RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 82201575 145 EECCICMDGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16545   1 EECCICMDRKADLILPCAHSYCQKCIDKWSDRHRTCPICR 40

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 82201575 145 EECCICMDGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16545   1 EECCICMDRKADLILPCAHSYCQKCIDKWSDRHRTCPICR 40

N1R/p28-like protein; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 82201575  144 EEECCICMDGKADL--------ILP-CAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:PHA02929 174 DKECAICMEKVYDKeiknmyfgILSnCNHVFCIECIDIWKKEKNTCPVCR 223

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 82201575 124 SSEDTCQASMWMGRVKQLTDEE--------ECCICMDG--KAD--LILPCAHSFCQKCIDKW-SGQSRNCPVCRIQV 187
Cdd:COG5540 295 SSSEAIPTTTTKGSLKPLSIERaveadkgvECAICMSNfiKNDrlRVLPCDHRFHVGCVDKWlLGYSNKCPVCRTAI 371

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 82201575 145 EECCICMDGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16545   1 EECCICMDRKADLILPCAHSYCQKCIDKWSDRHRTCPICR 40

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 82201575 145 EECCICMDGKADL--ILPCAHSFCQKCIDKWSGQSRNCPVCRIQVT 188
Cdd:cd23130   1 DVCPICLDDPEDEaiTLPCLHQFCYTCILRWLQTSPTCPLCKTPVT 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 82201575 143 DEEECCICM----DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16472   1 DQTQCVVCMcdyeKRQLLRVLPCSHEFHAKCIDKWLKTNRTCPICR 46

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 82201575   143 DEEECCICMDGKAD-LILPCAH-SFCQKCIDKWSGQSRNCPVCRIQVT 188
Cdd:pfam13920   1 EDLLCVICLDRPRNvVLLPCGHlCLCEECAERLLRKKKKCPICRQPIE 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 82201575 144 EEECCICMD----GKAdLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16574   1 DSSCPICLDrfenEKA-FLDGCFHAFCFTCILEWSKVKNECPLCK 44

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 82201575 141 LTDEEECCICMDGKAD-LILPCAHSFCQKCIDKWSGQSRN---CPVCR 184
Cdd:cd16611   1 LTEELHCPLCLDFFRDpVMLSCGHNFCQSCITGFWELQAEdttCPECR 48

N1R/p28-like protein; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 82201575  144 EEECCICMDGKADL--------ILP-CAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:PHA02929 174 DKECAICMEKVYDKeiknmyfgILSnCNHVFCIECIDIWKKEKNTCPVCR 223

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 82201575   146 ECCICMD--GKADLILPCAHSFCQKCIDKWSGQSRNCPVC 183
Cdd:pfam13923   1 MCPICMDmlKDPSTTTPCGHVFCQDCILRALEASNECPLC 40

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 82201575 144 EEECCICM----DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCRIQVTA 189
Cdd:cd16681  10 EEKCTICLsileEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICRVDIEA 59

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 82201575    147 CCICMDGKAD--LILPCAHSFCQKCIDKW-SGQSRNCPVC 183
Cdd:smart00184   1 CPICLEEYLKdpVILPCGHTFCRSCIRKWlESGNNTCPIC 40

first RING finger, HC subclass, found in Arabidopsis thaliana ORTHRUS and similar proteins; This subfamily includes Arabidopsis thaliana ORTHRUS 1-5. They are E3 ubiquitin-protein ligases that may participate in CpG methylation-dependent transcriptional regulation and/or epigenetic transcriptional silencing. ORTHRUS 1 mediates ubiquitination with the E2 ubiquitin-conjugating enzymes UBC11, UBC8 and UBC8 homologs (e.g. UBC10, UBC11, UBC28 and UBC29) but not with UBC27, UBC30, UBC32, UBC34 and UBC36. ORTHRUS 2 and 5 mediate ubiquitination with the E2 ubiquitin-conjugating enzyme UBC11. ORTHRUS 1 and 2 promote methylation-mediated gene silencing leading, for example, to early flowering. They can bind to CpG, CpNpG, and CpNpN DNA motifs, with a strong preference for methylated forms, and with highest affinity for CpG substrates. Members of this subfamily contain two typical C3HC4-type RING-HC fingers. This model corresponds to the first one.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 82201575 143 DEEECCICMDGKADLIL-PCAHSFCQKCIDKWSGQ-SRNCPVCR 184
Cdd:cd23138   1 DELNCSFCMQLPERPVTtPCGHNFCLKCFQKWMGQgKKTCGTCR 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 82201575 141 LTDEEECCICMDGKAD-LILPCAHSFCQKCIDK-W--SGQSRNCPVCR 184
Cdd:cd16594   2 LQEELTCPICLDYFTDpVTLDCGHSFCRACIARcWeePETSASCPQCR 49

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 82201575 146 ECCICMD----GKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16454   1 TCAICLEefkeGEKVRVLPCNHLFHKDCIDPWLEQHNTCPLCR 43

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
                ....*....|....*....|....*....|....*....|....*....
gi 82201575 141 LTDEEECCICMD-GKADLILPCAHSFCQKCIDK-WSGQ---SRNCPVCR 184
Cdd:cd16597   2 LEEELTCSICLElFKDPVTLPCGHNFCGVCIEKtWDSQhgsEYSCPQCR 50

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 82201575 141 LTDEEECCICMDGKAD-LILPCAHSFCQKCI-DKWSGQ-SRNCPVCR 184
Cdd:cd16608   3 LKDELLCSICLSIYQDpVSLGCEHYFCRQCItEHWSRSeHRDCPECR 49

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
                ....*....|....*....|....*....|....*....|....*...
gi 82201575 144 EEE--CCICMDGKAD-LILPCAHSFCQKCIDKW----SGQSRNCPVCR 184
Cdd:cd16609   1 EEEltCSICLGLYQDpVTLPCQHSFCRACIEDHwrqkDEGSFSCPECR 48

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 82201575 124 SSEDTCQASMWMGRVKQLTDEE--------ECCICMDG--KAD--LILPCAHSFCQKCIDKW-SGQSRNCPVCRIQV 187
Cdd:COG5540 295 SSSEAIPTTTTKGSLKPLSIERaveadkgvECAICMSNfiKNDrlRVLPCDHRFHVGCVDKWlLGYSNKCPVCRTAI 371

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 82201575 141 LTDEEECCICMDG-KADLILPCAHSFCQKCIDKW--SGQSRNCPVCRIQVTAAN 191
Cdd:cd16568   1 ILETQECIICHEYlYEPMVTTCGHTYCYTCLNTWfkSNRSLSCPDCRTKITTQP 54

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 82201575 145 EECCICMDGKAD----LILPCAHSFCQKCIDKWSGQSRNCPVCRIQV 187
Cdd:cd16460   1 TPCVICHEAFSDgdrlLVLPCAHKFHTQCIGPWLDGQQTCPTCRLHV 47

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 82201575 147 CCICMDG-KADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16532   3 CPICQDEfKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

RING finger, HC subclass, found in leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) and similar proteins; LRSAM1, also known as Tsg101-associated ligase (TAL), or RIFLE, is an E3 ubiquitin-protein ligase that physically associates with, and selectively ubiquitylates, Tsg101, an E2-like molecule that regulates vesicular trafficking processes in yeast and mammals. It regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane. LRSAM1 is a multidomain protein containing an N-terminal leucine-rich repeat (LRR), followed by several recognizable motifs, including an ezrin-radixin-moezin (ERM) domain, a coiled-coil (CC) region, a SAM domain, and a C-terminal C3HC4-type RING-HC finger domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 82201575 144 EEECCICMDGKADLI-LPCAH-SFCQKCidkwSGQSRNCPVCRIQVT 188
Cdd:cd16515   1 ESECVVCMDAESQVIfLPCGHvCCCQTC----SSSLSTCPLCRADIT 43

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. RNF6 also acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 82201575 147 CCICMD----GKADLILPCAHSFCQKCIDKWSGQSRNCPVCRIQVTAAN 191
Cdd:cd16673   3 CSVCINeyatGNKLRRLPCAHEFHIHCIDRWLSENSTCPICRQPVLGSN 51

RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ZNRF3, also known as RING finger protein 203 (RNF203), is a homolog of Ring finger protein 43 (RNF43). It is a transmembrane E3 ubiquitin-protein ligase that is associated with the Wnt receptor complex, and negatively regulates Wnt signaling by promoting the turnover of frizzled and lipoprotein receptor-related protein LRP6 in an R-spondin-sensitive manner. It inhibits gastric cancer cell growth and promotes cell apoptosis by affecting the Wnt/beta-catenin/TCF signaling pathway. ZNRF3 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 82201575 146 ECCICM----DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16799   1 DCAICLekyiDGEELRVIPCTHRFHKKCVDPWLLQHHTCPHCR 43

RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 is a nuclear E3 ubiquitin protein ligase that is widely expressed throughout the human body, and is especially highly expressed in the heart, brain, placenta and the testis. It recognizes p53 as a substrate for ubiquitination, and thus plays a role in regulating p53. The overexpression of RNF38 increases p53 ubiquitination and alters p53 localization. It is also capable of autoubiquitination. RNF38 expression is negatively regulated by the serotonergic system. Induction of RNF38 may be involved in the anxiety-like behavior or non-cell autonomy in Oryzias latipes by the decline of serotonin (5-HT) levels. RNF38 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), a C3H2C3-type RING-H2 finger, as well as two potential nuclear localization signals.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 82201575 142 TDEEECCICM---DGKADL-ILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16679  18 SEQTLCVVCMcdfESRQLLrVLPCNHEFHAKCVDKWLKANRTCPICR 64

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

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                ....*....|....*....|....*....|....*....|....*....
gi 82201575 147 CCICM-DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCRIQVTAANESW 194
Cdd:cd16742  16 CAICQaEFREPLILICQHVFCEECLCLWFDRERTCPLCRSVVVETLRCW 64

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. RNF12 also acts as a co-regulator for a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 82201575 147 CCICM----DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCRIQVTAA 190
Cdd:cd16674   3 CSVCIteytEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICRRAVLAS 50

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligase family, characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling by interacting with complexes of frizzled (FZD) receptors and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of FZD and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block FZD ubiquitination and enhances Wnt signaling.

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                ....*....|....*....|....*....|....*....|..
gi 82201575 147 CCICM----DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16666   2 CAICLeeyeEGQELRVLPCQHEFHRKCVDPWLLQNHTCPLCL 43

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.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 82201575 143 DEEECCICMDGKADLI--LPCAHSFCQKCIDKW-SGQSRNCPVCRIQVTAAN 191
Cdd:cd16503   1 ENLTCSICQDLLHDCVslQPCMHNFCAACYSDWmERSNTECPTCRATVQRVN 52

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).

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                ....*....|....*....|....*....|....*....|....*
gi 82201575 143 DEEECCICMDGKADLI--LPCAHSFCQKCI-DKWSGQSRNCPVCR 184
Cdd:cd16544   1 AELTCPVCQEVLKDPVelPPCRHIFCKACIlLALRSSGARCPLCR 45

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
                ....*....|....*....|....*....|....
gi 82201575 158 ILPCAHSFCQKCIDK-------WSGQSRNCPVCR 184
Cdd:cd16581  17 ILPCSHTFCKNCLEKllaasgyYLLASLKCPTCR 50

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 82201575   147 CCICMDGKADLILPCAHSFCQKCIDKWSGQSRNCPVC 183
Cdd:pfam13445   1 CPICLELFTDPVLPCGHTFCRECLEEMSQKKGGKFKC 37

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                ....*....|....*....|....*....|....*....|....*
gi 82201575 147 CCICMDG--KADL--ILPCAHSFCQKCIDKWSGQSRNCPVCRIQV 187
Cdd:cd16804   2 CAVCIENykSKDVvrILPCKHVFHRICIDPWLLEHRTCPMCKLDV 46

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four 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, 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

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                ....*....|....*....|....*....|....*....|....*....|
gi 82201575 143 DEEECCICMDG-KADLILPCAHSFCQKCIDKWSGQSRN------CPVCRI 185
Cdd:cd16591   5 EEVTCPICLELlTEPLSLDCGHSFCQACITANHKESVNqegessCPVCRT 54

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

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                ....*....|....*....|....*....|....*....|...
gi 82201575 146 ECCICMDGKAD-LILPCAHSFCQKCIDKW---SGQSRNCPVCR 184
Cdd:cd16534   2 ECNICLDTASDpVVTMCGHLFCWPCLYQWletRPDRQTCPVCK 44

Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3 and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination, and two modified RING-H2 fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This model corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.

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                ....*....|....*....|....*....|....*....|....*...
gi 82201575 146 ECCICMD----GKADLILPCAHSFCQKCIDKWSGQSRN-CPVCRIQVT 188
Cdd:cd16486   1 QCRICLKafqlGQHVRTLPCRHKFHRDCIDNWLLHSRNsCPIDGQVVY 48

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled (FZD)-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating FZD receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3'-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger followed by a long C-terminal region.

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                ....*....|....*....|....*....|....*....|....*....|.
gi 82201575 142 TDEEECCICM----DGKADLILPCAHSFCQKCIDKWSGQSRNCPVCRIQVT 188
Cdd:cd16798   1 SSAPVCAICLeefsEGQELRIISCSHEFHRECVDPWLHQHRTCPLCMFNII 51

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein and its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.

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                ....*....|....*....|....*....|....*....|....*....|
gi 82201575 142 TDEEECCICMDGKAD----LILPCAHSFCQKCIDKWSGQSRNCPVCRIQV 187
Cdd:cd16805   4 SDFDNCAVCIEGYKPndvvRILPCRHLFHKSCVDPWLLDHRTCPMCKMNI 53

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.

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                ....*....|....*....|....*....|....*....|.
gi 82201575 146 ECCICM-DGKADLILPCAH-SFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16789   2 ECVICLsDPRDTAVLPCRHlCLCSDCAEVLRYQSNKCPICR 42

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.

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                  ....*....|....*....|....*....|....*....|....*
gi 82201575   145 EECCICMDGKADLILP-----CAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:pfam12678  11 MEPCPECQAPGDDECPvvwgeCGHAFHLHCISRWLKTNNTCPLCR 55

RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; RNF146, also known as dactylidin, or iduna, is a cytoplasmic E3 ubiquitin-protein ligase that is responsible for PARylation-dependent ubiquitination (PARdU). It displays neuroprotective property due to its inhibition of Parthanatos, a PAR dependent cell death, via binding with Poly(ADP-ribose) (PAR). It also modulates PAR polymerase-1 (PARP-1)-mediated oxidative cell injury in cardiac myocytes. Moreover, RNF146 mediates tankyrase-dependent degradation of axin, thereby positively regulating Wnt signaling. It also facilitates DNA repair and protects against cell death induced by DNA damaging agents or gamma-irradiation by translocating to the nucleus after cellular injury and promoting the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. Furthermore, RNF146 is implicated in neurodegenerative disease and cancer development. It regulates the development and progression of non-small cell lung cancer (NSCLC) by enhancing cell growth, invasion, and survival. RNF146 contains an N-terminal C3HC4-type RING-HC finger followed by a WWE domain with a poly(ADP-ribose) (PAR) binding motif at the tail.

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                ....*....|....*....|....*....|....*....|
gi 82201575 146 ECCICMDG-KADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16546   2 ECPICLQTcIHPVKLPCGHIFCYLCVKGVAWQSKRCALCR 41

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This family includes two highly similar E3 ubiquitin-protein ligases, Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in the brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP)-dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.

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                ....*....|....*....|....*....|....*...
gi 82201575 147 CCICMDGKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16465   6 CSEYVKDEIATELPCHHLFHKPCITAWLQKSGTCPVCR 43

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) and similar proteins; RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). Moreover, RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. In addition, RNF126 and the related protein, RNF115 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF126 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.

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                ....*....|....*....|....*....|....*....|...
gi 82201575 146 ECCICMD----GKADLILPCAHSFCQKCIDKWSGQSRNCPVCR 184
Cdd:cd16801   1 ECPVCKEdytvGENVRQLPCNHLFHNDCIVPWLEQHDTCPVCR 43

RING finger, HC subclass, found in Arabidopsis thaliana MND1-interacting protein 1 (MIP1) and similar proteins; This subfamily includes Arabidopsis thaliana MIP1, RING finger protein 4 (RF4) and RING finger protein 298 (RF298). MIP1 interacts with MND1, HOP2 and XRI1. RF4 and RF298 are putative E3 ubiquitin-protein ligase that may mediate E2-dependent protein ubiquitination. Members of this subfamily contain a typical C3HC4-type RING-HC finger.

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                ....*....|....*....|....*....|....*....|....*...
gi 82201575 144 EEECCICMDGKADLI-LPCAHSF-CQKCIDKWSGQS-RNCPVCRIQVT 188
Cdd:cd23128   3 ERECVMCMEEERSVVfLPCAHQVvCSGCNDLHEKKGmRECPSCRGEIQ 50

Modified RING finger, HC subclass (C3HC5-type), found in mahogunin RING finger protein 1 (MGRN1) 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. Furthermore, MGRN1 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. MGRN1 contains a modified C3HC5-type RING-HC finger, a conserved PSAP motif necessary for interaction between MGRN1 and TSG101. In addition, MGRN1 harbors a functionally uncharacterized region, as known as the 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.

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                ....*....|....*....|....*....|....*....|....*....
gi 82201575 143 DEEECCICM-DGKADLILPCAH-SFCQKCIDKWSGQSRNCPVCRIQVTA 189
Cdd:cd16816   7 NSNECVVCLsDLRDTLILPCRHlCLCNSCADTLRYQANNCPICRLPFRA 55

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
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gi 82201575 147 CCICMDGKAD-LILPCAHSFCQKCIDKWSGQSRNCPVC 183
Cdd:cd16504   5 CPICFDIIKEaFVTKCGHSFCYKCIVKHLEQKNRCPKC 42