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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71998153 211 KTCGICMENIFEKNLRFGILNGCQHCFCLDCIRQWRSKDQENVElatkTVRSCPECR 267
Cdd:cd16521   1 IECGICMEVVLEKERRFGILSNCNHVFCLECIREWRSSKDFENS----IVRSCPICR 53

Zinc-finger containing family; zf-CCCH_3 family is found in eukaryotes, and is typically between 155 and 169 amino acids in length.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 71998153     1 MPRHETDCRYFANGYCSKGNTCTFTH-DVATRNENICHFNLVGKCsYGRACRFLHTR 56
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHcEAALGNETVCTLWQEGRC-FRPVCRFRHME 56

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71998153 211 KTCGICMENIFEKNLRFGILNGCQHCFCLDCIRQWRSKDQENVElatkTVRSCPECR 267
Cdd:cd16521   1 IECGICMEVVLEKERRFGILSNCNHVFCLECIREWRSSKDFENS----IVRSCPICR 53

zinc finger-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 71998153  208 TEQKTCGICMENIFEKNLR----FGILNGCQHCFCLDCIRQWRSKDQEnvelaTKTVRSCPECRQHSDYVIPSLFW 279
Cdd:PHA02926 168 SKEKECGICYEVVYSKRLEndryFGLLDSCNHIFCITCINIWHRTRRE-----TGASDNCPICRTRFRNITMSKFY 238

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998153 275 PSLFWVESGQEKDLLIEMYKENTKRKICKYYSNERSRG------ACPFGN-KCFYKHQLPDGSI 331
Cdd:COG5252 117 PDLYSDVRDKEEDVPLGKRPWINTDRVCKFFIEAMESGkygwgwTCPNGNmRCSYIHKLPDGYV 180

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        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 71998153    213 CGICMENIFEKnlrfGILNGCQHCFCLDCIRQWRSKDQenvelatktvRSCPEC 266
Cdd:smart00184   1 CPICLEEYLKD----PVILPCGHTFCRSCIRKWLESGN----------NTCPIC 40

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71998153 211 KTCGICMENIFEKNLRFGILNGCQHCFCLDCIRQWRSKDQENVElatkTVRSCPECR 267
Cdd:cd16521   1 IECGICMEVVLEKERRFGILSNCNHVFCLECIREWRSSKDFENS----IVRSCPICR 53

p28-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71998153  157 DMDCPFAHGNYCDMCQQWSLHPYNAELRKKHENECVANHTTEMERafllqkteqKTCGICMENIFEKNLR---FGILNGC 233
Cdd:PHA03096 134 GKYCEYLHGDICDICEKYLLHPTDIKQRYNEQKTCLSYQLRLLLS---------KICGICLENIKAKYIIkkyYGILSEI 204

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71998153  234 QHCFCLDCIRQWrskdqENVELATKTVRSCPECR----------QHSDYVIPSLFWVESGQEKDLLIEMYKENTKRKIC 302
Cdd:PHA03096 205 KHEFNIFCIKIW-----MTESLYKETEPENRRLNtvivfiekinEDLKNNIPSRYWIDDKYDKNLLSFRYKKMHIRKVC 278

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998153 212 TCGICMENIFEKNL----RFGILNGCQHCFCLDCIRQWR-SKDQENvelatKTVRSCPECRQHS 270
Cdd:cd16732   3 ACGICMDKVYEKAHakerVFGILPNCNHAFCVGCIKKWRkSKDFQN-----EVIKACPQCRVKS 61

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        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 71998153 212 TCGICMENIfeKNLRfGILNGCQHCFCLDCIRQWrskdqenvelaTKTVRSCPECRQH 269
Cdd:cd16574   3 SCPICLDRF--ENEK-AFLDGCFHAFCFTCILEW-----------SKVKNECPLCKQP 46

Zinc-finger containing family; zf-CCCH_3 family is found in eukaryotes, and is typically between 155 and 169 amino acids in length.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 71998153     1 MPRHETDCRYFANGYCSKGNTCTFTH-DVATRNENICHFNLVGKCsYGRACRFLHTR 56
Cdd:pfam15663   1 MENKGDDCYFFYYSTCTKGDSCPFRHcEAALGNETVCTLWQEGRC-FRPVCRFRHME 56

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71998153 275 PSLFWVESGQEKDLLIEMYKENTKRKICKYYSNERSRG------ACPFGN-KCFYKHQLPDGSI 331
Cdd:COG5252 117 PDLYSDVRDKEEDVPLGKRPWINTDRVCKFFIEAMESGkygwgwTCPNGNmRCSYIHKLPDGYV 180

Cleavage and polyadenylation specificity factor (CPSF) Clipper subunit and related makorin family Zn-finger proteins [General function prediction only];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 71998153   8 CRYFANGYCSKGNTCTFTHDVATRNENI--CH-FNLVGKCSYGRACRFLHTRP 57
Cdd:COG5084 107 CKFFLRGLCKSGFSCEFLHEYDLRSSQGppCRsFSLKGSCSSGPSCGYSHIDP 159

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71998153 208 TEQKTCGICMEnIFEKNlrfgILNGCQHCFCLDCIRQWRSKDQENVelatktvrSCPECRQ 268
Cdd:cd16611   2 TEELHCPLCLD-FFRDP----VMLSCGHNFCQSCITGFWELQAEDT--------TCPECRE 49

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 71998153 213 CGICMENIFEKNlrfgILNgCQHCFCLDCIRQWRSKDQEnvelatktvrsCPECRQ 268
Cdd:cd16535   4 CSICSELFIEAV----TLN-CSHSFCSYCITEWMKRKKE-----------CPICRK 43

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        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 71998153    213 CGICMENIFEKnlrfGILNGCQHCFCLDCIRQWRSKDQenvelatktvRSCPEC 266
Cdd:smart00184   1 CPICLEEYLKD----PVILPCGHTFCRSCIRKWLESGN----------NTCPIC 40

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 71998153 212 TCGICMENifeknLRFGILNGCQHCFCLDCIRQWRSKDQenvelatktvRSCPEC 266
Cdd:cd16449   2 ECPICLER-----LKDPVLLPCGHVFCRECIRRLLESGS----------IKCPIC 41