B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 38524612  87 KVCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19787   1 ESCPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 38524612  87 KVCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19787   1 ESCPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

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 38524612     16 CPICLEVFKESLM-LQCGHSYCKGCLvsLSYHLDTKVRCPMC 56
Cdd:smart00184   1 CPICLEEYLKDPViLPCGHTFCRSCI--RKWLESGNNTCPIC 40

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 38524612   6 SLLELEDWLQCPICLEVFKESLMLQCGHSYCKGCLVSlsyHLDTKVRCPMCWQVVDGSSSLPNVSLAWVIEALRLPGD 83
Cdd:COG5432  18 SLKGLDSMLRCRICDCRISIPCETTCGHTFCSLCIRR---HLGTQPFCPVCREDPCESRLRGSSGSREINESHARNRD 92

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 38524612     85 EPKVC-VHHRNPLSLFCEKDQELICGLCgLLGSHQHHPVTPV 125
Cdd:smart00336   2 RAPKCdSHGDEPAEFFCEECGALLCRTC-DEAEHRGHTVVLL 42

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 38524612  87 KVCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19787   1 ESCPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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 38524612  10 LEDWLQCPICLEVFKESLMLQCGHSYCKGClVSLSYHLDTKVRCPMCWQVV 60
Cdd:cd16599   1 FKEELLCPICYEPFREAVTLRCGHNFCKGC-VSRSWERQPRAPCPVCKEAS 50

B-box-type 2 zinc finger found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis via targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 38524612  89 CVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPVS 126
Cdd:cd19797   3 CEEHLDPLSVYCEQDRALICGVCASLGKHKGHNIITAA 40

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 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 two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38524612  11 EDWLQCPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVRCPMC 56
Cdd:cd16543   1 EDQLTCSICLDLLKDPVTIPCGHSFCMNCITLLWDRKQGVPSCPQC 46

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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVRCPMCWQVVDGSSSLPN 68
Cdd:cd16611   5 LHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEDTTCPECRELCQYRNLTPN 59

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 38524612   8 LELEDWLQCPICLEVFKESLMLQCGHSYCKGCLVSL---SYHLDTKVRCPMCWQVVDGSSSLPNVSLAWVIE 76
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANhkeSVNQEGESSCPVCRTSYQPENLRPNRHLANIVE 72

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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLvsLSYHLDTKVRCPMC 56
Cdd:cd16449   1 LECPICLERLKDPVLLPCGHVFCRECI--RRLLESGSIKCPIC 41

RING finger, HC subclass, found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of the peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis by targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTK-VRCPMC 56
Cdd:cd16612   5 LSCPLCLKLFQSPVTTECGHTFCQDCLSRVPKEEDGGsTSCPTC 48

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 38524612  15 QCPICLEVFKESLMLQCGHSYCKGCLVS-LSYHLDTKVRCPMCWQVV 60
Cdd:cd16536   2 QCPICLEPPVAPRITRCGHIFCWPCILRyLSLSEKKWRKCPICFESI 48

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM7, TRIM27 and similar proteins; The family includes TRIM7 and TRIM27, both of which belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by an 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. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM27, also termed RING finger protein 76 (RNF76), or RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. It also inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. Furthermore, TRIM27 promotes non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. In addition, TRIM27 forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is also a component of an estrogen receptor 1 (ESR1) regulatory complex, and is involved in estrogen receptor-mediated transcription in MCF-7 cells. Meanwhile, TRIM27 interacts with the hinge region of chromosome 3 protein (SMC3), a component of the multimeric cohesin complex that holds sister chromatids together and prevents their premature separation during mitosis.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 38524612  88 VCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19762   2 VCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPV 39

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM60, TRIM61, TRIM75 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM60, TRIM61 and TRIM75. 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. TRIM60 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). TRIM61 is closely related to TRIM60, but its biological function remains unclear. TRIM75 could be the product of a pseudogene. Its biological function remains unclear. TRIM60 and TRIM75 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 RING finger, Bbox2, and two coiled coil domains, as well as 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 TRIM family that contains RBCC domains only. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 38524612  88 VCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19791   2 LCEKHNQPLTKFCKKDLEPLCPQCSQSTDHQHHVVVPL 39

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 38524612    16 CPICLEVFKE-SLMLQCGHSYCKGCLVslSYHLDTKVRCPMC 56
Cdd:pfam00097   1 CPICLEEPKDpVTLLPCGHLFCSKCIR--SWLESGNVTCPLC 40

B-box-type 2 zinc finger found in tripartite motif-containing protein 59 (TRIM59) and similar proteins; TRIM59, also known as TRIM57, or 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. It is upregulated in gastric cancer and promotes gastric carcinogenesis by interacting with and targeting the P53 tumor suppressor for its ubiquitination and degradation. It also acts as a novel accessory molecule involved in cytotoxicity of BCG-activated macrophages (BAM). Moreover, TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. It interacts with ECSIT and negatively regulates nuclear factor-kappaB (NF- kappa B) and interferon regulatory factor (IRF)-3/7-mediated signal pathways. TRIM59 belongs to the C-XI subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region. In addition, TRIM59 contains a C-terminal transmembrane domain.

                        10        20        30
                ....*....|....*....|....*....|..
gi 38524612  91 HHRNPLSLFCEKDQELICGLCGLLGSHQHHPV 122
Cdd:cd19790   6 HYRQPLNLFCLLDRKLICGQCLTVGQHQGHPI 37

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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVRCPMC 56
Cdd:cd16601   2 ASCSLCKEYLKDPVIIECGHNFCRACITRFWEELDGDFPCPQC 44

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM4, TRIM17, TRIM41, TRIM52 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM4, TRIM17, TRIM41 and TRIM52. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at mitochondria. 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 mitotic spindle checkpoint, and negatively regulates cell proliferation. 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. TRIM4, TRIM17 and TRIM41 belong 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of TRIM family that contains only RBCC domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 38524612  87 KVCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19760   1 GLCEKHQEPLKLFCEEDEALICVICRESRAHRAHTVVPI 39

RING finger, HC subclass, found in Caenorhabditis elegans RING finger protein NHL-1 and similar proteins; NHL-1 functions as an E3 ubiquitin-protein ligase in the presence of both UBC-13 and UBC-1 within the ubiquitin pathway of Caenorhabditis elegans. It acts in chemosensory neurons to promote stress resistance in distal tissues by the transcription factor DAF-16 activation but is dispensable for the activation of heat shock factor 1 (HSF-1). NHL-1 belongs to the TRIM (tripartite motif)-NHL 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 NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 38524612   9 ELEDWLQCPICLEVFKESLMLQCGHSYC-KGCLVSLSYHLDTKVRCPMC 56
Cdd:cd16524   1 QIEQLLTCPICLDRYRRPKLLPCQHTFClSPCLEGLVDYVTRKLKCPEC 49

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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGClvsLSYHLDTKVRCPMCWQVV 60
Cdd:cd16514   2 LECSLCLRLLYEPVTTPCGHTFCRAC---LERCLDHSPKCPLCRTSL 45

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSL----SYHLDTKVRCPMC 56
Cdd:cd16581   3 LTCSICYNIFDDPKILPCSHTFCKNCLEKLlaasGYYLLASLKCPTC 49

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM39, TRIM58 and similar proteins; The family includes TRIM39 and TRIM58, both of which belong 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 SPRY/B30.2 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. TRIM39, also termed 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 and modulates cell cycle progression and DNA damage responses via stabilization of p21. TRIM39 also 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 (TNFalpha). 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. TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38524612  85 EPKVCVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPVS 126
Cdd:cd19780   1 EESLCARHREALSLFCEEDQEAVCLVCEISHDHRAHTLVPLQ 42

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 38524612  14 LQCPICLEVFKESL----MLQCGHSYCKGCLVSL--SYHLDTkVRCPMCWQV 59
Cdd:cd16587   1 LECPICLESFDEGQlrpkLLHCGHTICEQCLEKLlaSLSING-VRCPFCRKV 51

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLV-SLSyhlDTKVRCP 54
Cdd:cd16643   2 YECPICLMALREPVQTPCGHRFCKACILkSIR---EAGHKCP 40

RING finger, HC subclass, found in midline-2 (MID2) and similar proteins; MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), is a probable E3 ubiquitin-protein ligase and is highly related to MID1 that associates with cytoplasmic microtubules along their length and throughout the cell cycle. Like MID1, MID2 associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with Alpha 4, which is a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. MID2 can also substitute for MID1 to control exocytosis of lytic granules in cytotoxic T cells. Loss-of-function mutations in MID2 lead to the human X-linked intellectual disability (XLID). MID2 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 (carboxy-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. MID2 hetero-dimerizes in vitro with its paralog MID1.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 38524612  10 LEDWLQCPICLEVFKESLMLQCGHSYCKGC----LVSLSYHLD-----TKVRCPMCWQVV 60
Cdd:cd16754   4 LESELTCPICLELFEDPLLLPCAHSLCFSCahriLTSGCASGEsieppSAFQCPTCRYVI 63

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 38524612     16 CPICLEVFKESLM-LQCGHSYCKGCLvsLSYHLDTKVRCPMC 56
Cdd:smart00184   1 CPICLEEYLKDPViLPCGHTFCRSCI--RKWLESGNNTCPIC 40

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 38524612     6 SLLELEDWLQCPICLEVFKESLMLQCGHSYCKGCLVSlsyHLDTKVRCPMC 56
Cdd:TIGR00599  19 SLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRR---CLSNQPKCPLC 66

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 38524612    84 PEPKVC-VHHRNPLSLFCEKDQELICGLCgLLGSHQHHPVTPV 125
Cdd:pfam00643   1 SKERLCpEHEEEPLTLYCNDCQELLCEEC-SVGEHRGHTVVPL 42

Variant RING finger, HC subclass (C4C4-type), found in retinoblastoma-binding protein 6 (RBBP6) and similar proteins; RBBP6, also known as proliferation potential-related protein, protein P2P-R, retinoblastoma-binding Q protein 1 (RBQ-1), or p53-associated cellular protein of testis (PACT), is a nuclear E3 ubiquitin-protein ligase involved in multiple processes, such as the control of gene expression, mitosis, cell differentiation, and cell apoptosis. It plays a role in both promoting and inhibiting apoptosis in many human cancers, including esophageal, lung, hepatocellular, and colon cancers, familial myeloproliferative neoplasms, as well as in human immunodeficiency virus-associated nephropathy (HIVAN). It functions as an Rb- and p53-binding protein that plays an important role in chaperone-mediated ubiquitination and possibly in protein quality control. It acts as a scaffold protein to promote the assembly of the p53/TP53-MDM2 complex, resulting in an increase of MDM2-mediated ubiquitination and degradation of p53/TP53, and leading to both apoptosis and cell growth. It is also a double-stranded RNA-binding protein that plays a role in mRNA processing by regulating the human polyadenylation machinery and modulating expression of mRNAs with AU-rich 3' untranslated regions (UTRs). Moreover, RBBP6 ubiquitinates and destabilizes the transcriptional repressor ZBTB38 that negatively regulates transcription and levels of the MCM10 replication factor on chromatin. Furthermore, RBBP6 is involved in tunicamycin-induced apoptosis by mediating protein kinase (PKR) activation. RBBP6 contains an N-terminal ubiquitin-like domain and a C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger. RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. It promotes the ubiquitination of p53 by Hdm2 in an E4-like manner through its RING finger. It also interacts directly with the pro-proliferative transcription factor Y-box-binding protein-1 (YB-1) via its RING finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 38524612  14 LQCPICLEVFKESLMLQ-CGHSYCKGCLvsLSYHLDTKVRCPMC 56
Cdd:cd16620   4 LKCPICKDLMKDAVLTPcCGNSFCDECI--RTALLEEDFTCPTC 45

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3) and similar proteins; DTX3, also known as RING finger protein 154 (RNF154), is an E3 ubiquitin-protein ligase that belongs to the Deltex (DTX) family. In contrast to other DTXs, DTX3 does not contain two N-terminal Notch-binding WWE domains, but a short unique N-terminal domain, suggesting it does not interact with the intracellular domain of Notch. Its C-terminal region includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38524612  15 QCPICLEVFKESLML-QCGHSYCKGClvsLSYHLDTKVRCPMC 56
Cdd:cd16711   3 TCPICLGEIQNKKTLdKCKHSFCEDC---ITRALQVKKACPMC 42

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 38524612  14 LQCPICLEVFKESLMLQ-CGHSYCKGCLVSLSYHLDTKVRCPMCWQVV 60
Cdd:cd16554   3 LTCPVCLDLYYDPYMCYpCGHIFCEPCLRQLAKSSPKNTPCPLCRTTI 50

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 38524612  10 LEDWLQCPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVR---------CPMCWQVVDGSSSLPN 68
Cdd:cd16595   2 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGrrkqkgsfpCPECREMSPQRNLRPN 69

RING finger, HC subclass, found in tripartite motif-containing protein 31 (TRIM31) and similar proteins; TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM31 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, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 38524612  16 CPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVRCPMC 56
Cdd:cd16582   4 CPICLDILQKPVTIDCGHNFCLQCITQIGETSCGFFKCPLC 44

B-box-type 2 zinc finger 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 Sjogren'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 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 two coiled coil domains, 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
                ....*....|....*....|....*....|....*..
gi 38524612  89 CVHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPV 125
Cdd:cd19795   4 CERHKEKLNLFCEEDQELLCVVCEQSPEHKAHTVVPV 40

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 38524612  14 LQCPICLEVFKESLML-QCGHSYCKGCLVSLSYHldTKVRCPMCWQVVDGS 63
Cdd:cd16544   3 LTCPVCQEVLKDPVELpPCRHIFCKACILLALRS--SGARCPLCRGPVGKT 51

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
                ....*....|....*....|....*....|....*....|....*..
gi 38524612  16 CPICLEVFKESL-MLQCGHSYCKGCLVSLSyhLDTKVRCPMCWQVVD 61
Cdd:cd16564   3 CPVCYEDFDDAPrILSCGHSFCEDCLVKQL--VSMTISCPICRRVTF 47

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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSLsyhLDTKVRCPMC 56
Cdd:cd23135   4 LSCSICFSEIRSGAILKCGHFFCLSCIASW---LREKSTCPLC 43

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 38524612  11 EDWLQCPICLEVFKESLMLQCGHSYCKGCLV-SLSYHLDTKVRCPMC 56
Cdd:cd16609   1 EEELTCSICLGLYQDPVTLPCQHSFCRACIEdHWRQKDEGSFSCPEC 47

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 38524612  16 CPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVRCPMC 56
Cdd:cd16607   4 CPICLDYLKDPVTINCGHNFCRSCISMSWKDLQDTFPCPVC 44

RING finger, HC subclass, found in midline-1 (MID1), midline-2 (MID2) 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. MID2, also known as midin-2, midline defect 2, RING finger protein 60 (RNF60), or tripartite motif-containing protein 1 (TRIM1), associates with the microtubule network and may at least partially compensate for the loss of MID1. Both MID1 and MID2 interacts with Alpha 4, which is a regulatory subunit of PP2-type phosphatases, such as PP2A, and an integral component of the rapamycin-sensitive signaling pathway. They also play a central role in the regulation of granule exocytosis. Functional redundancy exists between MID1 and MID2 in cytotoxic lymphocytes (CTL). Both MID1 and MID2 belong to the C-I subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, 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
                ....*....|....*....|....*.
gi 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGC 39
Cdd:cd16575   1 LTCPICLELFEDPLLLPCAHSLCFNC 26

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSLSYHLDTKVRCPMC 56
Cdd:cd16551   2 LTCAGCLEVPVEPATLPCGHTLCRGCANRALDAAEAGPTCPRC 44

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 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 38524612   9 ELEDWLQCPICLEVFKESLMLQCGHSYCKGCLVSLSYH----LDTKVRCPMC 56
Cdd:cd16593   1 SLADEVNCPICQGTLREPVTIDCGHNFCRACLTRYCEIpgpdLEEPPTCPLC 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 38524612  16 CPICLEVFKESLMLQCGHSYCKGClvsLSYHLDTKVRCPMC 56
Cdd:cd16532   3 CPICQDEFKDPVVLRCKHIFCEDC---VSEWFERERTCPLC 40

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 38524612  14 LQCPICLEVFKESLMLQCGHSYCKGCLVSL----SYHLDTKVRCPMC 56
Cdd:cd16610   2 VACPICMTFLREPVSIDCGHSFCHSCLSGLwevpGESQNWGYTCPLC 48

RING finger found in polycomb group RING finger protein 6 (PCGF6) and similar proteins; PCGF6, also known as Mel18 and Bmi1-like RING finger (MBLR), or RING finger protein 134 (RNF134), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR). It serves as the core component of a noncanonical Polycomb repressive complex 1 (PRC1)-like L3MBTL2 complex, which is composed of some canonical components, such as RNF2, CBX3, CXB4, CXB6, CXB7, and CXB8, as well as some noncanonical components, such as L3MBTL2, E2F6, WDR5, HDAC1, and RYBP, and plays a critical role in epigenetic transcriptional silencing in higher eukaryotes. Like other PCGF homologs, PCGF6 possesses the transcriptional repression activity, and also associates with ring finger protein 2 (RNF2) to form a RNF2-PCGF heterodimer, which is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. Moreover, PCGF6 can regulate the enzymatic activity of JARID1d/KDM5D, a trimethyl H3K4 demethylase, through direct interaction. Furthermore, PCGF6 is expressed predominantly in meiotic and post-meiotic male germ cells and may play important roles in mammalian male germ cell development. It also regulates mesodermal lineage differentiation in mammalian embryonic stem cells (ESCs) and functions in induced pluripotent stem (iPS) reprogramming. The activity of PCGF6 is found to be regulated by cell cycle dependent phosphorylation. PCGF6 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38524612   7 LLELEDWLQCPICLEVFKESLML-QCGHSYCKGCLVSlsyHLDTKVRCPMCWQVVDGSSSL 66
Cdd:cd16738   1 LAELNPYILCSICKGYFIDATTItECLHTFCKSCIVR---HFYYSNRCPKCNIVVHQTQPL 58

B-box-type 2 zinc finger found in tripartite motif-containing protein 14 (TRIM14) and similar proteins; TRIM14 is a mitochondrial adaptor that facilitates innate immune signaling. It also plays a critical role in tumor development. TRIM14 belongs to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. It contains a Bbox2 zinc finger as well as a C-terminal SPRY/B30.2 domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 38524612  90 VHHRNPLSLFCEKDQELICGLCGLLGSHQHHPVTPVSTV 128
Cdd:cd19768   5 EHKDRPLELFCKTCKRCVCALCPILGQHRGHDVRLIDEE 43

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 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, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 38524612  16 CPICLEVFKESLMLQCGHSYCKGCLVSlsyHLDTK-----VRCPMC 56
Cdd:cd16583   8 CPICQEPLKEAVSTDCGHLFCRMCLTQ---HAKKAsasgvFSCPVC 50

RING finger, HC subclass, found in tripartite motif-containing protein 67 (TRIM67) and similar proteins; TRIM67, also known as TRIM9-like protein (TNL), is selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H (also known as glucosidase II beta), a protein kinase C substrate. It negatively regulates Ras signaling in cell proliferation via degradation of 80K-H, leading to neural differentiation including neuritogenesis. TRIM67 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 38524612  11 EDWLQCPICLEVFKESLMLQCGHSYCKGCLVSLS-------YHL--DTKVRCPMC 56
Cdd:cd16758   1 EEELKCPVCGSLFREPIILPCSHNVCLPCARTIAvqtpeseQHLphSSSITCPQC 55