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 1038986341 433 ALLEPCKLCRVRPRNGNIIHGRTAHLITCFPCARKLHKFHAPCPGCGQVIQKVIKTFIA 491
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 1038986341 433 ALLEPCKLCRVRPRNGNIIHGRTAHLITCFPCARKLHKFHAPCPGCGQVIQKVIKTFIA 491
Cdd:cd16784     1 NLLEPCSLCQKRPRNGNIVHGRTAHLVTCFHCARRLKKAGAPCPVCKKEIQMVIKIFIA 59

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1038986341  28 APLLQILKvagaqEEVFTLKEVMHYLGQYIMMKQLYDKQRQHIVHChDDPLGELLEVGSFS 88
Cdd:pfam02201   7 PELAELLG-----EEELSRPEVVKALWEYIKENNLQDPEDKREIIC-DEKLKKLFGGDRVK 61

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1038986341  26 PRAPLLQILKVAGAQEEVFTLKEVMHYLGQYIMMKQLYDKQRQHIVHCHDDPLGELLEVGSFSVKNpspVYEMLKRNL 103
Cdd:cd10566     1 PKPELLKLLKSVGAKGEVFTRKEVLHYLKQYISSRKLYDPLDPRIVYCKNDPLGKVFGVQSFTIKD---VLGLLAKNL 75

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1038986341  22 TQVHPRAPLLQILKVAGAQEEVFTLKEVMHYLGQYIMMKQLYDKQRQHIVHCHDDPLGELLEVGSFSVKNPSPVYEMLKR 101
Cdd:cd17672     2 KLVRPKPLLLKLLKSAGAQKDTFTMKEVLFYLGQYIMAKQLYDEKQQHIVHCSNDPLGDLFGVQSFSVKEHRRIYAMISR 81

                  ..
gi 1038986341 102 NL 103
Cdd:cd17672    82 NL 83

Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2, protein MDM4 and similar proteins; MDM2 (also known as HDM2) and MDM4 (also known as MDMX or HDMX) are the primary p53 tumor suppressor negative regulators. 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 modified C2H2C4-type RING-HC finger. Mdm2 can form homo-oligomers through its RING domain 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. 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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1038986341 436 EPCKLCRVRPRNGNIIHGRTAHLITCFPCARKLHKFHAPCPGCGQVIQKVIK 487
Cdd:cd16646     1 DLCVICLSRPRTAAIVHGKTGHQVACYTCAKKLKRRGKPCPVCRRPIQNVIK 52

Zinc finger, C3HC4 type (RING finger);

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1038986341 436 EPCKLCRVRPRNgnIIHGRTAHLITCFPCARKLHKFHAPCPGCGQVIQKV 485
Cdd:pfam13920   3 LLCVICLDRPRN--VVLLPCGHLCLCEECAERLLRKKKKCPICRQPIESV 50

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein NEURL1A, NEURL1B, and similar proteins; This subfamily includes Drosophila neuralized (D-neu) protein, and its two mammalian homologs, NEURL1A and NEURL1B. D-neu is a regulator of the developmentally important Notch signaling pathway. NEURL1A, also known as NEURL1, NEU, neuralized 1, or RING finger protein 67 (RNF67), is a mammalian homolog of D-neu. 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 medulloblastoma. NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is another mammalian homolog of D-neu protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling by working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. Members of this subfamily contain 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.

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                  ....*....|....*....|....*....|...
gi 1038986341 457 HLITCFPCARKLHKFHAPCPGCGQVIQKVIKTF 489
Cdd:cd16647    21 HMCMCYDCALQLKRRGGSCPICRAPIKDVIKIY 53

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....*.
gi 1038986341 304 WQCSECRKFNTPLQRYCMRCWALRKD 329
Cdd:pfam00641   5 WDCSKCLVQNFATSTKCVACQAPKPD 30

SWIB domain found in the 60 kda subunit of the ATP-dependent SWI/SNF chromatin-remodeling complexes and similar proteins; SWIB domain is a conserved region found within proteins in the SWI/SNF 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), among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit have at least three members: BAF60a, which is ubiquitous, BAF60b and BAF60c, which are expressed in muscle and pancreatic tissues, respectively. The family also includes Saccharomyces cerevisiae transcription regulatory protein SNF12 and remodel the structure of chromatin complex subunit 6 (RSC6), and Schizosaccharomyces pombe SWI/SNF and RSC complexes subunit SSR3. SNF12, also termed 73-kDa subunit of the SWI/SNF transcriptional regulatory complex, or SWI/SNF complex component SWP73, is involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). RSC6 and SSR3 are components of the RSC, which is involved in transcription regulation and nucleosome positioning. RSC6 is essential for mitotic growth and suppresses formamide sensitivity of the RSC8 mutants.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1038986341  29 PLLQILkvaGAQEEvfTLKEVMHYLGQYIMMKQLYDKQRQHIVHChDDPLGELLEVGSFSVKN 91
Cdd:cd10568     4 ALAQLL---GIKEG--TRPNIIYALWQYIKLNKLQDPEDRRLINC-DEALKQLFGVERFKFSE 60