UniProtKB - Q9NYB0 (TE2IP_HUMAN)
Protein
Telomeric repeat-binding factor 2-interacting protein 1
Gene
TERF2IP
Organism
Homo sapiens (Human)
Status
Functioni
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B signaling by promoting IKK-mediated phosphorylation of RELA/p65, leading to activate expression of NF-kappa-B target genes.2 Publications
Miscellaneous
Shares a bidirectional promoter with KARS1.1 Publication
Caution
Was reported to participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair in the absence of TERF2 (PubMed:19763083). However, this probably does not corresponds to its primary function and experiments in mouse showed that it is dispensible for such process and is required for repression of homology-directed repair (HDR).1 Publication
GO - Molecular functioni
- DNA binding Source: GO_Central
- G-rich strand telomeric DNA binding Source: BHF-UCL
- phosphatase binding Source: CAFA
- telomeric DNA binding Source: BHF-UCL
GO - Biological processi
- negative regulation of DNA recombination at telomere Source: UniProtKB
- negative regulation of protein phosphorylation Source: CAFA
- negative regulation of telomere maintenance Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of NIK/NF-kappaB signaling Source: CAFA
- positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
- positive regulation of protein acetylation Source: UniProtKB
- protection from non-homologous end joining at telomere Source: BHF-UCL
- protein localization to chromosome, telomeric region Source: BHF-UCL
- regulation of double-strand break repair via homologous recombination Source: UniProtKB
- regulation of telomere maintenance Source: BHF-UCL
- regulation of transcription, DNA-templated Source: CAFA
- telomere capping Source: Reactome
- telomere maintenance Source: BHF-UCL
- telomere maintenance via telomerase Source: ProtInc
- telomere maintenance via telomere lengthening Source: UniProtKB
Keywordsi
Molecular function | Activator |
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q9NYB0 |
Reactomei | R-HSA-110328, Recognition and association of DNA glycosylase with site containing an affected pyrimidine R-HSA-110329, Cleavage of the damaged pyrimidine R-HSA-110330, Recognition and association of DNA glycosylase with site containing an affected purine R-HSA-110331, Cleavage of the damaged purine R-HSA-1221632, Meiotic synapsis R-HSA-171306, Packaging Of Telomere Ends R-HSA-171319, Telomere Extension By Telomerase R-HSA-174411, Polymerase switching on the C-strand of the telomere R-HSA-174414, Processive synthesis on the C-strand of the telomere R-HSA-174417, Telomere C-strand (Lagging Strand) Synthesis R-HSA-174430, Telomere C-strand synthesis initiation R-HSA-174437, Removal of the Flap Intermediate from the C-strand R-HSA-2559586, DNA Damage/Telomere Stress Induced Senescence R-HSA-9670095, Inhibition of DNA recombination at telomere |
Names & Taxonomyi
Protein namesi | Recommended name: Telomeric repeat-binding factor 2-interacting protein 1Short name: TERF2-interacting telomeric protein 1 Short name: TRF2-interacting telomeric protein 1 Alternative name(s): Dopamine receptor-interacting protein 5 Repressor/activator protein 1 homolog Short name: RAP1 homolog Short name: hRap1 |
Gene namesi | Name:TERF2IP Synonyms:DRIP5, RAP1 ORF Names:PP8000 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000166848.5 |
HGNCi | HGNC:19246, TERF2IP |
MIMi | 605061, gene |
neXtProti | NX_Q9NYB0 |
Subcellular locationi
Nucleus
- Nucleus By similarity
Other locations
- Cytoplasm By similarity
- Chromosome By similarity
- telomere By similarity
Note: Associates with chromosomes, both at telomeres and in extratelomeric sites. Also exists as a cytoplasmic form, where it associates with the IKK complex.By similarity
Cytosol
- cytosol Source: HPA
Nucleus
- nuclear body Source: HPA
- nuclear chromosome Source: ProtInc
- nuclear chromosome, telomeric region Source: BHF-UCL
- nuclear envelope Source: Ensembl
- nuclear telomere cap complex Source: BHF-UCL
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
- shelterin complex Source: BHF-UCL
Other locations
- chromosome, telomeric region Source: BHF-UCL
- cytoplasm Source: CAFA
Keywords - Cellular componenti
Chromosome, Cytoplasm, Nucleus, TelomerePathology & Biotechi
Organism-specific databases
DisGeNETi | 54386 |
MalaCardsi | TERF2IP |
OpenTargetsi | ENSG00000166848 |
Orphaneti | 618, Familial melanoma |
PharmGKBi | PA134976325 |
Miscellaneous databases
Pharosi | Q9NYB0, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3751647 |
Polymorphism and mutation databases
BioMutai | TERF2IP |
DMDMi | 21542267 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000197126 | 2 – 399 | Telomeric repeat-binding factor 2-interacting protein 1Add BLAST | 398 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 36 | PhosphoserineCombined sources | 1 | |
Modified residuei | 43 | PhosphoserineCombined sources | 1 | |
Cross-linki | 114 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 154 | PhosphoserineCombined sources | 1 | |
Modified residuei | 156 | PhosphoserineCombined sources | 1 | |
Cross-linki | 194 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Modified residuei | 203 | PhosphoserineCombined sources | 1 | |
Modified residuei | 206 | PhosphoserineCombined sources | 1 | |
Cross-linki | 208 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 212 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 240 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | ||
Cross-linki | 372 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources |
Keywords - PTMi
Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q9NYB0 |
jPOSTi | Q9NYB0 |
MassIVEi | Q9NYB0 |
MaxQBi | Q9NYB0 |
PaxDbi | Q9NYB0 |
PeptideAtlasi | Q9NYB0 |
PRIDEi | Q9NYB0 |
ProteomicsDBi | 83206 |
PTM databases
iPTMneti | Q9NYB0 |
PhosphoSitePlusi | Q9NYB0 |
Expressioni
Tissue specificityi
Ubiquitous. Highly expressed.
Gene expression databases
Bgeei | ENSG00000166848, Expressed in pituitary gland and 250 other tissues |
ExpressionAtlasi | Q9NYB0, baseline and differential |
Genevisiblei | Q9NYB0, HS |
Organism-specific databases
HPAi | ENSG00000166848, Low tissue specificity |
Interactioni
Subunit structurei
Associates with the I-kappa-B-kinase (IKK) core complex, composed of CHUK, IKBKB and IKBKG (By similarity). Homodimer.
Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1.
Interacts with TERF2; the interaction is direct. Does not interact with TERF1.
Interacts with SLX4/BTBD12.
By similarity3 PublicationsBinary interactionsi
Q9NYB0
GO - Molecular functioni
- phosphatase binding Source: CAFA
Protein-protein interaction databases
BioGRIDi | 119942, 167 interactors |
ComplexPortali | CPX-152, Shelterin complex |
CORUMi | Q9NYB0 |
DIPi | DIP-34868N |
IntActi | Q9NYB0, 160 interactors |
MINTi | Q9NYB0 |
STRINGi | 9606.ENSP00000300086 |
Chemistry databases
BindingDBi | Q9NYB0 |
Miscellaneous databases
RNActi | Q9NYB0, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | Q9NYB0 |
SMRi | Q9NYB0 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9NYB0 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 78 – 101 | BRCTAdd BLAST | 24 | |
Domaini | 128 – 188 | Myb-likeAdd BLAST | 61 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 383 – 399 | Nuclear localization signalSequence analysisAdd BLAST | 17 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 214 – 304 | Asp/Glu-rich (acidic)Add BLAST | 91 |
Sequence similaritiesi
Belongs to the RAP1 family.Curated
Phylogenomic databases
eggNOGi | ENOG502RPXS, Eukaryota |
GeneTreei | ENSGT00390000005351 |
HOGENOMi | CLU_028192_0_0_1 |
InParanoidi | Q9NYB0 |
OMAi | TQHSWQA |
OrthoDBi | 602157at2759 |
PhylomeDBi | Q9NYB0 |
TreeFami | TF332348 |
Family and domain databases
Gene3Di | 1.10.10.2170, 1 hit 3.40.50.10190, 1 hit |
InterProi | View protein in InterPro IPR001357, BRCT_dom IPR036420, BRCT_dom_sf IPR009057, Homeobox-like_sf IPR021661, Rap1_C IPR038104, Rap1_C_sf IPR015010, Rap1_Myb_dom IPR039595, TE2IP/Rap1 |
PANTHERi | PTHR16466, PTHR16466, 2 hits |
Pfami | View protein in Pfam PF16589, BRCT_2, 1 hit PF08914, Myb_DNA-bind_2, 1 hit PF11626, Rap1_C, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q9NYB0-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAEAMDLGKD PNGPTHSSTL FVRDDGSSMS FYVRPSPAKR RLSTLILHGG
60 70 80 90 100
GTVCRVQEPG AVLLAQPGEA LAEASGDFIS TQYILDCVER NERLELEAYR
110 120 130 140 150
LGPASAADTG SEAKPGALAE GAAEPEPQRH AGRIAFTDAD DVAILTYVKE
160 170 180 190 200
NARSPSSVTG NALWKAMEKS SLTQHSWQSL KDRYLKHLRG QEHKYLLGDA
210 220 230 240 250
PVSPSSQKLK RKAEEDPEAA DSGEPQNKRT PDLPEEEYVK EEIQENEEAV
260 270 280 290 300
KKMLVEATRE FEEVVVDESP PDFEIHITMC DDDPPTPEED SETQPDEEEE
310 320 330 340 350
EEEEKVSQPE VGAAIKIIRQ LMEKFNLDLS TVTQAFLKNS GELEATSAFL
360 370 380 390
ASGQRADGYP IWSRQDDIDL QKDDEDTREA LVKKFGAQNV ARRIEFRKK
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A590UJT3 | A0A590UJT3_HUMAN | Telomeric repeat-binding factor 2-i... | TERF2IP | 342 | Annotation score: | ||
H3BMI8 | H3BMI8_HUMAN | Telomeric repeat-binding factor 2-i... | TERF2IP | 99 | Annotation score: | ||
H3BR63 | H3BR63_HUMAN | Telomeric repeat-binding factor 2-i... | TERF2IP | 122 | Annotation score: |
Sequence cautioni
The sequence AAL55783 differs from that shown. Reason: Frameshift.Curated
The sequence BAA91317 differs from that shown. Reason: Erroneous termination. Truncated C-terminus.Curated
The sequence BAG60996 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 83 | Y → H in BAA91317 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_050195 | 324 | K → E. Corresponds to variant dbSNP:rs4888444Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF262988 mRNA Translation: AAF72711.1 AF250393 mRNA Translation: AAQ14259.1 AF289599 mRNA Translation: AAL55783.1 Frameshift. AK000669 mRNA Translation: BAA91317.1 Sequence problems. AK298880 mRNA Translation: BAG60996.1 Different initiation. AC025287 Genomic DNA No translation available. CH471114 Genomic DNA Translation: EAW95616.1 CH471114 Genomic DNA Translation: EAW95618.1 BC004465 mRNA Translation: AAH04465.1 BC005841 mRNA Translation: AAH05841.1 BC022428 mRNA Translation: AAH22428.1 BC078171 mRNA Translation: AAH78171.1 |
CCDSi | CCDS32491.1 |
RefSeqi | NP_061848.2, NM_018975.3 |
Genome annotation databases
Ensembli | ENST00000300086; ENSP00000300086; ENSG00000166848 |
GeneIDi | 54386 |
KEGGi | hsa:54386 |
UCSCi | uc002fet.3, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF262988 mRNA Translation: AAF72711.1 AF250393 mRNA Translation: AAQ14259.1 AF289599 mRNA Translation: AAL55783.1 Frameshift. AK000669 mRNA Translation: BAA91317.1 Sequence problems. AK298880 mRNA Translation: BAG60996.1 Different initiation. AC025287 Genomic DNA No translation available. CH471114 Genomic DNA Translation: EAW95616.1 CH471114 Genomic DNA Translation: EAW95618.1 BC004465 mRNA Translation: AAH04465.1 BC005841 mRNA Translation: AAH05841.1 BC022428 mRNA Translation: AAH22428.1 BC078171 mRNA Translation: AAH78171.1 |
CCDSi | CCDS32491.1 |
RefSeqi | NP_061848.2, NM_018975.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1FEX | NMR | - | A | 132-190 | [»] | |
3K6G | X-ray | 1.95 | A/B/C | 303-399 | [»] | |
4RQI | X-ray | 2.44 | E/F/G/H | 89-106 | [»] | |
BMRBi | Q9NYB0 | |||||
SMRi | Q9NYB0 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 119942, 167 interactors |
ComplexPortali | CPX-152, Shelterin complex |
CORUMi | Q9NYB0 |
DIPi | DIP-34868N |
IntActi | Q9NYB0, 160 interactors |
MINTi | Q9NYB0 |
STRINGi | 9606.ENSP00000300086 |
Chemistry databases
BindingDBi | Q9NYB0 |
ChEMBLi | CHEMBL3751647 |
PTM databases
iPTMneti | Q9NYB0 |
PhosphoSitePlusi | Q9NYB0 |
Polymorphism and mutation databases
BioMutai | TERF2IP |
DMDMi | 21542267 |
Proteomic databases
EPDi | Q9NYB0 |
jPOSTi | Q9NYB0 |
MassIVEi | Q9NYB0 |
MaxQBi | Q9NYB0 |
PaxDbi | Q9NYB0 |
PeptideAtlasi | Q9NYB0 |
PRIDEi | Q9NYB0 |
ProteomicsDBi | 83206 |
Protocols and materials databases
Antibodypediai | 1877, 491 antibodies |
DNASUi | 54386 |
Genome annotation databases
Ensembli | ENST00000300086; ENSP00000300086; ENSG00000166848 |
GeneIDi | 54386 |
KEGGi | hsa:54386 |
UCSCi | uc002fet.3, human |
Organism-specific databases
CTDi | 54386 |
DisGeNETi | 54386 |
EuPathDBi | HostDB:ENSG00000166848.5 |
GeneCardsi | TERF2IP |
HGNCi | HGNC:19246, TERF2IP |
HPAi | ENSG00000166848, Low tissue specificity |
MalaCardsi | TERF2IP |
MIMi | 605061, gene |
neXtProti | NX_Q9NYB0 |
OpenTargetsi | ENSG00000166848 |
Orphaneti | 618, Familial melanoma |
PharmGKBi | PA134976325 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RPXS, Eukaryota |
GeneTreei | ENSGT00390000005351 |
HOGENOMi | CLU_028192_0_0_1 |
InParanoidi | Q9NYB0 |
OMAi | TQHSWQA |
OrthoDBi | 602157at2759 |
PhylomeDBi | Q9NYB0 |
TreeFami | TF332348 |
Enzyme and pathway databases
PathwayCommonsi | Q9NYB0 |
Reactomei | R-HSA-110328, Recognition and association of DNA glycosylase with site containing an affected pyrimidine R-HSA-110329, Cleavage of the damaged pyrimidine R-HSA-110330, Recognition and association of DNA glycosylase with site containing an affected purine R-HSA-110331, Cleavage of the damaged purine R-HSA-1221632, Meiotic synapsis R-HSA-171306, Packaging Of Telomere Ends R-HSA-171319, Telomere Extension By Telomerase R-HSA-174411, Polymerase switching on the C-strand of the telomere R-HSA-174414, Processive synthesis on the C-strand of the telomere R-HSA-174417, Telomere C-strand (Lagging Strand) Synthesis R-HSA-174430, Telomere C-strand synthesis initiation R-HSA-174437, Removal of the Flap Intermediate from the C-strand R-HSA-2559586, DNA Damage/Telomere Stress Induced Senescence R-HSA-9670095, Inhibition of DNA recombination at telomere |
Miscellaneous databases
BioGRID-ORCSi | 54386, 14 hits in 850 CRISPR screens |
ChiTaRSi | TERF2IP, human |
EvolutionaryTracei | Q9NYB0 |
GeneWikii | TERF2IP |
GenomeRNAii | 54386 |
Pharosi | Q9NYB0, Tchem |
PROi | PR:Q9NYB0 |
RNActi | Q9NYB0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000166848, Expressed in pituitary gland and 250 other tissues |
ExpressionAtlasi | Q9NYB0, baseline and differential |
Genevisiblei | Q9NYB0, HS |
Family and domain databases
Gene3Di | 1.10.10.2170, 1 hit 3.40.50.10190, 1 hit |
InterProi | View protein in InterPro IPR001357, BRCT_dom IPR036420, BRCT_dom_sf IPR009057, Homeobox-like_sf IPR021661, Rap1_C IPR038104, Rap1_C_sf IPR015010, Rap1_Myb_dom IPR039595, TE2IP/Rap1 |
PANTHERi | PTHR16466, PTHR16466, 2 hits |
Pfami | View protein in Pfam PF16589, BRCT_2, 1 hit PF08914, Myb_DNA-bind_2, 1 hit PF11626, Rap1_C, 1 hit |
SUPFAMi | SSF46689, SSF46689, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TE2IP_HUMAN | |
Accessioni | Q9NYB0Primary (citable) accession number: Q9NYB0 Secondary accession number(s): B4DQN4 Q9NWR2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2002 |
Last sequence update: | October 1, 2000 | |
Last modified: | December 2, 2020 | |
This is version 195 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- 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 - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - 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