Domain in Deltex and TRIP12 homologues. Possibly involved in regulation of ubiquitin-mediated proteolysis;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 193203358   130 MFWLYRGRHQGWWRFDPRIEKEIEEAFTHQMPMTEVTICGNPYIVDFSQMCQYPKNQSNySRNVKRVNSTDFD 202
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYNQATGT-TRKVRRVTYSPYS 72

Domain in Deltex and TRIP12 homologues. Possibly involved in regulation of ubiquitin-mediated proteolysis;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 193203358   130 MFWLYRGRHQGWWRFDPRIEKEIEEAFTHQMPMTEVTICGNPYIVDFSQMCQYPKNQSNySRNVKRVNSTDFD 202
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYNQATGT-TRKVRRVTYSPYS 72

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 193203358  22 KECAVCYSEMILPTTIPSCGHKFCFICLKGVSVSNNGDCPICRGPIDSQI 71
Cdd:cd16564    1 SECPVCYEDFDDAPRILSCGHSFCEDCLVKQLVSMTISCPICRRVTFISK 50

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 193203358   23 ECAVCYSEMILP--TTIPSCGHKFCFICLKGVSVSNNgDCPICR 64
Cdd:pfam13639   2 ECPICLEEFEEGdkVVVLPCGHHFHRECLDKWLRSSN-TCPLCR 44

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 193203358   24 CAVCYSEMILPTtIPSCGHKFCFICLKgVSVSNNGDCPICRGP 66
Cdd:TIGR00599  29 CHICKDFFDVPV-LTSCSHTFCSLCIR-RCLSNQPKCPLCRAE 69

Domain in Deltex and TRIP12 homologues. Possibly involved in regulation of ubiquitin-mediated proteolysis;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 193203358   130 MFWLYRGRHQGWWRFDPRIEKEIEEAFTHQMPMTEVTICGNPYIVDFSQMCQYPKNQSNySRNVKRVNSTDFD 202
Cdd:smart00678   1 YVWEYEGRNGKWWPYDPRVSEDIEEAYAAGKKLCELSICGFPYTIDFNAMTQYNQATGT-TRKVRRVTYSPYS 72

RING finger, HC subclass, found in RING finger protein 222 (RNF222) and similar proteins; RNF222 is an uncharacterized C3HC4-type RING-HC finger-containing protein. It may function as an E3 ubiquitin-protein ligase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 193203358  22 KECAVCYSEMILPTTIPSCGHKFCFICLKGVSVSNNGDCPICRGPIDSQI 71
Cdd:cd16564    1 SECPVCYEDFDDAPRILSCGHSFCEDCLVKQLVSMTISCPICRRVTFISK 50

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
                 ....*....|....*....|....*....|....*....|.
gi 193203358  23 ECAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNGDCPIC 63
Cdd:cd16449    2 ECPICLERLKDPVLLP-CGHVFCRECIRRLLESGSIKCPIC 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 193203358    24 CAVCYSEMILPTTIPSCGHKFCFICLKGVSVSNNGDCPIC 63
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

RING finger, HC subclass, found in zinc finger protein 598 (ZNF598) and similar proteins; ZNF598 associates with eukaryotic initiation factor 4E (eIF4E) homologous protein from mammals (m4EHP) by binding to Grb10-interacting GYF protein 2 (GIGYF2). The m4EHP-GIGYF2 complex functions as a translational repressor and is essential for normal embryonic development of mammalian. ZNF598 harbors a C3HC4-type RING-HC finger at its N-terminus.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 193203358  22 KECAVCYSEMILpTTIPSCGHKFCFIC-LKGVSVSNNGDCPICRGPIDSQIF 72
Cdd:cd16615    1 ETCVICCEEIEY-FAVGPCNHPVCYKCsLRMRVLYKDKYCPICRTELDKVIF 51

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 193203358  21 DKECAVCYSEMILPTT-IPSCGHKFCFIC-LKGVSVSNNgdCPICRGPI 67
Cdd:cd16574    1 DSSCPICLDRFENEKAfLDGCFHAFCFTCiLEWSKVKNE--CPLCKQPF 47

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
                 ....*....|....*....|....*....|....*....|....*...
gi 193203358  23 ECAVCySEMILPTTIPSCGHKFCFICLKGVSVSNNgDCPICRGPIDSQ 70
Cdd:cd16535    3 QCSIC-SELFIEAVTLNCSHSFCSYCITEWMKRKK-ECPICRKPITSK 48

RING finger, HC subclass, found in bifunctional apoptosis regulator (BAR); BAR, also known as RING finger protein 47, was originally identified as an inhibitor of Bax-induced apoptosis. It participates in the block of apoptosis induced by TNF-family death receptors (extrinsic pathway) and mitochondria-dependent apoptosis (intrinsic pathway). BAR is predominantly expressed by neurons in the central nervous system and is involved in the regulation of neuronal survival. It is an endoplasmic reticulum (ER)-associated RING-type E3 ubiquitin ligase that interacts with BI-1 protein and post-translationally regulates its stability, as well as functioning in ER stress. BAR contains an N-terminal C3HC4-type RING-HC finger, a SAM domain, a coiled-coil domain, and a C-terminal transmembrane (TM) domain. This model corresponds to the RING-HC finger responsible for the binding of ubiquitin conjugating enzymes (E2s).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 193203358  24 CAVCYSEMILPTTIpSCGHKFCFICL-KGVSVSNNGDCPICR 64
Cdd:cd16497    4 CHCCYDLLVNPTTL-NCGHSFCRHCLaLWWKSSKKTECPECR 44

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 193203358  23 ECAVCySEMILPTTIPSCGHKFCFICL----KGVSVSNngdCPICRGPID 68
Cdd:cd23132    4 LCCIC-LDLLYKPVVLECGHVFCFWCVhrcmNGYDESH---CPLCRRPYD 49

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 193203358  24 CAVCYSEMIL--PTTIPSCGHKFCFICLKGVSVSNNGDCPICR 64
Cdd:cd16448    1 CVICLEEFEEgdVVRLLPCGHVFHLACILRWLESGNNTCPLCR 43

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 193203358  23 ECAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNG-DCPICRGPIDSQ 70
Cdd:cd16568    6 ECIICHEYLYEPMVTT-CGHTYCYTCLNTWFKSNRSlSCPDCRTKITTQ 53

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        40
                 ....*....|....*....|....*....|....*....|....*.
gi 193203358  24 CAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNGDCPICRGPIDS 69
Cdd:cd16550    3 CPICLEILVEPVTLP-CNHTLCMPCFQSTVEKASLCCPLCRLRISS 47

RING finger, HC subclass, found in postreplication repair protein RAD18 and similar proteins; RAD18, also known as HR18 or RING finger protein 73 (RNF73), is an E3 ubiquitin-protein ligase involved in post replication repair of UV-damaged DNA via its recruitment to stalled replication forks. It associates to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on K164. It also interacts with another E2 ubiquitin conjugating enzyme RAD6 to form a complex that monoubiquitinates proliferating cell nuclear antigen at stalled replication forks in DNA translesion synthesis. Moreover, Rad18 is a key factor in double-strand break DNA damage response (DDR) pathways via its association with K63-linked polyubiquitylated chromatin proteins. It can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after ionizing radiation (IR) exposure. RAD18 contains a C3HC4-type RING-HC finger, a ubiquitin-binding zinc finger domain (UBZ), a SAP (SAF-A/B, Acinus and PIAS) domain, and a RAD6-binding domain (R6BD).

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 193203358  24 CAVCYSEMILPTTIPSCGHKFCFICLKGvSVSNNGDCPICRGPIDSQ 70
Cdd:cd16529    7 CPICFEYFNTAMMITQCSHNYCSLCIRR-FLSYKTQCPTCRAAVTES 52

RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 is an E3 ubiquitin-protein ligase that interacts with mesenchyme Homeobox 2 (MEOX2) transcription factor, a regulator of the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes; it enhances Meox2 activation of the p21 promoter. It also regulates the expression of myelin-associated glycoprotein (MAG) genes and is required for myelin production in Schwann cells of the peripheral nervous system. Moreover, RNF10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells. RNF10 contains a C3HC4-type RING-HC finger and three putative nuclear localization signals.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 193203358  23 ECAVCYSEMILPTtIPSCGHKFCFICLK---GVSVSNNGDCPICRGPI 67
Cdd:cd16536    2 QCPICLEPPVAPR-ITRCGHIFCWPCILrylSLSEKKWRKCPICFESI 48

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 193203358  23 ECAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNGDCPICRGPI 67
Cdd:cd23138    4 NCSFCMQLPERPVTTP-CGHNFCLKCFQKWMGQGKKTCGTCRSPI 47

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 193203358   24 CAVCYSEMILPTTIPSCGHKFCFICLKGVSVSNNGDCPIC 63
Cdd:pfam00097   1 CPICLEEPKDPVTLLPCGHLFCSKCIRSWLESGNVTCPLC 40

RING finger, HC subclass, found in RNA-binding protein MEX3B; MEX3B, also known as RING finger and KH domain-containing protein 3 (RKHD3), or RING finger protein 195 (RNF195), is an RNA-binding phosphoprotein that localizes in P-bodies and stress granules, which are two structures involved in the storage and turnover of mRNAs. It regulates the spatial organization of the Rap1 pathway that orchestrates Sertoli cell functions. It has a 3' long conserved untranslated region (3'LCU)-mediated fine-tuning system for mRNA regulation in early vertebrate development such as anteroposterior (AP) patterning and signal transduction. MEX3B contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3B shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 193203358  22 KECAVCYSEMILPTTIPsCGHK-FCFICLKGVSVSNNGDCPICRGPIDSQI 71
Cdd:cd16721    5 RDCSICFESEVIAALVP-CGHNlFCMECANRICEKNEPQCPVCHAAVTQAI 54

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 193203358  24 CAVCYSEMILPTTIPsCGHKFCFICLKGvSVSNNGDCPICR 64
Cdd:cd23135    6 CSICFSEIRSGAILK-CGHFFCLSCIAS-WLREKSTCPLCK 44

Transcriptional repressor [Transcription];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 193203358  14 QAINSTIDKE--CAVCYSEMILPTT--IP-SCGHKFCFICLKGVSVSNNGDCPICRGPIDSQIFK-KPLQAVDLKMDI 85
Cdd:COG5175    5 QEIHNSEDEEdyCPLCIEPMDITDKnfFPcPCGYQICQFCYNNIRQNLNGRCPACRRKYDDENVRyVTLSPEELKMEL 82

RING finger, HC subclass, found in Arabidopsis thaliana protein XB3 homolog 5 (XBAT35) and similar proteins; XBAT35, also known as ankyrin repeat domain and RING finger-containing protein XBAT35, or RING-type E3 ubiquitin transferase XBAT35, has no E3 ubiquitin-protein ligase activity observed when associated with the E2 enzyme UBC8 in vitro. It contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 193203358  22 KECAVCYSEMILPTTIPsCGH-KFCFICLKGVSVSNNGdCPICRGPIDSQI 71
Cdd:cd23129    3 DECVVCMDAPRDAVCVP-CGHvAGCMSCLKALMQSSPL-CPICRAPVRQVI 51

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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 193203358  24 CAVCYSEMILPTTIpSCGHKFCFICLKGVSVSNNGDCPICRGP 66
Cdd:cd16596   12 CPICLDPFVEPVSI-ECGHSFCQECISQVGKGGGSVCPVCRQR 53

RING finger, HC subclass, found in peroxin-2 (PEX2) and similar proteins; PEX2, also known as peroxisome biogenesis factor 2, 35 kDa peroxisomal membrane protein, peroxisomal membrane protein 3, peroxisome assembly factor 1 (PAF-1), or RING finger protein 72 (RNF72), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It may be involved in the biogenesis of peroxisomes, as well as in peroxisomal matrix protein import. Mutations in the PEX2 gene are the primary defect in a subset of patients with Zellweger syndrome and related peroxisome biogenesis disorders. Moreover, PEX2 functions as an E3-ubiquitin ligase that mediates the UBC4-dependent polyubiquitination of PEX5, a key player in peroxisomal matrix protein import, to control PEX5 receptor recycling or degradation.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 193203358  21 DKECAVCYSEMILPTTIPSCGHKFCFICLKGVSVSNNG-DCPICRGPID 68
Cdd:cd16526    1 LTECAICGEWPTNNPYSTGCGHVYCYYCIKSNLLADDSfTCPRCGSPVS 49

RING finger, HC subclass, found in constitutive photomorphogenesis protein 1 (COP1) and similar proteins; COP1, also known as RING finger and WD repeat domain protein 2 (RFWD2) or RING finger protein 200 (RNF200), is a central regulator of photomorphogenic development in plants, which targets key transcription factors for proteasome-dependent degradation. It is localized predominantly in the nucleus, but may also be present in the cytosol. Mammalian COP1 functions as an E3 ubiquitin-protein ligase that interacts with Jun transcription factors and modulates their transcriptional activity. It also interacts with and negatively regulates the tumor-suppressor protein p53. Moreover, COP1 associates with COP9 signalosome subunit 6 (CSN6), and is involved in 14-3-3sigma ubiquitin-mediated degradation. The CSN6-COP1 link enhances ubiquitin-mediated degradation of p27(Kip1), a critical CDK inhibitor involved in cell cycle regulation, to promote cancer cell growth. Furthermore, COP1 functions as the negative regulator of ETV1 and influences prognosis in triple-negative breast cancer. COP1 contains an N-terminal extension, a C3HC4-type RING-HC finger, a coiled coil domain, and seven WD40 repeats. In human COP1, a classic leucine-rich NES, and a novel bipartite NLS is bridged by the RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 193203358  21 DKECAVCYsEMILPTTIPSCGHKFCFICLKgVSVSNNGDCPICRGPID 68
Cdd:cd16504    2 DFLCPICF-DIIKEAFVTKCGHSFCYKCIV-KHLEQKNRCPKCNFYLT 47

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 193203358  24 CAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNGD--CPIC 63
Cdd:cd16601    4 CSLCKEYLKDPVIIE-CGHNFCRACITRFWEELDGDfpCPQC 44

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 193203358  21 DKECAVCYSEMILPTTIPsCGHKFCFICLKgVSVSNNGDCPICR 64
Cdd:cd16561    2 EQECSICLEDLNDPVKLP-CDHVFCEECIR-QWLPGQMSCPLCR 43

RING finger, HC subclass, found in RNA-binding proteins of the evolutionarily-conserved MEX-3 family; MEX-3 phosphoproteins are found in vertebrates. They are mediators of post-transcriptional regulation in different organisms, and have been implicated in many core biological processes, including embryonic development, epithelial homeostasis, immune responses, metabolism, and cancer. They contain two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. They shuttle between the nucleus and the cytoplasm via the CRM1-dependent export pathway. The RNA-binding protein MEX-3 from nematode Caenorhabditis elegans is the founding member of the MEX-3 family. Due to the lack of a RING-HC finger, it is not included here.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 193203358  22 KECAVCYSEMILPTTIPsCGHK-FCFICLKGVSVSNNGDCPICRGPI 67
Cdd:cd16518    1 RDCVVCFESEVVAALVP-CGHNlFCMECANRICEKSDPECPVCHTPV 46

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 193203358   24 CAVCYSEMILPTtIPSCGHKFCFICLKgVSVSNNGDCPICRGP 66
Cdd:TIGR00599  29 CHICKDFFDVPV-LTSCSHTFCSLCIR-RCLSNQPKCPLCRAE 69

Modified RING finger, HC subclass (C3HC5-type), found in neuralized-like protein 1B (NEURL1B); NEURL1B, also known as neuralized-2 (NEUR2) or neuralized-like protein 3, is a mammalian homolog of the Drosophila neuralized (D-neu) protein. It functions as an E3 ubiquitin-protein ligase that interacts with and ubiquitinates Delta. Thus, it plays a role in the endocytic pathways for Notch signaling through working cooperatively with another E3 ligase, Mind bomb-1 (Mib1), in Delta endocytosis to hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs)-positive vesicles. NEURL1B contains two neuralized homology regions (NHRs) responsible for Neural-ligand interactions and a modified C3HC5-type RING-HC finger required for ubiquitin ligase activity. The C3HC5-type RING-HC finger is distinguished from typical C3HC4-type RING-HC finger due to the existence of the additional cysteine residue in the middle portion of the RING finger domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 193203358  21 DKECAVCYSEMIlPTTIPSCGHK-FCFICLKGVSVSNNGDCPICRGPIDSQI 71
Cdd:cd16786    2 NGECTVCFDSEV-DTVIYTCGHMcLCNSCGLKLKRQINACCPICRRVIKDVI 52

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 193203358  21 DKECAVCYSEMI---LPTTIPSCGHKFCFICLKGVSVSNNGDCPICRGP 66
Cdd:cd23121    1 DDCCAICLSDFNsdeKLRQLPKCGHIFHHHCLDRWIRYNKITCPLCRAD 49

N1R/p28-like protein; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 193203358  17 NSTIDKECAVC----YSEMILPT---TIPSCGHKFCFICLKGVSVSNNgDCPICRGP----IDSQIFKK 74
Cdd:PHA02929 170 NRSKDKECAICmekvYDKEIKNMyfgILSNCNHVFCIECIDIWKKEKN-TCPVCRTPfisvIKSRFFTK 237

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 193203358  24 CAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNGD---CPICRGP 66
Cdd:cd16597    8 CSICLELFKDPVTLP-CGHNFCGVCIEKTWDSQHGSeysCPQCRAT 52

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; This subfamily contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 193203358  22 KECAVCYSEMILPTTIPSCGHKFCFICLKGvSVSNNGDCPICR 64
Cdd:cd16506    1 DTCPICLDEIQNKKTLEKCKHSFCEDCIDR-ALQVKPVCPVCG 42

Modified RING finger, HC subclass (C3HC3D-type), found in uncharacterized proteins similar to tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4); This subfamily corresponds to a group of uncharacterized proteins that shows high sequence similarity with tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4). TRAF4, also known as cysteine-rich domain associated with RING and Traf domains protein 1, or metastatic lymph node gene 62 protein (MLN 62), or RING finger protein 83 (RNF83), is a member of TRAF protein family, which mainly function in the immune system, where they mediate signaling through tumor necrosis factor receptors (TNFRs) and interleukin-1/Toll-like receptors (IL-1/TLRs). It also plays a critical role in the nervous system, as well as in carcinogenesis. Like TRAF4, members of this subfamily contain a modified C3HC3D-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 193203358  23 ECAVCYSEMILPTTIPSCGHKFCFICLKGVsVSNNGDCPICRGPID 68
Cdd:cd23126    6 ECPVCCQVLRYPVQFEECGHRVCSSCLPEL-LRVEPRCPIDQGPID 50

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 193203358  24 CAVCYSEMILPTTIPsCGHKFCFICLKGV-SVSNNG--DCPICRGPIDSQ 70
Cdd:cd16609    6 CSICLGLYQDPVTLP-CQHSFCRACIEDHwRQKDEGsfSCPECRAPFPEG 54

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 193203358   2 NASTSSPSQQLQQAINstidkeCAVCYSEMILPTTIPsCGHKFCFIC-LKGVSVSNNGDCPICRGPIDSQIFKK 74
Cdd:COG5236   48 NLTTSSADDTDEENMN------CQICAGSTTYSARYP-CGHQICHACaVRLRALYMQKGCPLCRTETEAVVFTA 114

RING finger, HC subclass, found in Candida albicans transcriptional regulator of yeast form adherence 3 (TRY3) and similar proteins; TRY3 acts as a transcription factor required for yeast cell adherence to silicone substrate. It contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 193203358  21 DKECAVCYSEMILPTTIpSCGHKFCFICLKGVSVSNNGDCPICRGP 66
Cdd:cd23137    2 DYACPICMNVAWKPVRL-ECSHVFCLRCLVKAQKQKKDNCPLCRAK 46

RING finger, HC subclass, found in really interesting new gene 1 protein (RING1) and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), was identified as a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. It is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase that transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING1 interacts with multiple PcG proteins and displays tumorigenic activity. It also shows zinc-dependent DNA binding activity. Moreover, RING1 inhibits transactivation of the DNA-binding protein recombination signal binding protein-Jkappa (RBP-J) by Notch through interaction with the LIM domains of KyoT2. RING1 contains a C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 193203358  24 CAVCYSEMILPTTIPSCGHKFCFICLKGVSVSNNGDCPICRGPIDSQ 70
Cdd:cd16739    6 CPICLDMLKNTMTTKECLHRFCSDCIVTALRSGNKECPTCRKKLVSK 52

RING finger, HC subclass, found in RNA-binding protein MEX3A; MEX3A, also known as RING finger and KH domain-containing protein 4 (RKHD4), is an RNA-binding phosphoprotein that localizes in P-bodies and stress granules, which are two structures involved in the storage and turnover of mRNAs. It has been implicated in the regulation of tumorigenesis. It controls the polarity and stemness of intestinal epithelial cells through the post-transcriptional regulation of the homeobox transcription factor CDX2, which plays a crucial role in intestinal cell fate specification, both during normal development and in tumorigenic processes involving intestinal reprogramming. Moreover, it exhibits a transforming activity when overexpressed in gastric epithelial cells. MEX3A contains two K homology (KH) domains that provide RNA-binding capacity, and a C-terminal C3HC4-type RING-HC finger. Like other MEX-3 family proteins, MEX3A shuttles between the nucleus and the cytoplasm via the CRM1-dependent export pathway.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 193203358  22 KECAVCYSEMILPTTIPsCGHK-FCFICLKGVSVSNNGDCPICRGPIDSQI 71
Cdd:cd16720    3 RDCMVCFESEVTAALVP-CGHNlFCMECAVRICERNEPECPVCHALATQAI 52

RING finger, HC subclass, found in Mus musculus tripartite motif-containing protein 43 (TRIM43) and similar propteins; This subfamily includes TRIM43A, TRIM43B and TRIM43C, which are expressed specifically in mouse preimplantation embryos. They contain a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 193203358  24 CAVCYSEMILPTTIpSCGHKFCFIC--LKGVSVSNNGDCPICRGPIDSQ 70
Cdd:cd23133    6 CSICQGIFMNPVYL-RCGHKFCEACllLFQEDIKFPAYCPMCRQPFNQE 53

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 193203358  24 CAVCYSEMILPTTIPsCGHKFCFICLKGVSVSNNG-DCPICRGP 66
Cdd:cd16608    9 CSICLSIYQDPVSLG-CEHYFCRQCITEHWSRSEHrDCPECRRT 51

RING finger, HC subclass, found in RING finger protein 186 (RNF186) and similar proteins; RNF186 is an E3 ubiquitin-protein ligase with an N-terminal C3HC4-type RING-HC finger and two putative C-terminal transmembrane domains which enable it to localize in a certain organelle. It regulates RING-dependent self-ubiquitination, as well as endoplasmic reticulum (ER) stress-mediated apoptosis through interaction with the Bcl-2 family protein BNip1.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 193203358  21 DKECAVC---YSEMILPTTIPSCGHKFCFICLKGVSVSNNG----DCPICR 64
Cdd:cd16557    1 DLECLVCrnpYSCFVRKPKLLACQHAFCAICLKLILCEQDGtwsvTCPLCR 51