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 698986368    7 DAFNVPDSTDWLGTPLACLMPVEQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKLRGNWAL 86
Cdd:TIGR00599   2 DELDITDSSDWLTTPIPSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESKLRSNWLV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368   87 REAVEAFKNSRKVLLEFARTPPTIQAILPDQAGPSSPSKRKATELEGPKEEDPETKRPRRSTRSTRARAAELTAAILQEE 166
Cdd:TIGR00599  82 SEIVESFKNLRPSLLEFLRIPKTTPVENPDLAGPENSSKIELIEESESDGVDAEDEDLQRSATSSRALAARSTADILQLS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368  167 QDTTPSADPDYVDQPPDDGLVACPICLTRMKEQQVDRHLDTSCPGSPQA-ASKRRPIPAQ-TSQPSTFPSFNSRLTSQT- 243
Cdd:TIGR00599 162 SDPSKRNDADYRSEPPNEGLVQCPICQQRMPEKAVERHLDSECLGSPSLgASTTFPTESNpHNKSSSRFSFRTVDKSSTg 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368  244 -------SIANQNQKPPERLPALAYSMLRDTALRKKLSELGLSTHGSRQLLEKRHKEWITLWNANCDSSRPKKRSELLRD 316
Cdd:TIGR00599 242 etshvdkYLNSMMSKPPERLPKINYSLLTDSQIRKKLSELGLSTNGTRQLLQKRHNEWETLWNSNCDSLEPVDKRELLRQ 321

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 698986368  317 LDEWERTVGNPGTAAGGGGGQQGLGLVARAQATGAQIKDKEFDGKAWATRYGGSFGDLIKQARKGIKRQTLDGNGE 392
Cdd:TIGR00599 322 LDSWERTQGKTPQNSGNKGGISKLMIMKSNGKTGAYRKLKKFNGKGWMVMYRKDFADLIREAKMKIKRSTSDSNGS 397

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 698986368    7 DAFNVPDSTDWLGTPLACLMPVEQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKLRGNWAL 86
Cdd:TIGR00599   2 DELDITDSSDWLTTPIPSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESKLRSNWLV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368   87 REAVEAFKNSRKVLLEFARTPPTIQAILPDQAGPSSPSKRKATELEGPKEEDPETKRPRRSTRSTRARAAELTAAILQEE 166
Cdd:TIGR00599  82 SEIVESFKNLRPSLLEFLRIPKTTPVENPDLAGPENSSKIELIEESESDGVDAEDEDLQRSATSSRALAARSTADILQLS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368  167 QDTTPSADPDYVDQPPDDGLVACPICLTRMKEQQVDRHLDTSCPGSPQA-ASKRRPIPAQ-TSQPSTFPSFNSRLTSQT- 243
Cdd:TIGR00599 162 SDPSKRNDADYRSEPPNEGLVQCPICQQRMPEKAVERHLDSECLGSPSLgASTTFPTESNpHNKSSSRFSFRTVDKSSTg 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368  244 -------SIANQNQKPPERLPALAYSMLRDTALRKKLSELGLSTHGSRQLLEKRHKEWITLWNANCDSSRPKKRSELLRD 316
Cdd:TIGR00599 242 etshvdkYLNSMMSKPPERLPKINYSLLTDSQIRKKLSELGLSTNGTRQLLQKRHNEWETLWNSNCDSLEPVDKRELLRQ 321

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 698986368  317 LDEWERTVGNPGTAAGGGGGQQGLGLVARAQATGAQIKDKEFDGKAWATRYGGSFGDLIKQARKGIKRQTLDGNGE 392
Cdd:TIGR00599 322 LDSWERTQGKTPQNSGNKGGISKLMIMKSNGKTGAYRKLKKFNGKGWMVMYRKDFADLIREAKMKIKRSTSDSNGS 397

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 698986368  29 EQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKL 80
Cdd:cd23148    1 DHALRCHICKDLLKAPMRTPCNHTFCSFCIRTHLNNDARCPLCKAEVTESGL 52

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 698986368    34 CHVCKD-FYDSPMLTSCNHTFCSLCIRRCLSVDS-KCPLC 71
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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368    7 DAFNVPDSTDWLGTPLACLMPVEQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKLRGNWAL 86
Cdd:TIGR00599   2 DELDITDSSDWLTTPIPSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQESKLRSNWLV 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368   87 REAVEAFKNSRKVLLEFARTPPTIQAILPDQAGPSSPSKRKATELEGPKEEDPETKRPRRSTRSTRARAAELTAAILQEE 166
Cdd:TIGR00599  82 SEIVESFKNLRPSLLEFLRIPKTTPVENPDLAGPENSSKIELIEESESDGVDAEDEDLQRSATSSRALAARSTADILQLS 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368  167 QDTTPSADPDYVDQPPDDGLVACPICLTRMKEQQVDRHLDTSCPGSPQA-ASKRRPIPAQ-TSQPSTFPSFNSRLTSQT- 243
Cdd:TIGR00599 162 SDPSKRNDADYRSEPPNEGLVQCPICQQRMPEKAVERHLDSECLGSPSLgASTTFPTESNpHNKSSSRFSFRTVDKSSTg 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 698986368  244 -------SIANQNQKPPERLPALAYSMLRDTALRKKLSELGLSTHGSRQLLEKRHKEWITLWNANCDSSRPKKRSELLRD 316
Cdd:TIGR00599 242 etshvdkYLNSMMSKPPERLPKINYSLLTDSQIRKKLSELGLSTNGTRQLLQKRHNEWETLWNSNCDSLEPVDKRELLRQ 321

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 698986368  317 LDEWERTVGNPGTAAGGGGGQQGLGLVARAQATGAQIKDKEFDGKAWATRYGGSFGDLIKQARKGIKRQTLDGNGE 392
Cdd:TIGR00599 322 LDSWERTQGKTPQNSGNKGGISKLMIMKSNGKTGAYRKLKKFNGKGWMVMYRKDFADLIREAKMKIKRSTSDSNGS 397

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 698986368  29 EQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKL 80
Cdd:cd23148    1 DHALRCHICKDLLKAPMRTPCNHTFCSFCIRTHLNNDARCPLCKAEVTESGL 52

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 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCL-SVDSKCPLC 71
Cdd:cd16449    1 LECPICLERLKDPVLLPCGHVFCRECIRRLLeSGSIKCPIC 41

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLC 71
Cdd:cd16504    3 FLCPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNRCPKC 42

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 698986368    34 CHVCKD-FYDSPMLTSCNHTFCSLCIRRCLSVDS-KCPLC 71
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLESGNnTCPIC 40

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 698986368  30 QAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSK---CPLCRATDQESKLRGNWALREAVEAFKN 95
Cdd:cd16498   15 KNLECPICLELLKEPVSTKCDHQFCRFCILKLLQKKKKpapCPLCKKSVTKRSLQESTRFKQLVEAVKK 83

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 698986368   34 CHVCKDFYDSPMLTS-CNHTFCSLCIRRCLSVDS-KCPLC 71
Cdd:pfam00097   1 CPICLEEPKDPVTLLpCGHLFCSKCIRSWLESGNvTCPLC 40

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 698986368  34 CHVCKDFYDSPMLTSCNHTFCSLCIRRC---LSVDSKCPLCRATDQESKLRGN 83
Cdd:cd16611    7 CPLCLDFFRDPVMLSCGHNFCQSCITGFwelQAEDTTCPECRELCQYRNLTPN 59

RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 (AtBARD1) and similar proteins; AtBARD1, also called protein REPRESSOR OF WUSCHEL 1, binds specifically to H3K4me3 regions of target gene (e.g. WUS and WOX5) promoters to repress their transcription via chromatin remodeling. It is required for the shoot apical meristem (SAM) organization and maintenance, by confining WUS expression to the organizing center, and for the quiescent center (QC) development in the root apical meristem (RAM), by repressing WOX5 expression in the root proximal meristem. AtBARD1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBARD1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKLR 81
Cdd:cd23146    5 LKCPICLKLLNRPVLLPCDHIFCSSCITDSTKVGSDCPVCKLPYHSQDLR 54

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

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 698986368   261 YSMLRDTALRKKLSELGLSTHGSRQLLEKRHKEWI 295
Cdd:smart00513   1 LAKLKVSELKDELKKRGLSTSGTKAELVDRLLEAL 35

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 698986368  31 AFRCHVCKDFYDSPM-LTSCNHTFCSLCIRRCLSVDS-KCPLCRA 73
Cdd:cd16549    1 QFSCPICLEVYHKPVvITSCGHTFCGECLQPCLQVASpLCPLCRM 45

RING finger, HC subclass, found in RING finger protein 114 (RNF114) and similar proteins; RNF114, also known as zinc finger protein 228 (ZNF228) or zinc finger protein 313 (ZNF313), is a p21(WAF1)-targeting ubiquitin E3 ligase that interacts with X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) and may play a role in p53-mediated cell-fate decisions. It is involved in the immune response to double-stranded RNA in disease pathogenesis. Moreover, RNF114 interacts with A20 and modulates its ubiquitylation. It negatively regulates nuclear factor-kappaB (NF-kappaB)-dependent transcription and positively regulates T-cell activation. RNF114 may play a putative role in the regulation of immune responses, since it corresponds to a novel psoriasis susceptibility gene, ZNF313. RNF114, together with three closely related proteins: RNF125, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 698986368  31 AFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSK-CPLCR 72
Cdd:cd16540    1 RFTCPVCLEIFETPVRVPCGHVFCNACLQECLKPKKPvCAVCR 43

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 698986368  28 VEQAFRCHVCKDFYDSPMLTSCNHTFC-SLCIRRCLSVDS---KCPLCRA 73
Cdd:cd16524    2 IEQLLTCPICLDRYRRPKLLPCQHTFClSPCLEGLVDYVTrklKCPECRA 51

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 698986368  34 CHVCKDFYDSP--MLTSCNHTFCSLCIRRCLSVDSKCPLCRA 73
Cdd:cd16574    4 CPICLDRFENEkaFLDGCFHAFCFTCILEWSKVKNECPLCKQ 45

RING finger, HC subclass, found in recombination activating gene-1 (RAG-1) and similar proteins; RAG-1, also known as V(D)J recombination-activating protein 1, RING finger protein 74 (RNF74), or endonuclease RAG1, is the catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. RAG1 is a lymphoid-specific factor that mediates DNA-binding to conserved recombination signal sequences (RSS) and catalyzes DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. It also functions as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3, which is required for the joining step of V(D)J recombination. RAG-1 contains an N-terminal C3HC4-type RING-HC finger that mediates monoubiquitylation of histone H3, an adjacent C2H2-type zinc finger, and a nonamer binding (NBD) DNA-binding domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 698986368  30 QAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSV-DSKCPLCR 72
Cdd:cd16530    1 KSVSCQVCEHILADPVQTPCKHLFCRTCILKCLKVmGSYCPSCR 44

zinc-RING finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 698986368   33 RCHVCKDFYDS---PMLTSCNHTFCSLCIRRCLSvDSKCPLCR 72
Cdd:pfam14634   1 HCNKCFKELSKtrpFYLTSCGHIFCEECLTRLLQ-ERQCPICK 42

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRATDQESKL 80
Cdd:cd16527    1 RKCSLCLEERRHPTATPCGHLFCWSCITEWCNEKPECPLCREPFQPQRL 49

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 698986368  32 FRCHVCKDFYDSPM-LTSCNHTFCSLCIRRCL-SVDSKCPLCR 72
Cdd:cd16544    3 LTCPVCQEVLKDPVeLPPCRHIFCKACILLALrSSGARCPLCR 45

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSK---CPLCRA 73
Cdd:cd16745    1 FECNICLDLAQDPVVTLCGHLFCWPCLHKWLRRQSSqpeCPVCKA 45

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        40
                 ....*....|....*....|....*....|....*....|
gi 698986368  34 CHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRA 73
Cdd:cd16561    5 CSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRT 44

RING finger, HC subclass, found in RING finger protein 207 (RNF207) and similar proteins; RNF207 is a cardiac-specific E3 ubiquitin-protein ligase that plays an important role in the regulation of cardiac repolarization. It regulates action potential duration, likely via effects on human ether-a-go-go-related gene (HERG) trafficking and localization in a heat shock protein-dependent manner. RNF207 contains a C3HC4-type RING-HC finger, Bbox 1 and Bbox C-terminal (BBC) domain, as well as a C-terminal non-homologous region (CNHR).

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 698986368  34 CHVCKDFYDSPMLTSCNHTFCSLCIR-RCLSVDSKCPLC 71
Cdd:cd16558    4 CYLCHEQYEHPCLLDCYHTFCASCLRgRAADGRLTCPLC 42

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 698986368  32 FRCHVCKDFYDSPMLTSC-NHTFCSLCIRRCL-SVDSKCPLCRATDQESKLR 81
Cdd:cd16620    4 LKCPICKDLMKDAVLTPCcGNSFCDECIRTALlEEDFTCPTCKEPDVSPDAL 55

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 698986368  34 CHVCKDFYDSPMLTSCNHTFCSLCI------------RRCLSVDSKCPLCRATDQESKLRGN 83
Cdd:cd16595    8 CSICLDYFTDPVMTTCGHNFCRACIqlswekargkkgRRKQKGSFPCPECREMSPQRNLRPN 69

SAP domain; The SAP (after SAF-A/B, Acinus and PIAS) motif is a putative DNA/RNA binding domain found in diverse nuclear and cytoplasmic proteins.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 698986368  261 YSMLRDTALRKKLSELGLSTHGSRQLLEKRHKEWI 295
Cdd:pfam02037   1 LSKLTVAELKEELRKRGLPTSGKKAELIERLQEYL 35

Rad18-like CCHC zinc finger; Yeast Rad18p functions with Rad5p in error-free post-replicative DNA repair. This zinc finger is likely to bind nucleic-acids.

                           10        20
                   ....*....|....*....|....*
gi 698986368   186 LVACPICLTRMKEQQVDRHLDtSCP 210
Cdd:smart00734   1 LVQCPVCFREVPENLINSHLD-SCL 24

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 698986368  32 FRCHVCKD-FYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCR 72
Cdd:cd16525    1 LTCSLCKGyLIDATTITECLHSFCKSCIVRHLETSKNCPVCD 42

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 698986368  34 CHVCKDFYDSP---MLTSCNHTFCSLCIRRCL-SVDSKCPLCR 72
Cdd:cd16448    1 CVICLEEFEEGdvvRLLPCGHVFHLACILRWLeSGNNTCPLCR 43

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
                 ....*....|....*....|....*....|....*....|
gi 698986368  33 RCHVCKDFY-DSPMLTSCNHTFCSLCIRRCLSVDSKCPLC 71
Cdd:cd16738    9 LCSICKGYFiDATTITECLHTFCKSCIVRHFYYSNRCPKC 48

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 698986368  29 EQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCR 72
Cdd:cd16547    1 DDDLICSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCR 44

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSKCPLCRA 73
Cdd:COG5152  197 FLCGICKKDYESPVVTECGHSFCSLCAIRKYQKGDECGVCGK 238

RING finger, HC subclass, found in RING finger protein RNF5, RNF185 and similar proteins; RNF5 and RNF185 are E3 ubiquitin-protein ligases that are anchored to the outer membrane of the endoplasmic reticulum (ER). RNF5 acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis, and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. RNF185 controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical endoplasmic reticulum-associated degradation (ERAD) model substrates. Moreover, both RNF5 and RNF185 play important roles in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) are also included in this family. They possess E3 ubiquitin-protein ligase activity and may play a role in the growth and development of Arabidopsis. All members of this family contain a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 698986368  32 FRCHVCKDFYDSPMLTSCNHTFCSLCIRRCL---SVDSKCPLCR 72
Cdd:cd16534    1 FECNICLDTASDPVVTMCGHLFCWPCLYQWLetrPDRQTCPVCK 44

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 698986368  26 MPVEQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVDSK--CPLCRAT 74
Cdd:cd16608    1 SSLKDELLCSICLSIYQDPVSLGCEHYFCRQCITEHWSRSEHrdCPECRRT 51

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 698986368   34 CHVCKDFYDSPMLTSCNHT-FCSLCIRRCLSVDSKCPLCRA 73
Cdd:pfam13920   5 CVICLDRPRNVVLLPCGHLcLCEECAERLLRKKKKCPICRQ 45

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 698986368  34 CHVCKDFYDSPMLTSCNHTFCSLCIRRCLSVdsKCPLCRATDQESKLRGN 83
Cdd:cd16602    6 CAICLDYFKDPVSIGCGHNFCRVCVTQLWGF--TCPQCRKSFPRRSFRPN 53

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 698986368  27 PVEQAFRCHVCKDFYDSPMLTSCNHTFCSLCIRRclSVDSKCPL 70
Cdd:cd16644    1 PPSVKLYCPLCQRVFKDPVITSCGHTFCRRCALT--APGEKCPV 42