RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger proteins PCGF2, PCGF4, and similar proteins; This family includes polycomb group RING finger proteins, PCGF2 (also known as Mel-18, or RNF110, or ZNF144) and PCGF4 (also known as BMI-1, or RNF51), both serving as the core component of a canonical polycomb repressive complex 1 (PRC1). PRC1 is composed of a chromodomain-containing protein (CBX2, CBX4, CBX6, CBX7 or CBX8) and a polyhomeotic protein (PHC1, PHC2, or PHC3). Like other PCGF homologs, PCGF2 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. PCGF4 associates with the Runx1/CBFbeta transcription factor complex to silence the target gene in a PRC2-independent manner. Both, PCGF2 and PCGF4, contain a C3HC4-type RING-HC finger and a RAWUL domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  371 MSLSLEYAELGELKTDSEPEL---------------VDTLRPRYLQCPAMCRVSHLKKFVYDKFEIDAQrFSIDIMYKVk 435
Cdd:cd17082    2 ISLSLEYYSPLRNQRKSEPESakepnvslkelekeeVQVPDKRYLRCPAAVTVGHLKKFIRMKFDLPPS-YEVEIMYSD- 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 24653251  436 tIVLLDYYTLMDIAYIYTWKRDAPMRFYYR 465
Cdd:cd17082   80 -EVLPDDYTLMDVAYIYTWRRKSPLRLYYR 108

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1160 AAKEAQKRQSPPAAVPGHLAAKLPPPPPSKAIPSPQHLVSRMTPPQLPKVATPPPPSSPRVITPPKTSPPANAAkvTPLK 1239
Cdd:PHA03247 2761 PTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSA--QPTA 2838

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1240 PvltptqvdKKTPSPEKRTAAQMGSHSPTASENKSPkggPAGVANSTGGAQNGDPAAKKFRPILPRQngmPELAPkLPTL 1319
Cdd:PHA03247 2839 P--------PPPPGPPPPSLPLGGSVAPGGDVRRRP---PSRSPAAKPAAPARPPVRRLARPAVSRS---TESFA-LPPD 2903

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24653251  1320 APfvgfNPLQNPAagkkvPPSKKSPNAGAAAHQSGQQKLVNGGQSQPAQQKTSPPAQKNQQQ 1381
Cdd:PHA03247 2904 QP----ERPPQPQ-----APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPS 2956

RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger proteins PCGF2, PCGF4, and similar proteins; This family includes polycomb group RING finger proteins, PCGF2 (also known as Mel-18, or RNF110, or ZNF144) and PCGF4 (also known as BMI-1, or RNF51), both serving as the core component of a canonical polycomb repressive complex 1 (PRC1). PRC1 is composed of a chromodomain-containing protein (CBX2, CBX4, CBX6, CBX7 or CBX8) and a polyhomeotic protein (PHC1, PHC2, or PHC3). Like other PCGF homologs, PCGF2 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. PCGF4 associates with the Runx1/CBFbeta transcription factor complex to silence the target gene in a PRC2-independent manner. Both, PCGF2 and PCGF4, contain a C3HC4-type RING-HC finger and a RAWUL domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  371 MSLSLEYAELGELKTDSEPEL---------------VDTLRPRYLQCPAMCRVSHLKKFVYDKFEIDAQrFSIDIMYKVk 435
Cdd:cd17082    2 ISLSLEYYSPLRNQRKSEPESakepnvslkelekeeVQVPDKRYLRCPAAVTVGHLKKFIRMKFDLPPS-YEVEIMYSD- 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 24653251  436 tIVLLDYYTLMDIAYIYTWKRDAPMRFYYR 465
Cdd:cd17082   80 -EVLPDDYTLMDVAYIYTWRRKSPLRLYYR 108

RAWUL domain RING finger- and WD40-associated ubiquitin-like; The RAWUL domain is found at the C-terminus of poly-comb group RING finger proteins. It is a ubiquitin-like domain. RAWUL binds directly to PUFD, a domain on BCOR proteins (BCL6 corepressor). BCOR has emerged as an important player in development and health.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24653251    398 RYLQCPAMCRVSHLKKFVYDKFEIDAQR-FSIDIMYKVKtiVLLDYYTLmDIAYIYTWKRDAPMRFYYR 465
Cdd:pfam16207    1 RYLKCPANATVDHLKKYLAMKLGLELQNeYIVEILYNGE--PLPDSYTL-DVAYIKYWKRNAPLELYYR 66

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 24653251     263 CHLCQGYLINATTIVECLHSFCHSCLINHLRKERF-CPRC 301
Cdd:smart00184    1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1160 AAKEAQKRQSPPAAVPGHLAAKLPPPPPSKAIPSPQHLVSRMTPPQLPKVATPPPPSSPRVITPPKTSPPANAAkvTPLK 1239
Cdd:PHA03247 2761 PTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSA--QPTA 2838

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1240 PvltptqvdKKTPSPEKRTAAQMGSHSPTASENKSPkggPAGVANSTGGAQNGDPAAKKFRPILPRQngmPELAPkLPTL 1319
Cdd:PHA03247 2839 P--------PPPPGPPPPSLPLGGSVAPGGDVRRRP---PSRSPAAKPAAPARPPVRRLARPAVSRS---TESFA-LPPD 2903

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24653251  1320 APfvgfNPLQNPAagkkvPPSKKSPNAGAAAHQSGQQKLVNGGQSQPAQQKTSPPAQKNQQQ 1381
Cdd:PHA03247 2904 QP----ERPPQPQ-----APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPS 2956

RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger proteins PCGF2, PCGF4, and similar proteins; This family includes polycomb group RING finger proteins, PCGF2 (also known as Mel-18, or RNF110, or ZNF144) and PCGF4 (also known as BMI-1, or RNF51), both serving as the core component of a canonical polycomb repressive complex 1 (PRC1). PRC1 is composed of a chromodomain-containing protein (CBX2, CBX4, CBX6, CBX7 or CBX8) and a polyhomeotic protein (PHC1, PHC2, or PHC3). Like other PCGF homologs, PCGF2 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. PCGF4 associates with the Runx1/CBFbeta transcription factor complex to silence the target gene in a PRC2-independent manner. Both, PCGF2 and PCGF4, contain a C3HC4-type RING-HC finger and a RAWUL domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  371 MSLSLEYAELGELKTDSEPEL---------------VDTLRPRYLQCPAMCRVSHLKKFVYDKFEIDAQrFSIDIMYKVk 435
Cdd:cd17082    2 ISLSLEYYSPLRNQRKSEPESakepnvslkelekeeVQVPDKRYLRCPAAVTVGHLKKFIRMKFDLPPS-YEVEIMYSD- 79

                         90       100       110
                 ....*....|....*....|....*....|
gi 24653251  436 tIVLLDYYTLMDIAYIYTWKRDAPMRFYYR 465
Cdd:cd17082   80 -EVLPDDYTLMDVAYIYTWRRKSPLRLYYR 108

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  252 VLLTAVNPHIICHLCQGYLINATTIVECLHSFCHSCLINHLRKERFCPRCEMVINNAKP--NIKSDTTLQAIVYKLVPGL 329
Cdd:cd16737    2 HLVRDFNPYITCRICKGYLIKPTTVTECLHTFCKSCIVQHFEDSNDCPECGIQVHETNPleMLRLDNTLEEIIFKLVPGL 81

                         90
                 ....*....|...
gi 24653251  330 YERELMRKRAFYK 342
Cdd:cd16737   82 RERELQREAEFWE 94

RING finger, HC subclass, found in Polycomb Group RING finger homologs (PCGF1, 2, 3, 4, 5 and 6), and similar proteins; This subfamily includes six Polycomb Group (PcG) RING finger homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) that use epigenetic mechanisms to maintain or repress expression of their target genes. They were first discovered in fruit flies and are well known for silencing Hox genes through modulation of chromatin structure during embryonic development. PCGF homologs play important roles in cell proliferation, differentiation, and tumorigenesis. They all have been found to associate with ring finger protein 2 (RNF2). The RNF2-PCGF heterodimer is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. Moreover, PCGF homologs are critical components in the assembly of distinct Polycomb Repression Complex 1 (PRC1) related complexes which is involved in the maintenance of gene repression and which target different genes through distinct mechanisms. The Drosophila PRC1 core complex is formed by the Polycomb (Pc), Polyhomeotic (Ph), Posterior sex combs (Psc), and Sex combs extra (Sce, also known as Ring) subunits. In mammals, the composition of PRC1 is much more diverse and varies depending on the cellular context. All PRC1 complexes contain homologs of the Drosophila Ring protein. Ring1A/RNF1 and Ring1B/RNF2 are E3 ubiquitin ligases that mark lysine 119 of histone H2A with a single ubiquitin group (H2AK119ub). Mammalian homologs of the Drosophila Psc protein, such as PCGF2/Mel-18 or PCGF4/BMI1, regulate PRC1 enzymatic activity. PRC1 complexes can be divided into at least two classes according to the presence or absence of CBX proteins, which are homologs of Drosophila Pc. Canonical PRC1 complexes contain CBX proteins that recognize and bind H3K27me3, the mark deposited by PRC2. Therefore, canonical PRC1 complexes and PRC2 can act together to repress gene transcription and maintain this repression through cell division. Non-canonical PRC1 complexes, containing RYBP (together with additional proteins, such as L3mbtl2 or Kdm2b) rather than the CBX proteins have recently been described in mammals. PCGF homologs contain a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 24653251  261 IICHLCQGYLINATTIVECLHSFCHSCLINHLRKERFCPRCE 302
Cdd:cd16525    1 LTCSLCKGYLIDATTITECLHSFCKSCIVRHLETSKNCPVCD 42

RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger protein 4 (PCGF4); PCGF4, also termed polycomb complex protein BMI-1 (B cell-specific Moloney murine leukemia virus integration site 1), or RING finger protein 51 (RNF51), 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 canonical Polycomb repressive complex 1 (PRC1), which is composed of a chromodomain-containing protein (CBX2, CBX4, CBX6, CBX7 or CBX8) and a Polyhomeotic protein (PHC1, PHC2, or PHC3), and plays important roles in chromatin compaction and H2AK119 monoubiquitination. PCGF4 associates with the Runx1/CBFbeta transcription factor complex to silence target gene in a PRC2-independent manner. Moreover, PCGF4 is expressed in the hair cells and supporting cells. It can regulate cell survival by controlling mitochondrial function and reactive oxygen species (ROS) level in thymocytes and neurons, thus having an important role in the survival and sensitivity to ototoxic drug of auditory hair cells. Furthermore, PCGF4 controls memory CD4 T-cell survival through direct repression of Noxa gene in an Ink4a- and Arf-independent manner. It is required in neurons to suppress p53-induced apoptosis via regulating the antioxidant defensive response, and also involved in the tumorigenesis of various cancer types. PCGF4 contains a C3HC4-type RING-HC finger, and a RAWUL domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  371 MSLSLEYAELGELK----TDSEPELVDTLRPRYLQCPAMCRVSHLKKFVYDKFEIdAQRFSIDIMYKVKTivLLDYYTLM 446
Cdd:cd17165    2 ISLSIEFFDQNKLErkgnKDKEKSKEEVNDKRYLRCPAAMTVMHLRKFLRSKMDI-PSTFQIDVMYEEEP--LKDYYTLM 78

                         90
                 ....*....|....*....
gi 24653251  447 DIAYIYTWKRDAPMRFYYR 465
Cdd:cd17165   79 DIAYIYTWRRNGPLPLKYR 97

RING finger, HC subclass, found in polycomb group RING finger protein 1 (PCGF1) and similar proteins; PCGF1, also known as nervous system Polycomb-1 (NSPc1) or RING finger protein 68 (RNF68), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR). It serves as the core component of a noncanonical Polycomb repressive complex 1 (PRC1)-like BCOR complex that also contains RING1, RNF2, RYBP, SKP1, as well as the BCL6 co-repressor BCOR and the histone demethylase KDM2B, and is required to maintain the transcriptionally repressive state of some genes, such as Hox genes, BCL6 and the cyclin-dependent kinase inhibitor, CDKN1A. PCGF1 promotes cell cycle progression and enhances cell proliferation as well. It is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the retinoid acid response element (RARE element). Moreover, PCGF1 functions as an epigenetic regulator involved in hematopoietic cell differentiation. It cooperates with the transcription factor runt-related transcription factor 1 (Runx1) in regulating differentiation and self-renewal of hematopoietic cells. Furthermore, PCGF1 represents a physical and functional link between Polycomb function and pluripotency. PCGF1 contains a C3HC4-type RING-HC finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653251  257 VNPHIICHLCQGYLINATTIVECLHSFCHSCLINHLRKERFCPRCEMVINNAKP--NIKSDTTLQ 319
Cdd:cd16733    6 LNEHIVCYLCAGYFIDATTITECLHTFCKSCIVKYLQTSKYCPMCNIKIHETQPllNLKLDRVMQ 70

RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger protein 2 (PCGF2); PCGF2, also termed DNA-binding protein Mel-18, or RING finger protein 110 (RNF110), or zinc finger protein 144 (ZNF144), 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 canonical polycomb repressive complex 1 (PRC1), which is composed of a chromodomain-containing protein (CBX2, CBX4, CBX6, CBX7 or CBX8) and a polyhomeotic protein (PHC1, PHC2, or PHC3). Like other PCGF homologs, PCGF2 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. Moreover, PCGF2 uniquely regulates PRC1 to specify mesoderm cell fate in embryonic stem cells. It is required for PRC1 stability and maintenance of gene repression in embryonic stem cells (ESCs) and essential for ESC differentiation into early cardiac-mesoderm precursors. PCGF2 also plays a significant role in the angiogenic function of endothelial cells (ECs) by regulating endothelial gene expression. Furthermore, PCGF2 is a SUMO-dependent regulator of hormone receptors. It facilitates the deSUMOylation process by inhibiting PCGF4/BMI1-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). It is also a novel negative regulator of breast cancer stem cells (CSCs) that inhibits the stem cell population, and in vitro and in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling. PCGF2 contains a C3HC4-type RING-HC finger, and a RAWUL domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  371 MSLSLEYAELGELKTDSEPELVDTLRP------RYLQCPAMCRVSHLKKFVYDKFEIdAQRFSIDIMYKVKTivLLDYYT 444
Cdd:cd17164    2 VSLSIEFYEGARDEKKQRPASPGDPFKeqrngkRFLRCPAAMTVMHLAKFLRNKMDV-PSKYRVEVLYEDEP--LKDYYT 78

                         90       100
                 ....*....|....*....|.
gi 24653251  445 LMDIAYIYTWKRDAPMRFYYR 465
Cdd:cd17164   79 LMDIAYIYPWRRNGPLPLKYR 99

RRING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in PCGF1-6, RING1 and -2, DRIP and similar proteins; structurally similar to a beta-grasp ubiquitin-like fold; The family includes six Polycomb Group (PcG) RING finger homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) that use epigenetic mechanisms to maintain or repress expression of their target genes. They were first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place, and are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies. PCGF homologs play important roles in cell proliferation, differentiation, and tumorigenesis. They all have been found to associate with ring finger protein 2 (RNF2). The RNF2-PCGF heterodimer is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. Moreover, PCGF homologs are critical components in the assembly of distinct Polycomb Repression Complex 1 (PRC1) related complexes which are involved in the maintenance of gene repression and target different genes through distinct mechanisms. The Drosophila PRC1 core complex is formed by the Polycomb (Pc), Polyhomeotic (Ph), Posterior sex combs (Psc), and Sex combs extra (Sce, also known as Ring) subunits. In mammals, the composition of PRC1 is much more diverse and varies depending on the cellular context. All PRC1 complexes contain homologs of the Drosophila Ring protein. Ring1A/RNF1 and Ring1B/RNF2 are E3 ubiquitin ligases that mark lysine 119 of histone H2A with a single ubiquitin group (H2AK119ub). Mammalian homologs of the Drosophila Psc protein, such as PCGF2/Mel-18 or PCGF4/BMI1, regulate PRC1 enzymatic activity. PRC1 complexes can be divided into at least two classes according to the presence or absence of CBX proteins, which are homologs of Drosophila Pc. Canonical PRC1 complexes contain CBX proteins that recognize and bind H3K27me3, the mark deposited by PRC2. Therefore, canonical PRC1 complexes and PRC2 can act together to repress gene transcription and maintain this repression through cell division. Non-canonical PRC1 complexes, containing RYBP (together with additional proteins, such as L3mbtl2 or Kdm2b) rather than the CBX proteins, have recently been described in mammals. PCGF homologs contain a C3HC4-type RING-HC finger, and a RAWUL domain that might be responsible for interaction with Cbx members of the Polycomb repression complexes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  370 DMSLSLEYAElgelktDSEPELVDTLRPRYLQCPAMCRVSHLKKFVYDKFEIDAQrFSIDIMYKvkTIVLLDYYTLMDIA 449
Cdd:cd16102    1 QVSLSLEPSE------SNLGGKLPQLEKPYLRCSARATVGHLKKFLRRKLKLDSE-QDLDILCR--GELLGKEHTLKFIW 71

                         90
                 ....*....|....*.
gi 24653251  450 YIYTWKRDAPMRFYYR 465
Cdd:cd16102   72 RTRWRKQDGPLVLQYR 87

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 24653251     263 CHLCQGYLINATTIVECLHSFCHSCLINHLRKERF-CPRC 301
Cdd:smart00184    1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 24653251  259 PHIICHLCQGYLINATTIVECLHSFCHSCLINHL-RKERFCPRC 301
Cdd:cd16503    1 ENLTCSICQDLLHDCVSLQPCMHNFCAACYSDWMeRSNTECPTC 44

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 24653251  262 ICHLCQGYLINaTTIVECLHSFCHSCLINHLRKERF-CPRC 301
Cdd:cd16449    2 ECPICLERLKD-PVLLPCGHVFCRECIRRLLESGSIkCPIC 41

RING finger, HC subclass, found in really interesting new gene 1 protein (RING1) and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), was identified as a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. It is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase that transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING1 interacts with multiple PcG proteins and displays tumorigenic activity. It also shows zinc-dependent DNA binding activity. Moreover, RING1 inhibits transactivation of the DNA-binding protein recombination signal binding protein-Jkappa (RBP-J) by Notch through interaction with the LIM domains of KyoT2. RING1 contains a C3HC4-type RING-HC finger.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24653251  261 IICHLCQGYLINATTIVECLHSFCHSCLINHLRK-ERFCPRCEMVInNAKPNIKSDTTLQAIVYKLVP 327
Cdd:cd16739    4 LMCPICLDMLKNTMTTKECLHRFCSDCIVTALRSgNKECPTCRKKL-VSKRSLRPDPNFDALISKIYP 70

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653251  262 ICHLCQGYLINATTIVeCLHSFCHSCLINHLRKER----FCPRCEMVInNAKPNIKSDTTLQAIV 322
Cdd:cd16597    7 TCSICLELFKDPVTLP-CGHNFCGVCIEKTWDSQHgseySCPQCRATF-PRRPELHKNTVLRNIV 69

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
                 ....*....|....*....|....*....|....*....|....*
gi 24653251  263 CHLCQGYLINATTIVECLHSFCHSCLINHLRKERFCPRCEMVINN 307
Cdd:cd16529    7 CPICFEYFNTAMMITQCSHNYCSLCIRRFLSYKTQCPTCRAAVTE 51

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 24653251  261 IICHLCQGyLINATTIVECLHSFCHSCLINHLRKERFCPRCEMVI 305
Cdd:cd16504    3 FLCPICFD-IIKEAFVTKCGHSFCYKCIVKHLEQKNRCPKCNFYL 46

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

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 24653251  262 ICHLCQGYLINATTIVECLHSFCHSCLINHLRKERFCP 299
Cdd:cd16451    2 ICPLCRKKRTNPTALATSGYVFCYPCIYRYVKEHGRCP 39

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 24653251  261 IICHLCQGYLINATTIvECLHSFCHSCLINHLRKERF---CPRCEMVIN 306
Cdd:cd23133    4 LTCSICQGIFMNPVYL-RCGHKFCEACLLLFQEDIKFpayCPMCRQPFN 51

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 24653251  261 IICHLC--QGYLInattivECLHSFCHSCLINHLR--KERFCPRCEMVINNA 308
Cdd:cd16568    8 IICHEYlyEPMVT------TCGHTYCYTCLNTWFKsnRSLSCPDCRTKITTQ 53

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, and TRIM64C, whose biological function remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of the target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members 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 as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. In RBCC region, they all have a C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 24653251  261 IICHLCQGYLINATTIvECLHSFCHSCLINHLRKERF---CPRCEMVINnaKPNIKSD 315
Cdd:cd16603    5 LTCPICMNYFIDPVTI-DCGHSFCRPCLYLNWQDIPFlaqCPECRKTTE--QRNLKTN 59

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  263 CHLCQGYLINATTIvECLHSFCHSCLINHLRKERFCPRCEMVINNAKPNIKSDTTLQAIV 322
Cdd:cd16535    4 CSICSELFIEAVTL-NCSHSFCSYCITEWMKRKKECPICRKPITSKTRSLVLDNCIDKMV 62

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 24653251  260 HIICHLCQGYLINATTIvECLHSFCHSCLI---NHLRKERFCPRC 301
Cdd:cd16601    1 EASCSLCKEYLKDPVII-ECGHNFCRACITrfwEELDGDFPCPQC 44

RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger protein 3 (PCGF3) and similar proteins; PCGF3, also termed RING finger protein 3A (RNF3A), is one of six PcG RING finger (PCGF) homologs (PCGF1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6) and serves as the core component of a Polycomb repressive complex 1 (PRC1). Like other PCGF homologs, PCGF3 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. PCGF3 contains a C3HC4-type RING-HC finger, and a RAWUL domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24653251  392 VDTLRPRYLQCPAMCRVSHLKKFVYDKFEIDAQRF-SIDIMYKVKtiVLLDYYTLMDIaYIYTWK-RDAPMRFYYR 465
Cdd:cd17083   13 LKPLKRKYIRCSSQATITHLKKFIAKKLFLDIFRYnEVDILCNEE--ILGKDHTLKFV-TVTRWRfKETPLLLHYR 85

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.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 24653251  261 IICHLCQGYLINATTiVECLHSFCHSCLINHLRKERFCP 299
Cdd:cd16779    2 LICHICLQALIQPLD-TPCGHTYCTLCLTNFLVEKDFCP 39

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1160 AAKEAQKRQSPPAAVPGHLAAKLPPPPPSKAIPSPQHLVSRMTPPQLPKVATPPPPSSPRVITPPKTSPPANAAkvTPLK 1239
Cdd:PHA03247 2761 PTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSA--QPTA 2838

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1240 PvltptqvdKKTPSPEKRTAAQMGSHSPTASENKSPkggPAGVANSTGGAQNGDPAAKKFRPILPRQngmPELAPkLPTL 1319
Cdd:PHA03247 2839 P--------PPPPGPPPPSLPLGGSVAPGGDVRRRP---PSRSPAAKPAAPARPPVRRLARPAVSRS---TESFA-LPPD 2903

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24653251  1320 APfvgfNPLQNPAagkkvPPSKKSPNAGAAAHQSGQQKLVNGGQSQPAQQKTSPPAQKNQQQ 1381
Cdd:PHA03247 2904 QP----ERPPQPQ-----APPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPS 2956

DNA polymerase III subunits gamma and tau; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1169 SPPAAVPGHLAAKLPPPPPSKA--IPSPQHLVSRMTPPQLPKVATPPPP-SSPRVITPPKTSPPANAAKVTPLK-PVLTP 1244
Cdd:PRK14950  362 PVPAPQPAKPTAAAPSPVRPTPapSTRPKAAAAANIPPKEPVRETATPPpVPPRPVAPPVPHTPESAPKLTRAAiPVDEK 441

                          90
                  ....*....|....*.
gi 24653251  1245 TQVDKKTPSPEKRTAA 1260
Cdd:PRK14950  442 PKYTPPAPPKEEEKAL 457

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
                 ....*....|....*....|....*....|....*....
gi 24653251  261 IICHLCQGYLINATTiVECLHSFCHSCLINHLRKERFCP 299
Cdd:cd16780    4 LVCHICLQPLLQPLD-TPCGHTFCFKCLRNFLQEKDFCP 41

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 24653251  261 IICHLCQGYLINATTIvECLHSFCHSCLinhLR-----KERF-CPRCEMVI--NNAKPN 311
Cdd:cd16594    6 LTCPICLDYFTDPVTL-DCGHSFCRACI---ARcweepETSAsCPQCRETCpqRNLRPN 60

Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation protein-1 (Nrdp1) and similar proteins; Nrdp1 (referred to as FLRF in mice), also known as RING finger protein 41 (RNF41), is an E3 ubiquitin-protein ligase that plays a critical role in the regulation of cell growth and apoptosis, inflammation and production of reactive oxygen species (ROS), as well as in doxorubicin (DOX)-induced cardiac injury. It promotes the degradation of the epidermal growth factor receptor (EGFR/ErbB) family member, ErbB3, which is independent of growth factor stimulation. It also promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) via Lys-63-linked ubiquitination. Moreover, Nrdp1 interacts with and modulates the activity of Parkin, a causative protein for early onset recessive juvenile parkinsonism (AR-JP). It also interacts with ubiquitin-specific protease 8 (USP8), which is involved in trafficking of various transmembrane proteins. Furthermore, Nrdp1 inhibits basal lysosomal degradation and enhances ectodomain shedding of JAK2-associated cytokine receptors. Its phosphorylation by the kinase Par-1b (also known as MARK2) is required for epithelial cell polarity. Nrdp1 contains an N-terminal modified C3HC3D-type RING-HC finger required for enhancing ErbB3 degradation, a B-box, a coiled-coil domain responsible for Nrdp1 oligomerization, and a C-terminal ErbB3-binding domain.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 24653251  261 IICHLCQGYLINATTIVECLHSFCHSCLINHLRKERFCP 299
Cdd:cd16634    2 LICPICSGVLEEPLQAPHCEHAFCNACITEWLSRQQTCP 40

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 24653251  261 IICHLCQGYLiNATTIVECLHSFCHSCLINHLRKERFCPRCEMVIN 306
Cdd:cd16547    4 LICSICHGVL-RCPVRLSCSHIFCKKCILQWLKRQETCPCCRKEVK 48

RING finger, HC subclass, found in radiation sensitivity protein 5 (RAD5) and similar proteins; RAD5, also known as revertibility protein 2 (REV2), or DNA repair protein RAD5, is a probable helicase, and a member of the UBC2/RAD6 epistasis group. It functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. It is involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. It may also be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. It recruits the UBC13-MMS2 dimer to chromatin for DNA repair. RAD5 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 24653251  263 CHLCQGYLINATTIV--ECLHSFCHSCLINHL------RKERFCPRCEMVINNAK 309
Cdd:cd23131    6 CSICTQEPIEVGEVVftECGHSFCEDCLLEYIefqnkkKLDLKCPNCREPISKYR 60

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 24653251    263 CHLCQGYLINAttIVECLHSFCHSCLINHLRKERFCPRC 301
Cdd:pfam13445    1 CPICLELFTDP--VLPCGHTFCRECLEEMSQKKGGKFKC 37

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

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 24653251  263 CHLCQGYlINATTIVECLHSFCHSCLINHLRKERFCPRC 301
Cdd:cd23135    6 CSICFSE-IRSGAILKCGHFFCLSCIASWLREKSTCPLC 43

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1153 QPQDQVQAAKEAQKRQSPPAAVPGHLAAKLPPPPPSKAIPSPQHLVSRMTPPQLPKVATPPPPSSPRVITPPKTSP-PAN 1231
Cdd:PRK07003  371 GVPARVAGAVPAPGARAAAAVGASAVPAVTAVTGAAGAALAPKAAAAAAATRAEAPPAAPAPPATADRGDDAADGDaPVP 450

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24653251  1232 AAKVTPLKPVLTPTQVDKKTPSPEKRTAAQMGSHSPTASENKSPKGGPAGVANSTGGAQNGDPAAKKfRPILPRQNGMPe 1311
Cdd:PRK07003  451 AKANARASADSRCDERDAQPPADSGSASAPASDAPPDAAFEPAPRAAAPSAATPAAVPDARAPAAAS-REDAPAAAAPP- 528

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24653251  1312 lAPKLPTLAPFVGFNP------------LQNpaAGKKVpPSKKSPNAGAAAHQSGQqklvnggqsQPAQQKTSPP 1374
Cdd:PRK07003  529 -APEARPPTPAAAAPAaraggaaaaldvLRN--AGMRV-SSDRGARAAAAAKPAAA---------PAAAPKPAAP 590

RING finger, HC subclass, found in Saccharomyces cerevisiae radiation sensitivity protein 18 (RAD18) and similar proteins; RAD18, also called RING-type E3 ubiquitin transferase RAD18, acts as a postreplication repair E3 ubiquitin-protein ligase that associates with the E2 ubiquitin conjugating enzyme UBC2/RAD6 to form the UBC2-RAD18 ubiquitin ligase complex involved in postreplicative repair (PRR) of damaged DNA. The UBC2-RAD18 complex cooperates with RAD5 and the UBC13-MMS2 dimer to attach mono-ubiquitin chains on 'Lys-164' of POL30, which is necessary for PRR. The UBC2-RAD18 complex is also involved in prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine. RAD18 is an E3 RING-finger protein belonging to the UBC2/RAD6 epistasis group. It contains a typical C3HC4-type RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 24653251  263 CHLCQGYLiNATTIVECLHSFCHSCLINHLRKERFCPRC 301
Cdd:cd23148    6 CHICKDLL-KAPMRTPCNHTFCSFCIRTHLNNDARCPLC 43