Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1; Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (Icos) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as an RNA-binding domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569    6 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16781    1 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 49

DNA translocase FtsK; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   440 QEELEKFRKMNKRLVPRRPL----SASLGQLNEVGLPSAPILSDESAVDLSNRKPPALPNGIASSGSTVTQLIPRGTDPS 515
Cdd:PRK10263  231 QHESRRARILRGALARRKRLaekfINPMGRQTDAALFSGKRMDDDEEITYTARGVAADPDDVLFSGNRATQPEYDEYDPL 310

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   516 FD--SSLKPVKLDHLSSSAP---GSPPDLLESAPKSISALPVNPHPV----PPRGPTDLPPMPVTKPIQMVPRGSQLYPA 586
Cdd:PRK10263  311 LNgaPITEPVAVAAAATTATqswAAPVEPVTQTPPVASVDVPPAQPTvawqPVPGPQTGEPVIAPAPEGYPQQSQYAQPA 390

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   587 QQADVYYQDP--------------RGSAPAFETAPYQQGMYYTPPPCVSRFVRPPPSAPEPGPPYLDH------YSPYLQ 646
Cdd:PRK10263  391 VQYNEPLQQPvqpqqpyyapaaeqPAQQPYYAPAPEQPAQQPYYAPAPEQPVAGNAWQAEEQQSTFAPqstyqtEQTYQQ 470

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   647 DRVINSQYgTQPQQYPPmypahydgrrvypaQSYTREEmfresPIPIDIPSAAVPSYVPE------SRERYQQVEGYYPV 720
Cdd:PRK10263  471 PAAQEPLY-QQPQPVEQ--------------QPVVEPE-----PVVEETKPARPPLYYFEeveekrAREREQLAAWYQPI 530

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 68131569   721 aPHPAQ----IRPSYPRDPPYSrLPPPQPHPSLDELHRRRKEIMAQLEERKVISPPPFAPSPTLPP 782
Cdd:PRK10263  531 -PEPVKepepIKSSLKAPSVAA-VPPVEAAAAVSPLASGVKKATLATGAAATVAAPVFSLANSGGP 594

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1; Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (Icos) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as an RNA-binding domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569    6 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16781    1 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 49

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 68131569      14 CPICtqtFDETIRKPISLGCGHTVCKMCLNKL---HRKACPF 52
Cdd:smart00184    1 CPIC---LEEYLKDPVILPCGHTFCRSCIRKWlesGNNTCPI 39

DNA translocase FtsK; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   440 QEELEKFRKMNKRLVPRRPL----SASLGQLNEVGLPSAPILSDESAVDLSNRKPPALPNGIASSGSTVTQLIPRGTDPS 515
Cdd:PRK10263  231 QHESRRARILRGALARRKRLaekfINPMGRQTDAALFSGKRMDDDEEITYTARGVAADPDDVLFSGNRATQPEYDEYDPL 310

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   516 FD--SSLKPVKLDHLSSSAP---GSPPDLLESAPKSISALPVNPHPV----PPRGPTDLPPMPVTKPIQMVPRGSQLYPA 586
Cdd:PRK10263  311 LNgaPITEPVAVAAAATTATqswAAPVEPVTQTPPVASVDVPPAQPTvawqPVPGPQTGEPVIAPAPEGYPQQSQYAQPA 390

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   587 QQADVYYQDP--------------RGSAPAFETAPYQQGMYYTPPPCVSRFVRPPPSAPEPGPPYLDH------YSPYLQ 646
Cdd:PRK10263  391 VQYNEPLQQPvqpqqpyyapaaeqPAQQPYYAPAPEQPAQQPYYAPAPEQPVAGNAWQAEEQQSTFAPqstyqtEQTYQQ 470

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   647 DRVINSQYgTQPQQYPPmypahydgrrvypaQSYTREEmfresPIPIDIPSAAVPSYVPE------SRERYQQVEGYYPV 720
Cdd:PRK10263  471 PAAQEPLY-QQPQPVEQ--------------QPVVEPE-----PVVEETKPARPPLYYFEeveekrAREREQLAAWYQPI 530

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 68131569   721 aPHPAQ----IRPSYPRDPPYSrLPPPQPHPSLDELHRRRKEIMAQLEERKVISPPPFAPSPTLPP 782
Cdd:PRK10263  531 -PEPVKepepIKSSLKAPSVAA-VPPVEAAAAVSPLASGVKKATLATGAAATVAAPVFSLANSGGP 594

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    478 SDESAVDLSNRK-PPALP---NGIASSGSTVTQLIPRGTDPSFDSSLKPVkldhLSSSAPGSPPDLLESAPKSISALPVN 553
Cdd:pfam03154  132 SDPKDIDQDNRStSPSIPspqDNESDSDSSAQQQILQTQPPVLQAQSGAA----SPPSPPPPGTTQAATAGPTPSAPSVP 207

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    554 PHPVPPRGPTDLPPMPVTKPIQMVPRGSQLYPaqqadvyyqdPRGSAPAfetAPYQQGMYYTPPPCVSRFVRPPPSAPEP 633
Cdd:pfam03154  208 PQGSPATSQPPNQTQSTAAPHTLIQQTPTLHP----------QRLPSPH---PPLQPMTQPPPPSQVSPQPLPQPSLHGQ 274

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    634 GPPY---LDHYSPYLQDRVINSQYGTQPQ----QYPP----MYPAHYDGRRVYPA--QSYTREEMFRESPI---PIDIPS 697
Cdd:pfam03154  275 MPPMphsLQTGPSHMQHPVPPQPFPLTPQssqsQVPPgpspAAPGQSQQRIHTPPsqSQLQSQQPPREQPLppaPLSMPH 354

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    698 AAVPSYVPESRERYQQVEGYYP--VAPHPAQIRPSYPRDP---PYSRLP---PPQPHPSLDELHRRRKEIMAqleerKVI 769
Cdd:pfam03154  355 IKPPPTTPIPQLPNPQSHKHPPhlSGPSPFQMNSNLPPPPalkPLSSLSthhPPSAHPPPLQLMPQSQQLPP-----PPA 429

                          330
                   ....*....|....*....
gi 68131569    770 SPPPFAPSPTLPP--AFHP 786
Cdd:pfam03154  430 QPPVLTQSQSLPPpaASHP 448

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1; Roquin-1, also known as RING finger and C3H zinc finger protein 1 (RC3H1), or RING finger protein 198 (RNF198), is a ubiquitously expressed RNA-binding protein essential for degradation of inflammation-related mRNAs and maintenance of immune homeostasis. It is localized in cytoplasmic granules and binds to the 3' untranslated region (3'UTR) of inducible costimulator (Icos) mRNA to post-transcriptionally repress its expression. Roquin-1 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Moreover, Roquin-1 shares functions with its paralog Roquin-2 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-1 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger that is involved in RNA recognition, typically contacting AU-rich elements. In addition, both N- and C-terminal to the ROQ domain are combined to form a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain that is highly likely to function as an RNA-binding domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569    6 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16781    1 PQWTDFLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 49

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 68131569   11 FLSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQ 54
Cdd:cd16638    1 FLSCPVCTNEFDGTQRKPISLGCGHTVCKTCLSKLHRKQCPFDQ 44

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is 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 a 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. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 68131569   12 LSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKA------CPF 52
Cdd:cd16587    1 LECPICLESFDEGQLRPKLLHCGHTICEQCLEKLLASLsingvrCPF 47

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 68131569      14 CPICtqtFDETIRKPISLGCGHTVCKMCLNKL---HRKACPF 52
Cdd:smart00184    1 CPIC---LEEYLKDPVILPCGHTFCRSCIRKWlesGNNTCPI 39

RING finger, HC subclass, found in Arabidopsis thaliana protein KEEP ON GOING (KEG) and similar proteins; KEG, also called RING-type E3 ubiquitin transferase KEG, is a RING E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. It is essential for Arabidopsis growth and development. It acts as a negative regulator of abscisic acid signaling. It is required for ABSCISIC ACID-INSENSITIVE5 (ABI5) degradation, by mediating its ubiquitination. Together with EDR1, KEG may regulate endocytic trafficking and/or the formation of signaling complexes on trans-Golgi network (TGN)/ early endosome (EE) vesicles during stress responses. KEG is a multidomain protein that includes a C3HC4-type RING-HC finger, a kinase domain, ankyrin repeats, and 12 HERC2-like (for HECT and RCC1-like) repeats.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 68131569   14 CPICTQTFDETIRKPISLGCGHTVCKMCLNKLHRKACPFDQT 55
Cdd:cd23140    4 CSVCSEGYNEDERVPLLLQCGHTFCKDCLSQMFIRCTDLTLK 45

Modified RING finger, HC subclass (C3HC3D-type), found in Caenorhabditis elegans putative GTP-binding protein trim-23 homolog (arc-1) and similar proteins; arc-1, also called RING-type E3 ubiquitin transferase arc-1, is an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. arc-1 contains a modified C3HC3D-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 68131569   11 FLSCPICTQTFDETI--RKP-ISLGCGHTVCKMCLNKLHRK-----ACPFDQT 55
Cdd:cd23124    1 ELECGICQQEYSADDplLIPrILTECGHTICTNCAGTILGQssgsiFCPFDRI 53

RING finger, HC subclass, found in RING finger protein 182 (RNF182) and similar proteins; RNF182 is a brain-enriched E3 ubiquitin-protein ligase that stimulates E2-dependent polyubiquitination in vitro. It is upregulated in Alzheimer"s disease (AD) brains and neuronal cells exposed to injurious insults. It interacts with ATP6V0C and promotes its degradation by the ubiquitin-proteosome pathway, suggesting a very specific role in controlling the turnover of an essential component of the neurotransmitter release machinery. RNF182 contains an N-terminal C3HC4-type RING-HC finger, and a C-terminal transmembrane domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569   12 LSCPICTQTFDETIRKPISLGCGHTVCKMCLNKLH--------RKACPF 52
Cdd:cd16555    2 LECKICYNRYDLRQRRPKVLECCHRVCAKCLYKIVdlgdsspsVLVCPF 50

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 68131569   12 LSCPICTqtfdETIRKPISLGCGHTVCKMCLNKL------HRKACPFDQTT 56
Cdd:cd16604    1 LSCPICL----DLLKDPVTLPCGHSFCMGCLGALwgagrgGRASCPLCRQT 47

RING finger, HC subclass, found in RING finger protein RNF183, RNF223, RNF225 and similar proteins; RNF183 is an E3 ubiquitin-protein ligase that is upregulated during intestinal inflammation and is negatively regulated by miR-7. It promotes intestinal inflammation by increasing the ubiquitination and degradation of inhibitor of kappa B, thereby resulting in secondary activation of the Nuclear factor-kappaB (NF-kB) pathway. The interaction between RNF183-mediated ubiquitination and miRNA may be an important novel epigenetic mechanism in the pathogenesis of inflammatory bowel disease (IBD). The biological function of RNF223 and RNF225 remains unclear. Members of this family contain an N-terminal C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569   12 LSCPICTQTFDETIRKPISLGCGHTVCKMCLNKL--------HRKACPF 52
Cdd:cd16556    1 LECSICFSSYDNTFKTPKLLDCGHTFCLECLARLslasppqaERVPCPL 49

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
                 ....*....|....*....|....*....|....*...
gi 68131569   14 CPICTQTFdetiRKPISLGCGHTVCKMCLNKLHRKACP 51
Cdd:cd16602    6 CAICLDYF----KDPVSIGCGHNFCRVCVTQLWGFTCP 39

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 68131569   12 LSCPICTQTFdetiRKPISLGCGHTVCKMCLNK----LHRKACPFDQTTINTDIelLPVNSALLQLV 74
Cdd:cd16599    5 LLCPICYEPF----REAVTLRCGHNFCKGCVSRswerQPRAPCPVCKEASSSDD--LRTNHTLNNLV 65

RING finger, HC subclass, found in Arabidopsis thaliana protein BENZOIC ACID HYPERSENSITIVE 1 (BAH1) and similar proteins; This subfamily includes Arabidopsis thaliana BAH1 and BAH1-like. BAH1, also known as protein NITROGEN LIMITATION ADAPTATION (NLA), or RING-type E3 ubiquitin transferase BAH1, acts as an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. It plays a role in salicylic acid-mediated negative feedback regulation of salicylic acid (SA) accumulation. It may be involved in the overall regulation of SA, benzoic acid and phenylpropanoid biosynthesis. It controls the adaptability to nitrogen limitation by channeling the phenylpropanoid metabolic flux to the induced anthocyanin synthesis. BAH1-like, also known as RING finger protein 178, or RING-type E3 ubiquitin transferase BAH1-like, is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

                         10        20        30
                 ....*....|....*....|....*....|
gi 68131569   12 LSCPICTqtfdETIRKPISLGCGHTVCKMC 41
Cdd:cd23127    9 LTCSICL----DTVFDPVALGCGHLFCNSC 34

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
                 ....*....|....*....|....*....|....*....|....*....|..
gi 68131569   12 LSCPICTqtfdETIRKPISLGCGHTVCKMCLNK-LHRKA----CPFDQTTIN 58
Cdd:cd16498   17 LECPICL----ELLKEPVSTKCDHQFCRFCILKlLQKKKkpapCPLCKKSVT 64

RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569   10 DFLSCPICTQTFdetiRKPISLGCGHTVCKMCLNKLHRKA-------CP 51
Cdd:cd16579    3 KFLRCPGCKAEY----KCPKLLPCLHTVCSGCLEALAEQAsettefqCP 47

Zinc finger C-x8-C-x5-C-x3-H type (and similar);

                           10        20
                   ....*....|....*....|....*..
gi 68131569    414 YKTYMCRDMKQRGGCPRGASCTFAHSQ 440
Cdd:pfam00642    1 YKTELCRFFLRTGYCKYGDRCKFAHGQ 27

RING finger, HC subclass, found in tripartite motif-containing protein 68 (TRIM68) and similar proteins; TRIM68, also known as RING finger protein 137 (RNF137) or SSA protein SS-56 (SS-56), is an E3 ubiquitin-protein ligase that negatively regulates Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I interferon production by degrading TRK fused gene (TFG), a novel driver of IFN-beta downstream of anti-viral detection systems. It also functions as a cofactor for androgen receptor-mediated transcription by regulating ligand-dependent transcription of androgen receptor in prostate cancer cells. Moreover, TRIM68 is a cellular target of autoantibody responses in Sjogre's syndrome (SS), as well as systemic lupus erythematosus (SLE). It is also an auto-antigen for T cells in SS and SLE. TRIM68 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
                 ....*....|....*....|....*....|....
gi 68131569   12 LSCPICtQTFdetIRKPISLGCGHTVCKMCLNKL 45
Cdd:cd16610    2 VACPIC-MTF---LREPVSIDCGHSFCHSCLSGL 31

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
                   ....*....|....*....|....*....
gi 68131569     14 CPICTQTFDETIRkpiSLGCGHTVCKMCL 42
Cdd:pfam00097    1 CPICLEEPKDPVT---LLPCGHLFCSKCI 26

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 68131569   12 LSCPICTQTFDEtirkPISLGCGHTVCKMCLNK--LHRKACP 51
Cdd:cd16504    3 FLCPICFDIIKE----AFVTKCGHSFCYKCIVKhlEQKNRCP 40

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 68131569   13 SCPICTQTFDetiRKPISLGCGHTVCKMCLNKL---HRKACP 51
Cdd:cd16564    2 ECPVCYEDFD---DAPRILSCGHSFCEDCLVKQlvsMTISCP 40

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 68131569   14 CPICTQTFDEtirkPISLGCGHTVCKMCLNKLHRKA---CPFDQTTINT 59
Cdd:cd16550    3 CPICLEILVE----PVTLPCNHTLCMPCFQSTVEKAslcCPLCRLRISS 47

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    478 SDESAVDLSNRK-PPALP---NGIASSGSTVTQLIPRGTDPSFDSSLKPVkldhLSSSAPGSPPDLLESAPKSISALPVN 553
Cdd:pfam03154  132 SDPKDIDQDNRStSPSIPspqDNESDSDSSAQQQILQTQPPVLQAQSGAA----SPPSPPPPGTTQAATAGPTPSAPSVP 207

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    554 PHPVPPRGPTDLPPMPVTKPIQMVPRGSQLYPaqqadvyyqdPRGSAPAfetAPYQQGMYYTPPPCVSRFVRPPPSAPEP 633
Cdd:pfam03154  208 PQGSPATSQPPNQTQSTAAPHTLIQQTPTLHP----------QRLPSPH---PPLQPMTQPPPPSQVSPQPLPQPSLHGQ 274

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    634 GPPY---LDHYSPYLQDRVINSQYGTQPQ----QYPP----MYPAHYDGRRVYPA--QSYTREEMFRESPI---PIDIPS 697
Cdd:pfam03154  275 MPPMphsLQTGPSHMQHPVPPQPFPLTPQssqsQVPPgpspAAPGQSQQRIHTPPsqSQLQSQQPPREQPLppaPLSMPH 354

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569    698 AAVPSYVPESRERYQQVEGYYP--VAPHPAQIRPSYPRDP---PYSRLP---PPQPHPSLDELHRRRKEIMAqleerKVI 769
Cdd:pfam03154  355 IKPPPTTPIPQLPNPQSHKHPPhlSGPSPFQMNSNLPPPPalkPLSSLSthhPPSAHPPPLQLMPQSQQLPP-----PPA 429

                          330
                   ....*....|....*....
gi 68131569    770 SPPPFAPSPTLPP--AFHP 786
Cdd:pfam03154  430 QPPVLTQSQSLPPpaASHP 448

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 68131569    9 TDFLSCPICTqtfdETIRKPISLGCGHTVCKMCLN----KLHRKACPFDQTTINT 59
Cdd:cd16568    2 LETQECIICH----EYLYEPMVTTCGHTYCYTCLNtwfkSNRSLSCPDCRTKITT 52

RING finger, HC subclass, found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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. This subfamily also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins that may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by N-terminal RBCC domains only.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 68131569   12 LSCPICTQTFDEtirkPISLGCGHTVCKMCLNKL 45
Cdd:cd16605    1 LLCPICLEVFKE----PLMLQCGHSYCKSCLVSL 30

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 68131569   14 CPICTqtfdETIRKPISLGCGHTVCKMCLNKLHRKA-------CP 51
Cdd:cd16583    8 CPICQ----EPLKEAVSTDCGHLFCRMCLTQHAKKAsasgvfsCP 48

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

                         10        20        30
                 ....*....|....*....|....*....|.
gi 68131569   12 LSCPICTQTFdetiRKPISLGCGHTVCKMCL 42
Cdd:cd16594    6 LTCPICLDYF----TDPVTLDCGHSFCRACI 32

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 68131569   14 CPICTQTFdetiRKPISLGCGHTVCKMCL----NKlhRKACPFDQTTI 57
Cdd:cd16741   17 CAICQAEF----RKPILLICQHVFCEECIslwfNR--EKTCPLCRTVI 58

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
                 ....*....|....*....|....*....|....*....|..
gi 68131569   11 FLSCPICTQTFDEtirkPISLG-CGHTVCKMCLNKLHRKACP 51
Cdd:cd16496   15 LLRCSRCASILKE----PVTLGgCEHVFCRSCVGDRLGNGCP 52

RING finger, HC subclass, found in RING finger protein 169 (RNF169) and similar proteins; RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to regulation of the DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. RNF169 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MIU (motif interacting with ubiquitin) domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 68131569   12 LSCPICTqtfdETIRKPISLGCGHTVCKMCLNKLHRKA-----CP 51
Cdd:cd16551    2 LTCAGCL----EVPVEPATLPCGHTLCRGCANRALDAAeagptCP 42

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 68131569   14 CPICTQTFDE--TIRKpislgCGHTVCKMCLNKL--HRKACP 51
Cdd:cd16506    3 CPICLDEIQNkkTLEK-----CKHSFCEDCIDRAlqVKPVCP 39

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 68131569   12 LSCPICTQTFDetirKPISLGCGHTVCKMCLNKLHRKACP 51
Cdd:cd16540    2 FTCPVCLEIFE----TPVRVPCGHVFCNACLQECLKPKKP 37

DNA translocase FtsK; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68131569   659 QQYPPMYPAHYDGRRVYPAQSYTREEmFRESPIPI---DIPSAAV--PSYVPESRERYQQVEGYY------PVAPHPAQI 727
Cdd:PRK10263  701 RQFAQTQQQRYSGEQPAGANPFSLDD-FEFSPMKAlldDGPHEPLftPIVEPVQQPQQPVAPQQQyqqpqqPVAPQPQYQ 779

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 68131569   728 RPSYPRDPPYSRLPPPQPHPSLDELHRRRKEIMAQLE----ERKVISPPPFApSPTLPPAFHPEEFL 790
Cdd:PRK10263  780 QPQQPVAPQPQYQQPQQPVAPQPQYQQPQQPVAPQPQyqqpQQPVAPQPQYQ-QPQQPVAPQPQDTL 845

RING finger, HC subclass, found in malin and similar proteins; Malin ("mal" for seizure in French), also known as NHL repeat-containing protein 1 (NHLRC1), or EPM2B, is a nuclear E3 ubiquitin-protein ligase that ubiquitinates and promotes the degradation of laforin (EPM2A encoding protein phosphatase). Malin and laforin operate as a functional complex that play key roles in regulating cellular functions such as glycogen metabolism, unfolded cellular stress response, and proteolytic processes. They act as pro-survival factors that negatively regulate the Hipk2-p53 cell death pathway. They also negatively regulate cellular glucose uptake by preventing plasma membrane targeting of glucose transporters. Moreover, they degrade polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase. Furthermore, they, together with Hsp70, form a new functional complex that suppress the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system. Defects in either malin or laforin may cause Lafora disease (LD), a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. In addition, malin may have function, independent of laforin, in lysosomal biogenesis and/or lysosomal glycogen disposal. Malin contains six NHL-repeat protein-protein interaction domains and a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 68131569   12 LSCPICTQTFDETI-RKPISLGCGHTVCKMCLNKLHRKA-----CPF 52
Cdd:cd16516    1 LECKVCFEKYSHQQeHRPRNLPCGHVLCRECVTALAHPRrskleCPF 47

zinc finger;

                            10        20
                    ....*....|....*....|....*..
gi 68131569     413 KYKTYMCRDMKqRGGCPRGASCTFAHS 439
Cdd:smart00356    1 KYKTELCKFFK-RGYCPRGDRCKFAHP 26

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 68131569   12 LSCPICTQTFdetiRKPISLGCGHTVCKMCLNK--LHRKACP 51
Cdd:cd23147    5 LKCPICLSLF----KSAANLSCNHCFCAGCIGEslKLSAICP 42

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 68131569   12 LSCPICTQTFDEtirkPISLGCGHTVCKMClnkLHRKACP 51
Cdd:cd16590    7 LTCPICLDYFQD----PVSIECGHNFCRGC---LHRNWAP 39