Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033  279 FHALRaGAHVRILDEQTVARLeHGRDERALVFTSRPVRVAETIFIKVTRSGGARPGALSFGVTTCDPGTLRPADLPFSPE 358
Cdd:pfam07177   1 FHPVH-GKNVRLSNDGRTARR-TNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALPDLAT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564334033  359 ALvdRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAPAG-MQLCVDASQPLWMLFSLHGAITQVRILG 430
Cdd:pfam07177  79 DL--RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGvALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 564334033 498 GQWSDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTYRS 556
Cdd:cd16785    1 GSWSDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPICRRAIKDIIKTYRS 59

Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033  279 FHALRaGAHVRILDEQTVARLeHGRDERALVFTSRPVRVAETIFIKVTRSGGARPGALSFGVTTCDPGTLRPADLPFSPE 358
Cdd:pfam07177   1 FHPVH-GKNVRLSNDGRTARR-TNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALPDLAT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564334033  359 ALvdRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAPAG-MQLCVDASQPLWMLFSLHGAITQVRILG 430
Cdd:pfam07177  79 DL--RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGvALSGVPDSQPLWAVFDLYGQTTQVSILG 149

Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033   48 FHpHTKGSQILMDLSHKAVKRQASFCNAITFSNRPVLIYEQVRLKITKKQCCWSGALRLGFTSKDPSRIHPDSLPkyACP 127
Cdd:pfam07177   1 FH-PVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALP--DLA 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564334033  128 DLVsQSGFWAKALPEEFANEGNIIAFWVDKKGRVFYRINESAAMLFFSGVRTADPLWALVDVYGLTRGVQLLD 200
Cdd:pfam07177  78 TDL-RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 564334033 498 GQWSDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTYRS 556
Cdd:cd16785    1 GSWSDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPICRRAIKDIIKTYRS 59

SPRY domain in neuralized homology repeat; This family contains the neuralized homology repeat 1 (NHR1) domain similar to the SPRY domain (known to mediate specific protein-protein interactions) at the C-terminus of a conserved region within eukaryotic neuralized and neuralized-like proteins. In Drosophila, the neuralized protein (Neur) belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the nervous system. Neur binds to the Notch receptor ligand Delta through its first NHR1 domain and mediates its ubiquitination for endocytosis. Multiple copies of this region are found in some members of the family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033 278 RFHALRaGAHVRILDEQTVARLEHGRDERALVFTSRPVRVAETIFIKVTRSGGARPGALSFGVTTCDPGTLrpaDLPFSP 357
Cdd:cd12887    1 RFHENH-GKNIRLSNDGRTATRVKASFNNGVVFSSRPLRPGELFEVRIDKLVDRWSGSLEIGVTTLNPETL---DLPPSA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033 358 EALvdRKEFW--AVCRVP----------GP----LHSGDILGLVVNADGELHLSHNGAPAGMqLCVDASQPLWMLFSLHG 421
Cdd:cd12887   77 TDL--KSGTWilSGSSVFkngnkirenyGPdldrLRVGDRVGVMRTSDGTLHFYVNGEDQGV-AASNVPQPVYAVVDLYG 153

                 ....*...
gi 564334033 422 AITQVRIL 429
Cdd:cd12887  154 QCEQVSIV 161

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 564334033   504 CTICYEH-AVDTVIYTCGHMcLCYSCGLRLKKALHACCPIC 543
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHT-FCRSCIRKWLESGNNTCPIC 40

Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033  279 FHALRaGAHVRILDEQTVARLeHGRDERALVFTSRPVRVAETIFIKVTRSGGARPGALSFGVTTCDPGTLRPADLPFSPE 358
Cdd:pfam07177   1 FHPVH-GKNVRLSNDGRTARR-TNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALPDLAT 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564334033  359 ALvdRKEFWAVCRVPGPLHSGDILGLVVNADGELHLSHNGAPAG-MQLCVDASQPLWMLFSLHGAITQVRILG 430
Cdd:pfam07177  79 DL--RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGvALSGVPDSQPLWAVFDLYGQTTQVSILG 149

Neuralized; This family contains a conserved region approximately 60 residues long within eukaryotic neuralized and neuralized-like proteins. Neuralized belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the Drosophila nervous system. Some family members contain multiple copies of this region.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033   48 FHpHTKGSQILMDLSHKAVKRQASFCNAITFSNRPVLIYEQVRLKITKKQCCWSGALRLGFTSKDPSRIHPDSLPkyACP 127
Cdd:pfam07177   1 FH-PVHGKNVRLSNDGRTARRTNSFNNGLVFSSRPLRPGELFEVRIDKLVDKWSGSLRFGVTSCDPATLRPKALP--DLA 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564334033  128 DLVsQSGFWAKALPEEFANEGNIIAFWVDKKGRVFYRINESAAMLFFSGVRTADPLWALVDVYGLTRGVQLLD 200
Cdd:pfam07177  78 TDL-RPGYWVVALSGSYLQEGDRLGFWVTSDGELHFSVNGEDQGVALSGVPDSQPLWAVFDLYGQTTQVSILG 149

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 564334033 498 GQWSDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTYRS 556
Cdd:cd16785    1 GSWSDECTICYENAVDTVIYTCGHMCLCYACGLRLKKMLNACCPICRRAIKDIIKTYRS 59

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 564334033 501 SDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKAlHACCPICRRPIKDIIKTY 554
Cdd:cd16647    1 GSECVICYERPVDTVLYRCGHMCMCYDCALQLKRR-GGSCPICRAPIKDVIKIY 53

SPRY domain in neuralized homology repeat; This family contains the neuralized homology repeat 1 (NHR1) domain similar to the SPRY domain (known to mediate specific protein-protein interactions) at the C-terminus of a conserved region within eukaryotic neuralized and neuralized-like proteins. In Drosophila, the neuralized protein (Neur) belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the nervous system. Neur binds to the Notch receptor ligand Delta through its first NHR1 domain and mediates its ubiquitination for endocytosis. Multiple copies of this region are found in some members of the family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033 278 RFHALRaGAHVRILDEQTVARLEHGRDERALVFTSRPVRVAETIFIKVTRSGGARPGALSFGVTTCDPGTLrpaDLPFSP 357
Cdd:cd12887    1 RFHENH-GKNIRLSNDGRTATRVKASFNNGVVFSSRPLRPGELFEVRIDKLVDRWSGSLEIGVTTLNPETL---DLPPSA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564334033 358 EALvdRKEFW--AVCRVP----------GP----LHSGDILGLVVNADGELHLSHNGAPAGMqLCVDASQPLWMLFSLHG 421
Cdd:cd12887   77 TDL--KSGTWilSGSSVFkngnkirenyGPdldrLRVGDRVGVMRTSDGTLHFYVNGEDQGV-AASNVPQPVYAVVDLYG 153

                 ....*...
gi 564334033 422 AITQVRIL 429
Cdd:cd12887  154 QCEQVSIV 161

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, CARP-2 and similar proteins; The CARP subfamily includes CARP-1 and CARP-2 proteins, both of which are E3 ubiquitin ligases that ubiquitinate apical caspases and target them for proteasome-mediated degradation. As a novel group of caspase regulators with a FYVE-type zinc finger domain, they do not localize to membranes in the cell and are involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8, and caspase 10. Moreover, they stabilize MDM2 by inhibiting MDM2 self-ubiquitination, as well as by targeting 14-3-3sigma for degradation. They work together with MDM2 to enhance p53 degradation, thereby inhibiting p53-mediated cell death. CARPs contain an N-terminal FYVE-like domain that can serve as a membrane-targeting or endosome localizing signal and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 564334033 502 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICRRPIKDIIKTY 554
Cdd:cd16500    1 DLCKICMDAAIDCVLLECGHMVTCTDCGKKLSE-----CPICRQYVVRVVHFF 48

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 564334033 502 DECTICYEHAVDTVIY--TCGHMCLCYSCGLRLKKAlHACCPICRRPIKDIIK 552
Cdd:cd16646    1 DLCVICLSRPRTAAIVhgKTGHQVACYTCAKKLKRR-GKPCPVCRRPIQNVIK 52

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 564334033 503 ECTICYEHAVDTVIYTCGHMClCYSCGLRLKKALHACCPIC 543
Cdd:cd16449    2 ECPICLERLKDPVLLPCGHVF-CRECIRRLLESGSIKCPIC 41

RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) and similar proteins; RSPRY1 is a hypothetical RING and SPRY domain-containing protein of unknown physiological function. Mutations in its corresponding gene RSPRY1 may associate with a distinct skeletal dysplasia syndrome. RSPRY1 contains a B30.2/SPRY domain and a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564334033 502 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKkalhaCCPICRRPI 547
Cdd:cd16566    3 DSCTLCFDKVADTELRPCGHSGFCMECALQLE-----TCPLCRQPI 43

RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein 1 (CARP1) and similar proteins; CARP1, also known as caspase regulator CARP1, FYVE-RING finger protein Momo, RING finger homologous to inhibitor of apoptosis protein (RFI), RING finger protein 34 (RNF34), or RING finger protein RIFF, is a nuclear protein that functions as a specific E3 ubiquitin ligase for the transcriptional coactivator PGC-1alpha, a master regulator of energy metabolism and adaptive thermogenesis in the brown fat cell which negatively regulates brown fat cell metabolism. It is preferentially expressed in esophageal, gastric, and colorectal cancers, suggesting a possible association with the development of digestive tract cancers. It regulates the p53 signaling pathway by degrading 14-3-3 sigma and stabilizing MDM2. CARP1 does not localize to membranes in the cell and is involved in the negative regulation of apoptosis, specifically targeting two initiator caspases, caspase 8 and caspase 10. CARP1 contains an N-terminal FYVE-like domain and a C-terminal C3HC4-type RING-HC finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 564334033 504 CTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICRRPIKDIIKTYRS 556
Cdd:cd16706    7 CRICMDAVIDCVLLECGHMVTCTKCGKRMSE-----CPICRQYVVRAVHVFKS 54

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 564334033 504 CTICYEHAVDTVIYTCGHMCLCYSCglrlKKALHAC--CPICRRPIKDIIKTY 554
Cdd:cd16648    4 CVICLSNPRSCVFLECGHVCSCIEC----YEALPSPkkCPICRSFIKRVVPLY 52

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 564334033 504 CTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhacCPICRRPIKDIIKTYRS 556
Cdd:cd16713   10 CKVCMDKEVSIVFIPCGHLVVCTECAPSLRK-----CPICRATIKGTVRTFLS 57

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1) 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. Furthermore, MGRN1 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. MGRN1 contains a modified C3HC5-type RING-HC finger, a conserved PSAP motif necessary for interaction between MGRN1 and TSG101. In addition, MGRN1 harbors a functionally uncharacterized region, as known as the 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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564334033 501 SDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHAcCPICRRPIKDIIK 552
Cdd:cd16816    8 SNECVVCLSDLRDTLILPCRHLCLCNSCADTLRYQANN-CPICRLPFRALLQ 58

RING finger, HC subclass, found in RNA-binding proteins of the evolutionarily-conserved MEX-3 family; MEX-3 phosphoproteins are found in vertebrates. They are mediators of post-transcriptional regulation in different organisms, and have been implicated in many core biological processes, including embryonic development, epithelial homeostasis, immune responses, metabolism, and cancer. They contain two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. They shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway. The RNA-binding protein MEX-3 from nematode Caenorhabditis elegans is the founding member of the MEX-3 family. Due to the lack of a RING-HC finger, it is not included here.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564334033 503 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTY 554
Cdd:cd16518    2 DCVVCFESEVVAALVPCGHNLFCMECANRICEKSDPECPVCHTPVTQAIRIF 53

RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 564334033 503 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIK 552
Cdd:cd23128    5 ECVMCMEEERSVVFLPCAHQVVCSGCNDLHEKKGMRECPSCRGEIQERIR 54

Modified RING finger, HC subclass (C3HC5-type), found in RING finger protein 157 (RNF157) and similar proteins; RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in 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. RNF157 contains 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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564334033 501 SDECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHAcCPICRRPIKDIIK 552
Cdd:cd16817    4 SAECVVCLSDVRDTLILPCRHLCLCNACADTLRYQANN-CPICRLPFRALLQ 54

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 564334033 502 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKalhACCPICR 544
Cdd:cd16649    1 GLCVVCLENPASVLLLPCRHLCLCEVCAKGLRG---KTCPICR 40

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
                 ....*....|....*....|....*....|....*
gi 564334033 520 GHMCLCYSCGLRLKKAlHACCPICRRPIKDIIKTY 554
Cdd:cd16784   24 AHLVTCFHCARRLKKA-GAPCPVCKKEIQMVIKIF 57

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 564334033   504 CTICYEH-AVDTVIYTCGHMcLCYSCGLRLKKALHACCPIC 543
Cdd:smart00184   1 CPICLEEyLKDPVILPCGHT-FCRSCIRKWLESGNNTCPIC 40

RING finger, HC subclass, found in zinc finger protein 598 (ZNF598) and similar proteins; ZNF598 associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammals (m4EHP) by binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian. ZNF598 harbors a C3HC4-type RING-HC finger at its N-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 564334033 502 DECTICYEHAVDTVIYTCGHMClCYSCGLRL-----KKAlhacCPICRRPIKDII 551
Cdd:cd16615    1 ETCVICCEEIEYFAVGPCNHPV-CYKCSLRMrvlykDKY----CPICRTELDKVI 50

RING finger, HC subclass, found in RNA-binding protein MEX3D; MEX3D, also known as RING finger and KH domain-containing protein 1 (RKHD1), RING finger protein 193 (RNF193), or TINO, is an RNA-binding phosphoprotein that controls the stability of the transcripts coding for the anti-apoptotic protein BCL-2, and negatively regulates BCL-2 in HeLa cells. MEX3D contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3D shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564334033 503 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKALHACCPICRRPIKDIIKTY 554
Cdd:cd16723   12 ECVVCFESEVIAALVPCGHNLFCMECAIRICGKSEPECPACHTPATQAIHIF 63

RING finger, HC subclass, found in Caenorhabditis elegans BRCA1-associated RING domain protein 1 (CeBARD1) and similar proteins; CeBARD1, also called Ce-BRD-1, Cebrd-1, or RING-type E3 ubiquitin transferase BARD1, is a constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity. It plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by ionizing radiation. It protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability. CeBARD1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564334033 503 ECTICYEHAVDTV-IYTCGHMcLCYSCGLRLKKALHaCCPICRRPI 547
Cdd:cd23143    3 ECVICSEPQIDTFlLSSCGHI-YCWECFTEFIEKRH-MCPSCRFPL 46

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 564334033 503 ECTICYEHAVDTVIYTCGHMcLCYSCGLRL--KKALHACCPICRRPI 547
Cdd:cd16498   18 ECPICLELLKEPVSTKCDHQ-FCRFCILKLlqKKKKPAPCPLCKKSV 63

first RING finger, HC subclass, found in mind bomb 2 (MIB2) and similar proteins; MIB2, also known as novel zinc finger protein (Novelzin), putative NF-kappa-B-activating protein 002N, skeletrophin, or zinc finger ZZ type with ankyrin repeat domain protein 1, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands. It promotes Delta ubiquitylation and endocytosis in Notch activation. Overexpression of MIB2 activates NF-kappaB and interferon-stimulated response element (ISRE) reporter activity. Moreover, MIB2 acts as a novel component of the activated B-cell CLL/lymphoma 10 (BCL10) complex and controls BCL10-dependent NF-kappaB activation. It also functions as a founder myoblast-specific protein that regulates myoblast fusion and muscle stability. MIB2 contains an MZM region with 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 consisting of two C3HC4-type RING-HC fingers. This model corresponds to the first RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 564334033 503 ECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKAL 536
Cdd:cd16726    2 ECLVCSELAALVRFEPCQHSIVCEECARRMKKCI 35

RING finger, HC subclass, found in RING domain ligase RGLG1, RGLG2 and similar proteins from plant; 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. Members of this subfamily contain a Von Willebrand factor type A (vWA) domain and a C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 564334033 501 SDECTICYEHAVDtVIYTCGHMClCYSCGLRLKKalhacCPICRRPIKDIIKTY 554
Cdd:cd16729    2 DQLCPICLSNPKD-MAFGCGHQT-CCECGQSLTH-----CPICRQPITTRIKLY 48

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 564334033 493 VTPGLGQWSDECTICYEHAVDTVIYTCGHMcLCYSC---GLRLKKALHacCPICRR---PIKDII 551
Cdd:COG5574  207 GLPFIPLADYKCFLCLEEPEVPSCTPCGHL-FCLSClliSWTKKKYEF--CPLCRAkvyPKKVII 268

RING finger, HC subclass, found in Mus musculus tripartite motif-containing protein 43 (TRIM43) and similar propteins; This subfamily includes TRIM43A, TRIM43B and TRIM43C, which are expressed specifically in mouse preimplantation embryos. They contain a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 564334033 504 CTICYEHAVDTVIYTCGHMcLCYSCGLRLKK--ALHACCPICRRPI 547
Cdd:cd23133    6 CSICQGIFMNPVYLRCGHK-FCEACLLLFQEdiKFPAYCPMCRQPF 50

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 564334033 504 CTICYEHAVDTVIYTCGHMcLCYSCGLR-LKKALHA---CCPICRRP 546
Cdd:cd16583    8 CPICQEPLKEAVSTDCGHL-FCRMCLTQhAKKASASgvfSCPVCRKP 53

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 564334033 504 CTICYEHAVDTVIYTCGHmCLCYSCGLRLKKalHAC-CPICRRPIKDIIK 552
Cdd:cd16539    8 CFICRKPFKNPVVTKCGH-YFCEKCALKHYR--KSKkCFVCGKQTNGVFN 54

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 564334033 504 CTICYEHAVDTVIYTCGHMcLCYSCGLRLKKALHACCPICRRPI 547
Cdd:cd16550    3 CPICLEILVEPVTLPCNHT-LCMPCFQSTVEKASLCCPLCRLRI 45

first RING finger, HC subclass, found in mind bomb 1 (MIB1) and similar proteins; MIB1, also known as DAPK-interacting protein 1 (DIP-1) or zinc finger ZZ type with ankyrin repeat domain protein 2, is a large, multi-domain E3 ubiquitin-protein ligase that promotes ubiquitination of the cytoplasmic tails of Notch ligands, and thus plays an essential role in controlling metazoan development by Notch signaling. It is also involved in Wnt/beta-catenin signaling and nuclear factor (NF)-kappaB signaling, and has been implicated in innate immunity, neuronal function, genomic stability, and cell death. MIB1 contains an MZM region with 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 consisting of three C3HC4-type RING-HC fingers. This model corresponds to the first RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 564334033 502 DECTICYEHAVDTVIYTCGHMCLCYSCGLRLKKAL 536
Cdd:cd16724    1 EECMVCSDMKRDTLFGPCGHIATCSLCSPRVKKCL 35

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 564334033  502 DECTIC---YEHAVDTVIYTCGHmCLCYSCGLRLKKAlHACCPICR 544
Cdd:pfam13639   1 DECPICleeFEEGDKVVVLPCGH-HFHRECLDKWLRS-SNTCPLCR 44

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 564334033 503 ECTICYEHAVDTVIYTCGHMcLCYSCGL-RLKKALHACCPICRRPIK 548
Cdd:cd16568    6 ECIICHEYLYEPMVTTCGHT-YCYTCLNtWFKSNRSLSCPDCRTKIT 51

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also known as Casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55 (RNF55), or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinase signaling. It contains a tyrosine kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70, and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with a SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through the RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 564334033 504 CTICYEHAVDTVIYTCGHMcLCYSCGLRLKKALHACCPICRRPIK 548
Cdd:cd16708   24 CKICAENDKDVKIEPCGHL-MCTSCLTSWQESEGQGCPFCRCEIK 67