Deltex C-terminal domain; This is the C-terminal domains found in members of the Deltex family of proteins which comprises five members (DTX1, 2, 3, 4, and 3L). This conserved C-terminal region of about 150 residues of the Deltex family, is preceded by a RING E3 ligase domain in four of the members. Crystal structure of the Deltex C-terminal (DTC) domain reveals a fold composed of a central beta-sheet lined with two long parallel alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2007539490 617 KGNQPEGTMAHTIQKDSLPGYEGCGTIVIQYSFGDGIQTKEHPNPGKAYSGTCRVAYLPDNAEGRKVLHLLRKAFDQKLI 696
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYSGTPRTAYLPDNEEGRKVLKLLKRAFDQRLI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2007539490 697 FTVGESRVLGISNVITWNDIHHKTAKFGGPSNFGYPDPDYLKRVKEELKSKGI 749
Cdd:pfam18102  81 FTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

RNA recognition motif (RRM) superfamily; RRM, also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), is a highly abundant domain in eukaryotes found in proteins involved in post-transcriptional gene expression processes including mRNA and rRNA processing, RNA export, and RNA stability. This domain is 90 amino acids in length and consists of a four-stranded beta-sheet packed against two alpha-helices. RRM usually interacts with ssRNA, but is also known to interact with ssDNA as well as proteins. RRM binds a variable number of nucleotides, ranging from two to eight. The active site includes three aromatic side-chains located within the conserved RNP1 and RNP2 motifs of the domain. The RRM domain is found in a variety heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing, and protein components of small nuclear ribonucleoproteins (snRNPs).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2007539490   8 PSPLLVRL---PESIPRAHMKLEIYFQS-RASGGGECSVHPVGPGaPDTFEVKFLEKADKENVLKRGKHKLLVDDKSVPI 83
Cdd:cd12300     1 PFPLLVEGdwdPSPPKKLKNKLEKYFQSkKRSGGGECTVETEGPS-PQTARVSFVNEEVRERVLEKKEHEILQGEGTVRL 79

                  ..
gi 2007539490  84 VL 85
Cdd:cd12300    80 TV 81

Deltex C-terminal domain; This is the C-terminal domains found in members of the Deltex family of proteins which comprises five members (DTX1, 2, 3, 4, and 3L). This conserved C-terminal region of about 150 residues of the Deltex family, is preceded by a RING E3 ligase domain in four of the members. Crystal structure of the Deltex C-terminal (DTC) domain reveals a fold composed of a central beta-sheet lined with two long parallel alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2007539490 617 KGNQPEGTMAHTIQKDSLPGYEGCGTIVIQYSFGDGIQTKEHPNPGKAYSGTCRVAYLPDNAEGRKVLHLLRKAFDQKLI 696
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYSGTPRTAYLPDNEEGRKVLKLLKRAFDQRLI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2007539490 697 FTVGESRVLGISNVITWNDIHHKTAKFGGPSNFGYPDPDYLKRVKEELKSKGI 749
Cdd:pfam18102  81 FTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

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 2007539490 566 KDEDNCVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVCLTPYGVQKGNQP 621
Cdd:cd16712     1 QEEDECPICMDRISNKKVLPKCKHVFCAACIDKAMKYKPVCPVCGTIYGVIKGNQP 56

Zinc finger, C3HC4 type (RING finger);

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:pfam13923   2 CPICMDMLKDPSTTTPCGHVFCQDCILRALEASNECPLC 40

N1R/p28-like protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2007539490 566 KDEDnCVICMDTIRNKQ-------VLPKCKHEFCSSCISKAMSFKPVCPVCLTPY 613
Cdd:PHA02929  173 KDKE-CAICMEKVYDKEiknmyfgILSNCNHVFCIECIDIWKKEKNTCPVCRTPF 226

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2007539490 543 NDSDVALLSFGSSASSPTAsKGNKDEDNCVICMDTIRNKqVLPKCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:COG5432     1 NELDATDPSDWNQTKIPSL-KGLDSMLRCRICDCRISIP-CETTCGHTFCSLCIRRHLGTQPFCPVCRED 68

Deltex C-terminal domain; This is the C-terminal domains found in members of the Deltex family of proteins which comprises five members (DTX1, 2, 3, 4, and 3L). This conserved C-terminal region of about 150 residues of the Deltex family, is preceded by a RING E3 ligase domain in four of the members. Crystal structure of the Deltex C-terminal (DTC) domain reveals a fold composed of a central beta-sheet lined with two long parallel alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2007539490 617 KGNQPEGTMAHTIQKDSLPGYEGCGTIVIQYSFGDGIQTKEHPNPGKAYSGTCRVAYLPDNAEGRKVLHLLRKAFDQKLI 696
Cdd:pfam18102   1 TGNQPDGTMTVSTIPTSLPGYENCGTIVITYNIPGGIQGPEHPNPGKPYSGTPRTAYLPDNEEGRKVLKLLKRAFDQRLI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2007539490 697 FTVGESRVLGISNVITWNDIHHKTAKFGGPSNFGYPDPDYLKRVKEELKSKGI 749
Cdd:pfam18102  81 FTVGTSRTTGASNVVTWNDIHHKTSISGGPTGFGYPDPDYLKRVKEELAAKGI 133

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 2007539490 566 KDEDNCVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVCLTPYGVQKGNQP 621
Cdd:cd16712     1 QEEDECPICMDRISNKKVLPKCKHVFCAACIDKAMKYKPVCPVCGTIYGVIKGNQP 56

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 2007539490   8 PSPLLVRL---PESIPRAHMKLEIYFQS-RASGGGECSVHPVGPGaPDTFEVKFLEKADKENVLKRGKHKLLVDDKSVPI 83
Cdd:cd12300     1 PFPLLVEGdwdPSPPKKLKNKLEKYFQSkKRSGGGECTVETEGPS-PQTARVSFVNEEVRERVLEKKEHEILQGEGTVRL 79

                  ..
gi 2007539490  84 VL 85
Cdd:cd12300    80 TV 81

RING finger, HC subclass, found in postreplication repair protein RAD18 and similar proteins; RAD18, also known as HR18 or RING finger protein 73 (RNF73), is an E3 ubiquitin-protein ligase involved in post replication repair of UV-damaged DNA via its recruitment to stalled replication forks. It associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on K164. It also interacts with another E2 ubiquitin conjugating enzyme RAD6 to form a complex that monoubiquitinates proliferating cell nuclear antigen at stalled replication forks in DNA translesion synthesis. Moreover, Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins. It can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after ionizing radiation (IR) exposure. RAD18 contains a C3HC4-type RING-HC finger, a ubiquitin-binding zinc finger domain (UBZ), a SAP (SAF-A/B, Acinus and PIAS) domain, and a RAD6-binding domain (R6BD).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:cd16529     7 CPICFEYFNTAMMITQCSHNYCSLCIRRFLSYKTQCPTCRAA 48

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 2007539490 568 EDNCVICMDTIRN-KQVLPKCKHEFCSSCISKAMSFKPVCPVCLTPY 613
Cdd:cd16574     1 DSSCPICLDRFENeKAFLDGCFHAFCFTCILEWSKVKNECPLCKQPF 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 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAMSF-KPVCPVCLTP 612
Cdd:cd16531     4 CPICLGIIKNTMTVKECLHRFCAECIEKALRLgNKECPTCRKH 46

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2007539490 571 CVICMDTIRNKQVLPkCKHEFCSSCISKAM-SFKPVCPVC 609
Cdd:cd16449     3 CPICLERLKDPVLLP-CGHVFCRECIRRLLeSGSIKCPIC 41

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2007539490 567 DEDnCVICMDTIRNKqVLPKCKHEFCSSCISKAM-SFKPVCPVC 609
Cdd:cd16509     3 DEE-CAICLDSLTNP-VITPCAHVFCRRCICEVIqREKAKCPMC 44

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 2007539490 567 DEDNCVICMD--TIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd23116     1 DEDVCPTCLEgyTEENPKLLTKCGHHFHLACIYEWMERSERCPVC 45

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2007539490 569 DNCVICMDTIRNKQVLP--KCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:cd16469     1 DTCAVCLEEFKLKEELGvcPCGHAFHTKCLKKWLEVRNSCPICKSP 46

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 2007539490 567 DEDNCVICMDTIRNKQ---VLPkCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16472     1 DQTQCVVCMCDYEKRQllrVLP-CSHEFHAKCIDKWLKTNRTCPIC 45

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 2007539490 568 EDNCVICMDTIRNKQVLPkCKHEFCSSCISKAMSFKPVCPVCLTPY 613
Cdd:cd23147     4 ELKCPICLSLFKSAANLS-CNHCFCAGCIGESLKLSAICPVCKIPA 48

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
                  ....*....|....*....|....*....|....*....
gi 2007539490 571 CVICMDTIRNKQVlPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16504     5 CPICFDIIKEAFV-TKCGHSFCYKCIVKHLEQKNRCPKC 42

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2007539490 571 CVICMDTIRNKQ----VLPKCKHEFCSSCI----SKAMSFKPV---CPVC 609
Cdd:cd16521     3 CGICMEVVLEKErrfgILSNCNHVFCLECIrewrSSKDFENSIvrsCPIC 52

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 2007539490 567 DEDNCVICMDTIRNKQVLPkCKHEFCSSCISKAMSFKPVCPVCLT 611
Cdd:cd16561     1 GEQECSICLEDLNDPVKLP-CDHVFCEECIRQWLPGQMSCPLCRT 44

zf-RING of BARD1-type protein; The RING domain of the breast and ovarian cancer tumour-suppressor BRCA1 interacts with multiple cognate proteins, including the RING protein BARD1. Proper function of the BRCA1 RING domain is critical, as evidenced by the many cancer-predisposing mutations found within this domain. A dimer is formed between the RING domains of BRCA1 and BARD1. The BRCA1-BARD1 structure provides a model for its ubiquitin ligase activity, illustrates how the BRCA1 RING domain can be involved in associations with multiple protein partners and provides a framework for understanding cancer-causing mutations at the molecular level. The corresponding BRCA1-RING domain is on family zf-C3HC4_2, pfam13923.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAmsFKPVCPVCLTPYGVQ 616
Cdd:pfam14835  10 CSRCTNILREPVCLGGCEHIFCSNCVSDC--IGTGCPVCYTPAWIQ 53

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
                  ....*....|....*....|....*....|....*....|....*
gi 2007539490 571 CVICMDTIRNKqVLPKCKHEFCSSCISKAMSFK---PVCPVCLTP 612
Cdd:cd16498    19 CPICLELLKEP-VSTKCDHQFCRFCILKLLQKKkkpAPCPLCKKS 62

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2007539490 543 NDSDVALLSFGSSASSPTAsKGNKDEDNCVICMDTIRNKqVLPKCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:COG5432     1 NELDATDPSDWNQTKIPSL-KGLDSMLRCRICDCRISIP-CETTCGHTFCSLCIRRHLGTQPFCPVCRED 68

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2007539490 568 EDNCVICMDTIRNKQVLPKCKHEFCSSCISKAMSF------KPVCPVCLTPYGVQ 616
Cdd:cd16572     4 ENECPICAEEPISELALTRCWHSACKDCLLDHIEFqkskneVPLCPTCRQPINEQ 58

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 2007539490 571 CVICMDTI--------RNKQVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd23117     7 CVICMSDIelpstnsvRRDYMVTPCNHIFHTNCLERWMDIKLECPTC 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 2007539490 571 CVICMDTIRNKQ---VLPkCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16454     2 CAICLEEFKEGEkvrVLP-CNHLFHKDCIDPWLEQHNTCPLC 42

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2007539490 571 CVICM-DTIRNKQ--VLPkCKHEFCSSCISKAM-SFKPVCPVCLTP 612
Cdd:COG5540   326 CAICMsNFIKNDRlrVLP-CDHRFHVGCVDKWLlGYSNKCPVCRTA 370

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
                  ....*....|....*....|....*....|....*....
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16525     3 CSLCKGYLIDATTITECLHSFCKSCIVRHLETSKNCPVC 41

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 2007539490 571 CVICMDTIrNKQVLPKCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:cd23148     6 CHICKDLL-KAPMRTPCNHTFCSFCIRTHLNNDARCPLCKAE 46

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2007539490 565 NKDEDNCVICM------DTIRNkqvLPkCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd23115     1 DEDNERCVICRleyeegEDLLT---LP-CKHCYHSECIQQWLQINKVCPVC 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 2007539490 567 DEDNCVICMDTIRNKQVLPKCKHEFCSSCISKAM-SFKPVCPVC 609
Cdd:cd16620     2 DELKCPICKDLMKDAVLTPCCGNSFCDECIRTALlEEDFTCPTC 45

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 2007539490 571 CVICMDTIRNKqVLPKCKHEFCSSCISKAMSFKP---VCPVC 609
Cdd:cd16744     3 CNICLDTAKDA-VVSLCGHLFCWPCLHQWLETRPnrqVCPVC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:cd23143     4 CVICSEPQIDTFLLSSCGHIYCWECFTEFIEKRHMCPSCRFP 45

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1), RING finger protein 157 (RNF157) and similar proteins; MGRN1, also known as RING finger protein 156 (RNF156), is a cytosolic E3 ubiquitin-protein ligase that inhibits signaling through the G protein-coupled melanocortin receptors-1 (MC1R), -2 (MC2R) and -4 (MC4R) via ubiquitylation-dependent and -independent processes. It suppresses chaperone-associated misfolded protein aggregation and toxicity. MGRN1 interacts with cytosolic prion proteins (PrPs) that are linked with neurodegeneration. It also interacts with expanded polyglutamine proteins, and suppresses misfolded polyglutamine aggregation and cytotoxicity. Moreover, MGRN1 inhibits melanocortin receptor signaling by competition with Galphas, suggesting a novel pathway for melanocortin signaling from the cell surface to the nucleus. MGRN1 also interacts with and ubiquitylates TSG101, a key component of the endosomal sorting complex required for transport (ESCRT)-I, and regulates endosomal trafficking. A null mutation in the gene encoding MGRN1 causes spongiform neurodegeneration, suggesting a link between dysregulation of endosomal trafficking and spongiform neurodegeneration. RNF157 is a cytoplasmic E3 ubiquitin ligase predominantly expressed in the brain. It is a homolog of the E3 ligase mahogunin ring finger-1 (MGRN1). In cultured neurons, it promotes neuronal survival in an E3 ligase-dependent manner. In contrast, it supports growth and maintenance of dendrites independent of its E3 ligase activity. RNF157 interacts with and ubiquitinates the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65), which regulates neuronal survival, but not dendritic growth downstream of RNF157. The nuclear localization of APBB1 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. Both MGRN1 and RNF157 contain a modified C3HC5-type RING-HC finger, and a functionally uncharacterized region, known as domain associated with RING2 (DAR2), N-terminal to the RING finger. The C3HC5-type RING-HC finger is distinguished from typical C3HC4 RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2007539490 569 DNCVICMDTIRNKQVLPkCKHE-FCSSCISKAMSFKPVCPVC 609
Cdd:cd16789     1 SECVICLSDPRDTAVLP-CRHLcLCSDCAEVLRYQSNKCPIC 41

RING finger, HC subclass, found in really interesting new gene 1 protein (RING1) and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), was identified as a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. It is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase that transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING1 interacts with multiple PcG proteins and displays tumorigenic activity. It also shows zinc-dependent DNA binding activity. Moreover, RING1 inhibits transactivation of the DNA-binding protein recombination signal binding protein-Jkappa (RBP-J) by Notch through interaction with the LIM domains of KyoT2. RING1 contains a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAM-SFKPVCPVC 609
Cdd:cd16739     6 CPICLDMLKNTMTTKECLHRFCSDCIVTALrSGNKECPTC 45

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2007539490 571 CVICMDTIRNKqVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16539     8 CFICRKPFKNP-VVTKCGHYFCEKCALKHYRKSKKCFVC 45

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 2007539490 571 CVICMDTIRNKQVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16563     3 CLICMDSYTMPLVSIQCWHVHCEECWLRTLGAKKLCPQC 41

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

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2007539490 571 CVICMDTIrNKQVLPKCKHEFCSSCISKAMSFKPVCPV 608
Cdd:cd16637     4 CHICLQPL-VEPLDTPCGHTFCYKCLTNYLKIQQCCPL 40

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 1 (XBAT31) and similar proteins; XBAT31, also called ankyrin repeat domain and RING finger-containing protein XBAT31, or RING-type E3 ubiquitin transferase XB31, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. XBAT31 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2007539490 566 KDEDNCVICMDTIRNKQVlPKCKHEFCSSCI---------SKAMSF--KPVCPVCLTP 612
Cdd:cd23144     4 SDEDVCCICFEHLCTIEI-KDCGHQMCATCAlklcchnkpNPSSSPprPPACPFCRQD 60

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2007539490 567 DEDNCVICMDTIRNKQVLPkCKHEFCSSCI----SKAMSFKPVCPVCLTPY 613
Cdd:cd16609     2 EELTCSICLGLYQDPVTLP-CQHSFCRACIedhwRQKDEGSFSCPECRAPF 51

RNA recognition motif in vertebrate RNA-binding protein 43 (RBM43); This subgroup corresponds to the RRM of RBM43, a putative RNA-binding protein containing one RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain). Although its biological function remains unclear, RBM43 shows high sequence homology to poly [ADP-ribose] polymerase 10 (PARP-10), which is a novel oncoprotein c-Myc-interacting protein with poly(ADP-ribose) polymerase activity.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2007539490  14 RLPESIPRAHM--KLEIYFQSRASGGGECSVHPVGPGAPDTFEVKFLEKADKENVLKRgKHKL 74
Cdd:cd12546     7 GLPDDLFEGALkdKLEIHFQRRKNGGGDVETVTYPTNTKGVAYVTFEEEEVAQNVLEK-EQVL 68

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 2007539490 571 CVICMDTIRNK---QVLPKCKHEFCSSCISKAMSFKPVCPVC 609
Cdd:cd16461     2 CAICLSDYENGeelRRLPECKHAFHKECIDEWLKSNSTCPLC 43

RING finger, HC subclass, found in Saccharomyces cerevisiae DNA repair protein RAD16, Schizosaccharomyces pombe rhp16, and similar proteins; Budding yeast RAD16, also known as ATP-dependent helicase RAD16, is encoded by a yeast excision repair gene homologous to the recombinational repair gene RAD54 and to the SNF2 gene involved in transcriptional activation. It is a component of the global genome repair (GGR) complex that promotes global genome nucleotide excision repair (GG-NER) by removing DNA damage from non-transcribing DNA. RAD16 is involved in differential repair of DNA after UV damage, and repairs preferentially the MAT-alpha locus compared with the HML-alpha locus. Fission yeast rhp16, also known as ATP-dependent helicase rhp16, is a RAD16 homolog. It is involved in GGR via nucleotide excision repair (NER), in conjunction with rhp7, after UV irradiation. Both RAD16 and rhp16 contain a C3HC4-type RING-HC finger, as well as a DEAD-like helicase domain and a helicase superfamily C-terminal domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 2007539490 571 CVICMDTIRNKqVLPKCKHEFCSSC----ISKAMSFKPVCPVCLTP 612
Cdd:cd16567     3 CGICHEEAEDP-VVARCHHVFCRACvkeyIESAPGGKVTCPTCHKP 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 2007539490 566 KDEDNCVICMDTIRNKqVLPKCKHEFCSSCISKAMSFkpVCPVC 609
Cdd:cd16602     1 QEEAVCAICLDYFKDP-VSIGCGHNFCRVCVTQLWGF--TCPQC 41

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

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                  ....*....|....*....|....*....|....*....|....
gi 2007539490 571 CVICMDTIRNKQVLP--KCKHEFCSSCISKAMSFKPVCPVCLTP 612
Cdd:cd16675     3 CAVCLEEFKPKDELGicPCKHAFHRKCLIKWLEVRKVCPLCNMP 46