B-box-type 2 zinc finger found in tripartite motif-containing protein 65 (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 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 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767993996  93 ARCPRHGRPLELFCRTEGRCVCSVCTVRECRLHERALLDAER 134
Cdd:cd19835    1 TLCQRHGRPLELYCRTEKRCVCCKCTVKECRNHNRVLLEEER 42

B-box-type 2 zinc finger found in tripartite motif-containing protein 65 (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 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 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767993996  93 ARCPRHGRPLELFCRTEGRCVCSVCTVRECRLHERALLDAER 134
Cdd:cd19835    1 TLCQRHGRPLELYCRTEKRCVCCKCTVKECRNHNRVLLEEER 42

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 767993996    12 CAICLGLY-QDPVTLPCGHNFCGACIRDWWDRCGKACPEC 50
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 767993996   12 CAICLGLYQDPV-TLPCGHNFCGACIRDWWDRCGKACPEC 50
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLESGNVTCPLC 40

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 767993996   94 RCPRHGR-PLELFCRTEGRCVCSVCTVRECRLHERALL 130
Cdd:pfam00643   5 LCPEHEEePLTLYCNDCQELLCEECSVGEHRGHTVVPL 42

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 767993996    92 AARCPRHG-RPLELFCRTEGRCVCSVCTVRECRLHERALL 130
Cdd:smart00336   3 APKCDSHGdEPAEFFCEECGALLCRTCDEAEHRGHTVVLL 42

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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGK---ACPECREPFPDGAELRRNVALSGVLE 71
Cdd:cd16597    2 LEEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQHGseySCPQCRATFPRRPELHKNTVLRNIVE 70

B-box-type 2 zinc finger found in tripartite motif-containing protein 65 (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 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 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767993996  93 ARCPRHGRPLELFCRTEGRCVCSVCTVRECRLHERALLDAER 134
Cdd:cd19835    1 TLCQRHGRPLELYCRTEKRCVCCKCTVKECRNHNRVLLEEER 42

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGK--ACPECREPFPDG 57
Cdd:cd16611    1 LTEELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEdtTCPECRELCQYR 54

PRY/SPRY domain in tripartite motif-containing domain 65 (TRIM65); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM65 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not been characterized.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767993996 335 LRRKLWQNYRNLTFDPVSANRHFYLSRQDQQVESC--SLKKTYSDPNPQDLW 384
Cdd:cd12896    1 LRAELWKDYRNLTFDPRTANKYLELSRQNRRAKHGrsAARGVPASPGSFELW 52

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 767993996   8 EKLTCAICLGLYQDPVTL-PCGHNFCGACIRDWWDRCGKACPECR 51
Cdd:cd16503    1 ENLTCSICQDLLHDCVSLqPCMHNFCAACYSDWMERSNTECPTCR 45

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 767993996   8 EKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECREPFP 55
Cdd:cd23138    1 DELNCSFCMQLPERPVTTPCGHNFCLKCFQKWMGQGKKTCGTCRSPIP 48

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        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA----CPECREPF 54
Cdd:cd16598    1 LEEEVTCSICLDYLRDPVTIDCGHNFCRSCITDYCPISGGHerpvCPLCRKPF 53

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V 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 domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWW--DRCGKACPECREPFPDGAELRRN 63
Cdd:cd16580    8 FEEELICPICLHVFVEPVQLPCKHNFCRGCIGEAWakDAGLVRCPECNQAYNQKPSLEKN 67

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 767993996   7 EEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWdrcGKACPECREPFP 55
Cdd:cd16602    1 QEEAVCAICLDYFKDPVSIGCGHNFCRVCVTQLW---GFTCPQCRKSFP 46

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIR-DWWDRCGKA----------CPECREPFP 55
Cdd:cd16595    2 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQlSWEKARGKKgrrkqkgsfpCPECREMSP 62

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 767993996  12 CAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA--CPEC 50
Cdd:cd16601    4 CSLCKEYLKDPVIIECGHNFCRACITRFWEELDGDfpCPQC 44

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 767993996   7 EEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWD--RCGKACPECREPF 54
Cdd:cd23133    1 EETLTCSICQGIFMNPVYLRCGHKFCEACLLLFQEdiKFPAYCPMCRQPF 50

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 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWW-DRCGKACPECREP 53
Cdd:cd16568    1 ILETQECIICHEYLYEPMVTTCGHTYCYTCLNTWFkSNRSLSCPDCRTK 49

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 767993996   12 CAICLGLYQDPV-TLPCGHNFCGACIRDWWDRCGKACPEC 50
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLESGNVTCPLC 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 767993996  10 LTCAICLGLYQDPVTLPCGHNFCGACIrdwwDRC---GKACPECREP 53
Cdd:cd16514    2 LECSLCLRLLYEPVTTPCGHTFCRACL----ERCldhSPKCPLCRTS 44

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 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        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA--------CPECREPF 54
Cdd:cd16600    2 MREEATCSICLQLMTEPVSINCGHSYCKRCIVSFLENQSQLepgletfsCPQCRAPF 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 767993996   12 CAICLGLYQDPVTLPCGHNFCGACIRDWW---DRCGKACPEC 50
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQkepDGESLLCPQC 42

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACI-----RDWWDRCGKACPECREPFPDGaELRRNVALSGVLE 71
Cdd:cd16591    3 IKEEVTCPICLELLTEPLSLDCGHSFCQACItanhkESVNQEGESSCPVCRTSYQPE-NLRPNRHLANIVE 72

RING finger, HC subclass, found in RING finger protein 180 (RNF180) and similar proteins; RNF180, also known as Rines, is a membrane-bound E3 ubiquitin-protein ligase well conserved among vertebrates. It is a critical regulator of the monoaminergic system, as well as emotional and social behavior. It interacts with brain monoamine oxidase A (MAO-A) and targets it for ubiquitination and degradation. It also functions as a novel tumor suppressor in gastric carcinogenesis. The hypermethylated CpG site count of the RNF180 DNA promoter can be used to predict survival of gastric cancer. RNF180 contains a novel conserved dual specificity protein phosphatase Rines conserved (DSPRC) domain, a basic coiled-coil domain, a C3HC4-type RING-HC finger, and a C-terminal hydrophobic region that is predicted to be a transmembrane domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 767993996   8 EKLTCAICLGLYQDPVTL-PCGHNFCGACIRDWW-DRCGKA-CPECREP 53
Cdd:cd16554    1 ESLTCPVCLDLYYDPYMCyPCGHIFCEPCLRQLAkSSPKNTpCPLCRTT 49

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        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 767993996   8 EKLTCAICLGLYQDPVTLPCGHNFCGACI------RDWWDRCGKACPECR 51
Cdd:cd16581    1 EELTCSICYNIFDDPKILPCSHTFCKNCLekllaaSGYYLLASLKCPTCR 50

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; 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). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates melanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 belongs 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. In addition, TRIM13 contains a C-terminal transmembrane domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767993996   7 EEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA--------CPECRE 52
Cdd:cd16762    1 EEDLTCPICCCLFDDPRVLPCSHNFCKKCLEGILEGNVRTmlwrppfkCPTCRK 54

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767993996   9 KLTCAICLGLYQDPVTLPCGHNFCGACIRDWWD--RCGKACPECREPFPDGA 58
Cdd:cd16551    1 ELTCAGCLEVPVEPATLPCGHTLCRGCANRALDaaEAGPTCPRCRAPLPGWA 52

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 767993996  10 LTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRcGKACPECREPF 54
Cdd:cd16535    2 LQCSICSELFIEAVTLNCSHSFCSYCITEWMKR-KKECPICRKPI 45

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767993996   4 QLLEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA--CPECREPFPdgaelRRNVA--------LSGVLEVV 73
Cdd:cd16498   11 SAMQKNLECPICLELLKEPVSTKCDHQFCRFCILKLLQKKKKPapCPLCKKSVT-----KRSLQestrfkqlVEAVKKLI 85

                 ..
gi 767993996  74 RA 75
Cdd:cd16498   86 DA 87

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM60, TRIM61, TRIM75 and similar proteins; TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. RNF33 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM75 mainly localizes within spindles, suggesting it may function in spindle organization and thereby affect meiosis. Both TRIM60 and TRIM75 belong 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 B2-box, and two coiled coil domains, as well as a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of the TRIM family that contains RBCC domains only. Its biological function remains unclear.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 767993996  12 CAICLGLYQDPVTLPCGHNFCGACIR-DWWDRCGK-ACPECREPF 54
Cdd:cd16607    4 CPICLDYLKDPVTINCGHNFCRSCISmSWKDLQDTfPCPVCRFCC 48

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 767993996  10 LTCAICLGLYQDPVTLPCGHNFCGACIRDWWdRCGKACP 48
Cdd:cd16637    2 LTCHICLQPLVEPLDTPCGHTFCYKCLTNYL-KIQQCCP 39

RING finger, HC subclass, found in BRCA1-associated RING domain protein 1 (BARD-1) and similar proteins; BARD-1 is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an C3HC4-type RING-HC finger that binds BRCA1 at its N-terminus and three tandem ankyrin repeats and tandem BRCT repeat domains at its C-terminus. The BRCT repeats bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767993996   2 AAQLLEEKLTCAICLGLYQDPVTL-PCGHNFCGACIRdwwDRCGKACPECREP 53
Cdd:cd16496    8 ALDELENLLRCSRCASILKEPVTLgGCEHVFCRSCVG---DRLGNGCPVCDTP 57

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1 or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway by interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 767993996  11 TCAICLGLYQDPVT---LPCGHNFCGACIRDWWDRCGKACPECREP 53
Cdd:cd16473    6 ECAICLENYQNGDLlrgLPCGHVFHQNCIDVWLERDNHCCPVCRWP 51

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 767993996  11 TCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECR 51
Cdd:cd16550    2 LCPICLEILVEPVTLPCNHTLCMPCFQSTVEKASLCCPLCR 42

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767993996   8 EKLTCAICLglyqDP---------VTLPCGHNFCGACIRDWWDRCGKACPECREPF 54
Cdd:cd16450    1 EGNTCPICF----EPwtssgehrlVSLKCGHLFGYSCIEKWLKGKGKKCPQCNKKA 52

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        40
                 ....*....|....*....|....*....|....*....|.
gi 767993996  11 TCAICLGLYQDPVTLPCGHNFCGACIRDWWDRcGKACPECR 51
Cdd:cd16532    2 ICPICQDEFKDPVVLRCKHIFCEDCVSEWFER-ERTCPLCR 41

RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 belongs 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, including 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. MID1 hetero-dimerizes in vitro with its paralog MID2.

                         10        20        30
                 ....*....|....*....|....*....|
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGAC 35
Cdd:cd16753    2 LESELTCPICLELFEDPLLLPCAHSLCFNC 31

RING finger, HC subclass, found in tripartite motif-containing protein 68 (TRIM68) and similar proteins; TRIM68, also known as RING finger protein 137 (RNF137) or SSA protein SS-56 (SS-56), is an E3 ubiquitin-protein ligase that negatively regulates Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I interferon production by degrading TRK fused gene (TFG), a novel driver of IFN-beta downstream of anti-viral detection systems. It also functions as a cofactor for androgen receptor-mediated transcription by regulating ligand-dependent transcription of androgen receptor in prostate cancer cells. Moreover, TRIM68 is a cellular target of autoantibody responses in Sjogre's syndrome (SS), as well as systemic lupus erythematosus (SLE). It is also an auto-antigen for T cells in SS and SLE. TRIM68 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 767993996   9 KLTCAICLGLYQDPVTLPCGHNFCGACIRDWWD------RCGKACPECR 51
Cdd:cd16610    1 EVACPICMTFLREPVSIDCGHSFCHSCLSGLWEvpgesqNWGYTCPLCR 49

RING finger, HC subclass, found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9, 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 the neurodegenerative disorders through its ligase activity. It interacts with the WD repeat region of beta-transducin repeat-containing protein (beta-TrCP) through its N-terminal degron motif depending on the phosphorylation status, and thus negatively regulates nuclear factor-kappaB (NF-kappaB) activation in the NF-kappaB pro-inflammatory signaling pathway. Moreover, TRIM9 acts as a critical catalytic link between Netrin-1 and the exocytic soluble NSF attachment receptor protein (SNARE) machinery in murine cortical neurons. It promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. TRIM9 belongs 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, including 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.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 767993996   7 EEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA--------CPEC 50
Cdd:cd16755    1 EEELKCPVCGSFYREPIILPCSHNLCLACARNILVQTPEAespqscltCPQC 52

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.

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                 ....*....|....*....|....*....|....*....|....*...
gi 767993996   8 EKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKA-CPECREPF 54
Cdd:cd23132    1 EEFLCCICLDLLYKPVVLECGHVFCFWCVHRCMNGYDEShCPLCRRPY 48

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

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                 ....*....|....*....|....*....|....*....|....*.
gi 767993996  11 TCAICLGLYQDPVTL--PCGHNFCGACIRDWWDRcGKACPECREPF 54
Cdd:cd16574    3 SCPICLDRFENEKAFldGCFHAFCFTCILEWSKV-KNECPLCKQPF 47

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, HIP116, RING finger protein 80, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767993996  12 CAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECREP 53
Cdd:cd16509    6 CAICLDSLTNPVITPCAHVFCRRCICEVIQREKAKCPMCRAP 47

RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 homolog (AtBRCA1) and similar proteins; AtBRCA1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBRCA1 contains a typical C3HC4-type RING-HC finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 767993996   6 LEEKLTCAICLGLYQDPVTLPCGHNFCGACIRDWWdRCGKACPECREP 53
Cdd:cd23147    1 LGKELKCPICLSLFKSAANLSCNHCFCAGCIGESL-KLSAICPVCKIP 47

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767993996  12 CAICLGLYQDPVTLPCGHNFCGACIRDWWDRCGKACPECREP 53
Cdd:cd16664    6 CPISLELMKDPVILATGQTYERAAIEKWLDSGNNTCPITGQP 47

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 767993996   11 TCAICLGLY---QDPVTLPCGHNFCGACIRDWWDRCGKaCPECR 51
Cdd:pfam13639   2 ECPICLEEFeegDKVVVLPCGHHFHRECLDKWLRSSNT-CPLCR 44

first 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 first RING-HC finger.

                         10        20
                 ....*....|....*....|....*...
gi 767993996  10 LTCAICLGLYQDPVTLPCGHNFCGACIR 37
Cdd:cd16513    3 LSCPLCRGLLFEPVTLPCGHTFCKRCLE 30

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 767993996  12 CAICLGLYQDPVTLPCGHNFCGACIRDWWD--RCGKACPECR 51
Cdd:cd16534    3 CNICLDTASDPVVTMCGHLFCWPCLYQWLEtrPDRQTCPVCK 44