NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|2222565016|ref|NP_001391532|]
View 

TERF1-interacting nuclear factor 2 isoform 6 [Mus musculus]

Protein Classification

TIN2_N and TIN2_TBM domain-containing protein( domain architecture ID 10359242)

TIN2_N and TIN2_TBM domain-containing protein

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
TIN2_TBM cd11741
TRF-binding motif region of TRF-Interacting Nuclear factor 2; The C-terminal region of TIN2 ...
 178-281 2.13e-29

TRF-binding motif region of TRF-Interacting Nuclear factor 2; The C-terminal region of TIN2 contains the TRF-binding motif (TBM), while the TIN2 N-terminal region acts in the modulation of TRF1 activity via the inhibition of tankyrase 1. TIN2 binding to TRF2 is primarily via the TRF binding motif (TBM) and the N-terminus, while the far C-terminal region interacts with lower affinity. The TIN2 TBM, but not the N-terminal region, is involved in TIN2 binding to TRF1. Truncation of the TIN2 N-terminus in mouse results in telomere elongation, suggesting a a negative regulatory function of this region. TIN2 is a shelterin complex protein identified in mammals, one of 6 factors that act to protect telomeres from DNA damage repair machinery. Three shelterin components (TRF1, TRF2, POT1) bind DNA and 3 components (TIN2, RAP1, TPP1) are recruited by these DNA binding factors. TIN2 binds directly to TRF1 and TRF2 and stabilizes TRF2 complex-telomere binding by tethering it to the TRF1 complex. TRF1 activity at telomeres is regulated in part by selective ubiquitination and degradation. Ubiquitination of TRF1 is mediated by Fbx4, which binds TRF1 in the TRFH domain, via a small GTPase module. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. F-box proteins act in substrate recognition as part of SCF complexes (SCF: Skp1-Cul1-Rbx1-F- box protein). Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, promoting telomere elongation. TIN2 also binds TPP1, which recruits POT1 to telomeres.


:

Pssm-ID: 240666 [Multi-domain]  Cd Length: 108  Bit Score: 109.14  E-value: 2.13e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016 178 HPEHLAGHRFNLAPLGKRKSRSHWTSAKACHKERPTVMLLPFRNMGLPAQDLSN-PKSREEPGA-ASAASVGTEPVCTEE 255
Cdd:cd11741     1 PPSSLTGRGFGLAPLSKRKSQSRWPSAPRSHKERPTTMLPPRRSTKLPTQKPSRsPASREEHGNnDAAASMGTRSSSTPK 80

                          90       100
                  ....*....|....*....|....*...
gi 2222565016 256 AKTP--SRPLGKRALEETPPDSPAAEQE 281
Cdd:cd11741    81 AKSPdpQDPLGRRSQERPPCSSAASNSF 108
TIN2_N super family cl18929
N-terminal domain of TRF-interacting nuclear factor 2; shelterin complex protein of telomeres; ...
 7-101 2.69e-27

N-terminal domain of TRF-interacting nuclear factor 2; shelterin complex protein of telomeres; TIN2 is one of the six proteins of shelterin complex, which acts to protect telomeres from DNA damage repair machinery. TIN2 binds directly to TRF1 and TRF2 and stabilizes TRF2 complex-telomere binding by tethering it to the TRF1 complex. TIN2 binding to TRF2 is primarily via the TRF binding motif (TBM) region and the N-terminus, while the far C-terminal region has lower affinity. The TIN2 TBM, but not the N-terminal region, is involved in TIN2 binding to TRF1. Truncation of the TIN2 N-terminus in mouse results in telomere elongation, suggesting a negative regulatory function of this region. Three shelterin components (TRF1, TRF2, POT1) bind DNA and 3 components (TIN2, RAP1, TPP1) are recruited by these DNA binding factors. TRF1 activity at telomeres is regulated in part by selective ubiquitination and degradation. Ubiquitination of TRF1 is mediated by Fbx4, which binds TRF1 in the TRFH domain, via a small GTPase module. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. F-box proteins act in substrate recognition as part of Skp1-Cul1-Rbx1-F- box (SCF) protein complexes. Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, promoting telomere elongation. TIN2 also binds PIP1, which recruits POT1 to telomeres.


The actual alignment was detected with superfamily member pfam14973:

Pssm-ID: 473127  Cd Length: 148  Bit Score: 105.05  E-value: 2.69e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016   7 VVVELILQARPwdQVLNALKHHFP-----AESRTTKE-DRKLLEARENFCLLVKHLSEDP---PSSLQE-LEQDYGESFL 76
Cdd:pfam14973  46 LILELCRGERP--QDLKAIQSHLDrlgptVSPKATKQdDVKVEEAQENFLQLVQSLLEDPverEHFFQEvFPVEYGPKFD 123

                          90       100
                  ....*....|....*....|....*
gi 2222565016  77 VAMEKLLFEYLCQLEKALPPVRAQE 101
Cdd:pfam14973 124 AALEKLVWEFLSRLEQLLPVPDLQQ 148
 
Name Accession Description Interval E-value
TIN2_TBM cd11741
TRF-binding motif region of TRF-Interacting Nuclear factor 2; The C-terminal region of TIN2 ...
 178-281 2.13e-29

TRF-binding motif region of TRF-Interacting Nuclear factor 2; The C-terminal region of TIN2 contains the TRF-binding motif (TBM), while the TIN2 N-terminal region acts in the modulation of TRF1 activity via the inhibition of tankyrase 1. TIN2 binding to TRF2 is primarily via the TRF binding motif (TBM) and the N-terminus, while the far C-terminal region interacts with lower affinity. The TIN2 TBM, but not the N-terminal region, is involved in TIN2 binding to TRF1. Truncation of the TIN2 N-terminus in mouse results in telomere elongation, suggesting a a negative regulatory function of this region. TIN2 is a shelterin complex protein identified in mammals, one of 6 factors that act to protect telomeres from DNA damage repair machinery. Three shelterin components (TRF1, TRF2, POT1) bind DNA and 3 components (TIN2, RAP1, TPP1) are recruited by these DNA binding factors. TIN2 binds directly to TRF1 and TRF2 and stabilizes TRF2 complex-telomere binding by tethering it to the TRF1 complex. TRF1 activity at telomeres is regulated in part by selective ubiquitination and degradation. Ubiquitination of TRF1 is mediated by Fbx4, which binds TRF1 in the TRFH domain, via a small GTPase module. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. F-box proteins act in substrate recognition as part of SCF complexes (SCF: Skp1-Cul1-Rbx1-F- box protein). Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, promoting telomere elongation. TIN2 also binds TPP1, which recruits POT1 to telomeres.


Pssm-ID: 240666 [Multi-domain]  Cd Length: 108  Bit Score: 109.14  E-value: 2.13e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016 178 HPEHLAGHRFNLAPLGKRKSRSHWTSAKACHKERPTVMLLPFRNMGLPAQDLSN-PKSREEPGA-ASAASVGTEPVCTEE 255
Cdd:cd11741     1 PPSSLTGRGFGLAPLSKRKSQSRWPSAPRSHKERPTTMLPPRRSTKLPTQKPSRsPASREEHGNnDAAASMGTRSSSTPK 80

                          90       100
                  ....*....|....*....|....*...
gi 2222565016 256 AKTP--SRPLGKRALEETPPDSPAAEQE 281
Cdd:cd11741    81 AKSPdpQDPLGRRSQERPPCSSAASNSF 108
TINF2_N pfam14973
TERF1-interacting nuclear factor 2 N-terminus; This is the N-terminus of TERF1-interacting ...
 7-101 2.69e-27

TERF1-interacting nuclear factor 2 N-terminus; This is the N-terminus of TERF1-interacting nuclear factor 2. It is required for the formation of the shelterin complex. The shelterin complex is involved in the protection and maintenance of telomeres.


Pssm-ID: 464415  Cd Length: 148  Bit Score: 105.05  E-value: 2.69e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016   7 VVVELILQARPwdQVLNALKHHFP-----AESRTTKE-DRKLLEARENFCLLVKHLSEDP---PSSLQE-LEQDYGESFL 76
Cdd:pfam14973  46 LILELCRGERP--QDLKAIQSHLDrlgptVSPKATKQdDVKVEEAQENFLQLVQSLLEDPverEHFFQEvFPVEYGPKFD 123

                          90       100
                  ....*....|....*....|....*
gi 2222565016  77 VAMEKLLFEYLCQLEKALPPVRAQE 101
Cdd:pfam14973 124 AALEKLVWEFLSRLEQLLPVPDLQQ 148
TIN2_N cd11657
N-terminal domain of TRF-interacting nuclear factor 2; shelterin complex protein of telomeres; ...
 7-112 4.60e-18

N-terminal domain of TRF-interacting nuclear factor 2; shelterin complex protein of telomeres; TIN2 is one of the six proteins of shelterin complex, which acts to protect telomeres from DNA damage repair machinery. TIN2 binds directly to TRF1 and TRF2 and stabilizes TRF2 complex-telomere binding by tethering it to the TRF1 complex. TIN2 binding to TRF2 is primarily via the TRF binding motif (TBM) region and the N-terminus, while the far C-terminal region has lower affinity. The TIN2 TBM, but not the N-terminal region, is involved in TIN2 binding to TRF1. Truncation of the TIN2 N-terminus in mouse results in telomere elongation, suggesting a negative regulatory function of this region. Three shelterin components (TRF1, TRF2, POT1) bind DNA and 3 components (TIN2, RAP1, TPP1) are recruited by these DNA binding factors. TRF1 activity at telomeres is regulated in part by selective ubiquitination and degradation. Ubiquitination of TRF1 is mediated by Fbx4, which binds TRF1 in the TRFH domain, via a small GTPase module. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. F-box proteins act in substrate recognition as part of Skp1-Cul1-Rbx1-F- box (SCF) protein complexes. Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, promoting telomere elongation. TIN2 also binds PIP1, which recruits POT1 to telomeres.


Pssm-ID: 240667  Cd Length: 188  Bit Score: 81.18  E-value: 4.60e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016   7 VVVELILqaRPWDQVLNALKHHFP-----AESRTTKEDRKLLEARENFCLLVKHLSEDPPSS----LQELEQDYGESFLV 77
Cdd:cd11657    57 VILELCR--NEKAADLAALNPHLPrllppYPNKCQREDALMEEPQLNFLQLVQSLLKDPEERehffQEVFPVEYGEEFDQ 134

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2222565016  78 AMEKLLFEYLCQLEKALPPVRAQELQDALSWSQPG 112
Cdd:cd11657   135 ALEKLLWEFLSRLEKLLPVPDLKQTVSWLSTSPSV 169
 
Name Accession Description Interval E-value
TIN2_TBM cd11741
TRF-binding motif region of TRF-Interacting Nuclear factor 2; The C-terminal region of TIN2 ...
 178-281 2.13e-29

TRF-binding motif region of TRF-Interacting Nuclear factor 2; The C-terminal region of TIN2 contains the TRF-binding motif (TBM), while the TIN2 N-terminal region acts in the modulation of TRF1 activity via the inhibition of tankyrase 1. TIN2 binding to TRF2 is primarily via the TRF binding motif (TBM) and the N-terminus, while the far C-terminal region interacts with lower affinity. The TIN2 TBM, but not the N-terminal region, is involved in TIN2 binding to TRF1. Truncation of the TIN2 N-terminus in mouse results in telomere elongation, suggesting a a negative regulatory function of this region. TIN2 is a shelterin complex protein identified in mammals, one of 6 factors that act to protect telomeres from DNA damage repair machinery. Three shelterin components (TRF1, TRF2, POT1) bind DNA and 3 components (TIN2, RAP1, TPP1) are recruited by these DNA binding factors. TIN2 binds directly to TRF1 and TRF2 and stabilizes TRF2 complex-telomere binding by tethering it to the TRF1 complex. TRF1 activity at telomeres is regulated in part by selective ubiquitination and degradation. Ubiquitination of TRF1 is mediated by Fbx4, which binds TRF1 in the TRFH domain, via a small GTPase module. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. F-box proteins act in substrate recognition as part of SCF complexes (SCF: Skp1-Cul1-Rbx1-F- box protein). Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, promoting telomere elongation. TIN2 also binds TPP1, which recruits POT1 to telomeres.


Pssm-ID: 240666 [Multi-domain]  Cd Length: 108  Bit Score: 109.14  E-value: 2.13e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016 178 HPEHLAGHRFNLAPLGKRKSRSHWTSAKACHKERPTVMLLPFRNMGLPAQDLSN-PKSREEPGA-ASAASVGTEPVCTEE 255
Cdd:cd11741     1 PPSSLTGRGFGLAPLSKRKSQSRWPSAPRSHKERPTTMLPPRRSTKLPTQKPSRsPASREEHGNnDAAASMGTRSSSTPK 80

                          90       100
                  ....*....|....*....|....*...
gi 2222565016 256 AKTP--SRPLGKRALEETPPDSPAAEQE 281
Cdd:cd11741    81 AKSPdpQDPLGRRSQERPPCSSAASNSF 108
TINF2_N pfam14973
TERF1-interacting nuclear factor 2 N-terminus; This is the N-terminus of TERF1-interacting ...
 7-101 2.69e-27

TERF1-interacting nuclear factor 2 N-terminus; This is the N-terminus of TERF1-interacting nuclear factor 2. It is required for the formation of the shelterin complex. The shelterin complex is involved in the protection and maintenance of telomeres.


Pssm-ID: 464415  Cd Length: 148  Bit Score: 105.05  E-value: 2.69e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016   7 VVVELILQARPwdQVLNALKHHFP-----AESRTTKE-DRKLLEARENFCLLVKHLSEDP---PSSLQE-LEQDYGESFL 76
Cdd:pfam14973  46 LILELCRGERP--QDLKAIQSHLDrlgptVSPKATKQdDVKVEEAQENFLQLVQSLLEDPverEHFFQEvFPVEYGPKFD 123

                          90       100
                  ....*....|....*....|....*
gi 2222565016  77 VAMEKLLFEYLCQLEKALPPVRAQE 101
Cdd:pfam14973 124 AALEKLVWEFLSRLEQLLPVPDLQQ 148
TIN2_N cd11657
N-terminal domain of TRF-interacting nuclear factor 2; shelterin complex protein of telomeres; ...
 7-112 4.60e-18

N-terminal domain of TRF-interacting nuclear factor 2; shelterin complex protein of telomeres; TIN2 is one of the six proteins of shelterin complex, which acts to protect telomeres from DNA damage repair machinery. TIN2 binds directly to TRF1 and TRF2 and stabilizes TRF2 complex-telomere binding by tethering it to the TRF1 complex. TIN2 binding to TRF2 is primarily via the TRF binding motif (TBM) region and the N-terminus, while the far C-terminal region has lower affinity. The TIN2 TBM, but not the N-terminal region, is involved in TIN2 binding to TRF1. Truncation of the TIN2 N-terminus in mouse results in telomere elongation, suggesting a negative regulatory function of this region. Three shelterin components (TRF1, TRF2, POT1) bind DNA and 3 components (TIN2, RAP1, TPP1) are recruited by these DNA binding factors. TRF1 activity at telomeres is regulated in part by selective ubiquitination and degradation. Ubiquitination of TRF1 is mediated by Fbx4, which binds TRF1 in the TRFH domain, via a small GTPase module. When bound to telomeres, TIN2 acts to protect TRF1 from SCF-Fbx4 mediated ubiquitination. F-box proteins act in substrate recognition as part of Skp1-Cul1-Rbx1-F- box (SCF) protein complexes. Tankyrase-mediated ADP-ribosylation releases TRF1 from telomeres, rendering them susceptible to ubiquitination and degradation, promoting telomere elongation. TIN2 also binds PIP1, which recruits POT1 to telomeres.


Pssm-ID: 240667  Cd Length: 188  Bit Score: 81.18  E-value: 4.60e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2222565016   7 VVVELILqaRPWDQVLNALKHHFP-----AESRTTKEDRKLLEARENFCLLVKHLSEDPPSS----LQELEQDYGESFLV 77
Cdd:cd11657    57 VILELCR--NEKAADLAALNPHLPrllppYPNKCQREDALMEEPQLNFLQLVQSLLKDPEERehffQEVFPVEYGEEFDQ 134

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2222565016  78 AMEKLLFEYLCQLEKALPPVRAQELQDALSWSQPG 112
Cdd:cd11657   135 ALEKLLWEFLSRLEKLLPVPDLKQTVSWLSTSPSV 169
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH