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 1958709437   5 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVP 84
Cdd:cd16736     1 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVP 80

                          90
                  ....*....|....*..
gi 1958709437  85 GLFKNEMKRRRDFYAAH 101
Cdd:cd16736    81 GLFKNEMKRRRDFYAAH 97

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 1958709437   5 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVP 84
Cdd:cd16736     1 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVP 80

                          90
                  ....*....|....*..
gi 1958709437  85 GLFKNEMKRRRDFYAAH 101
Cdd:cd16736    81 GLFKNEMKRRRDFYAAH 97

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 1958709437  18 CVLCGGYFIDATTIIECLHSFCKTCIVRYLE-TSKYCPIC 56
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLEsGNVTCPLC 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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958709437   8 KITELNP---HLMCVLCGGYFiDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRpllnIRSDKTLQDIVYKlvp 84
Cdd:TIGR00599  16 PIPSLYPldtSLRCHICKDFF-DVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESK----LRSNWLVSEIVES--- 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958709437  85 glFKNEMKRRRDFYAAHPSADAANGsnEDRGEVADEDRRVIADDEIISLSIEFFHP---SRSDRKVTKEKPKEEV----- 156
Cdd:TIGR00599  88 --FKNLRPSLLEFLRIPKTTPVENP--DLAGPENSSKIELIEESESDGVDAEDEDLqrsATSSRALAARSTADILqlssd 163

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1958709437 157 ----NDKRYLR---------CPAALTVMHLRKFLR 178
Cdd:TIGR00599 164 pskrNDADYRSeppneglvqCPICQQRMPEKAVER 198

tol-pal system protein YbgF; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958709437 222 KYRVRPTCKRMK-MSQQRDGLTAAGELESDSGSDKANSPAGGAPSTSSCLPSPSTPVQS 279
Cdd:PRK10803   81 QYQLNQVVERQKqIYLQIDSLSSGGAAAQSTSGDQSGAAASATPAADAGTANAGAPVQS 139

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 1958709437   5 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVP 84
Cdd:cd16736     1 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVP 80

                          90
                  ....*....|....*..
gi 1958709437  85 GLFKNEMKRRRDFYAAH 101
Cdd:cd16736    81 GLFKNEMKRRRDFYAAH 97

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 1958709437 130 IISLSIEFFHPSRSDRKVTKEKP----KEEVNDKRYLRCPAALTVMHLRKFLRSKMDIPNTFQIDVMYEEEPLKDYYTLM 205
Cdd:cd17164     1 IVSLSIEFYEGARDEKKQRPASPgdpfKEQRNGKRFLRCPAAMTVMHLAKFLRNKMDVPSKYRVEVLYEDEPLKDYYTLM 80

                          90
                  ....*....|....*....
gi 1958709437 206 DIAYIYTWRRNGPLPLKYR 224
Cdd:cd17164    81 DIAYIYPWRRNGPLPLKYR 99

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 1958709437  11 ELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPLLNIRSDKTLQDIVYKLVPGLFKNE 90
Cdd:cd16737     6 DFNPYITCRICKGYLIKPTTVTECLHTFCKSCIVQHFEDSNDCPECGIQVHETNPLEMLRLDNTLEEIIFKLVPGLRERE 85

                  ....*..
gi 1958709437  91 MKRRRDF 97
Cdd:cd16737    86 LQREAEF 92

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 1958709437 160 RYLRCPAALTVMHLRKFLRSKMDIP--NTFQIDVMYEEEPLKDYYTLmDIAYIYTWRRNGPLPLKYR 224
Cdd:pfam16207   1 RYLKCPANATVDHLKKYLAMKLGLElqNEYIVEILYNGEPLPDSYTL-DVAYIKYWKRNAPLELYYR 66

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 1958709437  16 LMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICD 57
Cdd:cd16525     1 LTCSLCKGYLIDATTITECLHSFCKSCIVRHLETSKNCPVCD 42

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 1958709437   9 ITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPL 66
Cdd:cd16738     1 LAELNPYILCSICKGYFIDATTITECLHTFCKSCIVRHFYYSNRCPKCNIVVHQTQPL 58

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 1958709437  18 CVLCGGYFIDATTIIECLHSFCKTCIVRYLE-TSKYCPIC 56
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLEsGNVTCPLC 40

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1958709437  17 MCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:pfam13923   1 MCPICMDMLKDPSTTTPCGHVFCQDCILRALEASNECPLC 40

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958709437  16 LMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETS-KYCPICDVQVHKTRPLlniRSDKTLQDIVYKL 82
Cdd:cd16531     2 LMCPICLGIIKNTMTVKECLHRFCAECIEKALRLGnKECPTCRKHLPSRRSL---RPDPNFDALISKI 66

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 1958709437  16 LMCVLCGGYFIDaTTIIECLHSFCKTCIVRYLET-SKYCPIC 56
Cdd:cd16449     1 LECPICLERLKD-PVLLPCGHVFCRECIRRLLESgSIKCPIC 41

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 1958709437 158 DKRYLRCPAALTVMHLRKFLRSKM--DIPNTFQIDVMYEEEPLKDYYTLMDIaYIYTWR-RNGPLPLKYR 224
Cdd:cd17083    17 KRKYIRCSSQATITHLKKFIAKKLflDIFRYNEVDILCNEEILGKDHTLKFV-TVTRWRfKETPLLLHYR 85

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 1958709437  14 PHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKY-CPICDVQV 60
Cdd:cd16503     1 ENLTCSICQDLLHDCVSLQPCMHNFCAACYSDWMERSNTeCPTCRATV 48

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958709437   8 KITELNP---HLMCVLCGGYFiDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRpllnIRSDKTLQDIVYKlvp 84
Cdd:TIGR00599  16 PIPSLYPldtSLRCHICKDFF-DVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESK----LRSNWLVSEIVES--- 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958709437  85 glFKNEMKRRRDFYAAHPSADAANGsnEDRGEVADEDRRVIADDEIISLSIEFFHP---SRSDRKVTKEKPKEEV----- 156
Cdd:TIGR00599  88 --FKNLRPSLLEFLRIPKTTPVENP--DLAGPENSSKIELIEESESDGVDAEDEDLqrsATSSRALAARSTADILqlssd 163

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1958709437 157 ----NDKRYLR---------CPAALTVMHLRKFLR 178
Cdd:TIGR00599 164 pskrNDADYRSeppneglvqCPICQQRMPEKAVER 198

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 1958709437  17 MCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16506     2 TCPICLDEIQNKKTLEKCKHSFCEDCIDRALQVKPVCPVC 41

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 1958709437  16 LMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16529     5 LRCPICFEYFNTAMMITQCSHNYCSLCIRRFLSYKTQCPTC 45

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958709437  16 LMCVLCGGYFIDATtIIECLHSFCKTCIVRYLETS---KYCPICDvQVHKTRPL 66
Cdd:cd16611     5 LHCPLCLDFFRDPV-MLSCGHNFCQSCITGFWELQaedTTCPECR-ELCQYRNL 56

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 1958709437  18 CVLCGGYFIDATTIiECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16514     4 CSLCLRLLYEPVTT-PCGHTFCRACLERCLDHSPKCPLC 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958709437  16 LMCVLCGGYFIDATTIIECLHSFCKTCIVRYLET-SKYCPICDVQVHKTRPLlniRSDKTLQDIVYKLVP 84
Cdd:cd16739     4 LMCPICLDMLKNTMTTKECLHRFCSDCIVTALRSgNKECPTCRKKLVSKRSL---RPDPNFDALISKIYP 70

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958709437  17 MCVLCGGYFI--DATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTRPL 66
Cdd:cd16675     2 ICAVCLEEFKpkDELGICPCKHAFHRKCLIKWLEVRKVCPLCNMPVLQLAQL 53

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 1958709437  17 MCVLCGGYFIDATTIIE-CLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16574     3 SCPICLDRFENEKAFLDgCFHAFCFTCILEWSKVKNECPLC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958709437  16 LMCVLCGGYFIDATTIiECLHSFCKTCIVRylETSKYCPICDVQVHK 62
Cdd:cd16513     3 LSCPLCRGLLFEPVTL-PCGHTFCKRCLER--DPSSRCRLCRLKLSP 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958709437  16 LMCVLCGGYFIDATTIiECLHSFCKTCIVRYLETSKYCPICDVQVHK 62
Cdd:cd23147     5 LKCPICLSLFKSAANL-SCNHCFCAGCIGESLKLSAICPVCKIPATR 50

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958709437  16 LMCVLCGGYFIDATTiIECLHSFCKTCIVRYLETSKY---CPICdvqvHKTRPLLNIRSD 72
Cdd:cd16603     5 LTCPICMNYFIDPVT-IDCGHSFCRPCLYLNWQDIPFlaqCPEC----RKTTEQRNLKTN 59

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        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958709437  12 LNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLET-SKYCPICDVQVHKTRPLlniRSDKTLQDIVYKL 82
Cdd:cd16740     9 LHSELMCPICLDMLKNTMTTKECLHRFCADCIITALRSgNKECPTCRKKLVSKRSL---RPDPNFDALISKI 77

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 1958709437  16 LMCVLCGGYFIDATTIiECLHSFCKTCIVRYLE---TSKYCPIC 56
Cdd:cd23133     4 LTCSICQGIFMNPVYL-RCGHKFCEACLLLFQEdikFPAYCPMC 46

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958709437  17 MCVLCGGYFIDATTIiECLHSFCKTCIVRYLE-------TSKYCPIC 56
Cdd:cd16593     7 NCPICQGTLREPVTI-DCGHNFCRACLTRYCEipgpdleEPPTCPLC 52

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1958709437  16 LMCVLCGGYFIDATTIIECLHSFCKTCIVRYL-ETSKYCPICDVQVHKTRP 65
Cdd:cd16544     3 LTCPVCQEVLKDPVELPPCRHIFCKACILLALrSSGARCPLCRGPVGKTER 53

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                          10        20
                  ....*....|....*....|....*....
gi 1958709437  28 ATTIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16545    11 ADLILPCAHSYCQKCIDKWSDRHRTCPIC 39

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1958709437   5 TRIKITELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSkyCPICDVQVH 61
Cdd:cd16496     5 TRAALDELENLLRCSRCASILKEPVTLGGCEHVFCRSCVGDRLGNG--CPVCDTPAW 59

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 1958709437  18 CVLCGGYFIDATTIiECLHSFCKTCIVRYLETSK-----YCPICDVQVHKTrpllNIRSDKTL 75
Cdd:cd16598     7 CSICLDYLRDPVTI-DCGHNFCRSCITDYCPISGgherpVCPLCRKPFKKE----NIRPNWQL 64

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

                          10        20
                  ....*....|....*....|....*...
gi 1958709437  33 ECLHSFCKTCIVRYLETSKYCPICDVQV 60
Cdd:cd16481    18 ECGHIFHKECIKQWLKEQSTCPTCRVHV 45

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1958709437  16 LMCVLCGGYFIDATTIiECLHSFCKTCIVRYLETSKYCPI 55
Cdd:cd16637     2 LTCHICLQPLVEPLDT-PCGHTFCYKCLTNYLKIQQCCPL 40

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 1958709437  11 ELNPHLMCVLCGGYFIDATTIIeCLHSFCKTCI---VRYLETSKY-CPICDVQvHKTRPLLN 68
Cdd:cd16597     1 DLEEELTCSICLELFKDPVTLP-CGHNFCGVCIektWDSQHGSEYsCPQCRAT-FPRRPELH 60

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1958709437  18 CVLCGGYFIDATTI--IECLHSFCKTCIVRYLETSKYCPICDV 58
Cdd:cd16474     3 CTICLSDFEEGEDVrrLPCMHLFHQECVDQWLSTNKRCPICRV 45

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It acts downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances TGF-beta signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. RNF11 also functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1958709437  18 CVLCGGYFI--DATTIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16468     2 CVICMADFVvgDPIRYLPCMHIYHVDCIDDWLMRSFTCPSC 42

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1958709437  21 CGGYFIDAT-TIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16465     6 CSEYVKDEIaTELPCHHLFHKPCITAWLQKSGTCPVC 42

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; This subfamily includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, -3, -4, -5, -6, and -7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergo degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1958709437  17 MCVLCGGYFI--DATTIIECLHSFCKTCIVRYLETSKYCPICDVQV 60
Cdd:cd16469     2 TCAVCLEEFKlkEELGVCPCGHAFHTKCLKKWLEVRNSCPICKSPV 47

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity to RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1958709437  17 MCVLCGGYF--IDATTIIECLHSFCKTCIVRYLETSKYCPIC 56
Cdd:cd16472     4 QCVVCMCDYekRQLLRVLPCSHEFHAKCIDKWLKTNRTCPIC 45