P28322
SS
Gene name |
Etv4 (Pea-3, Pea3) |
Protein name |
ETS translocation variant 4 |
Names |
Polyomavirus enhancer activator 3, Protein PEA3 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:18612 |
EC number |
|
Protein Class |
|
Descriptions
Etv4 is a aranscriptional activator playing a role in keratinocyte differentiation. Truncation of the autoinhibitory regions increases the transcriptional and DNA binding activities of Etv4. The autoinhibition of Etv4 is mediated by elements outside of ETS domain, and exists in two conformations: a closed, inhibited form and an open, active form that is competent to bind to DNA.
Autoinhibitory domains (AIDs)
Target domain |
341-426 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Target domain |
341-426 (Protein kinase domain) |
Relief mechanism |
Partner binding |
Assay |
|
Accessory elements
No accessory elements
References
- Bojović BB et al. (2001) "The PEA3 Ets transcription factor comprises multiple domains that regulate transactivation and DNA binding", The Journal of biological chemistry, 276, 4509-21
- Green SM et al. (2010) "DNA binding by the ETS protein TEL (ETV6) is regulated by autoinhibition and self-association", The Journal of biological chemistry, 285, 18496-504
- Garvie CW et al. (2002) "Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships", The Journal of biological chemistry, 277, 45529-36
- Nelson ML et al. (2010) "Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP", Proceedings of the National Academy of Sciences of the United States of America, 107, 10026-31
- Ning S et al. (2022) "The auto-inhibition mechanism of transcription factor Ets-1 induced by phosphorylation on the intrinsically disordered region", Computational and structural biotechnology journal, 20, 1132-1141
- Buchwalter G et al. (2004) "Ets ternary complex transcription factors", Gene, 324, 1-14
- Maira SM et al. (1996) "Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif", The EMBO journal, 15, 5849-65
- Batchelor AH et al. (1998) "The structure of GABPalpha/beta: an ETS domain- ankyrin repeat heterodimer bound to DNA", Science (New York, N.Y.), 279, 1037-41
- Currie SL et al. (2017) "Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5", Nucleic acids research, 45, 2223-2241
- Regan MC et al. (2013) "Structural and dynamic studies of the transcription factor ERG reveal DNA binding is allosterically autoinhibited", Proceedings of the National Academy of Sciences of the United States of America, 110, 13374-9
- Newman JA et al. (2015) "Structural insights into the autoregulation and cooperativity of the human transcription factor Ets-2", The Journal of biological chemistry, 290, 8539-49
- Samorodnitsky D et al. (2015) "A Role for Autoinhibition in Preventing Dimerization of the Transcription Factor ETS1", The Journal of biological chemistry, 290, 22101-10
- Basuyaux JP et al. (1997) "The Ets transcription factors interact with each other and with the c-Fos/c-Jun complex via distinct protein domains in a DNA-dependent and -independent manner", The Journal of biological chemistry, 272, 26188-95
- Shore P et al. (1996) "Determinants of DNA-binding specificity of ETS-domain transcription factors", Molecular and cellular biology, 16, 3338-49
- Dalton S et al. (1992) "Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element", Cell, 68, 597-612
Autoinhibited structure
Activated structure
1 structures for P28322
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P28322-F1 | Predicted | AlphaFoldDB |
5 variants for P28322
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs260245572 | 66 | A>V | No | Ensembl | |
| rs235382712 | 102 | R>C | No | Ensembl | |
| rs234101126 | 225 | N>S | No | Ensembl | |
| rs28234792 | 327 | I>F | No | Ensembl | |
| rs28234799 | 478 | G>S | No | Ensembl |
No associated diseases with P28322
4 regional properties for P28322
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| chromosome | A structure composed of a very long molecule of DNA and associated proteins (e.g. histones) that carries hereditary information. |
| nucleolus | A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| DNA binding | Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). |
| DNA-binding transcription activator activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II. |
| DNA-binding transcription factor activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II. |
| RNA polymerase II cis-regulatory region sequence-specific DNA binding | Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II. |
| sequence-specific double-stranded DNA binding | Binding to double-stranded DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA, e.g. promotor binding or rDNA binding. |
10 GO annotations of biological process
| Name | Definition |
|---|---|
| branching involved in mammary gland duct morphogenesis | The process in which the branching structure of the mammary gland duct is generated and organized. The mammary gland is a large compound sebaceous gland that in female mammals is modified to secrete milk. |
| cell differentiation | The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| motor neuron axon guidance | The process in which the migration of an axon growth cone of a motor neuron is directed to a specific target site in response to a combination of attractive and repulsive cues. |
| negative regulation of mammary gland epithelial cell proliferation | Any process that stops, prevents or reduces the rate or extent of mammary gland epithelial cell proliferation. |
| positive regulation of gene expression | Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). |
| positive regulation of keratinocyte differentiation | Any process that activates or increases the frequency, rate or extent of keratinocyte differentiation. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| positive regulation of transcription, DNA-templated | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. |
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| stem cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a stem cell. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells. |
39 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A1A4L6 | ETS2 | Protein C-ets-2 | Bos taurus (Bovine) | SS |
| Q2KIC2 | ETV1 | ETS translocation variant 1 | Bos taurus (Bovine) | SS |
| P15062 | ETS1 | Transforming protein p68/c-ets-1 | Gallus gallus (Chicken) | SS |
| P10157 | ETS2 | Protein C-ets-2 | Gallus gallus (Chicken) | SS |
| Q90837 | ERG | Transcriptional regulator Erg | Gallus gallus (Chicken) | SS |
| A2T762 | ETV3 | ETS translocation variant 3 | Pan troglodytes (Chimpanzee) | PR |
| Q04688 | Ets97D | DNA-binding protein Ets97D | Drosophila melanogaster (Fruit fly) | PR |
| P50548 | ERF | ETS domain-containing transcription factor ERF | Homo sapiens (Human) | PR |
| P41970 | ELK3 | ETS domain-containing protein Elk-3 | Homo sapiens (Human) | SS |
| P41161 | ETV5 | ETS translocation variant 5 | Homo sapiens (Human) | SS |
| Q06546 | GABPA | GA-binding protein alpha chain | Homo sapiens (Human) | SS |
| P28324 | ELK4 | ETS domain-containing protein Elk-4 | Homo sapiens (Human) | EV |
| P15036 | ETS2 | Protein C-ets-2 | Homo sapiens (Human) | EV |
| P41162 | ETV3 | ETS translocation variant 3 | Homo sapiens (Human) | PR |
| P14921 | ETS1 | Protein C-ets-1 | Homo sapiens (Human) | EV |
| P50549 | ETV1 | ETS translocation variant 1 | Homo sapiens (Human) | EV |
| P11308 | ERG | Transcriptional regulator ERG | Homo sapiens (Human) | EV |
| P19419 | ELK1 | ETS domain-containing protein Elk-1 | Homo sapiens (Human) | EV |
| P43268 | ETV4 | ETS translocation variant 4 | Homo sapiens (Human) | EV |
| P97360 | Etv6 | Transcription factor ETV6 | Mus musculus (Mouse) | EV |
| Q8VDK3 | Elf5 | ETS-related transcription factor Elf-5 | Mus musculus (Mouse) | SS |
| Q60775 | Elf1 | ETS-related transcription factor Elf-1 | Mus musculus (Mouse) | PR |
| Q9Z2U4 | Elf4 | ETS-related transcription factor Elf-4 | Mus musculus (Mouse) | PR |
| Q9JHC9 | Elf2 | ETS-related transcription factor Elf-2 | Mus musculus (Mouse) | PR |
| Q00422 | Gabpa | GA-binding protein alpha chain | Mus musculus (Mouse) | EV |
| Q9WTP3 | Spdef | SAM pointed domain-containing Ets transcription factor | Mus musculus (Mouse) | PR |
| P70459 | Erf | ETS domain-containing transcription factor ERF | Mus musculus (Mouse) | PR |
| P81270 | Erg | Transcriptional regulator ERG | Mus musculus (Mouse) | SS |
| Q9CXC9 | Etv5 | ETS translocation variant 5 | Mus musculus (Mouse) | SS |
| P41164 | Etv1 | ETS translocation variant 1 | Mus musculus (Mouse) | SS |
| P41971 | Elk3 | ETS domain-containing protein Elk-3 | Mus musculus (Mouse) | EV |
| P41158 | Elk4 | ETS domain-containing protein Elk-4 | Mus musculus (Mouse) | PR |
| P41969 | Elk1 | ETS domain-containing protein Elk-1 | Mus musculus (Mouse) | PR |
| P15037 | Ets2 | Protein C-ets-2 | Mus musculus (Mouse) | SS |
| P27577 | Ets1 | Protein C-ets-1 | Mus musculus (Mouse) | EV |
| P41156 | Ets1 | Protein C-ets-1 | Rattus norvegicus (Rat) | SS |
| A4GTP4 | Elk1 | ETS domain-containing protein Elk-1 | Rattus norvegicus (Rat) | PR |
| A3FEM2 | fev | Protein FEV | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| Q9PUQ1 | etv4 | ETS translocation variant 4 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MERRMKGGYL | DQRVPYTFCS | KSPGNGSLGE | ALMVPQGKLM | DPGSLPPSDS | EDLFQDLSHF |
| 70 | 80 | 90 | 100 | 110 | 120 |
| QETWLAEAQV | PDSDEQFVPD | FHSENSFHSP | TTRIKKEPQS | PRTDPALSCS | RKPPLPYHHG |
| 130 | 140 | 150 | 160 | 170 | 180 |
| EQCLYSSAYD | SPRQIAIKSP | APGAPGQSPL | QPFSRAEQQQ | SLLRASSSSQ | SHPGHGYLGE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| HSSVFQQPVD | MCHSFTSPQG | GGREPLPAPY | QHQLSEPCPP | YPQQNFKQEY | HDPLYEQAGQ |
| 250 | 260 | 270 | 280 | 290 | 300 |
| PASSQGGVSG | HRYPGAGVVI | KQERTDFAYD | SDVPGCASMY | LHPEGFSGPS | PGDGVMGYGY |
| 310 | 320 | 330 | 340 | 350 | 360 |
| EKSLRPFPDD | VCIVPEKFEG | DIKQEGIGAF | REGPPYQRRG | ALQLWQFLVA | LLDDPTNAHF |
| 370 | 380 | 390 | 400 | 410 | 420 |
| IAWTGRGMEF | KLIEPEEVAR | LWGIQKNRPA | MNYDKLSRSL | RYYYEKGIMQ | KVAGERYVYK |
| 430 | 440 | 450 | 460 | 470 | 480 |
| FVCEPEALFS | LAFPDNQRPA | LKAEFDRPVS | EEDTVPLSHL | DESPAYLPEL | TGPAPPFGHR |
| GGYSY |