Family of unknown function (DUF6539); This presumed domain contains 6 conserved cysteines and histidines that presumably form a zinc binding site. The function of this domain is unknown.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2462556665 4499 RVHWYTCPNGHPCSVGECGRPMEQSICIDCHAPIGGIDHKPRDGF 4543
Cdd:pfam20173    8 TGHWYKCPNGHPYVIGECGGPMETSRCPECGATIGGESHNLVAGN 52

hypothetical protein; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  134 PHSQAQQSGPTGQPSqPPGTAttPLEGDGLSaPTEVGDSplqaqalGEAGVATGSEAQSSP-QFQDHTEGEDQDASiPSG 212
Cdd:PHA03169    92 PSGSGSESVGSPTPS-PSGSA--EELASGLS-PENTSGS-------SPESPASHSPPPSPPsHPGPHEPAPPESHN-PSP 159

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  213 GRGLSQEgtgpptSAGEGHSRTEDAAQELLLPESKGGSSEPGTELQTTEQQAGASASMAVDAVAEPANAVKGAGKEMKEK 292
Cdd:PHA03169   160 NQQPSSF------LQPSHEDSPEEPEPPTSEPEPDSPGPPQSETPTSSPPPQSPPDEPGEPQSPTPQQAPSPNTQQAVEH 233

                          170
                   ....*....|....*..
gi 2462556665  293 TQRMKQPPATTPPFKTH 309
Cdd:PHA03169   234 EDEPTEPEREGPPFPGH 250

Family of unknown function (DUF6539); This presumed domain contains 6 conserved cysteines and histidines that presumably form a zinc binding site. The function of this domain is unknown.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2462556665 4499 RVHWYTCPNGHPCSVGECGRPMEQSICIDCHAPIGGIDHKPRDGF 4543
Cdd:pfam20173    8 TGHWYKCPNGHPYVIGECGGPMETSRCPECGATIGGESHNLVAGN 52

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 2462556665  3997 CSICLGD-AKDPVCLPCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:smart00184    1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462556665 3997 CSICLGDAKDPVC-LPCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:pfam00097    1 CPICLEEPKDPVTlLPCGHLFCSKCIRSWLESGNVTCPLC 40

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  159 EGDGLSAPTEvGDSPLQAQalGEAGVATGSEAQSSPQFQDHTEGEdQDASIPSGGRGlSQEGTGPPTSAGEGHSRTEDAA 238
Cdd:TIGR00927  639 EHTGERTGEE-GERPTEAE--GENGEESGGEAEQEGETETKGENE-SEGEIPAERKG-EQEGEGEIEAKEADHKGETEAE 713

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  239 QELLLPESKGGSSEPGTELQTTEQQAGASASMAVDAVAEPANAVKGAGKEMKEKTQRMKQPPATTPPFKTHCQE-AETKT 317
Cdd:TIGR00927  714 EVEHEGETEAEGTEDEGEIETGEEGEEVEDEGEGEAEGKHEVETEGDRKETEHEGETEAEGKEDEDEGEIQAGEdGEMKG 793

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 2462556665  318 KDEMAAAEEKVGKNEQGEPEDLKKPEGKNRSAAAVKNEKEQKNQEADVQ 366
Cdd:TIGR00927  794 DEGAEGKVEHEGETEAGEKDEHEGQSETQADDTEVKDETGEQELNAENQ 842

Family of unknown function (DUF6539); This presumed domain contains 6 conserved cysteines and histidines that presumably form a zinc binding site. The function of this domain is unknown.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2462556665 4499 RVHWYTCPNGHPCSVGECGRPMEQSICIDCHAPIGGIDHKPRDGF 4543
Cdd:pfam20173    8 TGHWYKCPNGHPYVIGECGGPMETSRCPECGATIGGESHNLVAGN 52

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
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:cd16449      3 CPICLERLKDPVLLPCGHVFCRECIRRLLESGSIKCPIC 41

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 2462556665  3997 CSICLGD-AKDPVCLPCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:smart00184    1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

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 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWF---ASEQMICPYC 4035
Cdd:cd16609      6 CSICLGLYQDPVTLPCQHSFCRACIEDHWrqkDEGSFSCPEC 47

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 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCL-RAWFA--SEQMICPYCLTALPD 4041
Cdd:cd16597      8 CSICLELFKDPVTLPCGHNFCGVCIeKTWDSqhGSEYSCPQCRATFPR 55

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 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCL-RAWFASEQ-MICPYC 4035
Cdd:cd16594      8 CPICLDYFTDPVTLDCGHSFCRACIaRCWEEPETsASCPQC 48

RING finger, HC subclass, found in tripartite motif-containing protein 39 (TRIM39) and similar proteins; TRIM39, also known as RING finger protein 23 (RNF23) or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability. It modulates cell cycle progression and DNA damage responses via stabilizing p21. Moreover, TRIM39 negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha. Furthermore, TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM39 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 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQ--MICPYC 4035
Cdd:cd16601      4 CSLCKEYLKDPVIIECGHNFCRACITRFWEELDgdFPCPQC 44

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFA--SEQMICPYC 4035
Cdd:cd16745      3 CNICLDLAQDPVVTLCGHLFCWPCLHKWLRrqSSQPECPVC 43

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 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMiCPYC 4035
Cdd:cd16532      3 CPICQDEFKDPVVLRCKHIFCEDCVSEWFERERT-CPLC 40

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
                   ....*....|....*....|....*....|....*....|..
gi 2462556665 3995 QPCSICLGDAKDPVCLPCDHVHCLRCLRAWFAS-EQMICPYC 4035
Cdd:cd16568      5 QECIICHEYLYEPMVTTCGHTYCYTCLNTWFKSnRSLSCPDC 46

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 (RNFT1); RNFT1, also known as protein PTD016, is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMiCPYCLTAL 4039
Cdd:cd16741     17 CAICQAEFRKPILLICQHVFCEECISLWFNREKT-CPLCRTVI 58

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWF---ASEQMICPYC 4035
Cdd:pfam15227    1 CPICLDYLEKPVSIECGHSFCLSCINSLQkepDGESLLCPQC 42

RING finger, HC subclass, found in RING finger protein 125 (RNF125); RNF125, also known as T-cell RING activation protein 1 (TRAC-1), is an E3 ubiquitin-protein ligase that is predominantly expressed in lymphoid cells, and functions as a positive regulator of T cell activation. It also down-modulates HIV replication and inhibits pathogen-induced cytokine production. It negatively regulates type I interferon signaling, which conjugates Lys(48)-linked ubiquitination to retinoic acid-inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. Further, RNF125 conjugates ubiquitin to melanoma differentiation-associated gene 5 (MDA5), a family protein of RIG-I. It thus acts as a negative regulator of RIG-I signaling, and is a direct target of miR-15b in the context of Japanese encephalitis virus (JEV) infection. Moreover, RNF125 binds to and ubiquitinates JAK1, prompting its degradation and inhibition of receptor tyrosine kinase (RTK) expression. It also negatively regulates p53 function through physical interaction and ubiquitin-mediated proteasome degradation. Mutations in RNF125 may lead to overgrowth syndromes (OGS). RNF125, together with three closely related proteins: RNF114, RNF138 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM). The UIM of RNF125 binds K48-linked poly-ubiquitin chains and is, together with the RING domain, required for auto-ubiquitination.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMICPYCLTALPDE 4042
Cdd:cd16542      4 CAVCLEVLHQPVRTRCGHVFCRPCIATSLRNNTWTCPYCRAYLSSE 49

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl and similar proteins; Cbl, also known as Casitas B-lineage lymphoma proto-oncogene, proto-oncogene c-Cbl, RING finger protein 55 (RNF55), or signal transduction protein Cbl, is a multi-domain protein that acts as a key negative regulator of various receptor and non-receptor tyrosine kinase signaling. It contains a tyrosine kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain), a proline-rich domain, a C3HC4-type RING-HC finger, and an ubiquitin-associated (UBA) domain. TKB is responsible for the interactions with many tyrosine kinases, such as the colony-stimulating factor-1 (CSF-1) receptor, Syk/ZAP-70, and Src-family of protein tyrosine kinases. The proline-rich domain can recruit proteins with a SH3 domain. Moreover, Cbl functions as an E3 ubiquitin ligase that can bind ubiquitin-conjugating enzymes (E2s) through the RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2462556665 3995 QPCSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:cd16708     22 QLCKICAENDKDVKIEPCGHLMCTSCLTSWQESEGQGCPFC 62

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), 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, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQ---MICPYC 4035
Cdd:cd16604      3 CPICLDLLKDPVTLPCGHSFCMGCLGALWGAGRggrASCPLC 44

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
                   ....*....|....*....|....*....|....*....|...
gi 2462556665 3997 CSICLGDAKDP---VCLPCDHV-HcLRCLRAWFASEQMICPYC 4035
Cdd:cd16448      1 CVICLEEFEEGdvvRLLPCGHVfH-LACILRWLESGNNTCPLC 42

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 2462556665 3997 CSICLGDAKDPVCL--PCDHVHCLRCLRAWFASEQMiCPYC 4035
Cdd:cd16574      4 CPICLDRFENEKAFldGCFHAFCFTCILEWSKVKNE-CPLC 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462556665 3997 CSICLGDAKDPVCL-PCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:cd16503      5 CSICQDLLHDCVSLqPCMHNFCAACYSDWMERSNTECPTC 44

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 2462556665 3997 CSICLgDAKDPVCLPCDHVHCLRCLRAWFASEQMiCPYC 4035
Cdd:cd16545      3 CCICM-DRKADLILPCAHSYCQKCIDKWSDRHRT-CPIC 39

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  2413 GIPVIIMGETGCGKT----RLIKFLSDLRR------GGTNADTIKLVKVHGGTTADMIYSRVREAENVAFANKDQHQLDt 2482
Cdd:smart00382    2 GEVILIVGPPGSGKTtlarALARELGPPGGgviyidGEDILEEVLDQLLLIIVGGKKASGSGELRLRLALALARKLKPD- 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 2462556665  2483 ILFFDEANT-TEAISCIKEVLCDHMVDGQPLAEDSGLHIIAACNP 2526
Cdd:smart00382   81 VLILDEITSlLDAEQEALLLLLEELRLLLLLKSEKNLTVILTTND 125

RING finger, HC subclass, found in RING finger protein 169 (RNF169) and similar proteins; RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to regulation of the DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. RNF169 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MIU (motif interacting with ubiquitin) domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCL-RAWFASE-QMICPYCLTALP 4040
Cdd:cd16551      4 CAGCLEVPVEPATLPCGHTLCRGCAnRALDAAEaGPTCPRCRAPLP 49

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWfASEQMICPYC 4035
Cdd:cd23135      6 CSICFSEIRSGAILKCGHFFCLSCIASW-LREKSTCPLC 43

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs 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, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCL----RAWFASEQMICPYC 4035
Cdd:cd16598      7 CSICLDYLRDPVTIDCGHNFCRSCItdycPISGGHERPVCPLC 49

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        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462556665 3981 CKETASKTLSRFGIQPCsiclgdakdpvclpCDHVHCLRCLRAWFASEQMI------CPYC 4035
Cdd:cd16521      6 CMEVVLEKERRFGILSN--------------CNHVFCLECIREWRSSKDFEnsivrsCPIC 52

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASeQMICPYC 4035
Cdd:cd16476      3 CAICYQEMKEARITPCNHFFHGLCLRKWLYV-QDTCPLC 40

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2462556665 3996 PCSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMiCPYCLTAL 4039
Cdd:cd16514      3 ECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPK-CPLCRTSL 45

RING finger, HC subclass, found in tripartite motif-containing protein TRIM2, TRIM3, and similar proteins; TRIM2, also known as RING finger protein 86 (RNF86), is an E3 ubiquitin-protein ligase that ubiquitinates the neurofilament light chain, a component of the intermediate filament in axons. Loss of function of TRIM2 results in early-onset axonal neuropathy. TRIM3, also known as brain-expressed RING finger protein (BERP), RING finger protein 97 (RNF97), or RING finger protein 22 (RNF22), is an E3 ubiquitin-protein ligase involved in the pathogenesis of various cancers. It also plays an important role in the central nervous system (CNS). In addition, TRIM3 may be involved in vesicular trafficking via its association with the cytoskeleton-associated-recycling or transport (CART) complex that is necessary for efficient transferrin receptor recycling, but not for epidermal growth factor receptor (EGFR) degradation. Both TRIM2 and TRIM3 belong to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMI--CPYC 4035
Cdd:cd16586      4 CGICLERYKNPKVLPCLHTFCERCLQNYIPAESLSlsCPVC 44

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMICPYC 4035
Cdd:cd16550      3 CPICLEILVEPVTLPCNHTLCMPCFQSTVEKASLCCPLC 41

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2462556665 3997 CSICLGDAKDP-VCLPCDHVHCLRClraWFAS--EQMICPYC 4035
Cdd:cd16563      3 CLICMDSYTMPlVSIQCWHVHCEEC---WLRTlgAKKLCPQC 41

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM9, TRIM67, and similar proteins; Tripartite motif-containing proteins TRIM9 and TRIM67 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, consisting of three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM9 (the human ortholog of rat Spring), also known as RING finger protein 91 (RNF91), is a brain-specific E3 ubiquitin-protein ligase collaborating with an E2 ubiquitin conjugating enzyme UBCH5b. TRIM9 plays an important role in the regulation of neuronal functions and participates in neurodegenerative disorders through its ligase activity. TRIM67, also known as TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H, also known as glucosidase II beta, a protein kinase C substrate.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRawfaSEQMICPYC 4035
Cdd:cd16576      6 CPVCGSLFTEPVILPCSHNLCLGCAL----NIQLTCPIC 40

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVcLPCDHVHCLRCLRAWFASEQMI--CP 4033
Cdd:pfam13445    1 CPICLELFTDPV-LPCGHTFCRECLEEMSQKKGGKfkCP 38

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMICPYCLTAL 4039
Cdd:cd16613      3 CICCQELVYKPITTPCKHNICKSCLQRSFKAEVYTCPACRHDL 45

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVH-CLRCLRAWFaSEQMICPYC 4035
Cdd:pfam13920    5 CVICLDRPRNVVLLPCGHLClCEECAERLL-RKKKKCPIC 43

DNA polymerase III subunits gamma and tau; Validated

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  124 SNPWPQDTALPHSQAQQSGPTGQPSQP--PGTATTPLEGDGLSAPTEV----------------GDSPLQAQALGEAGVA 185
Cdd:PRK07764   601 PAPASSGPPEEAARPAAPAAPAAPAAPapAGAAAAPAEASAAPAPGVAapehhpkhvavpdasdGGDGWPAKAGGAAPAA 680

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462556665  186 TGSEAQSSPQFQDHTEGEDQDASIPSGGRGLSQ------EGTGPPTSAGEGHSRTEDAAQELLLPESKGGSSEPGTELQT 259
Cdd:PRK07764   681 PPPAPAPAAPAAPAGAAPAQPAPAPAATPPAGQaddpaaQPPQAAQGASAPSPAADDPVPLPPEPDDPPDPAGAPAQPPP 760

                          170       180
                   ....*....|....*....|..
gi 2462556665  260 TEQQAGASASMAVDAVAEPANA 281
Cdd:PRK07764   761 PPAPAPAAAPAAAPPPSPPSEE 782

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQ------MICPYC 4035
Cdd:cd16581      5 CSICYNIFDDPKILPCSHTFCKNCLEKLLAASGyyllasLKCPTC 49

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of numb protein X 2 (LNX2); LNX2, also known as numb-binding protein 2, or PDZ domain-containing RING finger protein 1 (PDZRN1), is a PDZ domain-containing RING-type E3 ubiquitin ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. It interacts with contactin-associated protein 4 (Caspr4, also known as CNTNAP4) in a PDZ domain-dependent manner, which modulates the proliferation and neuronal differentiation of neural progenitor cells (NPCs). LNX2 contains an N-terminal modified C3HC3D-type RING-HC finger, a NPAF motif for Numb/ Numblike-LNX interaction, and four PDZ domains necessary for the binding of substrates, including ErbB2, RhoC, the presynaptic protein CAST, the melanoma/cancer-testis antigen MAGEB18 and several proteins associated with cell junctions, such as JAM4 and the Coxsackievirus and adenovirus receptor (CAR).

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAwFASEQMICP 4033
Cdd:cd16780      6 CHICLQPLLQPLDTPCGHTFCFKCLRN-FLQEKDFCP 41

RING finger, HC subclass, found in Ret finger protein-like 4B (RFPL4B) and similar proteins; RFPL4B, also called RING finger protein 211 (RNF211), is an uncharacterized RING finger protein containing a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQ---MICPYC 4035
Cdd:cd16623     11 CPICLDFFSHPISLSCAHIFCFDCIQKWMTKREdsiLTCPLC 52

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2462556665 3997 CSICLGDAKDPVCLPCDHVHCLRCLRAWFASEQMiCPYC 4035
Cdd:cd16684      5 CSICYQDMKSAVITPCSHFFHAGCLKKWLYVQET-CPLC 42