KilA-N domain; The amino-terminal module of the D6R/N1R proteins defines a novel, conserved DNA-binding domain (the KilA-N domain) that is found in a wide range of proteins of large bacterial and eukaryotic DNA viruses. The KilA-N domain family also includes the previously defined APSES domain. The KilA-N and APSES domains may also share a common fold with the nucleic acid-binding modules of the LAGLIDADG nucleases and the amino-terminal domains of the tRNA endonuclease.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849  38 IKYRDIKVIIMK-NNGYVNCSKLCKMRN---KYFSRWLRLSTSKALLDIY-NNKSVDNAIVKVYGKGKKLIITGFYLKQN 112
Cdd:pfam04383   1 IQYNDFEIIIRRdKDGYINATKLCKAAGektKRFRNWLRLESTKELIEELeEENNIPKIITIIGRKGKGGRLQGTYVHPD 80

                          90       100
                  ....*....|....*....|....*.
gi 1475045849 113 MIRYVIEWIGDDFTNDIYKMINFYNA 138
Cdd:pfam04383  81 LALAIASWISPEFALKVSKIIDEYKS 106

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849  205 DSLIVFKRSTSKK------CGIC---IEEINKKHISEQyfgiLPSCKHIFCLSCIRRWADTTRNtdteNTCPECRIVFPF 275
Cdd:COG5219   1453 DLLGLWKKNIDEKfsgheeCAICysvLDMVDRSLPSKR----CATCKNKFHTRCLYKWFASSAR----SNCPLCRSEITF 1524

                   .
gi 1475045849  276 I 276
Cdd:COG5219   1525 V 1525

N1R/p28-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849  33 GSFDSIKYRDIKVIIMKNNGYVNCSKLCKMRNKYFSRWLRLSTSKALLD---IYNNKSVDNAIVKVYGKGKKLIITGFYL 109
Cdd:PHA02929    8 NNFILLNGECIKIIILSSNNYINITKLCKPMKKSFCNWKNLKRSRQIIInisIEENIKVDKLSFRIYKSKYTKQIHGVFI 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849 110 KQNMIRYVIEWIGDDFTNDIYKMINFYNAlfgnDELKivsceNTLCpfielgrcyyGKKCKYIHGDQCDICGLYILHPTD 189
Cdd:PHA02929   88 HPKLLKYVLNWISEEYCAKVLSIINEYNQ----KILK-----NKPS----------NDKINYIYMRKEEDMFYAIINKKG 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849 190 INQRVSHKKTCLVDRDSLIVFKRSTSKKCGICIEEINKKHISEQYFGILPSCKHIFCLSCIRRWadttrnTDTENTCPEC 269
Cdd:PHA02929  149 KNYKKFLKTIPSVLSEYEKLYNRSKDKECAICMEKVYDKEIKNMYFGILSNCNHVFCIECIDIW------KKEKNTCPVC 222

                         250
                  ....*....|...
gi 1475045849 270 RIVFPFIIPSRYW 282
Cdd:PHA02929  223 RTPFISVIKSRFF 235

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 1475045849 216 KKCGICIEEINKKhisEQYFGILPSCKHIFCLSCIRRW-ADTTRNTDTENTCPECR 270
Cdd:cd16521     1 IECGICMEVVLEK---ERRFGILSNCNHVFCLECIREWrSSKDFENSIVRSCPICR 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1475045849 218 CGICIEEI-NKKHISEQYFGILPSCKHIFCLSCIRRWADTTR-NTDTENTCPECRIV 272
Cdd:cd16732     4 CGICMDKVyEKAHAKERVFGILPNCNHAFCVGCIKKWRKSKDfQNEVIKACPQCRVK 60

RING finger, HC subclass, found in makorin-2 (MKRN2) and similar proteins; MKRN2, also known as makorin RING finger protein 2, RING finger protein 62 (RNF62), or HSPC070, is a putative ribonucleoprotein that acts as a neurogenesis inhibitor acting upstream of glycogen synthase kinase-3beta (GSK-3beta) in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. It also functions in promoting cell proliferation of primary CD34+ progenitor cells and K562 cells, indicating its possible involvement in normal and malignant hematopoiesis. Mammalian MKRN2 contains three N-terminal C3H1-type zinc fingers, a motif rich in Cys and His residues (CH), a C3HC4-type RING-HC finger, and another C3H1-type zinc finger at the C-terminus. The third C3H1-type zinc finger, the CH motif, as well as the RING zinc finger are necessary for its anti-neurogenic activity.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1475045849 216 KKCGICIEEINKKHI-SEQYFGILPSCKHIFCLSCIRRWADTTR-NTDTENTCPECR 270
Cdd:cd16731     2 KVCSICMEVVYEKASaSERRFGILSNCNHTYCLSCIRQWRCAKQfENPIIKSCPECR 58

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1 (PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1475045849 215 SKKCGICIeeinkKHISEQYFGILPSCKHIFCLSCIRRWADTTrntdteNTCPECRIVF 273
Cdd:cd16635     4 SESCPICL-----NTFRDQAVGTPESCDHIFCLDCILEWSKNA------NTCPVDRIVF 51

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1475045849 218 CGICIEeinkkhiseqYFG--ILPSCKHIFCLSCIRRWADTTRNtdtENTCPECRIVFP 274
Cdd:cd16611     7 CPLCLD----------FFRdpVMLSCGHNFCQSCITGFWELQAE---DTTCPECRELCQ 52

H2 subclass of RING (RING-H2) fingers 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 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). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger 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 serves as a scaffold 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 1475045849 218 CGICIEEINKKHiseqyFGILPSCKHIFCLSCIRRWAdttrnTDTENTCPECR 270
Cdd:cd16448     1 CVICLEEFEEGD-----VVRLLPCGHVFHLACILRWL-----ESGNNTCPLCR 43

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849  205 DSLIVFKRSTSKK------CGIC---IEEINKKHISEQyfgiLPSCKHIFCLSCIRRWADTTRNtdteNTCPECRIVFPF 275
Cdd:COG5219   1453 DLLGLWKKNIDEKfsgheeCAICysvLDMVDRSLPSKR----CATCKNKFHTRCLYKWFASSAR----SNCPLCRSEITF 1524

                   .
gi 1475045849  276 I 276
Cdd:COG5219   1525 V 1525

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
                  ....*....|....*....|....*....|....*.
gi 1475045849 240 SCKHIFCLSCIRR-WADTTRNTdtenTCPECRIVFP 274
Cdd:cd16594    22 DCGHSFCRACIARcWEEPETSA----SCPQCRETCP 53

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1475045849 156 PFIELGRCYYGKKCKYIHgDQCDICGLYILhptdiNQRVSHKKtclvdRDSLIVF--KRSTSKKCGICieeinKKHISEQ 233
Cdd:COG5152   146 DYKETGYCGYGDSCKFLH-DRSDFKTGWKL-----NQEWNAEY-----EEAPVISgpGEKIPFLCGIC-----KKDYESP 209

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1475045849 234 yfgILPSCKHIFCLSC-IRRWADTTrntdtenTCPECRIVfpfiIPSRYWIDNKYDkKILYNR 295
Cdd:COG5152   210 ---VVTECGHSFCSLCaIRKYQKGD-------ECGVCGKA----TYGRFWVVSDLQ-KMLNKR 257

Modified RING finger, HC subclass (C4C4-type), found in tripartite motif-containing protein 37 (TRIM37) and similar proteins; TRIM37, also known as mulibrey nanism protein, or MUL, is a peroxisomal E3 ubiquitin-protein ligase that is involved in the tumorigenesis of several cancer types, including pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), breast cancer, and sporadic fibrothecoma. It mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. Moreover, TRIM37 possesses anti-HIV-1 activity, and interferes with viral DNA synthesis. Mutations in the human TRIM37 gene (also known as MUL) cause Mulibrey (muscle-liver-brain-eye) nanism, a rare growth disorder of prenatal onset characterized by dysmorphic features, pericardial constriction, and hepatomegaly. TRIM37 belongs to the C-VIII 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 C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a MATH (meprin and TRAF-C homology) domain positioned C-terminal to the RBCC domain. Its MATH domain has been shown to interact with the TRAF (TNF-Receptor-Associated Factor) domain of six known TRAFs in vitro.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1475045849 217 KCGICIEEINKKHISeqyfgilPSCKHIFCLSCIRRWadttrNTDTENTCPECR 270
Cdd:cd16619     2 RCFICMEKLRDPRLC-------PHCSKLFCKGCIRRW-----LSEQRSSCPHCR 43

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
                  ....*....|....*....|....*....|....
gi 1475045849 237 ILPsCKHIFCLSCIRRWadttrnTDTENTCPECR 270
Cdd:cd16545    14 ILP-CAHSYCQKCIDKW------SDRHRTCPICR 40

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1475045849 218 CGICIEEINKKHISEQyfgiLPSCKHIFCLSCIRRWadttrnTDTENTCPECR 270
Cdd:cd16461     2 CAICLSDYENGEELRR----LPECKHAFHKECIDEW------LKSNSTCPLCR 44

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.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1475045849 241 CKHIFCLSCIRRWADTTRNTDTENTCPECRIVFPF 275
Cdd:cd16591    24 CGHSFCQACITANHKESVNQEGESSCPVCRTSYQP 58

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1475045849 217 KCGICIEEINKKHISEQyfgiLPsCKHIFCLSCIRRWADTTrntdteNTCPECR 270
Cdd:cd16669     1 KCPICLLEFEEGETVKQ----LP-CKHSFHSDCILPWLGKT------NSCPLCR 43

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 1475045849 235 FGILPSCKHIFCLSCIRRWADTTRntdteNTCPECRIVFP 274
Cdd:cd23138    14 RPVTTPCGHNFCLKCFQKWMGQGK-----KTCGTCRSPIP 48

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1475045849 215 SKKCGICIEEINKKhiseqyFGILPSCKHIFCLSCIRRWADTTRNTDtentCPECRI 271
Cdd:cd23120     1 IEECPICLEEMNSG------TGYLADCGHEFHLTCIREWHNKSGNLD----CPICRV 47

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1475045849 217 KCGICIEeiNKKHISeqyfgiLPSCKHIFCLSCIRRWAdttrNTDTEntCPECR 270
Cdd:cd16527     2 KCSLCLE--ERRHPT------ATPCGHLFCWSCITEWC----NEKPE--CPLCR 41

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 1475045849 218 CGICIEEINKKHISEqyfgilpsCKHIFCLSCIRRWADTTRNTdteNTCPECR 270
Cdd:cd16534     3 CNICLDTASDPVVTM--------CGHLFCWPCLYQWLETRPDR---QTCPVCK 44

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.

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gi 1475045849 217 KCGICIEEINKKhiseqyfgILPSCKHIFCLSCIRRWAdttrnTDTENTCPEC 269
Cdd:cd16449     2 ECPICLERLKDP--------VLLPCGHVFCRECIRRLL-----ESGSIKCPIC 41

RING finger, HC subclass, found in RING finger protein 5 (RNF5) and similar proteins; RNF5, also known as protein G16 or Ram1, is an E3 ubiquitin-protein ligase anchored to the outer membrane of the endoplasmic reticulum (ER). It 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. It also regulates the turnover of specific G protein-coupled receptors by ubiquitinating JNK-associated membrane protein (JAMP) and preventing proteasome recruitment. RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection through the regulation of ATG4B stability. It is also involved in the degradation of Pendrin, a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. RNF5 plays an important role in cell adhesion and migration. It can modulate cell migration by ubiquitinating paxillin. Furthermore, RNF5 interacts with virus-induced signaling adaptor (VISA) at mitochondria in a viral infection-dependent manner, and further targets VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection. It also negatively regulates virus-triggered signaling by targeting MITA, also known as STING, for ubiquitination and degradation at the mitochondria. In addition, RNF5 determines breast cancer response to ER stress-inducing chemotherapies through the regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2). It also has been implicated in muscle organization and in recognition and processing of misfolded proteins. RNF5 contains a C3HC4-type RING-HC finger.

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gi 1475045849 217 KCGICIEEINKKHISeqyfgilpSCKHIFCLSCIRRWADTTRNtdtENTCPECR 270
Cdd:cd16743     2 ECNICLETARDAVVS--------LCGHLFCWPCLHQWLETRPE---RQECPVCK 44

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

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gi 1475045849 218 CGICIEEInkkhISEQYFGILPsCKHIFCLSCIRRWAdttrnTDTENTCPECRIVFP 274
Cdd:COG5540   326 CAICMSNF----IKNDRLRVLP-CDHRFHVGCVDKWL-----LGYSNKCPVCRTAIP 372

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

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gi 1475045849 218 CGICIEEInkkhisEQYFGILPsCKHIFCLSCIRRWADttrntDTENTCPEC 269
Cdd:pfam00097   1 CPICLEEP------KDPVTLLP-CGHLFCSKCIRSWLE-----SGNVTCPLC 40

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.

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gi 1475045849 218 CGICIEEINkkhiSEQYFGILPsCKHIFCLSCIRRWADTTRntdtenTCPECR 270
Cdd:cd16460     3 CVICHEAFS----DGDRLLVLP-CAHKFHTQCIGPWLDGQQ------TCPTCR 44