RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958663172 3995 GIQPCSICQGDAQDPVCLPCDHVYCLPCIQTWLaPGQMICPYCKTELPDKF 4045
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWL-PGQMSCPLCRTELPDDF 50

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663172  2427 GIPVIIMGETGCGKT----RLIKFLSDLRRGSIE-------AETMKLVKVHGGTTPSMIYSRVKDAERtaFFNKAQHNLE 2495
Cdd:smart00382    2 GEVILIVGPPGSGKTtlarALARELGPPGGGVIYidgedilEEVLDQLLLIIVGGKKASGSGELRLRL--ALALARKLKP 79

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1958663172  2496 TILFFDEANT-TDAVSCIKEVLCDRTVGGEHLNEDSGLHVIAACNPyRKHSQEMI 2549
Cdd:smart00382   80 DVLILDEITSlLDAEQEALLLLLEELRLLLLLKSEKNLTVILTTND-EKDLGPAL 133

Double zinc ribbon; This family consists of a pair of zinc ribbon domains.

                           10        20
                   ....*....|....*....|....*..
gi 1958663172    3 CPQCGHVSSeKAAKFCSQCGQKLSPAA 29
Cdd:pfam12773    1 CPNCGHPNP-PGAKFCPACGTPLKPDR 26

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958663172 3995 GIQPCSICQGDAQDPVCLPCDHVYCLPCIQTWLaPGQMICPYCKTELPDKF 4045
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWL-PGQMSCPLCRTELPDDF 50

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 1958663172  3999 CSICQGD-AQDPVCLPCDHVYCLPCIQTWLAPGQMICPYC 4037
Cdd:smart00184    1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663172  2427 GIPVIIMGETGCGKT----RLIKFLSDLRRGSIE-------AETMKLVKVHGGTTPSMIYSRVKDAERtaFFNKAQHNLE 2495
Cdd:smart00382    2 GEVILIVGPPGSGKTtlarALARELGPPGGGVIYidgedilEEVLDQLLLIIVGGKKASGSGELRLRL--ALALARKLKP 79

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1958663172  2496 TILFFDEANT-TDAVSCIKEVLCDRTVGGEHLNEDSGLHVIAACNPyRKHSQEMI 2549
Cdd:smart00382   80 DVLILDEITSlLDAEQEALLLLLEELRLLLLLKSEKNLTVILTTND-EKDLGPAL 133

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1958663172 3994 FGIQpCSICQGD---AQDPVCLPCDHVYCLPCIQTWLAPGQMICPYCKTELP 4042
Cdd:COG5540    322 KGVE-CAICMSNfikNDRLRVLPCDHRFHVGCVDKWLLGYSNKCPVCRTAIP 372

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958663172 3995 GIQPCSICQGDAQDPVCLPCDHVYCLPCIQTWLaPGQMICPYCKTELPDKF 4045
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWL-PGQMSCPLCRTELPDDF 50

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
                   ....*....|....*....|....*....|....*....
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMICPYC 4037
Cdd:cd16449      3 CPICLERLKDPVLLPCGHVFCRECIRRLLESGSIKCPIC 41

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQ-TW--LAPGQMICPYCKTELPDK 4044
Cdd:cd16597      8 CSICLELFKDPVTLPCGHNFCGVCIEkTWdsQHGSEYSCPQCRATFPRR 56

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 1958663172  3999 CSICQGD-AQDPVCLPCDHVYCLPCIQTWLAPGQMICPYC 4037
Cdd:smart00184    1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWL---APGQMICPYCKTELPDK 4044
Cdd:cd16609      6 CSICLGLYQDPVTLPCQHSFCRACIEDHWrqkDEGSFSCPECRAPFPEG 54

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQT-WLAPGQMICPYCK 4038
Cdd:cd16608      9 CSICLSIYQDPVSLGCEHYFCRQCITEhWSRSEHRDCPECR 49

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated (FHA) domain and a C3HC4-type RING-HC finger.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958663172 3999 CSICQGDAQDPVCL-PCDHVYCLPCIQTWLAPGQMICPYCKTELpdkfsPTVSQNH 4053
Cdd:cd16503      5 CSICQDLLHDCVSLqPCMHNFCAACYSDWMERSNTECPTCRATV-----QRVNKNH 55

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWL--APGQMICPYC 4037
Cdd:cd16601      4 CSLCKEYLKDPVIIECGHNFCRACITRFWeeLDGDFPCPQC 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 1958663172 3997 QPCSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQ-MICPYCKTEL 4041
Cdd:cd16568      5 QECIICHEYLYEPMVTTCGHTYCYTCLNTWFKSNRsLSCPDCRTKI 50

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMiCPYCK 4038
Cdd:cd16532      3 CPICQDEFKDPVVLRCKHIFCEDCVSEWFERERT-CPLCR 41

RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer's disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus, a genetic variant of RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQmICPYCKTEL 4041
Cdd:cd16562      4 CHICLGKVRQPVICSNNHVFCSSCMDVWLKNNN-QCPACRVPI 45

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMICPYCKTELP 4042
Cdd:cd16542      4 CAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNTWTCPYCRAYLS 47

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958663172  2427 GIPVIIMGETGCGKT----RLIKFLSDLRRGSIE-------AETMKLVKVHGGTTPSMIYSRVKDAERtaFFNKAQHNLE 2495
Cdd:smart00382    2 GEVILIVGPPGSGKTtlarALARELGPPGGGVIYidgedilEEVLDQLLLIIVGGKKASGSGELRLRL--ALALARKLKP 79

                            90       100       110       120       130
                    ....*....|....*....|....*....|....*....|....*....|....*
gi 1958663172  2496 TILFFDEANT-TDAVSCIKEVLCDRTVGGEHLNEDSGLHVIAACNPyRKHSQEMI 2549
Cdd:smart00382   80 DVLILDEITSlLDAEQEALLLLLEELRLLLLLKSEKNLTVILTTND-EKDLGPAL 133

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1958663172 3999 CSIC------QGDAQdPVCLPCDHVYCLPCIQTWLAPGQMICPYCK 4038
Cdd:cd16450      5 CPICfepwtsSGEHR-LVSLKCGHLFGYSCIEKWLKGKGKKCPQCN 49

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLApGQMICPYCK 4038
Cdd:cd23135      6 CSICFSEIRSGAILKCGHFFCLSCIASWLR-EKSTCPLCK 44

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1958663172 3999 CSICQGDAQDPVCL-PCDHVYCLPCIQTWLAPGQMICPYCKT 4039
Cdd:cd16544      5 CPVCQEVLKDPVELpPCRHIFCKACILLALRSSGARCPLCRG 46

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCI-QTWLAPGQ-MICPYCKTELPDKF 4045
Cdd:cd16594      8 CPICLDYFTDPVTLDCGHSFCRACIaRCWEEPETsASCPQCRETCPQRN 56

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGDAQDPVCL--PCDHVYCLPCIQTWLAPGQMiCPYCKT 4039
Cdd:cd16574      4 CPICLDRFENEKAFldGCFHAFCFTCILEWSKVKNE-CPLCKQ 45

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 1958663172 3999 CSICQGDAQDPVcLPCDHVYCLPCI--QTWLAPGQMICP 4035
Cdd:pfam13445    1 CPICLELFTDPV-LPCGHTFCRECLeeMSQKKGGKFKCP 38

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMICPYCKTEL 4041
Cdd:cd16613      3 CICCQELVYKPITTPCKHNICKSCLQRSFKAEVYTCPACRHDL 45

RING finger, HC subclass, found in tripartite motif-containing protein 67 (TRIM67) and similar proteins; TRIM67, also known as TRIM9-like protein (TNL), is selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H (also known as glucosidase II beta), a protein kinase C substrate. It negatively regulates Ras signaling in cell proliferation via degradation of 80K-H, leading to neural differentiation including neuritogenesis. TRIM67 belongs to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPgqmiCPYCKTELPDKFSPTVSQNHR 4054
Cdd:cd16758      6 CPVCGSLFREPIILPCSHNVCLPCARTIAVQ----TPESEQHLPHSSSITCPQCHR 57

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1958663172 3999 CSICQGDAQDPVCLPC-DHVYCLPCIQTWLAPGQMICPYCKTEL 4041
Cdd:cd16620      6 CPICKDLMKDAVLTPCcGNSFCDECIRTALLEEDFTCPTCKEPD 49

RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor protein family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity, which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-c, as well as two invertebrate Cbl-family proteins, D-Cbl in Drosophila and Sli-1 in C. elegans. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating activated tyrosine kinases and targeting them for degradation. D-Cbl associates with the Drosophila epidermal growth factor receptor (EGFR) and overexpression of D-Cbl in the eye of Drosophila embryos inhibits EGFR-dependent photoreceptor cell development. Sli-1 is a negative regulator of the Let-23 receptor tyrosine kinase, an EGFR homolog, in vulva development. Cbl proteins in this subfamily consist of a highly conserved N-terminal half that includes 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) and a C3HC4-type RING-HC finger, both of which are required for Cbl-mediated downregulation of RTKs, and a divergent C-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1958663172 3997 QPCSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMICPYCK 4038
Cdd:cd16502      2 QLCKICAENDKDVRIEPCGHLLCTPCLTSWQDSDGQTCPFCR 43

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWlapgQMICPYCK 4038
Cdd:cd16576      6 CPVCGSLFTEPVILPCSHNLCLGCALNI----QLTCPICH 41

RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 homolog (AtBRCA1) and similar proteins; AtBRCA1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBRCA1 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLApGQMICPYCK 4038
Cdd:cd23147      7 CPICLSLFKSAANLSCNHCFCAGCIGESLK-LSAICPVCK 45

RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; RNF170, also known as putative LAG1-interacting protein, is an endoplasmic reticulum (ER) membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate (IP3) receptors (ITPR1) via the endoplasmic-reticulum-associated protein degradation (ERAD) pathway. A point mutation (arginine to cysteine at position 199) in the RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. RNF170 contains a C3HC4-type RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLA----PGQMICPYCK 4038
Cdd:cd16553      4 CPICLQDARFPVETNCGHLFCGPCIITYWRhgswLGAVSCPVCR 47

RING finger, HC subclass, found in tripartite motif-containing protein 3 (TRIM3); TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It functions as a tumor suppressor that regulates asymmetric cell division in glioblastoma. It binds to the cdk inhibitor p21(WAF1/CIP1) and regulates its availability that promotes cyclin D1-cdk4 nuclear accumulation. Moreover, TRIM3 plays an important role in the central nervous system (CNS). It is encoded by the gene BERP (brain-expressed RING finger protein), a unique p53-regulated gene that modulates seizure susceptibility and GABAAR cell surface expression. Furthermore, TRIM3 mediates activity-dependent turnover of postsynaptic density (PSD) scaffold proteins GKAP/SAPAP1 and is a negative regulator of dendritic spine morphology. In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. It also regulates the motility of the kinesin superfamily protein KIF21B. TRIM3 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

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                   ....*....|....*....|....*....|....*....|..
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMI--CPYCK 4038
Cdd:cd16768      7 CSICLDRYHNPKVLPCLHTFCERCLQNYIPPQSLTlsCPVCR 48

RING finger, HC subclass, found in Saccharomyces cerevisiae DNA repair protein RAD16, Schizosaccharomyces pombe rhp16, and similar proteins; Budding yeast RAD16, also known as ATP-dependent helicase RAD16, is encoded by a yeast excision repair gene homologous to the recombinational repair gene RAD54 and to the SNF2 gene involved in transcriptional activation. It is a component of the global genome repair (GGR) complex that promotes global genome nucleotide excision repair (GG-NER) by removing DNA damage from non-transcribing DNA. RAD16 is involved in differential repair of DNA after UV damage, and repairs preferentially the MAT-alpha locus compared with the HML-alpha locus. Fission yeast rhp16, also known as ATP-dependent helicase rhp16, is a RAD16 homolog. It is involved in GGR via nucleotide excision repair (NER), in conjunction with rhp7, after UV irradiation. Both RAD16 and rhp16 contain a C3HC4-type RING-HC finger, as well as a DEAD-like helicase domain and a helicase superfamily C-terminal domain.

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                   ....*....|....*....|....*....|....*....|..
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLA---PGQMICPYC 4037
Cdd:cd16567      3 CGICHEEAEDPVVARCHHVFCRACVKEYIEsapGGKVTCPTC 44

RING finger, HC subclass, found in SNF2 histone-linker PHD finger RING finger helicase (SHPRH) and similar proteins; SHPRH is a yeast RAD5 homolog found in mammals. It functions as an E3 ubiquitin-protein ligase that associates with proliferating cell nuclear antigen (PCNA), RAD18, and the ubiquitin-conjugating enzyme UBC13 (E2), and suppresses genomic instability by proliferating methyl methanesulfonate (MMS)-induced PCNA polyubiquitination. SHPRH contains a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a linker histone domain (H15), a PHD-finger, and a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA. This subfamily also includes tripartite motif-containing protein 15 (TRIM15). TRIM15, also known as RING finger protein 93 (RNF93), zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM15 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

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                   ....*....|....*....|....*....|....*....|....*...
gi 1958663172 3998 PCSICQGDAQDPVC-LPCDHVYCLPCIQTWL---APGQMI---CPYCK 4038
Cdd:cd16569      3 PCPICARPLGKQWSvLPCGHCFCLECIAILIdqyAQSRRRslkCPICR 50

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

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gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWLAPgQMICPYC 4037
Cdd:cd16476      3 CAICYQEMKEARITPCNHFFHGLCLRKWLYV-QDTCPLC 40

RING finger, HC subclass, found in RING finger protein 169 (RNF169) and similar proteins; RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to regulation of the DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. RNF169 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MIU (motif interacting with ubiquitin) domain.

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                   ....*....|....*....|....*....|....*....|....*.
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWL--APGQMICPYCKTELP 4042
Cdd:cd16551      4 CAGCLEVPVEPATLPCGHTLCRGCANRALdaAEAGPTCPRCRAPLP 49

Zinc finger, C3HC4 type (RING finger);

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                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGDAQDPVCLPCDH-VYCLPCIQTWLApGQMICPYCKTE 4040
Cdd:pfam13920    5 CVICLDRPRNVVLLPCGHlCLCEECAERLLR-KKKKCPICRQP 46

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

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                   ....*....|....*....|....*....|....*....|....*
gi 1958663172 3999 CSICQ---GDAQDPVCLPCDHVYCLPCIQTWLAPGQmICPYCKTE 4040
Cdd:cd23115      7 CVICRleyEEGEDLLTLPCKHCYHSECIQQWLQINK-VCPVCSAE 50

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-c and similar proteins; Cbl-c, also known as RING finger protein 57 (RNF57), SH3-binding protein Cbl-3, SH3-binding protein Cbl-c, or signal transduction protein Cbl-c, is an E3 ubiquitin-protein ligase expressed exclusively in epithelial cells. 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 C3HC4-type RING-HC finger, and a short proline-rich region, but lacks the ubiquitin-associated (UBA) leucine zipper motif that are present in Cbl and Cbl-b. Cbl-c acts as a regulator of epidermal growth factor receptor (EGFR)-mediated signal transduction. It also suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Moreover, Cbl-c ubiquitinates and downregulates RETMEN2A and implicates Enigma (PDLIM7) as a positive regulator of RETMEN2A by blocking Cbl-mediated ubiquitination and degradation. The ubiquitin ligase activity of Cbl-c is increased via the interaction of its RING-HC finger domain with a LIM domain of the paxillin homolog, hydrogen peroxide induced construct 5 (Hic-5).

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                   ....*....|....*....|....*....|....*....|....*
gi 1958663172 3997 QPCSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMICPYCKTEL 4041
Cdd:cd16710     14 ELCKICAERDKDVRIEPCGHLLCSCCLAAWQHSDSQTCPFCRCEI 58

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958663172 3983 CKDKASKKFCRFGIQPCsicqgdaqdpvclpCDHVYCLPCIQTWLAPGQMI------CPYC 4037
Cdd:cd16521      6 CMEVVLEKERRFGILSN--------------CNHVFCLECIREWRSSKDFEnsivrsCPIC 52

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....
gi 1958663172 3998 PCSICQGDAQDPVCLPCDHVYCLPCIQTWLAPGQMiCPYCKTEL 4041
Cdd:cd16514      3 ECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPK-CPLCRTSL 45

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates AMPA-type glutamate receptor subunit GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGDAQDP---VCLPCDHVYCLPCIQTWLAPGQMICPYCK 4038
Cdd:cd16797      3 CAICLDEYEEGdklRVLPCSHAYHSKCVDPWLTQTKKTCPVCK 45

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

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                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGDAQDPVC---LPCDHVYCLPCIQTWLAPGQMICPYCK 4038
Cdd:cd16473      7 CAICLENYQNGDLlrgLPCGHVFHQNCIDVWLERDNHCCPVCR 49

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.

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                   ....*....|....*....|....*....|....*....|....*
gi 1958663172 3999 CSICQGDAQDPVCLPCDHVYCLPCIQTWL--APGQMICPYCKTEL 4041
Cdd:cd16498     19 CPICLELLKEPVSTKCDHQFCRFCILKLLqkKKKPAPCPLCKKSV 63

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

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                   ....*....|....*....|....*....|....*....|...
gi 1958663172 3999 CSICQGD--AQDPV-CLPCDHVYCLPCIQTWLAPgQMICPYCK 4038
Cdd:cd16468      2 CVICMADfvVGDPIrYLPCMHIYHVDCIDDWLMR-SFTCPSCM 43