RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477   1 MDHQITTASDFTTTSIPNLYQLDTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLCLFEFRESLLRSEFLV 80
Cdd:COG5432     1 NELDATDPSDWNQTKIPSLKGLDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCREDPCESRLRGSSGS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477  81 NEIIQSYTSIRSSLLNALKIRKPIPVPGNEEVPNPQdssliEVISESENDSPNAADDDLQIVATSERKLAKRSMTDILpl 160
Cdd:COG5432    81 REINESHARNRDLLRKVLESLCRLPRPIKEERPCRW-----ETVIAQDSASGDEEWEDDLASNSSPASIAKKTSRDSK-- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 161 sskpskrnftmfrseriKKKpkpNEQMAQCPICQQFYPLKALEkTHLDECLTLQSLgeKPKVPTNFPVDSKSHDKDTFKF 240
Cdd:COG5432   154 -----------------KRK---REDLVHCPACSNLVPHNQIN-QHLDSCLNSPSS--PSSSSSPYKNKDNSKSNSLLSF 210

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 241 KVQTPEVDKSPSDETSHVDKYLnsmtSAEHQRLPKINFTSMTQSQIKQKLSSLGLSTNGTRQNMIKRYNHYEMLWNSNfC 320
Cdd:COG5432   211 KTDDDSITKRRLRSFNSADELP----LKDRVRLPKLTYALLSESKIRSKLSEMGLPTDGHKQLLQRRHAKWVTLYNSN-L 285

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 321 DSLEPVDEAELKRQLLSWDVSHNKmpqnnnnKGGISKLMMMKSNgrsssyrkllenfkndkfnrkgWIVMFQKDFTRLIR 400
Cdd:COG5432   286 DQKQPVSKRNLIRQLIDWERVQSK-------SIGVEKEKLGGGD----------------------WEKAYAEDFADLIN 336

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 401 EAKLKikkgssddssspmRTDGENGVAQVQSVQGIRDQQMEGNQETVINEDKLVNEGNLpnEDLTDADLS 470
Cdd:COG5432   337 RAKQS-------------TTNKNDSLRNTAVESSTEPSTSNGFPATSVSPPLTIDLTNS--QTGSDGPQS 391

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1835457477  28 CHICKDFLKVPV-LTPCGHTFCSLCIRTHLN-NQPNCPLC 65
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLEsGNVTCPLC 40

E3 ubiquitin-protein ligase RMA2; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRT----------------HLNNQPNCPLCLFEFRESLL 74
Cdd:PLN03208   21 CNICLDQVRDPVVTLCGHLFCWPCIHKwtyasnnsrqrvdqydHKREPPKCPVCKSDVSEATL 83

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477   1 MDHQITTASDFTTTSIPNLYQLDTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLCLFEFRESLLRSEFLV 80
Cdd:COG5432     1 NELDATDPSDWNQTKIPSLKGLDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCREDPCESRLRGSSGS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477  81 NEIIQSYTSIRSSLLNALKIRKPIPVPGNEEVPNPQdssliEVISESENDSPNAADDDLQIVATSERKLAKRSMTDILpl 160
Cdd:COG5432    81 REINESHARNRDLLRKVLESLCRLPRPIKEERPCRW-----ETVIAQDSASGDEEWEDDLASNSSPASIAKKTSRDSK-- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 161 sskpskrnftmfrseriKKKpkpNEQMAQCPICQQFYPLKALEkTHLDECLTLQSLgeKPKVPTNFPVDSKSHDKDTFKF 240
Cdd:COG5432   154 -----------------KRK---REDLVHCPACSNLVPHNQIN-QHLDSCLNSPSS--PSSSSSPYKNKDNSKSNSLLSF 210

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 241 KVQTPEVDKSPSDETSHVDKYLnsmtSAEHQRLPKINFTSMTQSQIKQKLSSLGLSTNGTRQNMIKRYNHYEMLWNSNfC 320
Cdd:COG5432   211 KTDDDSITKRRLRSFNSADELP----LKDRVRLPKLTYALLSESKIRSKLSEMGLPTDGHKQLLQRRHAKWVTLYNSN-L 285

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 321 DSLEPVDEAELKRQLLSWDVSHNKmpqnnnnKGGISKLMMMKSNgrsssyrkllenfkndkfnrkgWIVMFQKDFTRLIR 400
Cdd:COG5432   286 DQKQPVSKRNLIRQLIDWERVQSK-------SIGVEKEKLGGGD----------------------WEKAYAEDFADLIN 336

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1835457477 401 EAKLKikkgssddssspmRTDGENGVAQVQSVQGIRDQQMEGNQETVINEDKLVNEGNLpnEDLTDADLS 470
Cdd:COG5432   337 RAKQS-------------TTNKNDSLRNTAVESSTEPSTSNGFPATSVSPPLTIDLTNS--QTGSDGPQS 391

RING finger, HC subclass, found in postreplication repair protein RAD18 and similar proteins; RAD18, also known as HR18 or RING finger protein 73 (RNF73), is an E3 ubiquitin-protein ligase involved in post replication repair of UV-damaged DNA via its recruitment to stalled replication forks. It associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on K164. It also interacts with another E2 ubiquitin conjugating enzyme RAD6 to form a complex that monoubiquitinates proliferating cell nuclear antigen at stalled replication forks in DNA translesion synthesis. Moreover, Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins. It can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after ionizing radiation (IR) exposure. RAD18 contains a C3HC4-type RING-HC finger, a ubiquitin-binding zinc finger domain (UBZ), a SAP (SAF-A/B, Acinus and PIAS) domain, and a RAD6-binding domain (R6BD).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1835457477  22 LDTLLRCHICKDFLKVPV-LTPCGHTFCSLCIRTHLNNQPNCPLCLFEFRESLL 74
Cdd:cd16529     1 LDDLLRCPICFEYFNTAMmITQCSHNYCSLCIRRFLSYKTQCPTCRAAVTESDL 54

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1835457477  28 CHICKDFLKVPV-LTPCGHTFCSLCIRTHLN-NQPNCPLC 65
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLEsGNVTCPLC 40

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1835457477  27 RCHICKDFLKVP-VLTPCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:pfam13923   1 MCPICMDMLKDPsTTTPCGHVFCQDCILRALRAGNECPLC 40

RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins; COP1, also known as RING finger and WD repeat domain protein 2 (RFWD2) or RING finger protein 200 (RNF200), is a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. It is localized predominantly in the nucleus, but may also be present in the cytosol. Mammalian COP1 functions as an E3 ubiquitin-protein ligase that interacts with Jun transcription factors and modulates their transcriptional activity. It also interacts with and negatively regulates the tumor-suppressor protein p53. Moreover, COP1 associates with COP9 signalosome subunit 6 (CSN6), and is involved in 14-3-3sigma ubiquitin-mediated degradation. The CSN6-COP1 link enhances ubiquitin-mediated degradation of p27(Kip1), a critical CDK inhibitor involved in cell cycle regulation, to promote cancer cell growth. Furthermore, COP1 functions as the negative regulator of ETV1 and influences prognosis in triple-negative breast cancer. COP1 contains an N-terminal extension, a C3HC4-type RING-HC finger, a coiled coil domain, and seven WD40 repeats. In human COP1, a classic leucine-rich NES, and a novel bipartite NLS is bridged by the RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLCLFE 68
Cdd:cd16504     5 CPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNRCPKCNFY 45

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLClfefRESL 73
Cdd:cd16514     2 LECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLC----RTSL 45

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 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQP----NCPLC 65
Cdd:cd16604     1 LSCPICLDLLKDPVTLPCGHSFCMGCLGALWGAGRggraSCPLC 44

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
                  ....*....|....*....|....*....|....*....
gi 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLCL 66
Cdd:cd16561     5 CSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCR 43

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQ----PNCPLCLFEFRES 72
Cdd:cd16597     6 LTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQhgseYSCPQCRATFPRR 56

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1835457477  27 RCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:cd16527     2 KCSLCLEERRHPTATPCGHLFCWSCITEWCNEKPECPLC 40

RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; RNF146, also known as dactylidin, or iduna, is a cytoplasmic E3 ubiquitin-protein ligase that is responsible for PARylation-dependent ubiquitination (PARdU). It displays neuroprotective property due to its inhibition of Parthanatos, a PAR dependent cell death, via binding with Poly(ADP-ribose) (PAR). It also modulates PAR polymerase-1 (PARP-1)-mediated oxidative cell injury in cardiac myocytes. Moreover, RNF146 mediates tankyrase-dependent degradation of axin, thereby positively regulating Wnt signaling. It also facilitates DNA repair and protects against cell death induced by DNA damaging agents or gamma-irradiation by translocating to the nucleus after cellular injury and promoting the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. Furthermore, RNF146 is implicated in neurodegenerative disease and cancer development. It regulates the development and progression of non-small cell lung cancer (NSCLC) by enhancing cell growth, invasion, and survival. RNF146 contains an N-terminal C3HC4-type RING-HC finger followed by a WWE domain with a poly(ADP-ribose) (PAR) binding motif at the tail.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLCLFEFRESLL 74
Cdd:cd16546     1 PECPICLQTCIHPVKLPCGHIFCYLCVKGVAWQSKRCALCRQEIPEDFL 49

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1835457477  28 CHICKDFLKVPVLtPCGHTFCSLCIRTH---LNNQPNCP 63
Cdd:pfam13445   1 CPICLELFTDPVL-PCGHTFCRECLEEMsqkKGGKFKCP 38

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 1835457477  24 TLLRCHICKDFLKVPV-LTPCGHTFCSLCIRTHLNNQP-NCPLC 65
Cdd:cd16544     1 AELTCPVCQEVLKDPVeLPPCRHIFCKACILLALRSSGaRCPLC 44

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 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPN---CPLC 65
Cdd:cd16534     3 CNICLDTASDPVVTMCGHLFCWPCLYQWLETRPDrqtCPVC 43

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 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQP--NCPLC 65
Cdd:cd16608     7 LLCSICLSIYQDPVSLGCEHYFCRQCITEHWSRSEhrDCPEC 48

RING finger found in polycomb group RING finger protein 5 (PCGF5) and similar proteins; PCGF5, also known as RING finger protein 159 (RNF159), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) and serves as the core component of a Polycomb repressive complex 1 (PRC1). Like other PCGF homologs, PCGF5 associates with ring finger protein 2 (RNF2) to form a RNF2-PCGF heterodimer, which is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. PCGF5 contains a C3HC4-type RING-HC finger.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1835457477  19 LYQLDTLLRCHICKDFLKVP-VLTPCGHTFCSLCIRTHLNNQPNCPLC----LFEFRESLLRSEFLVNEIIQ 85
Cdd:cd16737     4 VRDFNPYITCRICKGYLIKPtTVTECLHTFCKSCIVQHFEDSNDCPECgiqvHETNPLEMLRLDNTLEEIIF 75

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRTHLNN--QPNCPLC 65
Cdd:cd23132     5 CCICLDLLYKPVVLECGHVFCFWCVHRCMNGydESHCPLC 44

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
                  ....*....|....*....|....*....|....*...
gi 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:cd16532     3 CPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLC 40

Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation;

                           10        20        30
                   ....*....|....*....|....*....|....
gi 1835457477  278 FTSMTQSQIKQKLSSLGLSTNGTRQNMIKRYNHY 311
Cdd:smart00513   1 LAKLKVSELKDELKKRGLSTSGTKAELVDRLLEA 34

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.

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gi 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIR---THLNNQPNCPLCLFEFRESLLR 75
Cdd:cd16594     6 LTCPICLDYFTDPVTLDCGHSFCRACIArcwEEPETSASCPQCRETCPQRNLR 58

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs 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.

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gi 1835457477  28 CHICKDFLKVPVLTPCGHTFCSLCIRTHL-----NNQPNCPLCLFEFRESLLRS 76
Cdd:cd16598     7 CSICLDYLRDPVTIDCGHNFCRSCITDYCpisggHERPVCPLCRKPFKKENIRP 60

RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar proteins; BARD-1 is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an C3HC4-type RING-HC finger that binds BRCA1 at its N-terminus and three tandem ankyrin repeats and tandem BRCT repeat domains at its C-terminus. The BRCT repeats bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage.

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gi 1835457477  19 LYQLDTLLRCHICKDFLKVPV-LTPCGHTFCSLCIRTHLNNqpNCPLC 65
Cdd:cd16496     9 LDELENLLRCSRCASILKEPVtLGGCEHVFCRSCVGDRLGN--GCPVC 54

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.

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gi 1835457477  23 DTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:cd16547     1 DDDLICSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCC 43

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL 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 domain, as well as an 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 1835457477  21 QLDTLLRCHICKDFLKVPVLTPCGHTFC-SLCIR---THLNNQPNCPLC 65
Cdd:cd16524     1 QIEQLLTCPICLDRYRRPKLLPCQHTFClSPCLEglvDYVTRKLKCPEC 49

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.

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gi 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:cd23147     5 LKCPICLSLFKSAANLSCNHCFCAGCIGESLKLSAICPVC 44

RING finger, HC subclass, found in tripartite motif-containing protein 56 (TRIM56) and similar proteins; TRIM56, also known as RING finger protein 109 (RNF109), is a virus-inducible E3 ubiquitin ligase that restricts pestivirus infection. It positively regulates the Toll-like receptor 3 (TLR3) antiviral signaling pathway, and possesses antiviral activity against bovine viral diarrhea virus (BVDV), a ruminant pestivirus classified within the family Flaviviridae shared by tick-borne encephalitis virus (TBEV). It also possesses antiviral activity against two classical flaviviruses, yellow fever virus (YFV) and dengue virus (DENV), as well as a human coronavirus, HCoV-OC43, which is responsible for a significant share of common cold cases. It may not act on positive-strand RNA viruses indiscriminately. Moreover, TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses. TRIM56 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

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gi 1835457477  25 LLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQP-NCPLC 65
Cdd:cd16584     1 FLACKICLEQLRAPKTLPCLHTYCQDCLAQLADGGRvRCPEC 42

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.

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gi 1835457477  27 RCHICKDFLKV-PVLTPCGHTFCSLCIRTHLNNQPNCPLCLFEFRE 71
Cdd:cd23130     2 VCPICLDDPEDeAITLPCLHQFCYTCILRWLQTSPTCPLCKTPVTS 47

RING finger, HC subclass, found in ligand of numb protein X 4 (LNX4); LNX4, also known as PDZ domain-containing RING finger protein 4 (PDZRN4), or SEMACAP3-like protein (SEMCAP3L), is an E3 ubiquitin-protein ligase 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. LNX4 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

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gi 1835457477  22 LDTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPL 64
Cdd:cd16719     1 VDPDLKCKLCGKVLEEPLSTPCGHVFCAGCLLPWAVQRRLCPL 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.

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gi 1835457477  22 LDTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPNCPLCLFEFRESLLR 75
Cdd:cd23146     1 MELELKCPICLKLLNRPVLLPCDHIFCSSCITDSTKVGSDCPVCKLPYHSQDLR 54

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).

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gi 1835457477  28 CHICKDFLKVP--VLTPCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:cd16574     4 CPICLDRFENEkaFLDGCFHAFCFTCILEWSKVKNECPLC 43

RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

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gi 1835457477  23 DTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNNQPN-----CPLC 65
Cdd:cd16579     2 FKFLRCPGCKAEYKCPKLLPCLHTVCSGCLEALAEQASEttefqCPIC 49

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

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gi 1835457477  27 RCHICKDFLK---VPVLTpCGHTFCSLCIRTHLNNQPNCPLC 65
Cdd:cd16481     1 PCIICHDDLKpdqLAKLE-CGHIFHKECIKQWLKEQSTCPTC 41

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) and similar proteins; TRAF7, also known as RING finger and WD repeat-containing protein 1 or RING finger protein 119 (RNF119), is an E3 ubiquitin-protein ligase involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor by promoting K29-linked ubiquitination of several cellular targets, including the NF-kappaB essential modulator (NEMO) and the p65 subunit of NF-kappaB transcription factor. It is also involved in K29-linked polyubiquitination that has been implicated in lysosomal degradation of proteins. Moreover, TRAF7 is required for K48-linked ubiquitination of p53, a key tumor suppressor and a master regulator of various signaling pathways, such as those related to apoptosis, cell cycle and DNA repair. It is also required for tumor necrosis factor alpha (TNFalpha)-induced Jun N-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. Furthermore, TRAF7 functions as small ubiquitin-like modifier (SUMO) E3 ligase involved in other post-translational modification, such as sumoylation. It binds to and stimulates sumoylation of the proto-oncogene product c-Myb, a transcription factor regulating proliferation and differentiation of hematopoietic cells. It potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. Meanwhile, TRAF7 mediates MyoD1 regulation of the pathway and cell-cycle progression in myoblasts. It also plays a role in Toll-like receptors (TLR) signaling. TRAF7 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and an adjacent zinc finger, and a unique C-terminal domain that comprises a coiled coil domain and seven WD40 repeats.

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gi 1835457477  26 LRCHICKDFLKVPVLTPCGHTFCSLCIrTHLNNQPnCPL 64
Cdd:cd16644     6 LYCPLCQRVFKDPVITSCGHTFCRRCA-LTAPGEK-CPV 42

RING finger, HC subclass, found in yeast Bre1 and its homologs from eukaryotes; Bre1 is an E3 ubiquitin-protein ligase that catalyzes monoubiquitination of histone H2B in concert with the E2 ubiquitin-conjugating enzyme, Rad6. The Rad6-Bre1-mediated histone H2B ubiquitylation modulates the formation of double-strand breaks (DSBs) during meiosis in yeast. it is also required, indirectly, for the methylation of histone 3 on lysine 4 (H3K4) and 79. RNF20, also known as BRE1A and RNF40, also known as BRE1B, are the mammalian homologs of Bre1. They work together to form a heterodimeric Bre1 complex that facilitate the K120 monoubiquitination of histone H2B (H2Bub1), a DNA damage-induced histone modification that is crucial for recruitment of the chromatin remodeler SNF2h to DNA double-strand break (DSB) damage sites. Moreover, the Bre1 complex acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. Deficiency in the mammalian histone H2B ubiquitin ligase Bre1 leads to replication stress and chromosomal instability. All subfamily members contain a C3HC4-type RING-HC finger at its C-terminus.

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gi 1835457477  21 QLDTLLRCHICKDFLKVPVLTPCGHTFCSLCIRTHLNN-QPNCPLC 65
Cdd:cd16499     2 DLRELLKCSVCNDRFKDVIITKCGHVFCNECVQKRLETrQRKCPGC 47

RING finger, HC subclass, found in RING finger protein 180 (RNF180) and similar proteins; RNF180, also known as Rines, is a membrane-bound E3 ubiquitin-protein ligase well conserved among vertebrates. It is a critical regulator of the monoaminergic system, as well as emotional and social behavior. It interacts with brain monoamine oxidase A (MAO-A) and targets it for ubiquitination and degradation. It also functions as a novel tumor suppressor in gastric carcinogenesis. The hypermethylated CpG site count of the RNF180 DNA promoter can be used to predict survival of gastric cancer. RNF180 contains a novel conserved dual specificity protein phosphatase Rines conserved (DSPRC) domain, a basic coiled-coil domain, a C3HC4-type RING-HC finger, and a C-terminal hydrophobic region that is predicted to be a transmembrane domain.

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gi 1835457477  26 LRCHICKDFLKVP-VLTPCGHTFCSLCIRTHLNNQPN---CPLC 65
Cdd:cd16554     3 LTCPVCLDLYYDPyMCYPCGHIFCEPCLRQLAKSSPKntpCPLC 46