RING finger found in polycomb group RING finger protein 6 (PCGF6) and similar proteins; PCGF6, also known as Mel18 and Bmi1-like RING finger (MBLR), or RING finger protein 134 (RNF134), 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 L3MBTL2 complex, which is composed of some canonical components, such as RNF2, CBX3, CXB4, CXB6, CXB7, and CXB8, as well as some noncanonical components, such as L3MBTL2, E2F6, WDR5, HDAC1, and RYBP, and plays a critical role in epigenetic transcriptional silencing in higher eukaryotes. Like other PCGF homologs, PCGF6 possesses the transcriptional repression activity, and also 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, PCGF6 can regulate the enzymatic activity of JARID1d/KDM5D, a trimethyl H3K4 demethylase, through direct interaction. Furthermore, PCGF6 is expressed predominantly in meiotic and post-meiotic male germ cells and may play important roles in mammalian male germ cell development. It also regulates mesodermal lineage differentiation in mammalian embryonic stem cells (ESCs) and functions in induced pluripotent stem (iPS) reprogramming. The activity of PCGF6 is found to be regulated by cell cycle dependent phosphorylation. PCGF6 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 61557118 126 LVELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLY 184
Cdd:cd16738   1 LAELNPYILCSICKGYFIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLY 59

RING finger found in polycomb group RING finger protein 6 (PCGF6) and similar proteins; PCGF6, also known as Mel18 and Bmi1-like RING finger (MBLR), or RING finger protein 134 (RNF134), 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 L3MBTL2 complex, which is composed of some canonical components, such as RNF2, CBX3, CXB4, CXB6, CXB7, and CXB8, as well as some noncanonical components, such as L3MBTL2, E2F6, WDR5, HDAC1, and RYBP, and plays a critical role in epigenetic transcriptional silencing in higher eukaryotes. Like other PCGF homologs, PCGF6 possesses the transcriptional repression activity, and also 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, PCGF6 can regulate the enzymatic activity of JARID1d/KDM5D, a trimethyl H3K4 demethylase, through direct interaction. Furthermore, PCGF6 is expressed predominantly in meiotic and post-meiotic male germ cells and may play important roles in mammalian male germ cell development. It also regulates mesodermal lineage differentiation in mammalian embryonic stem cells (ESCs) and functions in induced pluripotent stem (iPS) reprogramming. The activity of PCGF6 is found to be regulated by cell cycle dependent phosphorylation. PCGF6 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 61557118 126 LVELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLY 184
Cdd:cd16738   1 LAELNPYILCSICKGYFIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLY 59

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 61557118    135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSN-RCPKC 173
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNnTCPIC 40

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
                  ....*....|....*....|....*....|....*....
gi 61557118   135 CSICKGYLiDATTITECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:TIGR00599  29 CHICKDFF-DVPVLTSCSHTFCSLCIRRCLSNQPKCPLC 66

RING finger found in polycomb group RING finger protein 6 (PCGF6) and similar proteins; PCGF6, also known as Mel18 and Bmi1-like RING finger (MBLR), or RING finger protein 134 (RNF134), 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 L3MBTL2 complex, which is composed of some canonical components, such as RNF2, CBX3, CXB4, CXB6, CXB7, and CXB8, as well as some noncanonical components, such as L3MBTL2, E2F6, WDR5, HDAC1, and RYBP, and plays a critical role in epigenetic transcriptional silencing in higher eukaryotes. Like other PCGF homologs, PCGF6 possesses the transcriptional repression activity, and also 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, PCGF6 can regulate the enzymatic activity of JARID1d/KDM5D, a trimethyl H3K4 demethylase, through direct interaction. Furthermore, PCGF6 is expressed predominantly in meiotic and post-meiotic male germ cells and may play important roles in mammalian male germ cell development. It also regulates mesodermal lineage differentiation in mammalian embryonic stem cells (ESCs) and functions in induced pluripotent stem (iPS) reprogramming. The activity of PCGF6 is found to be regulated by cell cycle dependent phosphorylation. PCGF6 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 61557118 126 LVELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLY 184
Cdd:cd16738   1 LAELNPYILCSICKGYFIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLY 59

RING finger found in polycomb group RING finger protein 4 (PCGF4) and similar proteins; PCGF4, also known as 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). It 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 genes 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 61557118 124 INLVELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLYNIRLDRQLQDIVYKLVVNL 203
Cdd:cd16736   3 IKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVPGL 82

                        90
                ....*....|..
gi 61557118 204 EEREKKQMHDFY 215
Cdd:cd16736  83 FKNEMKRRRDFY 94

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 61557118 124 INLVELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPLYNIRLDRQLQD 194
Cdd:cd16733   1 VKIKDLNEHIVCYLCAGYFIDATTITECLHTFCKSCIVKYLQTSKYCPMCNIKIHETQPLLNLKLDRVMQD 71

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 61557118 253 DVSLLLEFIGANEDtGHFKPLEKKFVRVSGEATIGHVEKFLRRKMGLDPACQVDIICGDHLLERYQTLREIRRAIGDTam 332
Cdd:cd16102   1 QVSLSLEPSESNLG-GKLPQLEKPYLRCSARATVGHLKKFLRRKLKLDSEQDLDILCRGELLGKEHTLKFIWRTRWRK-- 77

                ....*....
gi 61557118 333 QDGLLVLHY 341
Cdd:cd16102  78 QDGPLVLQY 86

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 61557118   135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNR-CPKC 173
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVtCPLC 40

Zinc finger, C3HC4 type (RING finger);

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 61557118   135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:pfam13923   2 CPICMDMLKDPSTTTPCGHVFCQDCILRALRAGNECPLC 40

RING finger- and WD40-associated ubiquitin-like (RAWUL) domain found in polycomb group RING finger protein 1 (PCGF1) and similar proteins; PCGF1, also termed 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) and 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 and a RAWUL domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 61557118 254 VSLLLEFIGANEDTG--HFKPLEKKFVRVSGEATIGHVEKFLRRKMGLDPACQVDIICGDHLLERYQTLREI 323
Cdd:cd17081   4 VSLCLERLSSGKSSKdkNKKPLQRKYVRCSVRAEVRHLKKLLRKKLAVPPLQQVQILCNNEVLPDHMTMKQI 75

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 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQ 181
Cdd:cd16529   7 CPICFEYFNTAMMITQCSHNYCSLCIRRFLSYKTQCPTCRAAVTESD 53

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase 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. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNR-CPKC 173
Cdd:cd16531   4 CPICLGIIKNTMTVKECLHRFCAECIEKALRLGNKeCPTC 43

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIV 176
Cdd:cd16506   3 CPICLDEIQNKKTLEKCKHSFCEDCIDRALQVKPVCPVCGVV 44

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
                ....*....|....*....|....*....|....*....
gi 61557118 135 CSICKGYLIDATTiTECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd16514   4 CSLCLRLLYEPVT-TPCGHTFCRACLERCLDHSPKCPLC 41

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3) and similar proteins; DTX3, also known as RING finger protein 154 (RNF154), is an E3 ubiquitin-protein ligase that belongs to the Deltex (DTX) family. In contrast to other DTXs, DTX3 does not contain two N-terminal Notch-binding WWE domains, but a short unique N-terminal domain, suggesting it does not interact with the intracellular domain of Notch. Its C-terminal region includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQ 179
Cdd:cd16711   4 CPICLGEIQNKKTLDKCKHSFCEDCITRALQVKKACPMCGEFYGQ 48

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 61557118 132 YILCSICKGYLIDATTItECLHTFCKSCIVRHFYYSNR---CPKC 173
Cdd:cd16601   1 EASCSLCKEYLKDPVII-ECGHNFCRACITRFWEELDGdfpCPQC 44

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 61557118 134 LCSICKGYLIDATtITECLHTFCKSCIVRHFYYSNRCPKCN 174
Cdd:cd16539   7 ACFICRKPFKNPV-VTKCGHYFCEKCALKHYRKSKKCFVCG 46

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 61557118 126 LVELTPYILCSICKGYLIDATTITECLHTFCKSCIVRHFyySNRCPKCNIVVHQTqplyNIRLDRQLQDIV 196
Cdd:cd16496   9 LDELENLLRCSRCASILKEPVTLGGCEHVFCRSCVGDRL--GNGCPVCDTPAWAR----DLQINRQLDSMV 73

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 61557118   135 CSICKGYLI--DATTITECLHTFCKSCIVRHFYYSNRCPKCN 174
Cdd:pfam13639   3 CPICLEEFEegDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 61557118 274 EKKFVRVSGEATIGHVEKFLRRKMGLDPACQVDIICGDHLLERYQTLREIrrAIGDTAMQDGLLVLHY 341
Cdd:cd17165  31 DKRYLRCPAAMTVMHLRKFLRSKMDIPSTFQIDVMYEEEPLKDYYTLMDI--AYIYTWRRNGPLPLKY 96

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 61557118 134 LCSICKGYLIDATTITE-CLHTFCKSCIVRHFYYSNRCPKCN 174
Cdd:cd16574   3 SCPICLDRFENEKAFLDgCFHAFCFTCILEWSKVKNECPLCK 44

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 61557118 134 LCSICKGYLIDATTITeCLHTFCKSCIVRHFYYSNR--CPKC 173
Cdd:cd16497   3 LCHCCYDLLVNPTTLN-CGHSFCRHCLALWWKSSKKteCPEC 43

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
                ....*....|....*....|....*....|....*....
gi 61557118 135 CSICKGYLIDATTITeCLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd16535   4 CSICSELFIEAVTLN-CSHSFCSYCITEWMKRKKECPIC 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
                ....*....|....*....|....*....|....*....|....*....
gi 61557118 128 ELTpyilCSICKGYLIDATTItECLHTFCKSCIVRHF---YYSNRCPKC 173
Cdd:cd16594   5 ELT----CPICLDYFTDPVTL-DCGHSFCRACIARCWeepETSASCPQC 48

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 61557118 254 VSLLLEFIGANEDTGHFKPLE-----------KKFVRVSGEATIGHVEKFLRRKMGLDPACQVDIICGDHLLERYQTLRE 322
Cdd:cd17164   2 VSLSIEFYEGARDEKKQRPASpgdpfkeqrngKRFLRCPAAMTVMHLAKFLRNKMDVPSKYRVEVLYEDEPLKDYYTLMD 81

                .
gi 61557118 323 I 323
Cdd:cd17164  82 I 82

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 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 two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 61557118 135 CSICKGYLIDATTITeCLHTFCKSCIV---RHFYYSNRCPKCN 174
Cdd:cd16543   6 CSICLDLLKDPVTIP-CGHSFCMNCITllwDRKQGVPSCPQCR 47

RING finger, HC subclass, found in Schizosaccharomyces pombe DNA repair protein Rad8 (SpRad8) and similar proteins; SpRad8 is a conserved protein homologous to Saccharomyces cerevisiae DNA repair protein Rad5 and human helicase-like transcription factor (HLTF) that is required for error-free postreplication repair by contributing to polyubiquitylation of PCNA. SpRad8 contains a C3HC4-type RING-HC finger responsible for the E3 ubiquitin ligase activity, a SNF2-family helicase domain including an ATP binding site, and a family-specific HIRAN domain (HIP116, Rad5p N-terminal domain) that contributes to nuclear localization.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSN------RCPKC 173
Cdd:cd16572   7 CPICAEEPISELALTRCWHSACKDCLLDHIEFQKsknevpLCPTC 51

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 61557118 133 ILCSICKGYLIDaTTITECLHTFCKSCIVRHFYYSNR-CPKCNI 175
Cdd:cd16499   7 LKCSVCNDRFKD-VIITKCGHVFCNECVQKRLETRQRkCPGCGK 49

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 61557118 133 ILCSICKGYLIDATTItECLHTFCKSCIVRHFYYSNR-----CPKCNIVVHQTqplyNIRLDRQL 192
Cdd:cd16598   5 VTCSICLDYLRDPVTI-DCGHNFCRSCITDYCPISGGherpvCPLCRKPFKKE----NIRPNWQL 64

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 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVH 178
Cdd:cd23130   3 CPICLDDPEDEAITLPCLHQFCYTCILRWLQTSPTCPLCKTPVT 46

RING finger, HC subclass, found in really interesting new gene 2 protein (RING2) and similar proteins; RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. RING2 is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase 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. The enzymatic activity of RING2 is enhanced by the interaction with BMI1/PCGF4, and it is dispensable for early embryonic development and much of the gene repression activity of PRC1. Moreover, RING2 plays a key role in terminating neural precursor cell (NPC)-mediated production of subcerebral projection neurons (SCPNs) during neocortical development. It also plays a critical role in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusions. Furthermore, RING2 is essential for expansion of hepatic stem/progenitor cells. It promotes hepatic stem/progenitor cell expansion through simultaneous suppression of cyclin-dependent kinase inhibitors (CDKIs) Cdkn1a and Cdkn2a, known negative regulators of cell proliferation. RING2 also negatively regulates p53 expression through directly binding with both p53 and MDM2 and promoting MDM2-mediated p53 ubiquitination in selective cancer cell types to stimulate tumor development. RING2 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 61557118 133 ILCSICKGYLIDATTITECLHTFCKSCIVRHFYYSNR-CPKC 173
Cdd:cd16740  13 LMCPICLDMLKNTMTTKECLHRFCADCIITALRSGNKeCPTC 54

RING finger, HC subclass, found in RING finger protein 220 (RNF220) and similar proteins; RNF220 is an E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of Sin3B, a scaffold protein of the Sin3/HDAC (histone deacetylase) corepressor complex. It can also bind E2 and mediate auto-ubiquitination of itself. Moreover, RNF220 specifically interacts with beta-catenin, and enhances canonical Wnt signaling through ubiquitin-specific protease 7 (USP7)-mediated deubiquitination and stabilization of beta-catenin, which is independent of its E3 ligase activity. RNF220 contains a characteristic C3HC4-type RING-HC finger at its C-terminus.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVV 177
Cdd:cd16563   3 CLICMDSYTMPLVSIQCWHVHCEECWLRTLGAKKLCPQCNTIT 45

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
                ....*....|....*....|....*....|....*....|....*....
gi 61557118 133 ILCSICkGYLIDATTITECLHTFCKSCIVRHFYYSNR-------CPKCN 174
Cdd:cd16581   3 LTCSIC-YNIFDDPKILPCSHTFCKNCLEKLLAASGYyllaslkCPTCR 50

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 61557118 135 CSICKGYLIDATTITeCLHTFCKSCIVRhfYYSNR-----------CPKC 173
Cdd:cd16600   8 CSICLQLMTEPVSIN-CGHSYCKRCIVS--FLENQsqlepgletfsCPQC 54

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 61557118 115 DSEDEEERLINLVELTPYILCSICKGYLiDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVH 178
Cdd:COG5152 179 NAEYEEAPVISGPGEKIPFLCGICKKDY-ESPVVTECGHSFCSLCAIRKYQKGDECGVCGKATY 241

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
                ....*....|....*....|....*....|....*....|....*...
gi 61557118 133 ILCSICKGYLIDATTItECLHTFCKSCivrhFYYS-------NRCPKC 173
Cdd:cd16603   5 LTCPICMNYFIDPVTI-DCGHSFCRPC----LYLNwqdipflAQCPEC 47

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

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 61557118 135 CSICKGYLIDATtITECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd16561   5 CSICLEDLNDPV-KLPCDHVFCEECIRQWLPGQMSCPLC 42

Modified RING finger, HC subclass (C3HC3D-type), found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also known as RBCK1, HOIL-1L, RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, Hepatitis B virus X-associated protein 4, RING finger protein 54 (RNF54), ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), form the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta, but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to the RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has an RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain uses an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction. This model corresponds to the RING domain, a modified C3HC3D-type RING-HC finger required for RBR-mediated ubiquitination.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 61557118 135 CSICKGYLI--DATTITECLHTFCKSCIVRHFYYSN----RCP 171
Cdd:cd16633  10 CPICFDDVPpgEGVVLRECLHSFCRECLRGAIQNSEeaevKCP 52

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 (RNFT1); RNFT1, also known as protein PTD016, is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

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                ....*....|....*....|....*....|....*....|....
gi 61557118 134 LCSICKGYLIDATTITeCLHTFCKSCIVRHFYYSNRCPKCNIVV 177
Cdd:cd16741  16 ICAICQAEFRKPILLI-CQHVFCEECISLWFNREKTCPLCRTVI 58

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM60, TRIM61, TRIM75 and similar proteins; TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. RNF33 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM75 mainly localizes within spindles, suggesting it may function in spindle organization and thereby affect meiosis. Both TRIM60 and TRIM75 belong 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 B2-box, and two coiled coil domains, as well as a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of the TRIM family that contains RBCC domains only. Its biological function remains unclear.

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gi 61557118 135 CSICKGYLIDATTItECLHTFCKSCIVRHFYYSNR---CPKC 173
Cdd:cd16607   4 CPICLDYLKDPVTI-NCGHNFCRSCISMSWKDLQDtfpCPVC 44

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

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gi 61557118 135 CSICKGYLIDATTITeCLHTFCKSCIVRHFYYSNRCPKCNIVVHQ 179
Cdd:cd23147   7 CPICLSLFKSAANLS-CNHCFCAGCIGESLKLSAICPVCKIPATR 50

RING finger, HC subclass, found in Caenorhabditis elegans BRCA1-associated RING domain protein 1 (CeBARD1) and similar proteins; CeBARD1, also called Ce-BRD-1, Cebrd-1, or RING-type E3 ubiquitin transferase BARD1, is a constituent of the CeBCD complex that possesses E3 ubiquitin-protein ligase activity. It plays a role in triggering cellular responses at damage sites in response to DNA damage that may be induced by ionizing radiation. It protects against chromosome non-disjunction and nuclear fragmentation during meiotic double-strand break repair to ensure sister chromatid recombination and aid chromosome stability. CeBARD1 contains a typical C3HC4-type RING-HC finger.

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gi 61557118 135 CSICKGYLIDATTITECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd23143   4 CVICSEPQIDTFLLSSCGHIYCWECFTEFIEKRHMCPSC 42

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.

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gi 61557118 135 CSICKGYlIDATTITECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd23135   6 CSICFSE-IRSGAILKCGHFFCLSCIASWLREKSTCPLC 43

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

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gi 61557118 134 LCSICKGYLIDATtITECLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd16476   2 VCAICYQEMKEAR-ITPCNHFFHGLCLRKWLYVQDTCPLC 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.

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gi 61557118 133 ILCSICKGYLIDATTITeCLHTFCKSCIVRHFYYSNRCPKC 173
Cdd:cd16547   4 LICSICHGVLRCPVRLS-CSHIFCKKCILQWLKRQETCPCC 43

H2 subclass of RING (RING-H2) fingers 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger 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 serves as a scaffold 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.

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gi 61557118 135 CSICKGYLI--DATTITECLHTFCKSCIVR-HFYYSNRCPKCN 174
Cdd:cd16448   1 CVICLEEFEegDVVRLLPCGHVFHLACILRwLESGNNTCPLCR 43