Pex2 / Pex12 amino terminal region; This region is found at the N terminal of a number of known and predicted peroxins including Pex2, Pex10 and Pex12. This conserved region is usually associated with a C terminal ring finger (pfam00097) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751898735   1 MRHHTATLTEQQRRALLRAVFVLRQGLACLQRLHVAWFYIHGVFYHLAKRLTGITYAlrpdplrvlmSVAPSALQLRVRS 80
Cdd:pfam04757 106 ESRNARDSLKSRLKRYLLKLYPFLESLYKLLNLHLFLFYLTGKYYSLSKRLLGIRYV----------RLKPLDIFSNERR 175

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1751898735  81 LPGEDLRARVSYRLLGVISLLHLVLSMGLQLYGFRQRQ 118
Cdd:pfam04757 176 VSYEQLLWNAFSELLGFLLPLLLAVILFLKLLEWWYSS 213

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1751898735 144 RNPLCTLCLEERRHPTATPCGHLFCWECI-TAWCSSKAE-CPLCREKFPPQKLIYLR 198
Cdd:COG5574   214 ADYKCFLCLEEPEVPSCTPCGHLFCLSCLlISWTKKKYEfCPLCRAKVYPKKVIILR 270

Pex2 / Pex12 amino terminal region; This region is found at the N terminal of a number of known and predicted peroxins including Pex2, Pex10 and Pex12. This conserved region is usually associated with a C terminal ring finger (pfam00097) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751898735   1 MRHHTATLTEQQRRALLRAVFVLRQGLACLQRLHVAWFYIHGVFYHLAKRLTGITYAlrpdplrvlmSVAPSALQLRVRS 80
Cdd:pfam04757 106 ESRNARDSLKSRLKRYLLKLYPFLESLYKLLNLHLFLFYLTGKYYSLSKRLLGIRYV----------RLKPLDIFSNERR 175

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1751898735  81 LPGEDLRARVSYRLLGVISLLHLVLSMGLQLYGFRQRQ 118
Cdd:pfam04757 176 VSYEQLLWNAFSELLGFLLPLLLAVILFLKLLEWWYSS 213

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCREKFPPQKL 194
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESKL 75

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1751898735 144 RNPLCTLCLEERRHPTATPCGHLFCWECI-TAWCSSKAE-CPLCREKFPPQKLIYLR 198
Cdd:COG5574   214 ADYKCFLCLEEPEVPSCTPCGHLFCLSCLlISWTKKKYEfCPLCRAKVYPKKVIILR 270

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1751898735 144 RNPLCTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCREKFPP 191
Cdd:cd16561     1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRTELPD 48

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis, and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAW---CSSKAECPLCR 186
Cdd:cd16534     3 CNICLDTASDPVVTMCGHLFCWPCLYQWletRPDRQTCPVCK 44

Pex2 / Pex12 amino terminal region; This region is found at the N terminal of a number of known and predicted peroxins including Pex2, Pex10 and Pex12. This conserved region is usually associated with a C terminal ring finger (pfam00097) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751898735   1 MRHHTATLTEQQRRALLRAVFVLRQGLACLQRLHVAWFYIHGVFYHLAKRLTGITYAlrpdplrvlmSVAPSALQLRVRS 80
Cdd:pfam04757 106 ESRNARDSLKSRLKRYLLKLYPFLESLYKLLNLHLFLFYLTGKYYSLSKRLLGIRYV----------RLKPLDIFSNERR 175

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1751898735  81 LPGEDLRARVSYRLLGVISLLHLVLSMGLQLYGFRQRQ 118
Cdd:pfam04757 176 VSYEQLLWNAFSELLGFLLPLLLAVILFLKLLEWWYSS 213

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 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWC-SSKAECPLC 185
Cdd:cd16449     3 CPICLERLKDPVLLPCGHVFCRECIRRLLeSGSIKCPIC 41

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 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSK---AECPLCREKF 189
Cdd:cd16498    19 CPICLELLKEPVSTKCDHQFCRFCILKLLQKKkkpAPCPLCKKSV 63

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1751898735 148 CTLCLEERRHPTAT-PCGHLFCWECITAWCSSKAECPLCREKF 189
Cdd:cd23130     3 CPICLDDPEDEAITlPCLHQFCYTCILRWLQTSPTCPLCKTPV 45

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 1751898735  148 CTLCLEER-RHPTATPCGHLFCWECITAWCSSK-AECPLC 185
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLESGnNTCPIC 40

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins; Cbl-b, also known as Casitas B-lineage lymphoma proto-oncogene b, RING finger protein 56 (RNF56), SH3-binding protein Cbl-b, or signal transduction protein Cbl-b, has been identified as a regulator of antigen-specific, T cell-intrinsic, peripheral immune tolerance, a state also known as clonal anergy. It may inhibit activation of the p85 subunit of phosphoinositide 3-kinase (PI3K), protein kinase C-theta (PKC-theta), and phospholipase C-gamma1 (PLC-gamma1) and negatively regulates T-cell receptor-induced transcription factor nuclear factor kappaB (NF-kappaB) activation. In addition, Cbl-b may target multiple signaling molecules involved in transforming growth factor (TGF)-beta-mediated transactivation pathways. Cbl-b contains a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline rich domain, a nuclear localization signal, a C3HC4-type RING-HC finger and an ubiquitin-associated (UBA) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITAWCSSKAE-CPLCR 186
Cdd:cd16709    22 LCKICAENDKDVKIEPCGHLMCTSCLTAWQESDGQgCPFCR 62

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 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITAWCSSKAE-CPLCR 186
Cdd:cd16708    23 LCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQgCPFCR 63

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAE---CPLCREKFPPQKLIYL 197
Cdd:cd16744     3 CNICLDTAKDAVVSLCGHLFCWPCLHQWLETRPNrqvCPVCKAGISRDKVIPL 55

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 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKA----ECPLCREKFPPQ 192
Cdd:cd16609     6 CSICLGLYQDPVTLPCQHSFCRACIEDHWRQKDegsfSCPECRAPFPEG 54

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), 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, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITA-WCSSK---AECPLCREKFP 190
Cdd:cd16604     3 CPICLDLLKDPVTLPCGHSFCMGCLGAlWGAGRggrASCPLCRQTFP 49

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 1751898735 146 PLCTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCR 186
Cdd:cd16532     1 DICPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCREKFPPQ-KLIYLRHY 200
Cdd:cd16535     4 CSICSELFIEAVTLNCSHSFCSYCITEWMKRKKECPICRKPITSKtRSLVLDNC 57

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCREKFPPQKL 194
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESKL 75

E3 ubiquitin-protein ligase RMA2; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSK----------------AECPLCREKFPPQKLI 195
Cdd:PLN03208   21 CNICLDQVRDPVVTLCGHLFCWPCIHKWTYASnnsrqrvdqydhkrepPKCPVCKSDVSEATLV 84

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 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 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAE---CPLCREKFP 190
Cdd:cd16611     7 CPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEdttCPECRELCQ 52

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1751898735 148 CTLCLEERRHP---TATPCGHLFCWECITAWCSSKAECPLCR 186
Cdd:cd16454     2 CAICLEEFKEGekvRVLPCNHLFHKDCIDPWLEQHNTCPLCR 43

RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 (AtBARD1) and similar proteins; AtBARD1, also called protein REPRESSOR OF WUSCHEL 1, binds specifically to H3K4me3 regions of target gene (e.g. WUS and WOX5) promoters to repress their transcription via chromatin remodeling. It is required for the shoot apical meristem (SAM) organization and maintenance, by confining WUS expression to the organizing center, and for the quiescent center (QC) development in the root apical meristem (RAM), by repressing WOX5 expression in the root proximal meristem. AtBARD1 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). AtBARD1 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCREKFPPQKL 194
Cdd:cd23146     7 CPICLKLLNRPVLLPCDHIFCSSCITDSTKVGSDCPVCKLPYHSQDL 53

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 1751898735 148 CTLCLEERRHPTATPCGHLFCWECIT-AWCSS--KAECPLCREKFPP 191
Cdd:cd16594     8 CPICLDYFTDPVTLDCGHSFCRACIArCWEEPetSASCPQCRETCPQ 54

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).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITAWCSSKAE-CPLCR 186
Cdd:cd16710    15 LCKICAERDKDVRIEPCGHLLCSCCLAAWQHSDSQtCPFCR 55

RING finger, HC subclass, found in ligand of numb protein X 3 (LNX3); LNX3, also known as PDZ domain-containing RING finger protein 3 (PDZRN3), or Semaphorin cytoplasmic domain-associated protein 3 (SEMACAP3), is an E3 ubiquitin-protein ligase that was first identified as a Semaphorin-binding partner. It is also responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. LNX3 acts as a negative regulator of osteoblast differentiation by inhibiting Wnt-beta-catenin signaling. LNX3 also plays an important role in neuromuscular junction formation. It interacts with and ubiquitinates the muscle specific tyrosine kinase (MuSK), thus promoting its endocytosis and negatively regulating the cell surface expression of this key regulator of postsynaptic assembly. LNX3 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPL-CR 186
Cdd:cd16718     7 CNLCNKVLEDPLTTPCGHVFCAGCVLPWVVQQGSCPVkCQ 46

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITA-WCSSKA----ECPLCREKF 189
Cdd:cd16553     4 CPICLQDARFPVETNCGHLFCGPCIITyWRHGSWlgavSCPVCRQTV 50

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCR 186
Cdd:cd16637     3 TCHICLQPLVEPLDTPCGHTFCYKCLTNYLKIQQCCPLDR 42

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
                  ....*....|....*....|....*....|....*....
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCR 186
Cdd:cd16562     4 CHICLGKVRQPVICSNNHVFCSSCMDVWLKNNNQCPACR 42

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1 (PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1751898735 148 CTLCLEE-RRHPTATP--CGHLFCWECITAWCSSKAECPLCREKF 189
Cdd:cd16635     7 CPICLNTfRDQAVGTPesCDHIFCLDCILEWSKNANTCPVDRIVF 51

RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 is an E3 ubiquitin-protein ligase that interacts with mesenchyme Homeobox 2 (MEOX2) transcription factor, a regulator of the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes; it enhances Meox2 activation of the p21 promoter. It also regulates the expression of myelin-associated glycoprotein (MAG) genes and is required for myelin production in Schwann cells of the peripheral nervous system. Moreover, RNF10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells. RNF10 contains a C3HC4-type RING-HC finger and three putative nuclear localization signals.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1751898735 146 PLCTLCLEERRHPTATPCGHLFCWECI--------TAWcsskAECPLC 185
Cdd:cd16536     1 PQCPICLEPPVAPRITRCGHIFCWPCIlrylslseKKW----RKCPIC 44

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1751898735 146 PLCTLCLEERRHPTATPCGHLFCWECITAWCSS----KAECPLC 185
Cdd:cd16567     1 LVCGICHEEAEDPVVARCHHVFCRACVKEYIESapggKVTCPTC 44

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1751898735 142 VSRNPLCTLCLEE---------RRHPTATPCGHLFCWECITAWCSSKAECPLCREKFPP 191
Cdd:cd23117     1 ENGSVDCVICMSDielpstnsvRRDYMVTPCNHIFHTNCLERWMDIKLECPTCRRPLPP 59

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 1751898735 147 LCTLCLEERRHPTATP-CGHLFCWECI-TAWCSSKAECPLCREKF 189
Cdd:cd16620     5 KCPICKDLMKDAVLTPcCGNSFCDECIrTALLEEDFTCPTCKEPD 49

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECIT-AWCSSKAECPLCR 186
Cdd:cd16509     6 CAICLDSLTNPVITPCAHVFCRRCICeVIQREKAKCPMCR 45

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1751898735 117 RQRARKEWRLHRGLShrrASLEERAVSRNP------LCTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLC 185
Cdd:COG5152   165 RSDFKTGWKLNQEWN---AEYEEAPVISGPgekipfLCGICKKDYESPVVTECGHSFCSLCAIRKYQKGDECGVC 236

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKA-------ECPLCREKFPP 191
Cdd:cd16593     8 CPICQGTLREPVTIDCGHNFCRACLTRYCEIPGpdleeppTCPLCKEPFRP 58

RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; RNF151 is a testis-specific RING finger protein that interacts with dysbindin, a synaptic and microtubular protein that binds brain snapin, a SNARE-binding protein that mediates intracellular membrane fusion in both neuronal and non-neuronal cells. Thus, it may be involved in acrosome formation of spermatids by interacting with multiple proteins participating in membrane biogenesis and microtubule organization. RNF151 contains a C3HC4-type RING finger domain, a putative nuclear localization signal (NLS), and a TNF receptor associated factor (TRAF)-type zinc finger domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLCRE 187
Cdd:cd16547     5 ICSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCRK 45

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1751898735 148 CTLCLEERRHPTATPCGHLFCWECITAWCSSKAE----CPLC 185
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPDGesllCPQC 42

Modified RING finger found in peroxin-12 (PEX12) and similar proteins; PEX12, also known as peroxisome assembly protein 12 or peroxisome assembly factor 3 (PAF-3), is a RING finger domain-containing integral membrane peroxin required for protein import into peroxisomes. Mutations in human PEX12 result in the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III), a lethal neurological disorder. PEX12 also functions as an E3-ubiquitin ligase that facilitates the PEX4-dependent monoubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation. PEX12 contains a modified RING finger that lacks the third, fourth, and eighth zinc-binding residues of the consensus RING finger motif, suggesting PEX12 may only bind one zinc ion.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1751898735 147 LCTLCLEERRHPTA-TPCGHLFCWECITAWCSSKAECP 183
Cdd:cd16451     2 ICPLCRKKRTNPTAlATSGYVFCYPCIYRYVKEHGRCP 39

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751898735 113 GFRQRQRARKEWRLHRGLSHRRASLEERAVSRNPL-----CTLCLEERRHPTATP-CGHLFCWECI-TAWCSSKAECPLC 185
Cdd:COG5222   237 GYVVAQPDVQSWEKYQQRTKAVAEIPDQVYKMQPPnislkCPLCHCLLRNPMKTPcCGHTFCDECIgTALLDSDFKCPNC 316

                  ...
gi 1751898735 186 REK 188
Cdd:COG5222   317 SRK 319

RING finger, HC subclass, found in bifunctional apoptosis regulator (BAR); BAR, also known as RING finger protein 47, was originally identified as an inhibitor of Bax-induced apoptosis. It participates in the block of apoptosis induced by TNF-family death receptors (extrinsic pathway) and mitochondria-dependent apoptosis (intrinsic pathway). BAR is predominantly expressed by neurons in the central nervous system and is involved in the regulation of neuronal survival. It is an endoplasmic reticulum (ER)-associated RING-type E3 ubiquitin ligase that interacts with BI-1 protein and post-translationally regulates its stability, as well as functioning in ER stress. BAR contains an N-terminal C3HC4-type RING-HC finger, a SAM domain, a coiled-coil domain, and a C-terminal transmembrane (TM) domain. This model corresponds to the RING-HC finger responsible for the binding of ubiquitin conjugating enzymes (E2s).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITAW--CSSKAECPLCREK 188
Cdd:cd16497     3 LCHCCYDLLVNPTTLNCGHSFCRHCLALWwkSSKKTECPECRQK 46

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1751898735 146 PLCTLCLeerRHPTATPCGHLFCWECITAWCSSKAE-CP 183
Cdd:cd16643     5 PICLMAL---REPVQTPCGHRFCKACILKSIREAGHkCP 40

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1751898735 147 LCTLCLEERRHPTATPCGHLFCWECITA-WCSSkaeCPLCREKFP 190
Cdd:cd16602     5 VCAICLDYFKDPVSIGCGHNFCRVCVTQlWGFT---CPQCRKSFP 46

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1751898735 148 CTLCL---EERRHPTATPCGHLFCWECITAWCSSKAECPLCR 186
Cdd:cd16681    13 CTICLsilEEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICR 54

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1751898735 148 CTLCLEE-------RRhptaTPCGHLFCWECITAWCSSKAECPLCR 186
Cdd:cd16474     3 CTICLSDfeegedvRR----LPCMHLFHQECVDQWLSTNKRCPICR 44

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; 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, 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. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1751898735 145 NPLCTLCLEERRHPTATPCGHLFCWECITAWCSSKAECPLC 185
Cdd:cd16684     2 NDICSICYQDMKSAVITPCSHFFHAGCLKKWLYVQETCPLC 42

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1751898735 148 CTLCLEERRHPTATP-CGHLFCWECITAWCSSKAECPLCRE 187
Cdd:cd16506     3 CPICLDEIQNKKTLEkCKHSFCEDCIDRALQVKPVCPVCGV 43