RNA recognition motif 1 in vertebrate poly [ADP-ribose] polymerase 14 (PARP-14); This subfamily corresponds to the RRM1 of PARP-14, also termed aggressive lymphoma protein 2, a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. It is expressed in B lymphocytes and interacts with the IL-4-induced transcription factor Stat6. It plays a fundamental role in the regulation of IL-4-induced B-cell protection against apoptosis after irradiation or growth factor withdrawal. It mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. PARP-14 acts as a transcriptional switch for Stat6-dependent gene activation. In the presence of IL-4, PARP-14 activates transcription by facilitating the binding of Stat6 to the promoter and release of HDACs from the promoter with an IL-4 signal. In contrast, in the absence of a signal, PARP-14 acts as a transcriptional repressor by recruiting HDACs. Moreover, the absence of PARP-14 protects against Myc-induced developmental block and lymphoma. Thus, PARP-14 may play an important role in Myc-induced oncogenesis. Research indicates that PARP-14 is also a binding partner with phosphoglucose isomerase (PGI)/ autocrine motility factor (AMF). It can inhibit PGI/AMF ubiquitination, thus contributing to its stabilization and secretion. PARP-14 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), three tandem macro domains, and C-terminal region with sequence homology to PARP catalytic domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923717   8 PSPLLVRVYKSG---PRVRRKLESYFQSSKSSGGGECTVSTQEhEAPGTFRVEFSERAAKERVLKKGEHQILVDEKPVPI 84
Cdd:cd12300   1 PFPLLVEGDWDPsppKKLKNKLEKYFQSKKRSGGGECTVETEG-PSPQTARVSFVNEEVRERVLEKKEHEILQGEGTVRL 79

                ...
gi 19923717  85 FLV 87
Cdd:cd12300  80 TVK 82

Domain found at the C-terminus of deltex-like; The deltex family of proteins is involved in the regulation of Notch signaling, and therefore may play roles in cell-to-cell communications that regulate mechanisms determining cell fate. They have a central RING-type zinc finger domain and contain a C-terminal domain, described here, that is also found in other domain architectures. Deltex-1 (DTX1) contains a RING finger and two WWE domains, indicating that it may be an E3 ubiquitin ligase. Human deltex 3-like, which contains an additional N-terminal domain (presumably with ubiquitin ligase activity) is also described as E3 ubiquitin-protein ligase DTX3L, B-lymphoma- and BAL-associated protein (BBAP), or rhysin-2. DTX3L mediates monoubiquitination of K91 of histone H4 in response to DNA damage.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923717 608 GNQPEGSMVFTVSRDSLPGYESFGTIVITYSMKAGIQTEEHPNPGKRYPGIQRTAYLPDNKEGRKVLKLLYRAFDQKLIF 687
Cdd:cd09633   1 GNQPPGTMTYHVIDTSLPGYEGCGTIVIVYNIPSGIQGPEHPGPGKPYRGTPRIAYLPDNEEGRKVLRLLKKAFDRRLIF 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 19923717 688 TVGYSRVLGVSDVITWNDIHHKTSRFGGPEMYGYPDPSYLKRVKEELKAKG 738
Cdd:cd09633  81 TVGTSVTTGREDVVVWNGIHHKTSLTGGPSGHGYPDPTYLDRVLEELAAKG 131

RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), is a RING-domain E3 ubiquitin-protein ligase that 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. DTX3L has a unique N-terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N-terminus and further enhance self-ubiquitination.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 19923717 556 KEKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSYGIQKGNQP 611
Cdd:cd16712   1 QEEDECPICMDRISNKKVLPKCKHVFCAACIDKAMKYKPVCPVCGTIYGVIKGNQP 56

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 19923717    561 CVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPI-CPTC 599
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19923717 542 LKGSVSSEASELDKkekGI-CVICM-DTISNKK--VLPkCKHEFCAPCINKAM-SYKPICPTCQT 601
Cdd:COG5540 309 LKPLSIERAVEADK---GVeCAICMsNFIKNDRlrVLP-CDHRFHVGCVDKWLlGYSNKCPVCRT 369

Domain found at the C-terminus of deltex-like; The deltex family of proteins is involved in the regulation of Notch signaling, and therefore may play roles in cell-to-cell communications that regulate mechanisms determining cell fate. They have a central RING-type zinc finger domain and contain a C-terminal domain, described here, that is also found in other domain architectures. Deltex-1 (DTX1) contains a RING finger and two WWE domains, indicating that it may be an E3 ubiquitin ligase. Human deltex 3-like, which contains an additional N-terminal domain (presumably with ubiquitin ligase activity) is also described as E3 ubiquitin-protein ligase DTX3L, B-lymphoma- and BAL-associated protein (BBAP), or rhysin-2. DTX3L mediates monoubiquitination of K91 of histone H4 in response to DNA damage.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923717 608 GNQPEGSMVFTVSRDSLPGYESFGTIVITYSMKAGIQTEEHPNPGKRYPGIQRTAYLPDNKEGRKVLKLLYRAFDQKLIF 687
Cdd:cd09633   1 GNQPPGTMTYHVIDTSLPGYEGCGTIVIVYNIPSGIQGPEHPGPGKPYRGTPRIAYLPDNEEGRKVLRLLKKAFDRRLIF 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 19923717 688 TVGYSRVLGVSDVITWNDIHHKTSRFGGPEMYGYPDPSYLKRVKEELKAKG 738
Cdd:cd09633  81 TVGTSVTTGREDVVVWNGIHHKTSLTGGPSGHGYPDPTYLDRVLEELAAKG 131

RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), is a RING-domain E3 ubiquitin-protein ligase that 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. DTX3L has a unique N-terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N-terminus and further enhance self-ubiquitination.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 19923717 556 KEKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSYGIQKGNQP 611
Cdd:cd16712   1 QEEDECPICMDRISNKKVLPKCKHVFCAACIDKAMKYKPVCPVCGTIYGVIKGNQP 56

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 19923717 561 CVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSYGIQKGNQP 611
Cdd:cd16711   4 CPICLGEIQNKKTLDKCKHSFCEDCITRALQVKKACPMCGEFYGQLIGNQP 54

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 19923717 560 ICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTCQT 601
Cdd:cd23130   2 VCPICLDDPEDEAITLPCLHQFCYTCILRWLQTSPTCPLCKT 43

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 19923717 561 CVICMDTISNKK-VLPKCKHEFCAPCINKAMSYKPICPTCQTSY 603
Cdd:cd16574   4 CPICLDRFENEKaFLDGCFHAFCFTCILEWSKVKNECPLCKQPF 47

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 19923717 561 CVICMDTISNKKVLPKCKHEFCAPCINKAM-SYKPICPTCQT 601
Cdd:cd16531   4 CPICLGIIKNTMTVKECLHRFCAECIEKALrLGNKECPTCRK 45

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 19923717 561 CVICMDTISNKKVLPkCKHEFCAPCINKAMSYKPICPTCQTS 602
Cdd:cd16514   4 CSLCLRLLYEPVTTP-CGHTFCRACLERCLDHSPKCPLCRTS 44

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 19923717 557 EKGICVICM---DTISNKKVLPkCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd16472   1 DQTQCVVCMcdyEKRQLLRVLP-CSHEFHAKCIDKWLKTNRTCPIC 45

RNA recognition motif 1 and 2 in poly [ADP-ribose] polymerase PARP-10, RNA recognition motif 2 in PARP-14, RNA recognition motif in N-myc-interactor (Nmi), interferon-induced 35 kDa protein (IFP 35), RNA-binding protein 43 (RBM43) and similar proteins; This subfamily corresponds to the RRM1 and RRM2 of PARP-10, RRM2 of PARP-14, RRM of N-myc-interactor (Nmi), interferon-induced 35 kDa protein (IFP 35) and RNA-binding protein 43 (RBM43). PARP-10 is a novel oncoprotein c-Myc-interacting protein with poly(ADP-ribose) polymerase activity. It is localized to the nuclear and cytoplasmic compartments. In addition to PARP activity, PARP-10 is also involved in the control of cell proliferation by inhibiting c-Myc- and E1A-mediated cotransformation of primary cells. PARP-10 may also play a role in nuclear processes including the regulation of chromatin, gene transcription, and nuclear/cytoplasmic transport. PARP-10 contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two overlapping C-terminal domains composed of a glycine-rich region and a region with homology to catalytic domains of PARP enzymes (PARP domain). In addition, PARP-10 contains two ubiquitin-interacting motifs (UIM). PARP-14, also termed aggressive lymphoma protein 2, is a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs. Like PARP-10, PARP-14 also includes two RRMs at the N-terminus. Nmi, also termed N-myc and STAT interactor, is an interferon inducible protein that interacts with c-Myc, N-Myc, Max and c-Fos, and other transcription factors containing bHLH-ZIP, bHLH or ZIP domains. Besides binding Myc proteins, Nmi also associates with all the Stat family of transcription factors except Stat2. In response to cytokine (e.g. IL-2 and IFN-gamma) stimulation, Nmi can enhance Stat-mediated transcriptional activity through recruiting the Stat1 and Stat5 transcriptional coactivators, CREB-binding protein (CBP) and p300. IFP 35 is an interferon-induced leucine zipper protein that can specifically form homodimers. Distinct from known bZIP proteins, IFP 35 lacks a basic domain critical for DNA binding. In addition, IFP 35 may negatively regulate other bZIP transcription factors by protein-protein interaction. For instance, it can form heterodimers with B-ATF, a member of the AP1 transcription factor family. Both Nmi and IFP35 harbor one RRM. RBM43 is a putative RNA-binding protein containing one RRM, but its biological function remains unclear.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 19923717  25 KLESYFQSSKSSGGGecTVSTQEHEAPGTFRVEFSERAAKERVLKKGEHQI 75
Cdd:cd12301  17 KLELYFENSRSGGGD--VEDVEYLGEKGSAVVTFKDHKVAQRVLAQKKHPL 65

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 19923717 560 ICVICMDTI--------SNKKVLPKCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd23117   6 DCVICMSDIelpstnsvRRDYMVTPCNHIFHTNCLERWMDIKLECPTC 53

RING finger, H2 subclass, found in Arabidopsis thaliana protein ABA INSENSITIVE RING PROTEIN 1 (AIRP1) and similar proteins; This subfamily includes Arabidopsis thaliana AIRP1 and RING-H2 finger B1a (RHB1A). AIRP1, also known as RING-type E3 ubiquitin transferase AIRP1, possesses E3 ubiquitin-protein ligase activity in vitro when associated with the E2 enzyme UBC8. It plays combinatory roles with AIRP2 in the positive regulation of the abscisic acid-mediated drought stress response. RHB1A is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 19923717 557 EKGICVICMD--TISNKKVLPKCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd23116   1 DEDVCPTCLEgyTEENPKLLTKCGHHFHLACIYEWMERSERCPVC 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 19923717 561 CVICMDTISNKkVLPKCKHEFCAPCINK---AMSYKPICPTCQ 600
Cdd:cd16745   3 CNICLDLAQDP-VVTLCGHLFCWPCLHKwlrRQSSQPECPVCK 44

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 19923717 557 EKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPI-CPTCQTSYGIQKG 608
Cdd:cd16544   1 AELTCPVCQEVLKDPVELPPCRHIFCKACILLALRSSGArCPLCRGPVGKTER 53

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19923717 542 LKGSVSSEASELDKkekGI-CVICM-DTISNKK--VLPkCKHEFCAPCINKAM-SYKPICPTCQT 601
Cdd:COG5540 309 LKPLSIERAVEADK---GVeCAICMsNFIKNDRlrVLP-CDHRFHVGCVDKWLlGYSNKCPVCRT 369

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 19923717 556 KEKGICVICMDTISNKKVLPkCKHEFCAPCINKA-MSYK---PICPTCQTSY 603
Cdd:cd16597   3 EEELTCSICLELFKDPVTLP-CGHNFCGVCIEKTwDSQHgseYSCPQCRATF 53

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 19923717 561 CVICMDTISNK---KVLPkCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd16454   2 CAICLEEFKEGekvRVLP-CNHLFHKDCIDPWLEQHNTCPLC 42

RING finger, HC subclass, found in RING finger protein 185 (RNF185) and similar proteins; RNF185 is an E3 ubiquitin-protein ligase of endoplasmic reticulum-associated degradation (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR). It controls the degradation of CFTR and CFTR F508del allele in a RING- and proteasome-dependent manner, but does not control that of other classical ERAD model substrates. It also negatively regulates osteogenic differentiation by targeting dishevelled2 (Dvl2), a key mediator of the Wnt signaling pathway, for degradation. Moreover, RNF185 regulates selective mitochondrial autophagy through interaction with the Bcl-2 family protein BNIP1. It also plays an important role in cell adhesion and migration through the modulation of cell migration by ubiquitinating paxillin. RNF185 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 19923717 561 CVICMDTiSNKKVLPKCKHEFCAPCINKAMSYKP---ICPTCQTS 602
Cdd:cd16744   3 CNICLDT-AKDAVVSLCGHLFCWPCLHQWLETRPnrqVCPVCKAG 46

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
                ....*....|....*....|....*....|....*....|...
gi 19923717 561 CVICMDTIsNKKVLPKCKHEFCAPCINKAMSYKPICPTCQTSY 603
Cdd:cd23146   7 CPICLKLL-NRPVLLPCDHIFCSSCITDSTKVGSDCPVCKLPY 48

RING finger, HC subclass, found in really interesting new gene 2 protein (RING2) and similar proteins; RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. RING2 is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. The enzymatic activity of RING2 is enhanced by the interaction with BMI1/PCGF4, and it is dispensable for early embryonic development and much of the gene repression activity of PRC1. Moreover, RING2 plays a key role in terminating neural precursor cell (NPC)-mediated production of subcerebral projection neurons (SCPNs) during neocortical development. It also plays a critical role in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusions. Furthermore, RING2 is essential for expansion of hepatic stem/progenitor cells. It promotes hepatic stem/progenitor cell expansion through simultaneous suppression of cyclin-dependent kinase inhibitors (CDKIs) Cdkn1a and Cdkn2a, known negative regulators of cell proliferation. RING2 also negatively regulates p53 expression through directly binding with both p53 and MDM2 and promoting MDM2-mediated p53 ubiquitination in selective cancer cell types to stimulate tumor development. RING2 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19923717 560 ICVICMDTISNKKVLPKCKHEFCAPCINKAM-SYKPICPTCQTSYGIQKGNQPEGSMVFTVSR 621
Cdd:cd16740  14 MCPICLDMLKNTMTTKECLHRFCADCIITALrSGNKECPTCRKKLVSKRSLRPDPNFDALISK 76

RING finger, HC subclass, found in Dictyostelium discoideum Ras guanine nucleotide exchange factor O (RasGEFO) and similar proteins; RasGEFO, also known as RasGEF domain-containing protein O, functions as a Ras guanine-nucleotide exchange factor (RasGEFs), activating Ras by catalyzing the replacement of GDP with GTP. RasGEFs are particularly important for signaling in development and chemotaxis in many organisms, including Dictyostelium. RasGEFO contains a C3HC4-type RING-HC finger that may be responsible for E3 ubiquitin ligase activity.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 19923717 561 CVICMDTISNKKVLPKCKHEFCAPCINKAMSyKPICPTCQTSYGIQKG 608
Cdd:cd16507  12 CGICQNLFKDPNTLIPCGHAFCLDCLTTNAS-IKNCIQCKVEYTTYIP 58

RING finger, HC subclass, found in makorin-4 (MKRN4) and similar proteins; MKRN4, also known as makorin RING finger protein pseudogene 4, makorin RING finger protein pseudogene 5, RING finger protein 64 (RNF64), zinc finger protein 127-Xp (ZNF127-Xp), or zinc finger protein 127-like 1, is a new divergent member of the makorin protein family in vertebrates. It may have an ancestral gonad-specific function and maternal embryonic expression before duplication in vertebrates. MKRN4 contains typical arrays of one to four C3H1-type zinc fingers, a motif rich in Cys and His residues (CH) and a C3HC4-type RING-HC finger. The RING-HC finger of mammalian MKRN4 shows high sequence similarity with that of MKRN3, and is not included in this model.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 19923717 561 CVICMDTISNKK--------VLPKCKHEFCAPCINKAMSYKPI-------CPTCQTS 602
Cdd:cd16732   4 CGICMDKVYEKAhakervfgILPNCNHAFCVGCIKKWRKSKDFqnevikaCPQCRVK 60

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 19923717 555 KKEKGICVICMDTISNK---KVLPkCKHEFCAPCINKAMSYKPICPTCQ 600
Cdd:cd16680   4 QSEQTLCVVCFSDFESRqllRVLP-CNHEFHTKCVDKWLKTNRTCPICR 51

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 19923717 561 CVICMDTISnKKVLPKCKHEFCAPCINKAMS--YKPICPTCQTSYG 604
Cdd:cd23132   5 CCICLDLLY-KPVVLECGHVFCFWCVHRCMNgyDESHCPLCRRPYD 49

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 19923717 557 EKGICVICMDTISNKKVLPkCKHEFCAPCINKAM----SYKPI---CPTC 599
Cdd:cd16581   1 EELTCSICYNIFDDPKILP-CSHTFCKNCLEKLLaasgYYLLAslkCPTC 49

RING finger, H2 subclass, found in Arabidopsis thaliana protein SUGAR INSENSITIVE 3 (SIS3) and similar proteins; SIS3 is an E3 ubiquitin-protein ligase that acts as a positive regulator of sugar signaling during early seedling development. SIS3 contains a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 19923717 561 CVICMDTISNK---KVLPkCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd23118   3 CTICLEDFEDGeklRVLP-CQHQFHSECVDQWLRRNPKCPVC 43

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
                  ....*....|....*....|....*....|....*....|..
gi 19923717   561 CVICMDTISNKkVLPKCKHEFCAPCINKAMSYKPICPTCQTS 602
Cdd:TIGR00599  29 CHICKDFFDVP-VLTSCSHTFCSLCIRRCLSNQPKCPLCRAE 69

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
                ....*....|....*....|....*....|....*....|....*
gi 19923717 561 CVICMDTISNKKVLPkCKHEFC-APCINKAMSY---KPICPTCQT 601
Cdd:cd16524   8 CPICLDRYRRPKLLP-CQHTFClSPCLEGLVDYvtrKLKCPECRA 51

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 19923717 561 CVICMDTISNKKVLPkCKHEFCAPCINKAM---SYKPICPTCQ 600
Cdd:cd16551   4 CAGCLEVPVEPATLP-CGHTLCRGCANRALdaaEAGPTCPRCR 45

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, 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). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 19923717 561 CVICMDtISNKKVLPKCKHEFCAPCINKAM-SYKPICPTCQT 601
Cdd:cd16542   4 CAVCLE-VLHQPVRTRCGHVFCRPCIATSLrNNTWTCPYCRA 44

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 19923717 560 ICVICMDTISNK---KVLPKCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd16461   1 ECAICLSDYENGeelRRLPECKHAFHKECIDEWLKSNSTCPLC 43

RNA recognition motif 1 and 2 in poly [ADP-ribose] polymerase 10 (PARP-10) and similar proteins; This subgroup corresponds to the RRM1 and RRM2 of PARP-10, a novel oncoprotein c-Myc-interacting protein with poly(ADP-ribose) polymerase activity. It is localized to the nuclear and cytoplasmic compartments. In addition to the PARP activity, PARP-10 is also involved in the control of cell proliferation by inhibiting c-Myc- and E1A-mediated cotransformation of primary cells. PARP-10 may play a role in nuclear processes including the regulation of chromatin, gene transcription, and nuclear/cytoplasmic transport. It contains two N-terminal RNA recognition motifs (RRMs), also termed RBDs (RNA binding domains) or RNPs (ribonucleoprotein domains), two overlapping C-terminal domains composed of a glycine-rich region and a region with homology to catalytic domains of PARP enzymes (PARP domain). In addition, PARP-10 contains two ubiquitin-interacting motifs (UIM).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 19923717  26 LESYFQSSKSSGGGECTVSTQEheaPGTFRVEFSERAAKERVLKKGEHQI 75
Cdd:cd12547  17 LELYFENKRRSGGGEVESIQRR---GDKAFITFEDPSVAERVLARAEHVL 63

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 19923717 560 ICVICMDTISNKKVLPKCKHEFCAPCINKAMSY-KPICPTCQTS 602
Cdd:cd16503   4 TCSICQDLLHDCVSLQPCMHNFCAACYSDWMERsNTECPTCRAT 47

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
                ....*....|....*....|....*....|....*....|....*...
gi 19923717 556 KEKGICVICMDTISNKkVLPKCKHEFCAPCINKAMSYKpiCPTCQTSY 603
Cdd:cd16602   1 QEEAVCAICLDYFKDP-VSIGCGHNFCRVCVTQLWGFT--CPQCRKSF 45

RING finger, HC subclass, found in tripartite motif-containing protein 3 (TRIM3); TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It functions as a tumor suppressor that regulates asymmetric cell division in glioblastoma. It binds to the cdk inhibitor p21(WAF1/CIP1) and regulates its availability that promotes cyclin D1-cdk4 nuclear accumulation. Moreover, TRIM3 plays an important role in the central nervous system (CNS). It is encoded by the gene BERP (brain-expressed RING finger protein), a unique p53-regulated gene that modulates seizure susceptibility and GABAAR cell surface expression. Furthermore, TRIM3 mediates activity-dependent turnover of postsynaptic density (PSD) scaffold proteins GKAP/SAPAP1 and is a negative regulator of dendritic spine morphology. In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. It also regulates the motility of the kinesin superfamily protein KIF21B. TRIM3 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 19923717 560 ICVICMDTISNKKVLPkCKHEFCAPCINK---AMSYKPICPTCQ 600
Cdd:cd16768   6 VCSICLDRYHNPKVLP-CLHTFCERCLQNyipPQSLTLSCPVCR 48

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
                ....*....|....*....|....*....|....*....|.
gi 19923717 561 CVICMDTIsNKKVLPKCKHEFCAPCINKAMSYKPICPTCQT 601
Cdd:cd23148   6 CHICKDLL-KAPMRTPCNHTFCSFCIRTHLNNDARCPLCKA 45

RING finger, HC subclass, found in tripartite motif-containing protein TRIM2, TRIM3, and similar proteins; TRIM2, also known as RING finger protein 86 (RNF86), is an E3 ubiquitin-protein ligase that ubiquitinates the neurofilament light chain, a component of the intermediate filament in axons. Loss of function of TRIM2 results in early-onset axonal neuropathy. TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It also plays an important role in the central nervous system (CNS). In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. Both TRIM2 and TRIM3 belong 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 19923717 560 ICVICMDTISNKKVLPkCKHEFCAPCINKAM---SYKPICPTCQ 600
Cdd:cd16586   3 SCGICLERYKNPKVLP-CLHTFCERCLQNYIpaeSLSLSCPVCR 45

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 19923717 554 DKKEKGICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd16733   5 DLNEHIVCYLCAGYFIDATTITECLHTFCKSCIVKYLQTSKYCPMC 50

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 19923717 560 ICVICMDTISNKKVLPKCKHEFCAPCINKAMSYKPICPTC 599
Cdd:cd16525   2 TCSLCKGYLIDATTITECLHSFCKSCIVRHLETSKNCPVC 41

RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This family includes uncharacterized protein RNF215 and similar proteins. Although its biological function remains unclear, RNF215 shares high sequence similarity with PA-TM-RING ubiquitin ligases, which have been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 19923717 561 CVICMDTISNK---KVLPkCKHEFCAPCINKAMSYKPICPTCQ 600
Cdd:cd16670   3 CAVCLDQFYKNqclRVLP-CLHEFHRDCVDPWLLLQQTCPLCK 44

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 19923717 560 ICVICMDTISNKKVLPkCKHEFCAPCINKAMSYKPI---CPTCQTSY 603
Cdd:cd16543   5 TCSICLDLLKDPVTIP-CGHSFCMNCITLLWDRKQGvpsCPQCRESF 50