RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 17533927 132 IECEICTLEFSSVVDNQIPRIL-QCGHSICQSCASKLAKN--CVILCPFCRNET 182
Cdd:cd23124   2 LECGICQQEYSADDPLLIPRILtECGHTICTNCAGTILGQssGSIFCPFDRIVT 55

VAMP-associated protein involved in inositol metabolism [Intracellular trafficking and secretion];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533927   8 LEVPPELVFSGPFDHVITTYMTLTNISQSPVCFLVKTTVPNSYCVRPNRGILNIGDSKQIEVMLQPLEKVP-PDAK-QHK 85
Cdd:COG5066   3 VEISPQTTFYVPLTNKSKEMFSVQNNSPEPVGFKVKTTAPKDYCVRPNMGLIEPMSTVEVEVILQGLTEEPaPDFKcRDK 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17533927  86 FLVQSC-VAPSIDVSDLESVWKNVKPDELTYNRLVVTFVDNTDSKSNIEC 134
Cdd:COG5066  83 FLIQSYrFDWRLSGSDFADHWTSSSKKPIWTRKIRCVYSEEEISKNVHEC 132

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 17533927    134 CEICTLEFSSVvdnqiPRILQCGHSICQSCASKLAKNCVILCPFC 178
Cdd:smart00184   1 CPICLEEYLKD-----PVILPCGHTFCRSCIRKWLESGNNTCPIC 40

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 17533927 136 ICTLEFSSVVDNQIPRILQCGHSICQSCASKLAKNCVIL--CPFCRNETNVSSV 187
Cdd:COG5109 338 ICPVLKELCTDENPPVMLECGHVISKEALSVLSQNGVLSfkCPYCPEMSKYENI 391

VAMP-associated protein involved in inositol metabolism [Intracellular trafficking and secretion];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17533927   8 LEVPPELVFSGPFDHVITTYMTLTNISQSPVCFLVKTTVPNSYCVRPNRGILNIGDSKQIEVMLQPLEKVP-PDAK-QHK 85
Cdd:COG5066   3 VEISPQTTFYVPLTNKSKEMFSVQNNSPEPVGFKVKTTAPKDYCVRPNMGLIEPMSTVEVEVILQGLTEEPaPDFKcRDK 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 17533927  86 FLVQSC-VAPSIDVSDLESVWKNVKPDELTYNRLVVTFVDNTDSKSNIEC 134
Cdd:COG5066  83 FLIQSYrFDWRLSGSDFADHWTSSSKKPIWTRKIRCVYSEEEISKNVHEC 132

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 17533927 133 ECEICTLEFSSvvDNQIPRILQCGHSICQSCASKLAKNC---VILCPFCR 179
Cdd:cd16587   2 ECPICLESFDE--GQLRPKLLHCGHTICEQCLEKLLASLsinGVRCPFCR 49

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 17533927    134 CEICTLEFSSVvdnqiPRILQCGHSICQSCASKLAKNCVILCPFC 178
Cdd:smart00184   1 CPICLEEYLKD-----PVILPCGHTFCRSCIRKWLESGNNTCPIC 40

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17533927 132 IECEICTLEFSsvVDNQIPRILQCGHSICQSCASKL-----AKNCVILCPFCRNET 182
Cdd:cd16555   2 LECKICYNRYD--LRQRRPKVLECCHRVCAKCLYKIvdlgdSSPSVLVCPFCRFET 55

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 17533927 132 IECEICTLEFSSVvDNQIPRILQCGHSICQSCASKLAKNCVIL--CPFCR 179
Cdd:cd16516   1 LECKVCFEKYSHQ-QEHRPRNLPCGHVLCRECVTALAHPRRSKleCPFCR 49

Modified RING finger, HC subclass (C3HC3D-type), found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a modified C3HC3D-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 17533927 132 IECEICTLEFSSVVDnQIPRILQCGHSICQSCASKLA-KNCVILCPFCR 179
Cdd:cd16645   2 LECGVCEDVFSLQGD-KVPRLLLCGHTVCHDCLTRLPlHGRAVRCPFDR 49

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 17533927 134 CEICTLEFSSVvdNQIPRILQCGHSICQSCASKLAKNcviLCPF 177
Cdd:cd16638   4 CPVCTNEFDGT--QRKPISLGCGHTVCKTCLSKLHRK---QCPF 42

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 17533927 129 KSNIECEICTLEFSSvvdnqiPRILQCGHSICQSCASKLAKNCVIlCPFCR 179
Cdd:cd23135   1 KQKLSCSICFSEIRS------GAILKCGHFFCLSCIASWLREKST-CPLCK 44

RING finger, HC subclass, found in RING finger protein RNF224 and similar proteins; RNF224 is uncharacterized C3HC4-type RING-HC finger-containing proteins. It may function as an E3 ubiquitin-protein ligase.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 17533927 132 IECEICtleFSSV-VDNQIPRILQCGHSICQSCASKL----AKNCVILCPFCRNET 182
Cdd:cd16565   1 LDCIIC---YSAYdLSTRLPRRLYCGHTFCQACLKRLdtviNEQRWIPCPQCRQNT 53

RING finger, HC subclass, found in radiation sensitivity protein 5 (RAD5) and similar proteins; RAD5, also known as revertibility protein 2 (REV2), or DNA repair protein RAD5, is a probable helicase, and a member of the UBC2/RAD6 epistasis group. It functions with the DNA repair protein RAD18 in error-free postreplication DNA repair. It is involved in the maintenance of wild-type rates of instability of simple repetitive sequences such as poly(GT) repeats. It may also be involved in maintaining a balance which acts in favor of error-prone non-homologous joining during DNA double-strand breaks repairs. It recruits the UBC13-MMS2 dimer to chromatin for DNA repair. RAD5 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 17533927 131 NIECEICT---LEFSSVVdnqiprILQCGHSICQSCAS-----KLAKNCVILCPFCRNETNVSSVASL 190
Cdd:cd23131   3 EVECSICTqepIEVGEVV------FTECGHSFCEDCLLeyiefQNKKKLDLKCPNCREPISKYRLLKL 64

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17533927 129 KSNIECEICTLEFSSVVdnqiprILQCGHSICQSCASKLAKNCV-ILCPFCRnetNVSSVASLPKNFALLQAI 200
Cdd:cd16599   2 KEELLCPICYEPFREAV------TLRCGHNFCKGCVSRSWERQPrAPCPVCK---EASSSDDLRTNHTLNNLV 65

RING finger, HC subclass, found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of the peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis by targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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 17533927 130 SNIECEICTLEFSSvvdnqiPRILQCGHSICQSCASKLAK---NCVILCPFCRNETNV 184
Cdd:cd16612   3 QDLSCPLCLKLFQS------PVTTECGHTFCQDCLSRVPKeedGGSTSCPTCQAPTKP 54

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 17533927 131 NIECEICtLEfssvVDNQiPRILQCGHSICQSCASKLAKNCVILCPFCR 179
Cdd:cd16542   1 NFDCAVC-LE----VLHQ-PVRTRCGHVFCRPCIATSLRNNTWTCPYCR 43

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 17533927 134 CEICTLEFSsvvDNQIPRILQCGHSICQSCASKLAKNCVILCPFC 178
Cdd:cd00162   1 CPICREEMN---DRRPVVLLSCGHTFSRSAIARWLEGSKQKCPFC 42

RING finger, HC subclass, found in SNF2 histone-linker PHD finger RING finger helicase (SHPRH) and similar proteins; SHPRH is a yeast RAD5 homolog found in mammals. It functions as an E3 ubiquitin-protein ligase that associates with proliferating cell nuclear antigen (PCNA), RAD18, and the ubiquitin-conjugating enzyme UBC13 (E2), and suppresses genomic instability by proliferating methyl methanesulfonate (MMS)-induced PCNA polyubiquitination. SHPRH contains a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a linker histone domain (H15), a PHD-finger, and a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA. This subfamily also includes tripartite motif-containing protein 15 (TRIM15). TRIM15, also known as RING finger protein 93 (RNF93), zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM15 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 SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 17533927 134 CEICT--LEFSSVVdnqipriLQCGHSICQSCASKLAKNCV------ILCPFCRNET 182
Cdd:cd16569   4 CPICArpLGKQWSV-------LPCGHCFCLECIAILIDQYAqsrrrsLKCPICRETT 53

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 17533927 130 SNIECEICtleFSsvvDNQIPRILQCGHSICQSCASKLAKNCV------ILCPFCR 179
Cdd:cd16581   1 EELTCSIC---YN---IFDDPKILPCSHTFCKNCLEKLLAASGyyllasLKCPTCR 50

RING finger, HC subclass, found in RING finger and SPRY domain-containing protein 1 (RSPRY1) and similar proteins; RSPRY1 is a hypothetical RING and SPRY domain-containing protein of unknown physiological function. Mutations in its corresponding gene RSPRY1 may associate with a distinct skeletal dysplasia syndrome. RSPRY1 contains a B30.2/SPRY domain and a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 17533927 137 CTLEFSSVVDNQIpriLQCGHS-ICQSCAsklakNCVILCPFCRNE 181
Cdd:cd16566   5 CTLCFDKVADTEL---RPCGHSgFCMECA-----LQLETCPLCRQP 42

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 17533927   133 ECEICTLEFSSVVdnqiprILQCGH-SICQSCASKLAKNCvILCPFCR 179
Cdd:pfam13920   4 LCVICLDRPRNVV------LLPCGHlCLCEECAERLLRKK-KKCPICR 44

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

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gi 17533927 134 CEICtLEFssVVDnqiPRILQCGHSICQSCASKL--AKNCVILCPFCR 179
Cdd:cd16594   8 CPIC-LDY--FTD---PVTLDCGHSFCRACIARCweEPETSASCPQCR 49

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 17533927 118 LVVTFVDNTDSKSNIeCEICT--LEFSSVVDnqiprilqCGHSICQSCASKLakncVIL-----CPFCRNET 182
Cdd:COG5236  49 LTTSSADDTDEENMN-CQICAgsTTYSARYP--------CGHQICHACAVRL----RALymqkgCPLCRTET 107