70 80 90 100
YILFPLRFTL KTPGPKRERL IQSVVECLTF VLSSTCVKEQ ELLQELFSEL
110 120 130 140 150
SACLYSPSSQ KPAAVSEELK LAVIQGLSTL MHSAYGDIIL TFYEPSILPR
160 170 180 190 200
LGFAVSLLLG LAEQEKSKQI KIAALKCLQV LLLQCDCQDH PRSLDELEQK
210 220 230 240 250
QLGDLFASFL PGISTALTRL ITGDFKQGHS IVVSSLKIFY KTVSFIMADE
260 270 280 290 300
QLKRISKVQA KPAVEHRVAE LMVYREADWV KKTGDKLTIL IKKIIECVSV
310 320 330 340 350
HPHWKVRLEL VELVEDLLLK CSQSLVECAG PLLKALVGLV NDESPEIQAQ
360 370 380 390 400
CNKVLRHFAD QKVVVGNKAL ADILSESLHS LATSLPRLMN SQDDQGKFST
410 420 430 440 450
LSLLLGYLKL LGPKINFVLN SVAHLQRLSK ALIQVLELDV ADIKIVEERR
460 470 480 490 500
WNSDDLNASP KTSATQPWNR IQRRYFRFFT DERIFMLLRQ VCQLLGYYGN
510 520 530 540 550
LYLLVDHFME LYHQSVVYRK QAAMILNELV TGAAGLEVED LHEKHIKTNP
560 570 580 590 600
EELREIVTSI LEEYTSQENW YLVTCLETEE MGEELMMEHP GLQAITSGEH
610 620 630 640 650
TCQVTSFLAF SKPSPTICSM NSNIWQICIQ LEGIGQFAYA LGKDFCLLLM
660 670 680 690 700
SALYPVLEKA GDQTLLISQV ATSTMMDVCR ACGYDSLQHL INQNSDYLVN
710 720 730 740 750
GISLNLRHLA LHPHTPKVLE VMLRNSDANL LPLVADVVQD VLATLDQFYD
760 770 780 790 800
KRAASFVSVL HALMAALAQW FPDTGNLGHL QEQSLGEEGS HLNQRPAALE
810 820 830 840 850
KSTTTAEDIE QFLLNYLKEK DVADGNVSDF DNEEEEQSVP PKVDENDTRP
860 870 880 890 900
DVEPPLPLQI QIAMDVMERC IHLLSDKNLQ IRLKVLDVLD LCVVVLQSHK
910 920 930 940 950
NQLLPLAHQA WPSLVHRLTR DAPLAVLRAF KVLRTLGSKC GDFLRSRFCK
960 970 980 990 1000
DVLPKLAGSL VTQAPISARA GPVYSHTLAF KLQLAVLQGL GPLCERLDLG
1010 1020 1030 1040 1050
EGDLNKVADA CLIYLSVKQP VKLQEAARSV FLHLMKVDPD STWFLLNELY
1060 1070 1080
CPVQFTPPHP SLHPVQLHGA SGQQNPYTTN VLQLLKELQ
Length:1,089
Mass (Da):122,069
Last modified:October 10, 2002 - v3
Checksum:i27F4D3EFAC18A54E
GO

Sequence cautioni

The sequence BAA23702 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034033450R → H.Corresponds to variant rs36059660dbSNPEnsembl.1
Natural variantiVAR_014082671A → V.Corresponds to variant rs1057238dbSNPEnsembl.1
Natural variantiVAR_049509751K → E.Corresponds to variant rs6091654dbSNPEnsembl.1
Natural variantiVAR_014083979A → T.Corresponds to variant rs1064275dbSNPEnsembl.1
Natural variantiVAR_0340341028R → K.Corresponds to variant rs34900517dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007866 mRNA. Translation: BAA23702.2. Different initiation.
BR000854 mRNA. Translation: FAA00688.1.
AL109823 Genomic DNA. Translation: CAI19022.1.
CH471077 Genomic DNA. Translation: EAW76047.1.
CH471077 Genomic DNA. Translation: EAW76048.1.
BC013121 mRNA. Translation: AAH13121.1.
BC013755 mRNA. Translation: AAH13755.1.
CCDSiCCDS13300.1.
PIRiT00052.
RefSeqiNP_001290386.1. NM_001303457.1.
NP_055472.1. NM_014657.2.
UniGeneiHs.655481.

Genome annotation databases

EnsembliENST00000373447; ENSP00000362546; ENSG00000101407.
ENST00000373448; ENSP00000362547; ENSG00000101407.
ENST00000449821; ENSP00000407270; ENSG00000101407.
GeneIDi9675.
KEGGihsa:9675.
UCSCiuc002xhl.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007866 mRNA. Translation: BAA23702.2. Different initiation.
BR000854 mRNA. Translation: FAA00688.1.
AL109823 Genomic DNA. Translation: CAI19022.1.
CH471077 Genomic DNA. Translation: EAW76047.1.
CH471077 Genomic DNA. Translation: EAW76048.1.
BC013121 mRNA. Translation: AAH13121.1.
BC013755 mRNA. Translation: AAH13755.1.
CCDSiCCDS13300.1.
PIRiT00052.
RefSeqiNP_001290386.1. NM_001303457.1.
NP_055472.1. NM_014657.2.
UniGeneiHs.655481.

3D structure databases

ProteinModelPortaliO43156.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115030. 45 interactors.
DIPiDIP-50660N.
IntActiO43156. 21 interactors.
STRINGi9606.ENSP00000362546.

PTM databases

iPTMnetiO43156.
PhosphoSitePlusiO43156.

Polymorphism and mutation databases

BioMutaiTTI1.

Proteomic databases

EPDiO43156.
MaxQBiO43156.
PaxDbiO43156.
PeptideAtlasiO43156.
PRIDEiO43156.

Protocols and materials databases

DNASUi9675.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000373447; ENSP00000362546; ENSG00000101407.
ENST00000373448; ENSP00000362547; ENSG00000101407.
ENST00000449821; ENSP00000407270; ENSG00000101407.
GeneIDi9675.
KEGGihsa:9675.
UCSCiuc002xhl.4. human.

Organism-specific databases

CTDi9675.
DisGeNETi9675.
GeneCardsiTTI1.
HGNCiHGNC:29029. TTI1.
HPAiCAB034230.
MIMi614425. gene.
neXtProtiNX_O43156.
OpenTargetsiENSG00000101407.
PharmGKBiPA165392722.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4524. Eukaryota.
ENOG410XSN6. LUCA.
GeneTreeiENSGT00390000009748.
HOGENOMiHOG000234009.
HOVERGENiHBG052183.
InParanoidiO43156.
KOiK20403.
OMAiEERRWNS.
OrthoDBiEOG091G06Y4.
PhylomeDBiO43156.
TreeFamiTF315296.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000101407-MONOMER.
SIGNORiO43156.

Miscellaneous databases

ChiTaRSiTTI1. human.
GenomeRNAii9675.
PROiO43156.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101407.
CleanExiHS_KIAA0406.
ExpressionAtlasiO43156. baseline and differential.
GenevisibleiO43156. HS.

Family and domain databases

Gene3Di1.25.10.10. 4 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR016441. Tti1.
[Graphical view]
PIRSFiPIRSF005250. UCP005250. 1 hit.
SUPFAMiSSF48371. SSF48371. 5 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiTTI1_HUMAN
AccessioniPrimary (citable) accession number: O43156
Secondary accession number(s): D6W4K3
, Q5JX67, Q96A38, Q9BR47, Q9H4K0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: October 10, 2002
Last modified: November 30, 2016
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.