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Conserved domains on  [gi|530418813|ref|XP_005260992|]
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protein C-ets-2 isoform X1 [Homo sapiens]

Protein Classification

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List of domain hits

 Name Accession Description Interval E-value
SAM_PNT-ETS-2 cd08543
Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ...
 85-173 1.34e-56

Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ETS transcriptional regulators is a protein-protein interaction domain. It contains a docking site for Cdk10 (cyclin-dependent kinase 10), a member of the Cdc2 kinase family. The interaction between ETS-2 and Cdk10 kinase inhibits ETS-2 transactivation activity in mammals. ETS-2 is also regulated by ERK2 MAP kinase. ETS-2, which is phosphorylated by ERK2, can interact with coactivators and enhance transactivation. ETS-2 transcriptional activators are involved in embryonic development and cell cycle control. The Ets-2 gene is a proto-oncogene. It is overexpressed in breast and prostate cancer cells and its overexpression is necessary for transformation of such cells. Members of ETS-2 subfamily are potential molecular targets for selective cancer therapy.


:

Pssm-ID: 188884  Cd Length: 89  Bit Score: 182.37  E-value: 1.34e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  85 ATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLE 164
Cdd:cd08543    1 DTFSGFSKEQRRLGIPKNPWLWTEQQVCQWLLWATNEFSLVNVNFQQFLMNGQELCNLGKERFLELAPDFVGDILWEHLE 80


                 ....*....
gi 530418813 165 QMIKENQEK 173
Cdd:cd08543   81 QMIKENQEK 89
ETS smart00413
erythroblast transformation specific domain; variation of the helix-turn-helix motif
 362-446 1.06e-49

erythroblast transformation specific domain; variation of the helix-turn-helix motif


:

Pssm-ID: 197710  Cd Length: 87  Bit Score: 164.36  E-value: 1.06e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813   362 PIQLWQFLLELLSDKSCQSFISWTG-DGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRGLRYYYDKNIIHKTSGKRYVY 440
Cdd:smart00413   1 GIQLWQFLLDLLLDPENSDIIKWTDrDEGEFKLVDPEEVARLWGQRKNKPNMNYEKLSRALRYYYKKNILEKVPGKRLVY 80


                   ....*.
gi 530418813   441 RFVCDL 446
Cdd:smart00413  81 KFVKNP 86
Ets1_N_flank super family cl44939
Ets1 N-terminal flanking region of Ets domain; Ets1 is a member of the Ets family of ...
 276-362 3.19e-19

Ets1 N-terminal flanking region of Ets domain; Ets1 is a member of the Ets family of transcription factors in which the DNA-binding activity is in an autoinhibited state. The autoinhibition of Ets1 is mediated by structural coupling of the regions flanking the Ets domain. The inhibitory regions are folded as helices HI1 and HI2 N-terminal to the ETS domain and as H4 C-terminal to the ETS domain, which are packed together to form an inhibitory module. This domain represents the N-terminal flanking region of Ets domain which contains the residues forming HI1 and HI2 helices and additional residues(244-301) N-terminal to HI1. HI1 and HI2 exert the autoinhibitory function by directing the inhibitory residues N-terminal to HI1 to mask the Ets domain DNA-binding surface. These residues are flexible and function by masking the DNA-binding surface of the Ets domain. Phosphorylation of serine residues present in this region enhances autoinhibition dramatically. These inhibitory sequences are required for cooperative DNA binding.


The actual alignment was detected with superfamily member pfam19525:

Pssm-ID: 466113  Cd Length: 188  Bit Score: 85.43  E-value: 3.19e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  276 HDSPENgADSFESSDSLLQSWNSQSSLLDVQRVPSFESFE-DDCSQSLCLNKPTMSFKDYIQERSDpVEQGKPVIPAAVL 354
Cdd:pfam19525 103 QDSFES-IESYDSCDRLTQSWSSQSSFQSLQRVPSYDSFDsEDYPAALPSHKPKGTFKDYVRDRAD-LNKDKPVIPAAAL 180


                  ....*...
gi 530418813  355 AGFTGSGP 362
Cdd:pfam19525 181 AGYTGRMM 188
 
Name Accession Description Interval E-value
SAM_PNT-ETS-2 cd08543
Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ...
 85-173 1.34e-56

Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ETS transcriptional regulators is a protein-protein interaction domain. It contains a docking site for Cdk10 (cyclin-dependent kinase 10), a member of the Cdc2 kinase family. The interaction between ETS-2 and Cdk10 kinase inhibits ETS-2 transactivation activity in mammals. ETS-2 is also regulated by ERK2 MAP kinase. ETS-2, which is phosphorylated by ERK2, can interact with coactivators and enhance transactivation. ETS-2 transcriptional activators are involved in embryonic development and cell cycle control. The Ets-2 gene is a proto-oncogene. It is overexpressed in breast and prostate cancer cells and its overexpression is necessary for transformation of such cells. Members of ETS-2 subfamily are potential molecular targets for selective cancer therapy.


Pssm-ID: 188884  Cd Length: 89  Bit Score: 182.37  E-value: 1.34e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  85 ATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLE 164
Cdd:cd08543    1 DTFSGFSKEQRRLGIPKNPWLWTEQQVCQWLLWATNEFSLVNVNFQQFLMNGQELCNLGKERFLELAPDFVGDILWEHLE 80


                 ....*....
gi 530418813 165 QMIKENQEK 173
Cdd:cd08543   81 QMIKENQEK 89
ETS smart00413
erythroblast transformation specific domain; variation of the helix-turn-helix motif
 362-446 1.06e-49

erythroblast transformation specific domain; variation of the helix-turn-helix motif


Pssm-ID: 197710  Cd Length: 87  Bit Score: 164.36  E-value: 1.06e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813   362 PIQLWQFLLELLSDKSCQSFISWTG-DGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRGLRYYYDKNIIHKTSGKRYVY 440
Cdd:smart00413   1 GIQLWQFLLDLLLDPENSDIIKWTDrDEGEFKLVDPEEVARLWGQRKNKPNMNYEKLSRALRYYYKKNILEKVPGKRLVY 80


                   ....*.
gi 530418813   441 RFVCDL 446
Cdd:smart00413  81 KFVKNP 86
Ets pfam00178
Ets-domain;
364-442 3.06e-45

Ets-domain;


Pssm-ID: 459700  Cd Length: 80  Bit Score: 152.27  E-value: 3.06e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  364 QLWQFLLELLSDKSCQSFISWT-GDGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRGLRYYYDKNIIHKTSGKRYVYRF 442
Cdd:pfam00178   1 QLWQFLLDLLTDPEYSDIIKWTdKEEGEFRLVDPEAVARLWGKRKGNPKMTYEKLSRALRYYYKKGILEKVPGKRLTYRF 80
SAM_PNT pfam02198
Sterile alpha motif (SAM)/Pointed domain;
87-170 1.65e-35

Sterile alpha motif (SAM)/Pointed domain;


Pssm-ID: 460486  Cd Length: 83  Bit Score: 126.63  E-value: 1.65e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813   87 FSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPdFVGDILWEHLEQM 166
Cdd:pfam02198   1 LPSFEKEQLRLWIPADPRLWTKDHVLEWLEWAVDEFDLSKIDFSQFDMNGKALCSLGKEEFLQRAP-GPGDILWSHLQIL 79


                  ....
gi 530418813  167 IKEN 170
Cdd:pfam02198  80 RKAS 83
SAM_PNT smart00251
SAM / Pointed domain; A subfamily of the SAM domain
 87-169 2.33e-35

SAM / Pointed domain; A subfamily of the SAM domain


Pssm-ID: 128547  Cd Length: 82  Bit Score: 126.22  E-value: 2.33e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813    87 FSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPdFVGDILWEHLEQM 166
Cdd:smart00251   1 PPNFEKEQKRLGIPADPQLWTEDHVLEWLEWAVKEFSLSPIDFSKFDMSGKELCSMSKEEFLERAP-FGGDILWSHLQIL 79


                   ...
gi 530418813   167 IKE 169
Cdd:smart00251  80 RKA 82
Ets1_N_flank pfam19525
Ets1 N-terminal flanking region of Ets domain; Ets1 is a member of the Ets family of ...
 276-362 3.19e-19

Ets1 N-terminal flanking region of Ets domain; Ets1 is a member of the Ets family of transcription factors in which the DNA-binding activity is in an autoinhibited state. The autoinhibition of Ets1 is mediated by structural coupling of the regions flanking the Ets domain. The inhibitory regions are folded as helices HI1 and HI2 N-terminal to the ETS domain and as H4 C-terminal to the ETS domain, which are packed together to form an inhibitory module. This domain represents the N-terminal flanking region of Ets domain which contains the residues forming HI1 and HI2 helices and additional residues(244-301) N-terminal to HI1. HI1 and HI2 exert the autoinhibitory function by directing the inhibitory residues N-terminal to HI1 to mask the Ets domain DNA-binding surface. These residues are flexible and function by masking the DNA-binding surface of the Ets domain. Phosphorylation of serine residues present in this region enhances autoinhibition dramatically. These inhibitory sequences are required for cooperative DNA binding.


Pssm-ID: 466113  Cd Length: 188  Bit Score: 85.43  E-value: 3.19e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  276 HDSPENgADSFESSDSLLQSWNSQSSLLDVQRVPSFESFE-DDCSQSLCLNKPTMSFKDYIQERSDpVEQGKPVIPAAVL 354
Cdd:pfam19525 103 QDSFES-IESYDSCDRLTQSWSSQSSFQSLQRVPSYDSFDsEDYPAALPSHKPKGTFKDYVRDRAD-LNKDKPVIPAAAL 180


                  ....*...
gi 530418813  355 AGFTGSGP 362
Cdd:pfam19525 181 AGYTGRMM 188
 
Name Accession Description Interval E-value
SAM_PNT-ETS-2 cd08543
Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ...
 85-173 1.34e-56

Sterile alpha motif (SAM)/Pointed domain of ETS-2; SAM Pointed domain of ETS-2 subfamily of ETS transcriptional regulators is a protein-protein interaction domain. It contains a docking site for Cdk10 (cyclin-dependent kinase 10), a member of the Cdc2 kinase family. The interaction between ETS-2 and Cdk10 kinase inhibits ETS-2 transactivation activity in mammals. ETS-2 is also regulated by ERK2 MAP kinase. ETS-2, which is phosphorylated by ERK2, can interact with coactivators and enhance transactivation. ETS-2 transcriptional activators are involved in embryonic development and cell cycle control. The Ets-2 gene is a proto-oncogene. It is overexpressed in breast and prostate cancer cells and its overexpression is necessary for transformation of such cells. Members of ETS-2 subfamily are potential molecular targets for selective cancer therapy.


Pssm-ID: 188884  Cd Length: 89  Bit Score: 182.37  E-value: 1.34e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  85 ATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLE 164
Cdd:cd08543    1 DTFSGFSKEQRRLGIPKNPWLWTEQQVCQWLLWATNEFSLVNVNFQQFLMNGQELCNLGKERFLELAPDFVGDILWEHLE 80


                 ....*....
gi 530418813 165 QMIKENQEK 173
Cdd:cd08543   81 QMIKENQEK 89
ETS smart00413
erythroblast transformation specific domain; variation of the helix-turn-helix motif
 362-446 1.06e-49

erythroblast transformation specific domain; variation of the helix-turn-helix motif


Pssm-ID: 197710  Cd Length: 87  Bit Score: 164.36  E-value: 1.06e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813   362 PIQLWQFLLELLSDKSCQSFISWTG-DGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRGLRYYYDKNIIHKTSGKRYVY 440
Cdd:smart00413   1 GIQLWQFLLDLLLDPENSDIIKWTDrDEGEFKLVDPEEVARLWGQRKNKPNMNYEKLSRALRYYYKKNILEKVPGKRLVY 80


                   ....*.
gi 530418813   441 RFVCDL 446
Cdd:smart00413  81 KFVKNP 86
Ets pfam00178
Ets-domain;
364-442 3.06e-45

Ets-domain;


Pssm-ID: 459700  Cd Length: 80  Bit Score: 152.27  E-value: 3.06e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  364 QLWQFLLELLSDKSCQSFISWT-GDGWEFKLADPDEVARRWGKRKNKPKMNYEKLSRGLRYYYDKNIIHKTSGKRYVYRF 442
Cdd:pfam00178   1 QLWQFLLDLLTDPEYSDIIKWTdKEEGEFRLVDPEAVARLWGKRKGNPKMTYEKLSRALRYYYKKGILEKVPGKRLTYRF 80
SAM_PNT-ETS-1 cd08542
Sterile alpha motif (SAM)/Pointed domain of ETS-1; SAM Pointed domain of ETS-1 subfamily of ...
 85-172 9.11e-41

Sterile alpha motif (SAM)/Pointed domain of ETS-1; SAM Pointed domain of ETS-1 subfamily of ETS transcriptional activators is a protein-protein interaction domain. The ETS-1 activator is regulated by phosphorylation. It contains a docking site for the ERK2 MAP (Mitogen Activated Protein) kinase, while the ERK2 phosphorylation site is located in the N-terminal disordered region upstream of the SAM Pointed domain. Mutations of the kinase docking site residues inhibit phosphorylation. ETS-1 activators play a role in a number of different physiological processes, and they are expressed during embryonic development, including blood vessel formation, hematopoietic, lymphoid, neuronal and osteogenic differentiation. The Ets-1 gene is a proto-oncogene involved in progression of different tumors (including breast cancer, meningioma, and prostate cancer). Members of this subfamily are potential molecular targets for selective cancer therapy.


Pssm-ID: 176092  Cd Length: 88  Bit Score: 140.89  E-value: 9.11e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  85 ATFSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLE 164
Cdd:cd08542    1 ATFSGFTKEQQRLGIPKDPREWTETHVREWVMWAVNEFSLKGVDFQKFCMSGAALCALGKECFLELAPDFVGDILWEHLE 80


                 ....*...
gi 530418813 165 QMIKENQE 172
Cdd:cd08542   81 ILQKEDPK 88
SAM_PNT-ETS-1,2 cd08533
Sterile alpha motif (SAM)/Pointed domain of ETS-1,2 family; SAM Pointed domain of ETS-1,2 ...
 100-170 4.55e-40

Sterile alpha motif (SAM)/Pointed domain of ETS-1,2 family; SAM Pointed domain of ETS-1,2 family of transcriptional activators is a protein-protein interaction domain. It carries a kinase docking site and mediates interaction between ETS transcriptional activators and protein kinases. This group of transcriptional factors is involved in the Ras/MAP kinase signaling pathway. MAP kinases phosphorylate the transcription factors. Phosphorylated factors then recruit coactivators and enhance transactivation. Members of this group play a role in regulation of different embryonic developmental processes. ETS-1,2 transcriptional activators are proto-oncogenes involved in malignant transformation and tumor progression. They are potential molecular targets for selective cancer therapy.


Pssm-ID: 188879  Cd Length: 71  Bit Score: 138.27  E-value: 4.55e-40
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418813 100 PKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLEQMIKEN 170
Cdd:cd08533    1 PKDPRQWSETQVAYWLDWAANEFSLEGVNLSNFCMSGRDMCALGKEAFLSLAPPFVGDILWEHLDILQKEC 71
SAM_PNT pfam02198
Sterile alpha motif (SAM)/Pointed domain;
87-170 1.65e-35

Sterile alpha motif (SAM)/Pointed domain;


Pssm-ID: 460486  Cd Length: 83  Bit Score: 126.63  E-value: 1.65e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813   87 FSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPdFVGDILWEHLEQM 166
Cdd:pfam02198   1 LPSFEKEQLRLWIPADPRLWTKDHVLEWLEWAVDEFDLSKIDFSQFDMNGKALCSLGKEEFLQRAP-GPGDILWSHLQIL 79


                  ....
gi 530418813  167 IKEN 170
Cdd:pfam02198  80 RKAS 83
SAM_PNT smart00251
SAM / Pointed domain; A subfamily of the SAM domain
 87-169 2.33e-35

SAM / Pointed domain; A subfamily of the SAM domain


Pssm-ID: 128547  Cd Length: 82  Bit Score: 126.22  E-value: 2.33e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813    87 FSGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPdFVGDILWEHLEQM 166
Cdd:smart00251   1 PPNFEKEQKRLGIPADPQLWTEDHVLEWLEWAVKEFSLSPIDFSKFDMSGKELCSMSKEEFLERAP-FGGDILWSHLQIL 79


                   ...
gi 530418813   167 IKE 169
Cdd:smart00251  80 RKA 82
SAM_PNT-GABP-alpha cd08534
Sterile alpha motif (SAM)/Pointed domain of GA-binding protein (GABP) alpha chain; SAM Pointed ...
 88-164 8.74e-26

Sterile alpha motif (SAM)/Pointed domain of GA-binding protein (GABP) alpha chain; SAM Pointed domain of GA-binding protein (GABP) alpha subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. This type of transcriptional regulators forms heterotetramers containing two alpha and two beta subunits. It interacts with GA repeats (purine rich repeats). GABP transcriptional factors control gene expression in cell cycle control, apoptosis, and cellular respiration. GABP participates in regulation of transmembrane receptors and key hormones especially in myeloid cells and at the neuromuscular junction.


Pssm-ID: 176084  Cd Length: 89  Bit Score: 100.50  E-value: 8.74e-26
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418813  88 SGFKKEQRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLE 164
Cdd:cd08534    4 SNYRKEQERLKIPYDPMEWTEDHVLHWLQWAVKEFGLTGINLSDWNITGRELCSLTQEEFLQRVPKDPGDIFWTHLE 80
SAM_PNT cd08203
Sterile alpha motif (SAM)/Pointed domain; Sterile alpha motif (SAM)/Pointed domain is found in ...
 102-164 5.00e-20

Sterile alpha motif (SAM)/Pointed domain; Sterile alpha motif (SAM)/Pointed domain is found in about 40% of transcriptional regulators of ETS family (initially named for Erythroblastosis virus, E26-E Twenty Six). SAM Pointed domain containing proteins of this family additionally have a C-terminal ETS DNA-binding domain. In a few cases, SAM Pointed domain appears as a single domain protein. Members of this group are mostly involved in regulation of embryonic development and growth control in eukaryotes. SAM Pointed domains mediate protein-protein interactions. Depending on the subgroup, they can interact with other SAM Pointed domains forming homo or hetero dimers/oligomers and/or they can recruit a protein kinase to its target which can be a SAM Pointed domain containing protein itself or another protein that has no kinase docking site. Thus, SAM Pointed domains participate in transcriptional regulation and signal transduction. Some genes coding ETS family transcriptional regulators are proto-oncogenes. They are prone to chromosomal translocations resulting in gene fusions. Chimeric proteins with SAM Pointed domains were found in a number of different human tumors including myeloid leukemia, lymphoblastic leukemia, Ewing's sarcoma and primitive neuroectodermal tumor. Members of this family are potential targets for cancer therapy.


Pssm-ID: 188876  Cd Length: 67  Bit Score: 83.53  E-value: 5.00e-20
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530418813 102 NPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLE 164
Cdd:cd08203    1 DPLEWTPEHVQQWLSWVSKKFSLDPIDPDRFPMNGKELCALSKEDFRERAPSRGGDVLASHLA 63
Ets1_N_flank pfam19525
Ets1 N-terminal flanking region of Ets domain; Ets1 is a member of the Ets family of ...
 276-362 3.19e-19

Ets1 N-terminal flanking region of Ets domain; Ets1 is a member of the Ets family of transcription factors in which the DNA-binding activity is in an autoinhibited state. The autoinhibition of Ets1 is mediated by structural coupling of the regions flanking the Ets domain. The inhibitory regions are folded as helices HI1 and HI2 N-terminal to the ETS domain and as H4 C-terminal to the ETS domain, which are packed together to form an inhibitory module. This domain represents the N-terminal flanking region of Ets domain which contains the residues forming HI1 and HI2 helices and additional residues(244-301) N-terminal to HI1. HI1 and HI2 exert the autoinhibitory function by directing the inhibitory residues N-terminal to HI1 to mask the Ets domain DNA-binding surface. These residues are flexible and function by masking the DNA-binding surface of the Ets domain. Phosphorylation of serine residues present in this region enhances autoinhibition dramatically. These inhibitory sequences are required for cooperative DNA binding.


Pssm-ID: 466113  Cd Length: 188  Bit Score: 85.43  E-value: 3.19e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530418813  276 HDSPENgADSFESSDSLLQSWNSQSSLLDVQRVPSFESFE-DDCSQSLCLNKPTMSFKDYIQERSDpVEQGKPVIPAAVL 354
Cdd:pfam19525 103 QDSFES-IESYDSCDRLTQSWSSQSSFQSLQRVPSYDSFDsEDYPAALPSHKPKGTFKDYVRDRAD-LNKDKPVIPAAAL 180


                  ....*...
gi 530418813  355 AGFTGSGP 362
Cdd:pfam19525 181 AGYTGRMM 188
SAM_PNT-Tel_Yan cd08535
Sterile alpha motif (SAM)/Pointed domain of Tel/Yan protein; SAM Pointed domain of Tel ...
 103-169 5.06e-18

Sterile alpha motif (SAM)/Pointed domain of Tel/Yan protein; SAM Pointed domain of Tel (Translocation, Ets, Leukemia)/Yan subfamily of ETS transcriptional repressors is a protein-protein interaction domain. SAM Pointed domains of this type of regulators can interact with each other, forming head-to-tail homodimers or homooligomers, and/or interact with SAM Pointed domains of another subfamily of ETS factors forming heterodimers. The oligomeric form is able to block transcription of target genes and is involved in MAPK signaling. They participate in regulation of different processes during embryoniv development including hematopoietic differentiation and eye development. Tel/Yan transcriptional factors are frequent targets of chromosomal translocations resulting in fusions of SAM domain with new neighboring genes. Such chimeric proteins were found in different tumors. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 176085  Cd Length: 68  Bit Score: 78.20  E-value: 5.06e-18
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418813 103 PWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPdFVGDILWEHLEQMIKE 169
Cdd:cd08535    3 PRQWSREDVLQWLRWAENEFSLPPIDSNTFEMNGKALCLLTKEDFRYRCP-HAGDVLYNLLQHLLKQ 68
SAM_PNT-ERG_FLI-1 cd08531
Sterile alpha motif (SAM)/Pointed domain of ERG (Ets related gene) and FLI-1 (Friend leukemia ...
 99-163 7.39e-16

Sterile alpha motif (SAM)/Pointed domain of ERG (Ets related gene) and FLI-1 (Friend leukemia integration 1) transcription factors; SAM Pointed domain of ERG/FLI-1 subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. The ERG and FLI regulators are involved in endothelial cell differentiation, bone morphogenesis and neural crest development. They are proto-oncogenes implicated in cancer development such as myeloid leukemia, Ewing's sarcoma and erythroleukemia. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 188877  Cd Length: 75  Bit Score: 72.06  E-value: 7.39e-16
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530418813  99 IPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRF-GMNGQMLCNLGKERFLELAPDFVGDILWEHL 163
Cdd:cd08531    1 VPADPLLWTREHVRQWVEWAIKEYSLKDVDVSRFdNIDGKELCRMTRDDFLRLTSAYNGDVLISHL 66
SAM_PNT-FLI-1 cd08541
Sterile alpha motif (SAM)/Pointed domain of friend leukemia integration 1 transcription ...
 94-163 2.24e-13

Sterile alpha motif (SAM)/Pointed domain of friend leukemia integration 1 transcription activator; SAM Pointed domain of FLI-1 (Friend Leukemia Integration) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. The FLI-1 protein participates in regulation of cellular differentiation, proliferation, and survival. The Fli-1 gene was initially described in Friend virus-induced erythroleukemias as a site for virus integration. It is highly expressed in hematopoietic tissues and at lower level in lungs, heart, and ovaries. Fli-1 is a proto-oncogene implicated in Ewing's sarcoma and erythroleukemia. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 188883  Cd Length: 91  Bit Score: 65.84  E-value: 2.24e-13
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 530418813  94 QRRLGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRF-GMNGQMLCNLGKERFLELAPDFVGDILWEHL 163
Cdd:cd08541    8 ERRVIVPADPTLWSQDHVRQWLEWAIKEYGLMEIDTSLFqNMDGKELCKMSKEDFLRLTSLYNTEVLLSHL 78
SAM_PNT-ERG cd08540
Sterile alpha motif (SAM)/Pointed domain of ERG transcription factor; SAM Pointed domain of ...
 99-163 2.51e-13

Sterile alpha motif (SAM)/Pointed domain of ERG transcription factor; SAM Pointed domain of ERG subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It may participate in formation of homodimers or heterodimers with ETS-2, Fli-1, ER81, and Pu-1. However, dimeric forms are inactive and SAM Pointed domain is not essential for dimerization, since ER81 and Pu-1 do not have it. In mouse, a regulator of this type binds the ESET histone H3-specific methyltransferase (human homolog is SETDB1), which leads to modification of the local chromatin structure through histone methylation. ERG regulators are involved in endothelial cell differentiation, bone morphogenesis and neural crest development. The Erg gene is a proto-oncogene. It is a target of chromosomal translocations resulting in fusions with other neighboring genes. Chimeric proteins were found in solid tumors such as myeloid leukemia or Ewing's sarcoma. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 176090  Cd Length: 75  Bit Score: 64.98  E-value: 2.51e-13
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530418813  99 IPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRF-GMNGQMLCNLGKERFLELAPDFVGDILWEHL 163
Cdd:cd08540    1 VPADPTLWSTDHVRQWLEWAVKEYGLPDVDVLLFqNIDGKELCKMTKEDFQRLTPSYNADILLSHL 66
SAM_PNT-PDEF-like cd08532
Sterile alpha motif (SAM)/Pointed domain of prostate-derived ETS factor; SAM Pointed domain of ...
 97-164 2.43e-11

Sterile alpha motif (SAM)/Pointed domain of prostate-derived ETS factor; SAM Pointed domain of PDEF-like (Prostate-Derived ETS Factor) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. In human males this activator is highly expressed in the prostate gland and enhances androgen-mediated activation of the PSA promoter though interaction with the DNA binding domain of androgen receptor. PDEF may play a role in prostate cancer development as well as in goblet cell formation and mucus production in the epithelial lining of respiratory and intestinal tracts.


Pssm-ID: 188878  Cd Length: 81  Bit Score: 59.68  E-value: 2.43e-11
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530418813  97 LGIPKNPWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDfVGDILWEHLE 164
Cdd:cd08532    8 LGISPDPYQWSTANVQAWLQWTEHQYRLPPNPPRCFQMNGKTLCALSEEDFVRRAPQ-GGDTLHAQLE 74
SAM_PNT-Mae cd08536
Sterile alpha motif (SAM)/Pointed domain of Mae protein homolog; Mae (Modulator of the ...
 103-161 1.20e-08

Sterile alpha motif (SAM)/Pointed domain of Mae protein homolog; Mae (Modulator of the Activity of ETS) subfamily represents a group of SAM Pointed monodomain proteins. SAM Pointed domain is a protein-protein interaction domain. It can interact with other SAM pointed domains forming head-to-tail heterodimers and also provides a kinase docking site. For example, in Drosophila Mae is required for facilitating phosphorylation of the Yan factor and for blocking phosphorylation of the ETS-2 regulator. Mae interacts with the SAM Pointed domains of Yan and ETS-2. Binding enhances access of the kinase to the Yan phosphorylation site by providing a kinase docking site, or inhibits phosphorylation of ETS-2 by blocking its docking site. This type of factors participates in regulation of kinase signaling particularly during embryogenesis.


Pssm-ID: 176086  Cd Length: 66  Bit Score: 51.56  E-value: 1.20e-08
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 530418813 103 PWLWSEQQVCQWLLWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDfVGDILWE 161
Cdd:cd08536    2 PRSWSREHVRTWLRWVSARYQLEVVDLDKFLMNGKGLCLMSLEGFLYRVPV-GGKLLYE 59
SAM_PNT_ESE cd08757
Sterile alpha motif (SAM)/Pointed domain of ESE-like ETS transcriptional regulators; SAM ...
 103-165 1.28e-05

Sterile alpha motif (SAM)/Pointed domain of ESE-like ETS transcriptional regulators; SAM Pointed domain of ESE-like (Epithelium-Specific ETS) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It can act as a major transactivator by providing a potential docking site for co-activators. ETS factors are important for cell differentiation. They can be involved in regulation of gene expression in different types of epithelial cells. They are expressed in salivary gland, intestine, stomach, pancreas, lungs, kidneys, colon, mammary gland, and prostate. Members of this group are proto-oncogenes. Expression profiles of these factors are altered in epithelial cancers, which makes them potential targets for cancer therapy.


Pssm-ID: 188885  Cd Length: 69  Bit Score: 43.09  E-value: 1.28e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530418813 103 PWLWSEQQVCQWLL-WA-TNEFSLVNVNLQRF-GMNGQMLCNLGKERFLELAPDFvGDILWEHLEQ 165
Cdd:cd08757    2 PQHWTKNDVLDWLLfVAeQNKIDAEEINFQKFdNIDGQTLCSMSLEEFIERDGVY-GNLLYAELRR 66
SAM_PNT-ESE-1-like cd08537
Sterile alpha motif (SAM)/Pointed domain of ESE-1 like ETS transcriptional regulators; SAM ...
 102-166 1.31e-04

Sterile alpha motif (SAM)/Pointed domain of ESE-1 like ETS transcriptional regulators; SAM Pointed domain of ESE-1-like (Epithelium-Specific ETS) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. SAM Pointed domain of ESE-1 provides a potential docking site for signaling kinase Pak1 in humans. ESE-1 factors are involved in regulation of gene expression in different types of epithelial cells. ESE-1 is expressed in many different organs including intestine, stomach, pancreas, lungs, kidneys, and prostate. The DNA binding consensus motif for ESE-1 consists of a purine-rich GGA[AT] core sequence. The expression profile of these factors is altered in epithelial cancers if compared to normal tissues. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 188880  Cd Length: 81  Bit Score: 40.60  E-value: 1.31e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418813 102 NPWLWSEQQVCQWLLW--ATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDFVGDILWEHLEQM 166
Cdd:cd08537   11 NPQFWSKQNVLEWISYhvEKNKYDASSLDLSYCTMDGLTLCACAKEQLMLVFGPELGDLLHHSLEEL 77
SAM_PNT-ESE-3-like cd08539
Sterile alpha motif (SAM)/Pointed domain of ESE-3 like ETS transcriptional regulators; SAM ...
 102-166 4.91e-04

Sterile alpha motif (SAM)/Pointed domain of ESE-3 like ETS transcriptional regulators; SAM Pointed domain of ESE-3-like (Epithelium-Specific ETS) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It can act as a major transactivator by providing a potential docking site for co-activators. The ESE-3 transcriptional activator is involved in regulation of glandular epithelium differentiation through the MAP kinase signaling cascade. It is found to be expressed in glandular epithelium of prostate, pancreas, salivary gland, and trachea. Additionally, ESE-3 is differentially expressed during monocyte-derived dendritic cells development. DNA binding consensus motif for ESE-3 consists of purine-rich GGAA/T core sequence. The expression profiles of these factors are altered in epithelial cancers. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 188882  Cd Length: 78  Bit Score: 38.86  E-value: 4.91e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 530418813 102 NPWLWSEQQVCQWL--LWATNEFSLVNVNLQRFGMNGQMLCNLGKERFLELAPDfVGDILWEHLEQM 166
Cdd:cd08539    8 HPQYWTKFQVWEWLqhLLDTNQLDANCIPFQEFDINGEHLCSMSLQEFTRAAGT-AGQLLYSNLQHL 73
SAM_PNT-ESE-2-like cd08538
Sterile alpha motif (SAM)/Pointed domain of ESE-2 like ETS transcriptional regulators; SAM ...
 102-151 5.31e-04

Sterile alpha motif (SAM)/Pointed domain of ESE-2 like ETS transcriptional regulators; SAM Pointed domain of ESE-2-like (Epithelium-Specific ETS) subfamily of ETS transcriptional regulators is a putative protein-protein interaction domain. It can act as a major transactivator by providing a potential docking site for co-activators. ESE-2 factors are involved in regulation of gene expression in a variety of epithelial (glandular and secretory) cells. ESE-2 mRNA was found in skin keratinocytes, salivary gland, mammary gland, stomach, prostate, and kidneys. The DNA binding consensus motif for ESE-2 consists of a GGA core and AT-rich flanks. The expression profiles of these factors are altered in epithelial cancers. Members of this subfamily are potential targets for cancer therapy.


Pssm-ID: 188881  Cd Length: 84  Bit Score: 38.85  E-value: 5.31e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 530418813 102 NPWLWSEQQVCQWLLWATNEFSLVN--VNLQRFGMNGQMLCNLGKERFLELA 151
Cdd:cd08538   12 HPEYWTKRHVWEWLQFCCDQYKLDAncISFCHFNISGLQLCSMTQEEFLDAA 63
 
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.
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