UniProtKB - P54274 (TERF1_HUMAN)
(max 400 entries)x
Your basket is currently empty.
Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)
Protein
Telomeric repeat-binding factor 1
Gene
TERF1
Organism
Homo sapiens (Human)
Status
Functioni
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and negatively regulates telomere length. Involved in the regulation of the mitotic spindle. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways.1 Publication
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| DNA bindingi | 403 – 428 | H-T-H motifPROSITE-ProRule annotationAdd BLAST | 26 |
GO - Molecular functioni
- ankyrin repeat binding Source: BHF-UCL
- DNA binding Source: UniProtKB
- DNA binding, bending Source: BHF-UCL
- double-stranded telomeric DNA binding Source: UniProtKB
- G-rich strand telomeric DNA binding Source: BHF-UCL
- microtubule binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: BHF-UCL
- telomeric DNA binding Source: BHF-UCL
- ubiquitin binding Source: BHF-UCL
GO - Biological processi
- cell division Source: UniProtKB-KW
- G2/M transition of mitotic cell cycle Source: UniProtKB
- meiotic telomere clustering Source: Ensembl
- mitotic spindle assembly checkpoint Source: UniProtKB
- negative regulation of DNA replication Source: BHF-UCL
- negative regulation of establishment of macromolecular complex localization to telomere Source: BHF-UCL
- negative regulation of establishment of protein localization to telomere Source: BHF-UCL
- negative regulation of establishment of RNA localization to telomere Source: BHF-UCL
- negative regulation of exonuclease activity Source: BHF-UCL
- negative regulation of telomerase activity Source: BHF-UCL
- negative regulation of telomere maintenance via semi-conservative replication Source: BHF-UCL
- negative regulation of telomere maintenance via telomerase Source: BHF-UCL
- negative regulation of telomere maintenance via telomere lengthening Source: BHF-UCL
- negative regulation of telomeric D-loop disassembly Source: BHF-UCL
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of microtubule polymerization Source: UniProtKB
- positive regulation of mitotic cell cycle Source: UniProtKB
- positive regulation of mitotic nuclear division Source: UniProtKB
- positive regulation of shelterin complex assembly Source: BHF-UCL
- protein homooligomerization Source: UniProtKB
- response to drug Source: Ensembl
- t-circle formation Source: BHF-UCL
- telomere capping Source: Reactome
- telomere maintenance Source: BHF-UCL
- telomere maintenance via telomerase Source: BHF-UCL
- telomeric D-loop disassembly Source: BHF-UCL
- telomeric loop formation Source: GO_Central
Keywordsi
| Molecular function | DNA-binding |
| Biological process | Cell cycle, Cell division, Mitosis |
Enzyme and pathway databases
| Reactomei | R-HSA-1221632. Meiotic synapsis. R-HSA-171306. Packaging Of Telomere Ends. R-HSA-2559586. DNA Damage/Telomere Stress Induced Senescence. |
| SIGNORi | P54274. |
Names & Taxonomyi
| Protein namesi | Recommended name: Telomeric repeat-binding factor 1Alternative name(s): NIMA-interacting protein 2 TTAGGG repeat-binding factor 1 Telomeric protein Pin2/TRF1 |
| Gene namesi | Name:TERF1 Synonyms:PIN2, TRBF1, TRF, TRF1 |
| 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
| HGNCi | HGNC:11728. TERF1. |
Subcellular locationi
- Nucleus
- Cytoplasm › cytoskeleton › spindle
- Chromosome › telomere
Note: Colocalizes with telomeric DNA in interphase and prophase cells. Telomeric localization decreases in metaphase, anaphase and telophase. Associates with the mitotic spindle.
GO - Cellular componenti
- chromosome, telomeric region Source: UniProtKB
- cytoplasm Source: UniProtKB-KW
- fibrillar center Source: HPA
- nuclear body Source: HPA
- nuclear chromosome, telomeric region Source: BHF-UCL
- nuclear telomere cap complex Source: BHF-UCL
- nucleolus Source: BHF-UCL
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
- shelterin complex Source: BHF-UCL
- spindle Source: UniProtKB-SubCell
Keywords - Cellular componenti
Chromosome, Cytoplasm, Cytoskeleton, Nucleus, TelomerePathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 74 | A → D: Abolishes dimerization and telomere binding; when associated with P-75. 1 Publication | 1 | |
| Mutagenesisi | 75 | A → P: Abolishes dimerization and telomere binding; when associated with D-74. 1 Publication | 1 | |
| Mutagenesisi | 77 | W → P: Abolishes telomere binding. 1 Publication | 1 | |
| Mutagenesisi | 81 | F → P: Abolishes telomere binding. 1 Publication | 1 | |
| Mutagenesisi | 90 | F → P: Diminishes telomere binding. | 1 | |
| Mutagenesisi | 115 | L → R: Loss of interaction with FBXO4. 1 Publication | 1 | |
| Mutagenesisi | 120 | L → R: Loss of interaction with FBXO4. 1 Publication | 1 | |
| Mutagenesisi | 219 | S → A: Loss of phosphorylation; induction of mitotic entry and apoptosis and increased radiation hypersensitivity of ataxia-telangiectasia cells. 1 Publication | 1 | |
| Mutagenesisi | 219 | S → D or E: Fails to induce apoptosis and decreases radiation hypersensitivity of ataxia-telangiectasia cells (phospho-mimicking mutants). 1 Publication | 1 |
Organism-specific databases
| DisGeNETi | 7013. |
| OpenTargetsi | ENSG00000147601. |
| PharmGKBi | PA36445. |
Polymorphism and mutation databases
| BioMutai | TERF1. |
| DMDMi | 206729904. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Initiator methioninei | RemovedCombined sources | |||
| ChainiPRO_0000197129 | 2 – 439 | Telomeric repeat-binding factor 1Add BLAST | 438 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
| Modified residuei | 11 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 219 | Phosphoserine; by ATM1 Publication | 1 |
Post-translational modificationi
Phosphorylated preferentially on Ser-219 in an ATM-dependent manner in response to ionizing DNA damage.1 Publication
ADP-ribosylation by TNKS1 or TNKS2 diminishes its ability to bind to telomeric DNA.
Ubiquitinated by RLIM/RNF12, leading to its degradation by the proteasome. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.2 Publications
Keywords - PTMi
Acetylation, ADP-ribosylation, Phosphoprotein, Ubl conjugationProteomic databases
| EPDi | P54274. |
| MaxQBi | P54274. |
| PaxDbi | P54274. |
| PeptideAtlasi | P54274. |
| PRIDEi | P54274. |
PTM databases
| iPTMneti | P54274. |
| PhosphoSitePlusi | P54274. |
Expressioni
Tissue specificityi
Highly expressed and ubiquitous. Isoform Pin2 predominates.
Inductioni
Expression is tightly regulated during the cell cycle; levels are low in G1 and S phase and increase during G2 phase and mitosis.
Gene expression databases
| Bgeei | ENSG00000147601. |
| CleanExi | HS_TERF1. |
| ExpressionAtlasi | P54274. baseline and differential. |
| Genevisiblei | P54274. HS. |
Organism-specific databases
| HPAi | HPA048379. |
Interactioni
Subunit structurei
Homodimer; can contain both isoforms. Found in a complex with POT1; TINF2 and TNKS1. Interacts with ATM, TINF2, TNKS1, TNKS2, PINX1, NEK2 and MAPRE1. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Interacts with RLIM (via N-terminus). Interacts with FBXO4. Interaction with TINF2 protects against interaction with FBXO4 and subsequent polyubiquitination and proteasomal degradation. Interacts with GNL3L; this interaction promotes homodimerization. Interacts with TIN2. Interacts with RTEL1. Interactions with GNL3L and TIN2 are mutually exclusive. Interacts with CCDC79/TERB1 (By similarity).By similarity
Binary interactionsi
GO - Molecular functioni
- ankyrin repeat binding Source: BHF-UCL
- microtubule binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein homodimerization activity Source: BHF-UCL
- ubiquitin binding Source: BHF-UCL
Protein-protein interaction databases
| BioGridi | 112872. 309 interactors. |
| DIPi | DIP-29412N. |
| IntActi | P54274. 208 interactors. |
| MINTi | MINT-221323. |
| STRINGi | 9606.ENSP00000276603. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 63 – 92 | Combined sources | 30 | |
| Helixi | 95 – 110 | Combined sources | 16 | |
| Beta strandi | 113 – 115 | Combined sources | 3 | |
| Helixi | 117 – 133 | Combined sources | 17 | |
| Turni | 134 – 136 | Combined sources | 3 | |
| Beta strandi | 143 – 145 | Combined sources | 3 | |
| Helixi | 150 – 158 | Combined sources | 9 | |
| Helixi | 167 – 186 | Combined sources | 20 | |
| Helixi | 190 – 200 | Combined sources | 11 | |
| Beta strandi | 203 – 205 | Combined sources | 3 | |
| Helixi | 211 – 219 | Combined sources | 9 | |
| Helixi | 226 – 230 | Combined sources | 5 | |
| Helixi | 233 – 251 | Combined sources | 19 | |
| Beta strandi | 252 – 254 | Combined sources | 3 | |
| Helixi | 255 – 265 | Combined sources | 11 | |
| Beta strandi | 377 – 379 | Combined sources | 3 | |
| Helixi | 385 – 398 | Combined sources | 14 | |
| Helixi | 403 – 409 | Combined sources | 7 | |
| Helixi | 417 – 428 | Combined sources | 12 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1BA5 | NMR | - | A | 378-430 | [»] | |
| 1H6O | X-ray | 2.90 | A | 62-265 | [»] | |
| 1ITY | NMR | - | A | 371-439 | [»] | |
| 1IV6 | NMR | - | A | 371-439 | [»] | |
| 1W0T | X-ray | 2.00 | A/B | 379-431 | [»] | |
| 3BQO | X-ray | 2.00 | A | 58-268 | [»] | |
| 3L82 | X-ray | 2.40 | A | 58-268 | [»] | |
| 5HKP | X-ray | 2.20 | C/D | 1-55 | [»] | |
| ProteinModelPortali | P54274. | |||||
| SMRi | P54274. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | P54274. |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 375 – 432 | HTH myb-typePROSITE-ProRule annotationAdd BLAST | 58 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 58 – 268 | TRFH dimerizationAdd BLAST | 211 | |
| Regioni | 265 – 378 | Interaction with RLIM1 PublicationAdd BLAST | 114 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 337 – 356 | Nuclear localization signalSequence analysisAdd BLAST | 20 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 2 – 71 | Asp/Glu-rich (acidic)Add BLAST | 70 | |
| Compositional biasi | 55 – 62 | Poly-Glu | 8 |
Domaini
The acidic N-terminal domain binds to the ankyrin repeats of TNKS1 and TNKS2. The C-terminal domain binds microtubules.1 Publication
The TRFH dimerization region mediates the interaction with TINF2.1 Publication
The HTH domain is an independent structural unit and mediates binding to telomeric DNA.1 Publication
Phylogenomic databases
| eggNOGi | ENOG410IIKA. Eukaryota. ENOG4111QH9. LUCA. |
| GeneTreei | ENSGT00530000063796. |
| HOGENOMi | HOG000132847. |
| HOVERGENi | HBG054097. |
| InParanoidi | P54274. |
| KOi | K11110. |
| OMAi | LRTVYIC. |
| OrthoDBi | EOG091G04CC. |
| PhylomeDBi | P54274. |
| TreeFami | TF333209. |
Family and domain databases
| InterProi | View protein in InterPro IPR009057. Homeobox-like. IPR017930. Myb_dom. IPR001005. SANT/Myb. IPR013867. Telomere_rpt-bd_fac_dimer_dom. |
| Pfami | View protein in Pfam PF00249. Myb_DNA-binding. 1 hit. PF08558. TRF. 1 hit. |
| ProDomi | View protein in ProDom or Entries sharing at least one domain PD014243. Telomere_repeat-bd_fac_dimer. 1 hit. |
| SMARTi | View protein in SMART SM00717. SANT. 1 hit. |
| SUPFAMi | SSF46689. SSF46689. 1 hit. SSF63600. SSF63600. 1 hit. |
| PROSITEi | View protein in PROSITE PS51294. HTH_MYB. 1 hit. |
Sequences (2)i
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P54274-1) [UniParc]FASTAAdd to basket
Also known as: TRF1
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MAEDVSSAAP SPRGCADGRD ADPTEEQMAE TERNDEEQFE CQELLECQVQ
60 70 80 90 100
VGAPEEEEEE EEDAGLVAEA EAVAAGWMLD FLCLSLCRAF RDGRSEDFRR
110 120 130 140 150
TRNSAEAIIH GLSSLTACQL RTIYICQFLT RIAAGKTLDA QFENDERITP
160 170 180 190 200
LESALMIWGS IEKEHDKLHE EIQNLIKIQA IAVCMENGNF KEAEEVFERI
210 220 230 240 250
FGDPNSHMPF KSKLLMIISQ KDTFHSFFQH FSYNHMMEKI KSYVNYVLSE
260 270 280 290 300
KSSTFLMKAA AKVVESKRTR TITSQDKPSG NDVEMETEAN LDTRKSVSDK
310 320 330 340 350
QSAVTESSEG TVSLLRSHKN LFLSKLQHGT QQQDLNKKER RVGTPQSTKK
360 370 380 390 400
KKESRRATES RIPVSKSQPV TPEKHRARKR QAWLWEEDKN LRSGVRKYGE
410 420 430
GNWSKILLHY KFNNRTSVML KDRWRTMKKL KLISSDSED
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 14 | G → R in AAB54036 (PubMed:7502076).Curated | 1 | |
| Sequence conflicti | 14 | G → R in AAB17975 (PubMed:9326950).Curated | 1 | |
| Sequence conflicti | 14 | G → R in AAB81137 (PubMed:9326950).Curated | 1 | |
| Sequence conflicti | 14 | G → R in AAB53363 (PubMed:9391075).Curated | 1 | |
| Sequence conflicti | 338 | K → E in CAA63768 (PubMed:8614633).Curated | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_003303 | 296 – 315 | Missing in isoform 2. 3 PublicationsAdd BLAST | 20 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U40705 mRNA. Translation: AAB54036.1. AF003001 mRNA. Translation: AAB81137.1. AH003684 Genomic DNA. Translation: AAB17975.1. U74382 mRNA. Translation: AAB53363.1. EU088287 Genomic DNA. Translation: ABV02580.1. AC022893 Genomic DNA. No translation available. BC029378 mRNA. Translation: AAH29378.1. X93511 mRNA. Translation: CAA63768.1. |
| CCDSi | CCDS6210.1. [P54274-2] CCDS6211.1. [P54274-1] |
| PIRi | A57573. |
| RefSeqi | NP_003209.2. NM_003218.3. [P54274-2] NP_059523.2. NM_017489.2. [P54274-1] |
| UniGenei | Hs.442707. |
Genome annotation databases
| Ensembli | ENST00000276602; ENSP00000276602; ENSG00000147601. [P54274-2] ENST00000276603; ENSP00000276603; ENSG00000147601. [P54274-1] |
| GeneIDi | 7013. |
| KEGGi | hsa:7013. |
| UCSCi | uc003xzd.3. human. [P54274-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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. |
Entry informationi
| Entry namei | TERF1_HUMAN | |
| Accessioni | P54274Primary (citable) accession number: P54274 Secondary accession number(s): A7XP29 Q93029 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
| Last sequence update: | September 23, 2008 | |
| Last modified: | June 7, 2017 | |
| This is version 195 of the entry and version 3 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, Complete proteome, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - 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
