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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKDGL 467
Cdd:cd16514   1 DLECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

first 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 first RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 37622896 154 DGFKCRKCHGFLSDPVSLSCGHTFCKLCLERGRAadRRCALCGVKLSAL 202
Cdd:cd16513   1 DLLSCPLCRGLLFEPVTLPCGHTFCKRCLERDPS--SRCRLCRLKLSPG 47

Predicted O-linked N-acetylglucosamine transferase, SPINDLY family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 37622896 240 PARASQLRHEGNRLYRERQVEAALLKYNEAVKLAPNDHLLYSNRSQIYFTLESHENALHDAEIACKLRP 308
Cdd:COG3914 109 PDNAEALFNLGNLLLALGRLEEALAALRRALALNPDFAEAYLNLGEALRRLGRLEEAIAALRRALELDP 177

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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKDGL 467
Cdd:cd16514   1 DLECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

ATP-dependent protease La (LON) substrate-binding domain; This domain has been shown to be part of the PUA superfamily. This domain represents a general protein and polypeptide interaction domain for the ATP-dependent serine peptidase, LON, Peptidase_S16, pfam05362. ATP-dependent Lon proteases are conserved in all living organizms and catalyze rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37622896   514 NVPIFVC--TMAYPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL---------GDPVKGFAEYGCILEIRNVQFFADG 582
Cdd:pfam02190   1 ELPLLPLrnTVLFPGMVLPLFVGRPRSIAAIEAALNKD-KLYGVLLvsqkdaedeEPTPDDLYEVGTVAKIVQILKLPDG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37622896   583 RSVVDSIGKRRFRVLH-QSQRDGYNTADIEYIEDQKVQGEDcaELMGLHncvyqqaslwfhslkLSLKNRILNHFGPMPE 661
Cdd:pfam02190  80 TYKVLVEGLERVRIVElVKKEEPYLRAEVEDLPEDSDELSE--ALKALV---------------KELIEKLRRLLKLLLP 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 37622896   662 KDADPQMN--PNGPAWCWWMLAVLPLESRAQLPFLAMRSLKDRLngiRRVLAFISR 715
Cdd:pfam02190 143 LELLLKIKdiENPGRLADLVAAILPLSPEEKQELLETLDVKERL---EKVLELLNR 195

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37622896   404 TDQGDKPALSLP-LASFDASdLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKDGLSQClasrKYSKNVIM 482
Cdd:TIGR00599   7 TDSSDWLTTPIPsLYPLDTS-LRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQES----KLRSNWLV 81

                  ....*..
gi 37622896   483 EELIAKF 489
Cdd:TIGR00599  82 SEIVESF 88

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 37622896    426 CALCM-RLFYEPVTTPCGHTFCLKCLERCLD-HNAKCPLC 463
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCL--ERCLDHNAKCPLCK 464
Cdd:COG5574 215 DYKCFLCLEEPEVPSCTPCGHLFCLSCLliSWTKKKYEFCPLCR 258

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 37622896  420 DASDLECALCMRLFYEP--------VTTPCGHTFCLKCLERCLDHNAKCPLCKDGLSQCLASRKYSK 478
Cdd:PHA02929 171 RSKDKECAICMEKVYDKeiknmyfgILSNCNHVFCIECIDIWKKEKNTCPVCRTPFISVIKSRFFTK 237

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

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 37622896 157 KCRKCHGFLSDPVSLSCGHTFCKLCLERGRAADRRCALC 195
Cdd:COG5432  27 RCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVC 65

mitochondrial precursor proteins import receptor (72 kDa mitochondrial outermembrane protein) (mitochondrial import receptor for the ADP/ATP carrier) (translocase of outermembrane tom70); [Transport and binding proteins, Amino acids, peptides and amines]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 37622896   243 ASQLRHEGNRLYRERQVEAALLKYNEAVKLAPnDHLLYSNRSQIYFTLESHENALHDAEIACKLRP 308
Cdd:TIGR00990 127 AAKLKEKGNKAYRNKDFNKAIKLYSKAIECKP-DPVYYSNRAACHNALGDWEKVVEDTTAALELDP 191

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 37622896    158 CRKCHG-FLSDPVSLSCGHTFCKLCLER-GRAADRRCALC 195
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKwLESGNNTCPIC 40

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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKDGL 467
Cdd:cd16514   1 DLECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

ATP-dependent protease La (LON) substrate-binding domain; This domain has been shown to be part of the PUA superfamily. This domain represents a general protein and polypeptide interaction domain for the ATP-dependent serine peptidase, LON, Peptidase_S16, pfam05362. ATP-dependent Lon proteases are conserved in all living organizms and catalyze rapid turnover of short-lived regulatory proteins and many damaged or denatured proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37622896   514 NVPIFVC--TMAYPTVPCPLHIFEPCYRLMIRRCIETGtRQFGMCL---------GDPVKGFAEYGCILEIRNVQFFADG 582
Cdd:pfam02190   1 ELPLLPLrnTVLFPGMVLPLFVGRPRSIAAIEAALNKD-KLYGVLLvsqkdaedeEPTPDDLYEVGTVAKIVQILKLPDG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37622896   583 RSVVDSIGKRRFRVLH-QSQRDGYNTADIEYIEDQKVQGEDcaELMGLHncvyqqaslwfhslkLSLKNRILNHFGPMPE 661
Cdd:pfam02190  80 TYKVLVEGLERVRIVElVKKEEPYLRAEVEDLPEDSDELSE--ALKALV---------------KELIEKLRRLLKLLLP 142

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 37622896   662 KDADPQMN--PNGPAWCWWMLAVLPLESRAQLPFLAMRSLKDRLngiRRVLAFISR 715
Cdd:pfam02190 143 LELLLKIKdiENPGRLADLVAAILPLSPEEKQELLETLDVKERL---EKVLELLNR 195

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 37622896 422 SDLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCKDGLS 468
Cdd:cd16504   1 NDFLCPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNRCPKCNFYLT 47

first 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 first RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 37622896 424 LECALCMRLFYEPVTTPCGHTFCLKCLERclDHNAKCPLCKD 465
Cdd:cd16513   3 LSCPLCRGLLFEPVTLPCGHTFCKRCLER--DPSSRCRLCRL 42

first RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the first one.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 37622896 422 SDLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK-CPLCK 464
Cdd:cd23138   1 DELNCSFCMQLPERPVTTPCGHNFCLKCFQKWMGQGKKtCGTCR 44

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLER----CLDHNAKCPLCK 464
Cdd:cd16597   5 ELTCSICLELFKDPVTLPCGHNFCGVCIEKtwdsQHGSEYSCPQCR 50

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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLE----RCLDHNAKCPLCKD 465
Cdd:cd16609   3 ELTCSICLGLYQDPVTLPCQHSFCRACIEdhwrQKDEGSFSCPECRA 49

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 37622896 424 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK---CPLCKDGLSQclasRKYSKNVIMEELIAKFL 490
Cdd:cd16498  17 LECPICLELLKEPVSTKCDHQFCRFCILKLLQKKKKpapCPLCKKSVTK----RSLQESTRFKQLVEAVK 82

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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 462
Cdd:cd16637   1 DLTCHICLQPLVEPLDTPCGHTFCYKCLTNYLKIQQCCPL 40

RING finger, HC subclass, found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of the peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis by targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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 37622896 422 SDLECALCMRLFYEPVTTPCGHTFCLKCLERCL----DHNAKCPLCK 464
Cdd:cd16612   3 QDLSCPLCLKLFQSPVTTECGHTFCQDCLSRVPkeedGGSTSCPTCQ 49

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 37622896 424 LECALCMRLFYEPVTTPCGHTFCLKCLERCLDHN----AKCPLCKDGLS 468
Cdd:cd16604   1 LSCPICLDLLKDPVTLPCGHSFCMGCLGALWGAGrggrASCPLCRQTFP 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 37622896 422 SDLECALCMRLFYEPVTTPCGHTFCLKCLERCLD-HNAKCPLCKDGLSQ 469
Cdd:cd16509   2 SDEECAICLDSLTNPVITPCAHVFCRRCICEVIQrEKAKCPMCRAPLSA 50

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 37622896    426 CALCM-RLFYEPVTTPCGHTFCLKCLERCLD-HNAKCPLC 463
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLEsGNNTCPIC 40

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK--CPLCKDGLS 468
Cdd:cd16599   4 ELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRapCPVCKEASS 51

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 2 (LNX2); LNX2, also known as numb-binding protein 2, or PDZ domain-containing RING finger protein 1 (PDZRN1), is a PDZ domain-containing RING-type E3 ubiquitin 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. It interacts with contactin-associated protein 4 (Caspr4, also known as CNTNAP4) in a PDZ domain-dependent manner, which modulates the proliferation and neuronal differentiation of neural progenitor cells (NPCs). LNX2 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAF motif for Numb/ Numblike-LNX interaction, and four PDZ domains necessary for the binding of substrates, including ErbB2, RhoC, the presynaptic protein CAST, the melanoma/cancer-testis antigen MAGEB18 and several proteins associated with cell junctions, such as JAM4 and the Coxsackievirus and adenovirus receptor (CAR).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 462
Cdd:cd16780   3 DLVCHICLQPLLQPLDTPCGHTFCFKCLRNFLQEKDFCPL 42

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.

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                ....*....|....*....|....*....|....*....|....*
gi 37622896 422 SDLECALCMRLFYEPVTTP-CGHTFCLKCLERCL-DHNAKCPLCK 464
Cdd:cd16620   2 DELKCPICKDLMKDAVLTPcCGNSFCDECIRTALlEEDFTCPTCK 46

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong 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, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 37622896 422 SDLECALCMRLFYEPVTTPCGHTFCLKCLE-------RCLDHNAKCPLCK 464
Cdd:cd16581   1 EELTCSICYNIFDDPKILPCSHTFCKNCLEkllaasgYYLLASLKCPTCR 50

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 37622896 425 ECALCMR-LFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 464
Cdd:cd23130   2 VCPICLDdPEDEAITLPCLHQFCYTCILRWLQTSPTCPLCK 42

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

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                ....*....|....*....|....*....|....*....|....
gi 37622896 156 FKCRKCHGFLSDPVSLSCGHTFCKLCLERGRAADRRCALCGVKL 199
Cdd:cd16514   2 LECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

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 37622896 423 DLECALCMRLFYEPVTT-PCGHTFCLKCLERCLDH-NAKCPLCKD 465
Cdd:cd16544   2 ELTCPVCQEVLKDPVELpPCRHIFCKACILLALRSsGARCPLCRG 46

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.

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                ....*....|....*....|....*....|....*....|...
gi 37622896 425 ECALCMRLFYEPVTTPCGHTFCLKCLERCLD---HNAKCPLCK 464
Cdd:cd16745   2 ECNICLDLAQDPVVTLCGHLFCWPCLHKWLRrqsSQPECPVCK 44

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 37622896 424 LECALCMRLFYEPVTTPCGHTFCLKCLERCLdhNAKCPLCKDGL 467
Cdd:cd16644   6 LYCPLCQRVFKDPVITSCGHTFCRRCALTAP--GEKCPVDNMKL 47

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 37622896   426 CALCMRLFYEPVTtPCGHTFCLKCLE---RCLDHNAKCP 461
Cdd:pfam13445   1 CPICLELFTDPVL-PCGHTFCRECLEemsQKKGGKFKCP 38

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates melanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 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. In addition, TRIM13 contains a C-terminal transmembrane domain.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNA---------KCPLCK 464
Cdd:cd16762   3 DLTCPICCCLFDDPRVLPCSHNFCKKCLEGILEGNVrtmlwrppfKCPTCR 53

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, 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 37622896 426 CALCMRLFYEPV-TTPCGHTFCLKCLERCLDHNA-KCPLCK 464
Cdd:cd16549   4 CPICLEVYHKPVvITSCGHTFCGECLQPCLQVASpLCPLCR 44

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

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                ....*....|....*....|....*....|....*....|....*..
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCL-DHNAKCPLCKDGLS 468
Cdd:cd16542   1 NFDCAVCLEVLHQPVRTRCGHVFCRPCIATSLrNNTWTCPYCRAYLS 47

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 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 464
Cdd:cd23146   4 ELKCPICLKLLNRPVLLPCDHIFCSSCITDSTKVGSDCPVCK 45

RING finger, HC subclass, found in tripartite motif-containing protein 31 (TRIM31) and similar proteins; TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM31 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 37622896 426 CALCMRLFYEPVTTPCGHTFCLKCLERCLDHNA---KCPLC 463
Cdd:cd16582   4 CPICLDILQKPVTIDCGHNFCLQCITQIGETSCgffKCPLC 44

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.

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                ....*....|....*....|....*....|....*....
gi 37622896 424 LECALCMRLFYEPVTTPCGHTFCLKCLERCL-DHNAKCP 461
Cdd:cd16643   2 YECPICLMALREPVQTPCGHRFCKACILKSIrEAGHKCP 40

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.

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                ....*....|....*....|....*....|....*....|..
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 464
Cdd:cd16535   1 ELQCSICSELFIEAVTLNCSHSFCSYCITEWMKRKKECPICR 42

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.

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                ....*....|....*....|....*....|....*....|....*
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAK---CPLCK 464
Cdd:cd16611   4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEdttCPECR 48

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 1 (LNX1); LNX1, also known as numb-binding protein 1 or PDZ domain-containing RING finger protein 2, is a PDZ domain-containing RING-type E3 ubiquitin 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. LNX1 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAY motif for Numb-LNX interaction, and four PDZ domains necessary for the binding of substrates, including CAR, ErbB2, SKIP, JAM4, CAST, c-Src, Claudins, RhoC, KCNA4, PAK6, PLEKHG5, PKC-alpha1, TYK2, PDZ-binding kinase (PBK), LNX2, and itself.

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                ....*....|....*....|....*....|....*....|
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPL 462
Cdd:cd16779   1 DLICHICLQALIQPLDTPCGHTYCTLCLTNFLVEKDFCPM 40

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 37622896 423 DLECALCMRLFYEPVTTPCGHTFCLKCLERCLDHNAKCPLCK 464
Cdd:cd23147   4 ELKCPICLSLFKSAANLSCNHCFCAGCIGESLKLSAICPVCK 45