Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins; MDM4, also known as double minute 4 protein (Hdm4), MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding 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 by directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. Meanwhile, MDM4 has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal modified C2H2C4-type RING-HC finger 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958672332 431 NVLKPCSLCEKRPRDGNIIHGKTSHLTTCFHCARRLKKSGASCPACKKEIQLVIKVFIA 489
Cdd:cd16784     1 NLLEPCSLCQKRPRNGNIVHGRTAHLVTCFHCARRLKKAGAPCPVCKKEIQMVIKIFIA 59

Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins; MDM4, also known as double minute 4 protein (Hdm4), MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding 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 by directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. Meanwhile, MDM4 has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal modified C2H2C4-type RING-HC finger 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958672332 431 NVLKPCSLCEKRPRDGNIIHGKTSHLTTCFHCARRLKKSGASCPACKKEIQLVIKVFIA 489
Cdd:cd16784     1 NLLEPCSLCQKRPRNGNIVHGRTAHLVTCFHCARRLKKAGAPCPVCKKEIQMVIKIFIA 59

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1958672332 434 KPCSLCEKRPRdgNIIHGKTSHLTTCFHCARRLKKSGASCPACKKEIQLV 483
Cdd:pfam13920   3 LLCVICLDRPR--NVVLLPCGHLCLCEECAERLLRKKKKCPICRQPIESV 50

Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins; MDM4, also known as double minute 4 protein (Hdm4), MDM2-like p53-binding protein, protein MDMX, HDMX, or p53-binding protein MDM4, exerts its oncogenic activity predominantly by binding 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 by directly interacting with protein phosphatase 1 (PP1), which may increase its stability and thus inhibit p53 activity. Meanwhile, MDM4 has a p53-independent role in tumorigenesis and cell growth regulation. MDM4 contains an N-terminal p53-binding domain and a C-terminal modified C2H2C4-type RING-HC finger 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958672332 431 NVLKPCSLCEKRPRDGNIIHGKTSHLTTCFHCARRLKKSGASCPACKKEIQLVIKVFIA 489
Cdd:cd16784     1 NLLEPCSLCQKRPRNGNIVHGRTAHLVTCFHCARRLKKAGAPCPVCKKEIQMVIKIFIA 59

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958672332  29 PKLQLLKILQAAGAQGEVFTMKEVMHYLGQYIMVKQLYDQQEQHLVYCGGDLLGDLLGCQSFSVKDpspLYDMLRKNL 106
Cdd:cd10566     1 PKPELLKLLKSVGAKGEVFTRKEVLHYLKQYISSRKLYDPLDPRIVYCKNDPLGKVFGVQSFTIKD---VLGLLAKNL 75

Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and similar proteins; MDM2, also known as double minute 2 protein (Hdm2), oncoprotein MDM2, or p53-binding protein, exerts its oncogenic activity predominantly by binding p53 tumor suppressor and blocking its transcriptional activity. It forms homo-oligomers and displays E3 ubiquitin ligase activity that catalyzes the attachment of ubiquitin to p53 as an essential step in the regulation of its levels in cells. Moreover, in response to ribosomal stress, MDM2-mediated p53 ubiquitination and degradation can be inhibited through its interaction with ribosomal proteins L5, L11, and L23. MDM2 can be phosphorylated in the DNA damage. Meanwhile, MDM2 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 modified C2H2C4-type RING-HC finger 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. The zf-RanBP2 domain plays an important role in mediating MDM2 binding to ribosomal proteins and thus is involved in MDM2-mediated p53 suppression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958672332 433 LKPCSLCEKRPRDGNIIHGKTSHLTTCFHCARRLKKSGASCPACKKEIQLVIKVFIA 489
Cdd:cd16783     1 IEPCVICQTRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP 57

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958672332  37 LQAAGAQGEVFTMKEVMHYLGQYIMVKQLYDQQEQHLVYCgGDLLGDLLGCQSFSVKDpspLYDMLRKN 105
Cdd:cd00855     5 LEALLKSYETFTLKEILQALWQYIKKKNLMDPDDPSIVVC-DERLRQLFEVPSFPFSE---IPKALKKH 69

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958672332 436 CSLCEKRPRDGNIIhgKTSHLTTCFHCARRLKKSGASCPACKKEIQLVIKVF 487
Cdd:cd23129     5 CVVCMDAPRDAVCV--PCGHVAGCMSCLKALMQSSPLCPICRAPVRQVIKVY 54

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1A (NEURL1A) and similar proteins; NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that directly interacts with and monoubiquitinates cytoplasmic polyadenylation element-binding protein 3 (CPEB3), an RNA binding protein and a translational regulator of local protein synthesis, which facilitates hippocampal plasticity and hippocampal-dependent memory storage. It also acts as a potential tumor suppressor that causes apoptosis and downregulates Notch target genes in the medulloblastoma. NEURL1A contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958672332 436 CSLCEKRPRDGNIIhgKTSHLTTCFHCARRLKK-SGASCPACKKEIQLVIKVF 487
Cdd:cd16785     7 CTICYENAVDTVIY--TCGHMCLCYACGLRLKKmLNACCPICRRAIKDIIKTY 57