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Conserved domains on  [gi|512125235|ref|NP_001265445|]
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protein Mdm4 isoform 4 [Homo sapiens]

Protein Classification

protein Mdm4( domain architecture ID 13026189)

protein Mdm4 exerts its oncogenic activity predominantly by binding the p53 tumor suppressor and blocking its transcriptional activity

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
MDM4 cd17673
p53-binding domain found in MDM4 and similar proteins; MDM4, also known as double minute 4 ...
 29-107 6.17e-47

p53-binding domain found in MDM4 and similar proteins; MDM4, also known as double minute 4 protein, MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding the p53 tumor suppressor and blocking its transcriptional activity. MDM4 is phosphorylated and destabilized in response to DNA damage stress. It can also be specifically dephosphorylated through directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. MDM4 also has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal zinc RING-finger domain responsible for its hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. MDM4 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region.


:

Pssm-ID: 349492  Cd Length: 79  Bit Score: 146.51  E-value: 6.17e-47
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 512125235  29 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLV 107
Cdd:cd17673    1 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDKQQQHIVYCGGDPLGELLGVQSFSVKDPSPLYDMLKRNLV 79
 
Name Accession Description Interval E-value
MDM4 cd17673
p53-binding domain found in MDM4 and similar proteins; MDM4, also known as double minute 4 ...
 29-107 6.17e-47

p53-binding domain found in MDM4 and similar proteins; MDM4, also known as double minute 4 protein, MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding the p53 tumor suppressor and blocking its transcriptional activity. MDM4 is phosphorylated and destabilized in response to DNA damage stress. It can also be specifically dephosphorylated through directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. MDM4 also has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal zinc RING-finger domain responsible for its hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. MDM4 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region.


Pssm-ID: 349492  Cd Length: 79  Bit Score: 146.51  E-value: 6.17e-47
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 512125235  29 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLV 107
Cdd:cd17673    1 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDKQQQHIVYCGGDPLGELLGVQSFSVKDPSPLYDMLKRNLV 79
SWIB pfam02201
SWIB/MDM2 domain; This family includes the SWIB domain and the MDM2 domain. The p53-associated ...
 26-76 3.49e-03

SWIB/MDM2 domain; This family includes the SWIB domain and the MDM2 domain. The p53-associated protein (MDM2) is an inhibitor of the p53 tumour suppressor gene binding the transactivation domain and down regulating the ability of p53 to activate transcription. This family contains the p53 binding domain of MDM2.


Pssm-ID: 460488 [Multi-domain]  Cd Length: 73  Bit Score: 34.00  E-value: 3.49e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 512125235   26 QVRPKLPLLKILHAagaqgEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYC 76
Cdd:pfam02201   2 PFKLSPELAELLGE-----EELSRPEVVKALWEYIKENNLQDPEDKREIIC 47
 
Name Accession Description Interval E-value
MDM4 cd17673
p53-binding domain found in MDM4 and similar proteins; MDM4, also known as double minute 4 ...
 29-107 6.17e-47

p53-binding domain found in MDM4 and similar proteins; MDM4, also known as double minute 4 protein, MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding the p53 tumor suppressor and blocking its transcriptional activity. MDM4 is phosphorylated and destabilized in response to DNA damage stress. It can also be specifically dephosphorylated through directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. MDM4 also has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal zinc RING-finger domain responsible for its hetero-oligomerization, which is crucial for the suppression of P53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. MDM4 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region.


Pssm-ID: 349492  Cd Length: 79  Bit Score: 146.51  E-value: 6.17e-47
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 512125235  29 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLV 107
Cdd:cd17673    1 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDKQQQHIVYCGGDPLGELLGVQSFSVKDPSPLYDMLKRNLV 79
MDM2_like cd10566
p53-binding domain found in E3 ubiquitin-protein ligase MDM2, MDM4, and similar proteins; MDM2 ...
 29-106 3.24e-29

p53-binding domain found in E3 ubiquitin-protein ligase MDM2, MDM4, and similar proteins; MDM2 (also termed HDM2) and MDM4 (also termed MDMX or HDMX) are the primary negative regulators of p53 tumor suppressor. They have non-redundant roles in the regulation of p53. MDM2 mainly functions to control p53 stability, while MDM4 controls p53 transcriptional activity. Both MDM2 and MDM4 contain an N-terminal p53-binding domain, a RanBP2-type zinc finger (zf-RanBP2) domain near the central acidic region, and a C-terminal RING domain. Mdm2 can form homo-oligomers through its RING domain and display E3 ubiquitin ligase activity that catalyzes the attachment of ubiquitin to p53 as an essential step in the regulation of its level in cells. Despite its RING domain and structural similarity with MDM2, MDM4 does not homo-oligomerize and lacks ubiquitin-ligase function, but inhibits the transcriptional activity of p53. In addition, both their RING domains are responsible for the hetero-oligomerization, which is crucial for the suppression of p53 activity during embryonic development and the recruitment of E2 ubiquitin-conjugating enzymes. Moreover, MDM2 and MDM4 can be phosphorylated and destabilized in response to DNA damage stress. In response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through the interaction with ribosomal proteins L5, L11 and L23. However, MDM4 is not bound to ribosomal proteins, suggesting its different response to regulation by small basic proteins such as ribosomal proteins and ARF.


Pssm-ID: 349488  Cd Length: 75  Bit Score: 101.49  E-value: 3.24e-29
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 512125235  29 PKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDpspLYDMLRKNL 106
Cdd:cd10566    1 PKPELLKLLKSVGAKGEVFTRKEVLHYLKQYISSRKLYDPLDPRIVYCKNDPLGKVFGVQSFTIKD---VLGLLAKNL 75
MDM2 cd17672
p53-binding domain found in E3 ubiquitin-protein ligase MDM2 and similar proteins; MDM2, also ...
 26-106 1.98e-27

p53-binding domain found in E3 ubiquitin-protein ligase MDM2 and similar proteins; MDM2, also known as double minute 2 protein (Hdm2), or oncoprotein MDM2, or p53-binding protein, exerts its oncogenic activity predominantly by binding the p53 tumor suppressor and blocking its transcriptional activity. It forms homo-oligomers and displays E3 ubiquitin ligase activity, catalyzing the attachment of ubiquitin to p53 as an essential step in the regulation of its expression levels in cells. Moreover, in response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through the interaction with ribosomal proteins L5, L11, and L23. MDM2 also has a p53-independent role in tumorigenesis and cell growth regulation. In addition, it binds interferon (IFN) regulatory factor-2 (IRF-2), an IFN-regulated transcription factor, and mediates its ubiquitination. MDM2 contains an N-terminal p53-binding domain and a C-terminal zinc RING-finger domain conferring E3 ligase activity that is required for ubiquitination and nuclear export of p53. It is also responsible for the hetero-oligomerization of MDM2, which is crucial for the suppression of P53 activity during embryonic development, and the recruitment of E2 ubiquitin-conjugating enzymes. MDM2 also harbors a RanBP2-type zinc finger (zf-RanBP2) domain, as well as a nuclear localization signal (NLS) and a nuclear export signal (NES), near the central acidic region.


Pssm-ID: 349491  Cd Length: 83  Bit Score: 97.20  E-value: 1.98e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 512125235  26 QVRPKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKN 105
Cdd:cd17672    3 LVRPKPLLLKLLKSAGAQKDTFTMKEVLFYLGQYIMAKQLYDEKQQHIVHCSNDPLGDLFGVQSFSVKEHRRIYAMISRN 82


                 .
gi 512125235 106 L 106
Cdd:cd17672   83 L 83
SWIB-MDM2 cd00855
SWIB/MDM2 domain family; The SWIB/MDM2 protein domain, short for SWI/SNF complex B/MDM2, has ...
 32-76 3.28e-07

SWIB/MDM2 domain family; The SWIB/MDM2 protein domain, short for SWI/SNF complex B/MDM2, has been found in both SWI/SNF complex B (SWIB) and the negative regulator of the p53 tumor suppressor MDM2, which are homologous and share a common fold. The SWIB domain is a conserved region found within proteins in the SWI/SNF (SWItch/Sucrose Non-Fermentable) family of complexes. SWI/SNF complex proteins display helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The mammalian complexes are made up of 9-12 proteins called BAFs (BRG1-associated factors). MDM2 is an inhibitor of p53 tumor repressor. It binds to the transactivation domain and down-regulates the ability of p53 to activate transcription. This family corresponds to the SWIB domain and the p53 binding domain of MDM2.


Pssm-ID: 349487 [Multi-domain]  Cd Length: 69  Bit Score: 44.91  E-value: 3.28e-07
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 512125235  32 PLLKILHAAgaqgEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYC 76
Cdd:cd00855    4 ELEALLKSY----ETFTLKEILQALWQYIKKKNLMDPDDPSIVVC 44
SWIB pfam02201
SWIB/MDM2 domain; This family includes the SWIB domain and the MDM2 domain. The p53-associated ...
 26-76 3.49e-03

SWIB/MDM2 domain; This family includes the SWIB domain and the MDM2 domain. The p53-associated protein (MDM2) is an inhibitor of the p53 tumour suppressor gene binding the transactivation domain and down regulating the ability of p53 to activate transcription. This family contains the p53 binding domain of MDM2.


Pssm-ID: 460488 [Multi-domain]  Cd Length: 73  Bit Score: 34.00  E-value: 3.49e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 512125235   26 QVRPKLPLLKILHAagaqgEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYC 76
Cdd:pfam02201   2 PFKLSPELAELLGE-----EELSRPEVVKALWEYIKENNLQDPEDKREIIC 47
 
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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