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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359357  25 ETLVRPKPLLLKLLKSVGAQKDIYTMKEIIFYIGQYIMTKRLYDEKQQHIVYCSNDLLGDVFGVPSFSVKEHRKIYAMIY 104
Cdd:cd17672    1 EKLVRPKPLLLKLLKSAGAQKDTFTMKEVLFYLGQYIMAKQLYDEKQQHIVHCSNDPLGDLFGVQSFSVKEHRRIYAMIS 80

                 ...
gi 564359357 105 RNL 107
Cdd:cd17672   81 RNL 83

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 564359357  292 LADYWKCTSCNEMNPPLPSHCNRCWTLREN 321
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 30

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359357  25 ETLVRPKPLLLKLLKSVGAQKDIYTMKEIIFYIGQYIMTKRLYDEKQQHIVYCSNDLLGDVFGVPSFSVKEHRKIYAMIY 104
Cdd:cd17672    1 EKLVRPKPLLLKLLKSAGAQKDTFTMKEVLFYLGQYIMAKQLYDEKQQHIVHCSNDPLGDLFGVQSFSVKEHRRIYAMIS 80

                 ...
gi 564359357 105 RNL 107
Cdd:cd17672   81 RNL 83

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 564359357  427 IEPCVICQGRPKNGCIVHgkTGHLMSCFTCAKKLKKRNKPCPVCRQPIQMI 477
Cdd:pfam13920   2 DLLCVICLDRPRNVVLLP--CGHLCLCEECAERLLRKKKKCPICRQPIESV 50

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 564359357   49 TMKEIIFYIGQYIMTKRLYDEKQQHIVYCsNDLLGDVFGVPSFS 92
Cdd:pfam02201  19 SRPEVVKALWEYIKENNLQDPEDKREIIC-DEKLKKLFGGDRVK 61

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564359357  25 ETLVRPKPLLLKLLKSVGAQKDIYTMKEIIFYIGQYIMTKRLYDEKQQHIVYCSNDLLGDVFGVPSFSVKEHRKIYAMIY 104
Cdd:cd17672    1 EKLVRPKPLLLKLLKSAGAQKDTFTMKEVLFYLGQYIMAKQLYDEKQQHIVHCSNDPLGDLFGVQSFSVKEHRRIYAMIS 80

                 ...
gi 564359357 105 RNL 107
Cdd:cd17672   81 RNL 83

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564359357  40 SVGAQKDIYTMKEIIFYIGQYIMTKRLYDEKQQHIVYCSNDLLGDVFGVPSFSVKEhrkIYAMIYRNL 107
Cdd:cd10566   11 SVGAKGEVFTRKEVLHYLKQYISSRKLYDPLDPRIVYCKNDPLGKVFGVQSFTIKD---VLGLLAKNL 75

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 564359357 428 EPCVICQGRPKNGCIVHGKTGHLMSCFTCAKKLKKRNKPCPVCRQPIQMIV 478
Cdd:cd16646    1 DLCVICLSRPRTAAIVHGKTGHQVACYTCAKKLKRRGKPCPVCRRPIQNVI 51

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564359357  48 YTMKEIIFYIGQYIMTKRLYDEKQQHIVYCsNDLLGDVFGVPSFSVKEhrkIYAMIYRN 106
Cdd:cd00855   15 FTLKEILQALWQYIKKKNLMDPDDPSIVVC-DERLRQLFEVPSFPFSE---IPKALKKH 69

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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564359357 428 EPCVICQGRPKNgCIVHgKTGHLMSCFTCAKKLKKRNKPCPVCRQPIQMIVLTY 481
Cdd:cd16647    2 SECVICYERPVD-TVLY-RCGHMCMCYDCALQLKRRGGSCPICRAPIKDVIKIY 53

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 564359357  292 LADYWKCTSCNEMNPPLPSHCNRCWTLREN 321
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 30

RING finger, HC subclass, found in Dictyostelium discoideum Cbl-like protein A (CblA) and similar proteins; CblA is a Dictyostelium homolog of the Cbl proteins which are multi-domain proteins acting as key negative regulators of various receptor and non-receptor tyrosine kinase signaling. CblA upregulates STATc tyrosine phosphorylation by downregulating PTP3, the protein tyrosine phosphatase responsible for dephosphorylating STATc. STATc is a signal transducer and activator of transcription protein. Like other Cbl proteins, CblA contains a tyrosine-kinase-binding domain (TKB), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB, also known as a phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain. This family also includes Drosophila melanogaster defense repressor 1 (Dnr1) that was identified as an inhibitor of Dredd activity in the absence of a microbial insult in Drosophila S2 cells. It inhibits the Drosophila initiator caspases Dredd and Dronc. Moreover, Dnr1 acts as a negative regulator of the Imd (immune deficiency) innate immune-response pathway. Its mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain. Dnr1 contains a FERM N-terminal domain followed by a region rich in glutamine and serine residues, a central FERM domain, and a C-terminal C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564359357 430 CVICQGRPKNgcIVHGKTGHLMSCFTCAKKLKKrnkpCPVCRQPIQMIVLTY 481
Cdd:cd16501    8 CVVCMDAPID--TVFLECGHLACCRLCSKRLRV----CPICRQPISRVVRIF 53

Modified RING finger, HC subclass (C3HC5-type), found in mitochondrial-anchored protein ligase (MAPL) and similar proteins; MAPL, also known as MULAN, mitochondrial ubiquitin ligase activator of NFKB 1, E3 SUMO-protein ligase MUL1, E3 ubiquitin-protein ligase MUL1, growth inhibition and death E3 ligase (GIDE), putative NF-kappa-B-activating protein 266, or RING finger protein 218 (RNF218), is a multifunctional mitochondrial outer membrane protein involved in several processes specific to metazoan (multicellular animal) cells, such as NF-kappaB activation, innate immunity and antiviral signaling, suppression of PINK1/parkin defects, mitophagy in skeletal muscle, and caspase-dependent apoptosis. MAPL contains a unique BAM (beside a membrane)/GIDE (growth inhibition death E3 ligase) domain and a C-terminal modified cytosolic C3HC5-type RING-HC finger which 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 564359357 429 PCVICQGRPKnGCIVHgKTGHLMSCFTCAKKLKKRNKpCPVCRQPIQMIVLTY 481
Cdd:cd16648    3 ACVICLSNPR-SCVFL-ECGHVCSCIECYEALPSPKK-CPICRSFIKRVVPLY 52

RING finger, HC subclass, found in mind bomb MIB1, MIB2, RGLG1, RGLG2, and similar proteins; MIBs are large, multi-domain E3 ubiquitin-protein ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. They are also responsible for TBK1 K63-linked ubiquitination and activation, promoting interferon production and controlling antiviral immunity. Moreover, MIBs selectively control responses to cytosolic RNA and regulate type I interferon transcription. Both MIB1 and MIB2 have similar domain architectures, which consist of two Mib-Herc2 domains flanking a ZZ zinc finger, a REP region including two tandem Mib repeats, an ANK region that spans ankyrin repeats, and a RNG region, where MIB1 and MIB2 contain three and two C3HC4-type RING-HC fingers, respectively. This model corresponds to the third RING-HC finger of MIB1, as well as the second RING-HC finger of MIB2. In addition to MIB1 and MIB2, the RING-HC fingers of RING domain ligase RGLG1, RGLG2 and similar proteins from plant are also included in this model. RGLG1 is a ubiquitously expressed E3 ubiquitin-protein ligase that interacts with UBC13 and, together with UBC13, catalyzes the formation of K63-linked polyubiquitin chains, which is involved in DNA damage repair. RGLG1 mediates the formation of canonical, K48-linked polyubiquitin chains that target proteins for degradation. It also regulates apical dominance by acting on the auxin transport proteins abundance. RGLG1 has overlapping functions with its closest sequelog, RGLG2. They both function as RING E3 ligases that interact with ethylene response factor 53 (ERF53) in the nucleus and negatively regulate the plant drought stress response. All RGLG proteins contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 564359357 430 CVICQGRPKN---GCivhgktGHlMSCFTCAKKLKKrnkpCPVCRQPI 474
Cdd:cd16520    3 CPICMERKKNvvfLC------GH-GTCQKCAEKLKK----CPICRKPI 39

RING finger, HC subclass, found in Arabidopsis thaliana SP1-like protein 2 (SPL2) and similar proteins; SPL2, also known as RING-type E3 ubiquitin transferase SPL2, acts as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. SPL2 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564359357 428 EPCVICQGRPKNGCIVHgkTGHLMSCFTCAKKLKKRNKP-CPVCRQ 472
Cdd:cd23145    4 ELCVVCLLRRRRVAFIE--CGHRVCCELCARRVTREANPrCPVCRQ 47

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1), RING finger protein 157 (RNF157) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. MGRN1 also interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase mahogunin ring finger-1 (MGRN1). In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. Both MGRN1 and RNF157 contain a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 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
                 ....*....|....*....|....*....|....*....|..
gi 564359357 430 CVICQGRPKNGCIVHGKtgHLMSCFTCAKKLKKRNKPCPVCR 471
Cdd:cd16789    3 CVICLSDPRDTAVLPCR--HLCLCSDCAEVLRYQSNKCPICR 42

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 564359357  430 CVICQGRPKNGCIVHGKT-GHLMsCFTCAKKLKKRNKPCPVCR 471
Cdd:pfam13639   3 CPICLEEFEEGDKVVVLPcGHHF-HRECLDKWLRSSNTCPLCR 44

Modified RING finger, HC subclass (C3HC5-type), found in RING finger proteins, RNF26, RNF197 (CGRRF1), RNF156 (MGRN1), RNF157 and similar proteins; This subfamily corresponds to a group of RING finger proteins containing a modified C3HC5-type RING-HC finger, which is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain. Cell growth regulator with RING finger domain protein 1 (CGRRF1), also known as cell growth regulatory gene 19 protein (CGR19) or RING finger protein 197 (RNF197), functions as a novel biomarker to monitor endometrial sensitivity and response to insulin-sensitizing drugs, such as metformin, in the context of obesity. RNF26 is an E3 ubiquitin ligase that temporally regulates virus-triggered type I interferon induction by increasing the stability of Mediator of IRF3 activation, MITA, also known as STING, through K11-linked polyubiquitination after viral infection and promoting degradation of IRF3, another important component required for virus-triggered interferon induction. Mahogunin ring finger-1 (MGRN1), also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase MGRN1. In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 564359357 430 CVICQGRPKngCIVHGKTGHLMSCFTCAKKLkkRNKPCPVCR 471
Cdd:cd16649    3 CVVCLENPA--SVLLLPCRHLCLCEVCAKGL--RGKTCPICR 40

RING finger, HC subclass, found in apoptosis protein c-IAP1, c-IAP2, livin, and similar proteins; The cellular inhibitor of apoptosis protein c-IAPs function as ubiquitin E3 ligases that mediate the ubiquitination of substrates involved in apoptosis, nuclear factor-kappaB (NF-kappaB) signaling, and oncogenesis. Unlike other IAPs, such as XIAP, c-IAPs exhibit minimal binding to caspases and may not play an important role in the inhibition of these proteases. c-IAP1, also known as baculoviral IAP repeat-containing protein BIRC2, IAP-2, RING finger protein 48, or TNFR2-TRAF-signaling complex protein 2, is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-kappaB signaling pathways in the cytoplasm. It can also regulate E2F1 transcription factor-mediated control of cyclin transcription in the nucleus. c-IAP2, also known as BIRC3, IAP-1, apoptosis inhibitor 2 (API2), or IAP homolog C, also influences ubiquitin-dependent pathways that modulate innate immune signalling by activation of NF-kappaB. c-IAPs contain three N-terminal baculoviral IAP repeat (BIR) domains that enable interactions with proteins, a ubiquitin-association (UBA) domain that is responsible for the binding of polyubiquitin (polyUb), a caspase activation and recruitment domain (CARD) that serves as a protein interaction surface, and a C3HC4-type RING-HC finger at the carboxyl terminus that is required for ubiquitin ligase activity. Livin, also known as baculoviral IAP repeat-containing protein 7 (BIRC7), kidney inhibitor of apoptosis protein (KIAP), melanoma inhibitor of apoptosis protein (ML-IAP), or RING finger protein 50, was identified as the melanoma IAP. It plays crucial roles in apoptosis, cell proliferation, and cell cycle control. Its anti-apoptotic activity is regulated by the inhibition of caspase-3, -7, and -9. Its E3 ubiquitin-ligase-like activity promotes degradation of Smac/DIABLO, a critical endogenous regulator of all IAPs. Unlike other family members, mammalian livin contains a single BIR domain and a C3HC4-type RING-HC finger. The UBA domain can be detected in non-mammalian homologs of livin.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564359357 430 CVICQGRPKNgcIVHGKTGHLMSCFTCAKKLKKrnkpCPVCRQPIQMIVLTY 481
Cdd:cd16713   10 CKVCMDKEVS--IVFIPCGHLVVCTECAPSLRK----CPICRATIKGTVRTF 55