RING finger, HC subclass, found in muscle-specific RING finger protein 1 (MuRF-1) and similar proteins; MuRF-1, also known as tripartite motif-containing protein 63 (TRIM63), RING finger protein 28 (RNF28), iris RING finger protein, or striated muscle RING zinc finger, is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain. It also participates in muscle stress response pathways and gene expression. MuRF-1 belongs to the C-II subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19924163  18 EKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWTSRGSSVSMSGGRFRCPTCRH 80
Cdd:cd16759   1 EKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWQSRGTSMLGSGGRFRCPSCRH 63

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163    188 ITQLEDSRRVTKENSHQVKEELSQKFDTLYAILDEKKSELLQRITQEQEKKLSFIEALIQQYQEQLDKSTKLVETAIQSL 267
Cdd:smart00502  23 LKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQLESLTQKQEKLSHAINFTEEAL 102

                           90
                   ....*....|....*.
gi 19924163    268 DEPGGATFLLTAKQLI 283
Cdd:smart00502 103 NSGDPTELLLSKKLII 118

RING finger, HC subclass, found in muscle-specific RING finger protein 1 (MuRF-1) and similar proteins; MuRF-1, also known as tripartite motif-containing protein 63 (TRIM63), RING finger protein 28 (RNF28), iris RING finger protein, or striated muscle RING zinc finger, is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain. It also participates in muscle stress response pathways and gene expression. MuRF-1 belongs to the C-II subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19924163  18 EKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWTSRGSSVSMSGGRFRCPTCRH 80
Cdd:cd16759   1 EKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWQSRGTSMLGSGGRFRCPSCRH 63

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 19924163    23 CPICLEMFTKPVviLPCQHNLCRKCANDIFQAanpywtsrgssvsmSGGRFRCP 76
Cdd:pfam13445   1 CPICLELFTDPV--LPCGHTFCRECLEEMSQK--------------KGGKFKCP 38

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        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 19924163     23 CPICLEMFTKPVVILPCQHNLCRKCANDIFQAANpywtsrgssvsmsggrFRCPTC 78
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGN----------------NTCPIC 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 19924163    120 PMCKEHEDEKINIYCLTCEVPTCSMCKVFgIHKACEVAPL 159
Cdd:smart00336   4 PKCDSHGDEPAEFFCEECGALLCRTCDEA-EHRGHTVVLL 42

recombination and DNA strand exchange inhibitor protein; Reviewed

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163  181 NDRVQTIITQLEDSRRVTKENSHQVKEELSQkfdtlyaiLDEKKSELLQRITQEQEKKLSFIEALIQQYQEQLDKSTKLV 260
Cdd:PRK00409 515 KEKLNELIASLEELERELEQKAEEAEALLKE--------AEKLKEELEEKKEKLQEEEDKLLEEAEKEAQQAIKEAKKEA 586

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 19924163  261 ETAIQSLDEPG-GATFLLTAKQLI---KSIVEASKGCQLGKTEQGFENMDF 307
Cdd:PRK00409 587 DEIIKELRQLQkGGYASVKAHELIearKRLNKANEKKEKKKKKQKEKQEEL 637

RING finger, HC subclass, found in muscle-specific RING finger protein 1 (MuRF-1) and similar proteins; MuRF-1, also known as tripartite motif-containing protein 63 (TRIM63), RING finger protein 28 (RNF28), iris RING finger protein, or striated muscle RING zinc finger, is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain. It also participates in muscle stress response pathways and gene expression. MuRF-1 belongs to the C-II subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19924163  18 EKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWTSRGSSVSMSGGRFRCPTCRH 80
Cdd:cd16759   1 EKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWQSRGTSMLGSGGRFRCPSCRH 63

RING finger, HC subclass, found in muscle-specific RING finger protein 3 (MuRF-3) and similar proteins; MuRF-3, also known as tripartite motif-containing protein 54 (TRIM54), or RING finger protein 30 (RNF30), is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is ubiquitously detected in all fibre types, is developmentally upregulated, associates with microtubules, the sarcomeric M-line and Z-line, and is required for microtubule stability and myogenesis. It associates with glutamylated microtubules during skeletal muscle development, and is required for skeletal myoblast differentiation and development of cellular microtubular networks. MuRF-3 controls the degradation of four-and-a-half LIM domain (FHL2) and gamma-filamin and is required for maintenance of ventricular integrity after myocardial infarction (MI). MuRF-3 belongs to the C-II subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 19924163  21 LICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPYWTSRGSSVSMSGGRFRCPTCR 79
Cdd:cd16761   1 LICPICLEMFTKPVVILPCQHNLCRKCANDVFQASNPLWQSRGSSTVSSGGRFRCPSCR 59

B-box-type 2 zinc finger found in muscle-specific RING finger protein 1 (MuRF-1) and similar proteins; MuRF-1, also known as tripartite motif-containing protein 63 (TRIM63), RING finger protein 28 (RNF28), iris RING finger protein, or striated muscle RING zinc finger, is an E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover. It is predominantly fast (type II) fibre-associated in skeletal muscle and can bind to many myofibrillar proteins, including titin, nebulin, the nebulin-related protein NRAP, troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin, and T-cap. The early and robust upregulation of MuRF-1 is triggered by disuse, denervation, starvation, sepsis, or steroid administration resulting in skeletal muscle atrophy. It also plays a role in maintaining titin M-line integrity. It associates with the periphery of the M-line lattice and may be involved in the regulation of the titin kinase domain. It also participates in muscle stress response pathways and gene expression. MuRF-1 belongs to the C-II 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 COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 19924163 118 SHPMCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQ 160
Cdd:cd19831   1 GHPMCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQ 43

B-box-type 2 zinc finger found in muscle-specific RING finger protein 2 (MuRF-2) and similar proteins; MuRF-2, also known as tripartite motif-containing protein 55 (TRIM55) or RING finger protein 29 (RNF29), is a muscle-specific E3 ubiquitin-protein ligase in ubiquitin-mediated muscle protein turnover and also a ligand of the transactivation domain of the serum response transcription factor (SRF). It is predominantly slow-fibre associated and highly expressed in embryonic skeletal muscle. MuRF-2 associates transiently with microtubules, myosin, and titin during sarcomere assembly. It has been implicated in microtubule, intermediate filament, and sarcomeric M-line maintenance in striated muscle development, as well as in signalling from the sarcomere to the nucleus. It plays an important role in the earliest stages of skeletal muscle differentiation and myofibrillogenesis. It is developmentally downregulated and is assembled at the M-line region of the sarcomere and with microtubules. MuRF-2 belongs to the C-II 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 COS (carboxyl-terminal subgroup one signature) box, and an acidic residue-rich (AR) domain. It also harbors a MURF family-specific conserved box (MFC) between its RING-HC finger and Bbox domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 19924163 120 PMCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQSVFQ 164
Cdd:cd19832   1 PMCEEHEEERINIYCLNCEVPTCSLCKVFGAHKDCQVAPLTHVFQ 45

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        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19924163  17 LEKQLICPICLEMFTKPvVILPCQHNLCRKCANDIFQAanpYWTSRGSSVSMSGgrFRCPTCRHEVIMDRHGVYGLQ 93
Cdd:cd16753   2 LESELTCPICLELFEDP-LLLPCAHSLCFNCAHRILVS---HCASNESVESITA--FQCPTCRYVITLNQRGLEGLK 72

B-box-type zinc finger superfamily; The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 19924163 121 MCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPL 159
Cdd:cd00021   1 MCQEHDEEKANKYCVTCEVLYCALCKKSGAHPDHEVAPL 39

RING finger, HC subclass, found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, the human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently dorsal axis formation. It is also potentially associated with chromosome segregation by interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 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, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 19924163  18 EKQLICPICLEMFTKPVvILPCQHNLCRKCANDIFQAanpywtsrgssvsmsggrFRCPTCRHEV 82
Cdd:cd16756   1 ERELICPSCKELFTHPL-ILPCQHSVCHKCVKELLTT------------------FPCPGCQHDV 46

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 19924163  18 EKQLICPICLEMFTKPVViLPCQHNLCRKCANDIFQAANPYWTSRGSsvsmsggrFRCPTCRHE 81
Cdd:cd16762   1 EEDLTCPICCCLFDDPRV-LPCSHNFCKKCLEGILEGNVRTMLWRPP--------FKCPTCRKE 55

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 19924163  17 LEKQLICPICLEMFTKPVViLPCQHNLCRKCANDIFqaanpywtsrgssvSMSGGRFRCPTCRH 80
Cdd:cd16580   8 FEEELICPICLHVFVEPVQ-LPCKHNFCRGCIGEAW--------------AKDAGLVRCPECNQ 56

B-box-type 2 zinc finger (Bbox2); The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interaction. Based on different consensus sequence and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2). The family corresponds to type 2 B-box (Bbox2).

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 19924163 121 MCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPL 159
Cdd:cd19756   1 LCPEHPEEPLKLFCETCQELVCVLCLLSGEHRGHKVVPL 39

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163  17 LEKQLICPICLEMFTKPVViLPCQHNLCRKCANDIfqaanpyWTSRGSSVsmsggrFRCPTCRhEVIMDRHgvyGLQRNL 96
Cdd:cd16597   2 LEEELTCSICLELFKDPVT-LPCGHNFCGVCIEKT-------WDSQHGSE------YSCPQCR-ATFPRRP---ELHKNT 63

                ....*..
gi 19924163  97 LVENIID 103
Cdd:cd16597  64 VLRNIVE 70

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 19924163  21 LICPICLEMFTKPVvILPCQHNLCRKCANDIFQAanpywtsrgsSVSMSGGRFRCPTCR 79
Cdd:cd16581   3 LTCSICYNIFDDPK-ILPCSHTFCKNCLEKLLAA----------SGYYLLASLKCPTCR 50

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 19924163  16 NLEKQLICPICLEMFTKPvVILPCQHNLCRKCandIFQAanpyWTSrgssvsmSGGRFRCPTCR 79
Cdd:cd16594   1 SLQEELTCPICLDYFTDP-VTLDCGHSFCRAC---IARC----WEE-------PETSASCPQCR 49

RING finger, HC subclass, found in RING finger protein 166 (RNF166) and similar proteins; RNF166 is encoded by the gene RNF166 targeted by thyroid hormone receptor alpha1 (TRalpha1), which is important in brain development. It plays an important role in RNA virus-induced interferon-beta production by enhancing the ubiquitination of TRAF3 and TRAF6. RNF166, together with three closely related proteins: RNF114, RNF125 and RNF138, 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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163  20 QLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPywtsrgssvsmsggrfRCPTCR 79
Cdd:cd16549   1 QFSCPICLEVYHKPVVITSCGHTFCGECLQPCLQVASP----------------LCPLCR 44

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

                        10        20        30
                ....*....|....*....|....*....|....
gi 19924163  18 EKQLICPICLEMFTKPVvILPCQHNLCRKCANDI 51
Cdd:cd16576   1 EEELKCPVCGSLFTEPV-ILPCSHNLCLGCALNI 33

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19924163  18 EKQLICPICLEMFTKPVvILPCQHNLCRKCANDIFqAANPYWTSRGSSVSmsggrfrCPTC 78
Cdd:cd16755   1 EEELKCPVCGSFYREPI-ILPCSHNLCLACARNIL-VQTPEAESPQSCLT-------CPQC 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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 19924163  21 LICPICLEMFTKPVVILPCQHNLCRKCANDifqaanpyWTSRGSSvsmsggrfRCPTCRHEVI 83
Cdd:cd16503   3 LTCSICQDLLHDCVSLQPCMHNFCAACYSD--------WMERSNT--------ECPTCRATVQ 49

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 19924163    23 CPICLEMFTKPVviLPCQHNLCRKCANDIFQAanpywtsrgssvsmSGGRFRCP 76
Cdd:pfam13445   1 CPICLELFTDPV--LPCGHTFCRECLEEMSQK--------------KGGKFKCP 38

B-box-type 2 zinc finger 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 that is highly related to MID1 that associate 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. It heterodimerizes in vitro with its paralog MID1. Loss-of-function mutations in MID2 lead to the human X-linked intellectual disability (XLID). MID2 belongs to the C-I 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 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 19924163 121 MCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPL 159
Cdd:cd19823   2 TCLEHENEKVNMYCVVDDQLICALCKLVGRHRDHQVASL 40

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
                ....*....|....*....|....*....|....
gi 19924163  18 EKQLICPICLEMFTKPVvILPCQHNLCRKCANDI 51
Cdd:cd16758   1 EEELKCPVCGSLFREPI-ILPCSHNVCLPCARTI 33

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 19924163  22 ICPICLEMFTKPVViLPCQHNLCRKCANDIFQAANpywtsrgssvsmsggrFRCPTCRHEV 82
Cdd:cd16550   2 LCPICLEILVEPVT-LPCNHTLCMPCFQSTVEKAS----------------LCCPLCRLRI 45

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 19924163  16 NLEKQLICPICLEMFTKPVVIlPCQHNLCRKCANDIFQAANPYWTSRGSSvsmsgGRFRCPTCR 79
Cdd:cd16595   1 RLQEEATCSICLDYFTDPVMT-TCGHNFCRACIQLSWEKARGKKGRRKQK-----GSFPCPECR 58

B-box-type 2 zinc finger found in tripartite motif-containing protein 67 (TRIM67) and similar proteins; TRIM67, also termed TRIM9-like protein (TNL), is a protein selectively expressed in the cerebellum. It interacts with PRG-1, an important molecule in the control of hippocampal excitability dependent on presynaptic LPA2 receptor signaling, and 80K-H (also known as glucosidase II beta), a protein kinase C substrate. 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 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 COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 19924163 120 PMCKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQSVFQ 164
Cdd:cd19827   1 PTCAEHELENYSMYCASCRTPVCYQCLEEGKHAKHEVKALGAMWK 45

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163  15 ENLEKQLICPICLEMFTKPVViLPCQHNLCRKCAndifqaanpywTSRGSSVSMSGGRFRCPTCRhevimDRHGVYGLQR 94
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLS-LDCGHSFCQACI-----------TANHKESVNQEGESSCPVCR-----TSYQPENLRP 63

                ....*....
gi 19924163  95 NLLVENIID 103
Cdd:cd16591  64 NRHLANIVE 72

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19924163  18 EKQLICPICLEMFTKPVVIlPCQHNLCRKCANDIFQAANpywtsrgssvsmsgGRFRCPTCR 79
Cdd:cd16543   1 EDQLTCSICLDLLKDPVTI-PCGHSFCMNCITLLWDRKQ--------------GVPSCPQCR 47

Ring finger domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 19924163    23 CPICLEMFTKP--VVILPCQHNLCRKCANDIFQAANpywtsrgssvsmsggrfRCPTCR 79
Cdd:pfam13639   3 CPICLEEFEEGdkVVVLPCGHHFHRECLDKWLRSSN-----------------TCPLCR 44

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 19924163   119 HPMCKEHEDEKINIYCLTCEVPTCSMCKVfGIHKACEVAPL 159
Cdd:pfam00643   3 ERLCPEHEEEPLTLYCNDCQELLCEECSV-GEHRGHTVVPL 42

B-box-type 2 zinc finger found in tripartite motif-containing protein 46 (TRIM46) and similar proteins; TRIM46, also known as gene Y protein (GeneY) or tripartite, fibronectin type-III and C-terminal SPRY motif protein (TRIFIC), is a microtubule-associated protein that specifically localizes to the proximal axon, partly overlaps with the axon initial segment (AIS) at later stages, and organizes uniform microtubule orientation in axons. It controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 belongs to the C-I subclass of TRIM (tripartite motif) family of proteins, which 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 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 19924163 121 MCKEHeDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQSVFQ 164
Cdd:cd19786   4 MCPEH-KEEVTHYCKTCQRLVCQLCRVRRTHAGHKITPVLSAYQ 46

RING finger, HC subclass, found in tripartite motif-containing protein TRIM58 and similar proteins; 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. TRIM58 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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 19924163  23 CPICLEMFTKPVVILpCQHNLCRKCANDIFQAANpywtsrgssvSMSGGRFRCPTCR 79
Cdd:cd16606   5 CPVCLDFLQEPVSVD-CGHSFCLRCISEFCEKSD----------SAQGGVYACPQCR 50

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        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163  20 QLICPICLEMFTKPVViLPCQHNLCRKCANDIFQAANPYWTsrgssvsmsggrfrCPTCR 79
Cdd:cd16551   1 ELTCAGCLEVPVEPAT-LPCGHTLCRGCANRALDAAEAGPT--------------CPRCR 45

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19924163  18 EKQLICPICLEMFTKPVVIlPCQHNLCRKCANDIFQaanpywtsrgssvsmsggrFRCPTCR 79
Cdd:cd16602   1 QEEAVCAICLDYFKDPVSI-GCGHNFCRVCVTQLWG-------------------FTCPQCR 42

RING finger, HC subclass, found in promyelocytic leukemia protein (PML) and similar proteins; Protein PML, also known as RING finger protein 71 (RNF71) or tripartite motif-containing protein 19 (TRIM19), is predominantly a nuclear protein with a broad intrinsic antiviral activity. It is the eponymous component of PML nuclear bodies (PML NBs) and has been implicated in a wide variety of cell processes, including DNA damage signaling, apoptosis, and transcription. PML interferes with the replication of many unrelated viruses, including human immunodeficiency virus 1 (HIV-1), human foamy virus (HFV), poliovirus, influenza virus, rabies virus, EMCV, adeno-associated virus (AAV), and vesicular stomatitis virus (VSV). It also selectively interacts with misfolded proteins through distinct substrate recognition sites and conjugates these proteins with the small ubiquitin-like modifiers (SUMOs) through its SUMO ligase activity. PML 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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 19924163  18 EKQLICPICLEMFTKPVvILPCQHNLCRKCANDIfqaanpywtsrgSSVSMSGGRFRCPTCR 79
Cdd:cd16579   2 FKFLRCPGCKAEYKCPK-LLPCLHTVCSGCLEAL------------AEQASETTEFQCPICK 50

RING finger, HC subclass, found in SH3 domain-containing RING finger proteins SH3RF1, SH3RF2, SH3RF3, and similar proteins; SH3RF1, also known as plenty of SH3s (POSH), RING finger protein 142 (RNF142), or SH3 multiple domains protein 2 (SH3MD2), is a trans-Golgi network-associated pro-apoptotic scaffold protein with E3 ubiquitin-protein ligase activity. SH3RF2, also known as heart protein phosphatase 1-binding protein (HEPP1), plenty of SH3s (POSH)-eliminating RING protein (POSHER), protein phosphatase 1 regulatory subunit 39, or RING finger protein 158 (RNF158), is a putative E3 ubiquitin-protein ligase that acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway by binding to and promoting the proteasomal degradation of SH3RF1 (or POSH) that is required for pro-apoptotic JNK activation. SH3RF3, also known as plenty of SH3s 2 (POSH2) or SH3 multiple domains protein 4 (SH3MD4), is a scaffold protein with E3 ubiquitin-protein ligase activity. It was identified in the screen for interacting partners of p21-activated kinase 2 (PAK2) and may play a role in regulating c-Jun N-terminal kinase (JNK) mediated apoptosis in certain conditions. Members of this subfamily contain an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains, which are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 19924163  21 LICPICLEMFTKPVVILPCQHNLCRKCANDIFQaanpywtsrgssvsmSGGRFRCPTCR 79
Cdd:cd16570   1 LECPVCLERLDVSAKVLPCQHTFCKRCLQIIVA---------------SRGELRCPECR 44

Zinc finger, C3HC4 type (RING finger);

                          10        20
                  ....*....|....*....|....*
gi 19924163    23 CPICLEMFTKPVVILPCQHNLCRKC 47
Cdd:pfam13923   2 CPICMDMLKDPSTTTPCGHVFCQDC 26

B-box-type 2 zinc finger found in tripartite motif-containing protein 9 (TRIM9) and similar proteins; TRIM9 (the human ortholog of rat Spring), also termed 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-transducer repeat-containing protein (beta-TCP) through its N-terminal degron motif (DSGXXS) depending on the phosphorylation status, and thus negatively regulate 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 exocytosis 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 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 COS (carboxyl-terminal subgroup one signature) box, the fibronectin type III domain and the 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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 19924163 122 CKEHEDEKINIYCLTCEVPTCSMCKVFGIHKACEVAPLQSVFQ 164
Cdd:cd19826   7 CTDHELENHSMYCVQCKMPVCYQCLEEGKHSSHEVKALGAMWK 49

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 19924163  19 KQLICPICLEMFTKPVVILPCQHNLCRKCandIFQAANPywtsrgssvsmsgGRFRCPTCRHEVIMD 85
Cdd:cd16620   2 DELKCPICKDLMKDAVLTPCCGNSFCDEC---IRTALLE-------------EDFTCPTCKEPDVSP 52

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 19924163  18 EKQLICPICLEMFTKPVVILPCQHNLCRKCAndifqaanpywtsrgsSVSMSGGRFRCPTCRHEVIMDR 86
Cdd:cd16739   1 HSELMCPICLDMLKNTMTTKECLHRFCSDCI----------------VTALRSGNKECPTCRKKLVSKR 53

RING finger, HC subclass, found in Saccharomyces cerevisiae translation termination inhibitor protein ITT1 and similar proteins; ITT1 is a protein that modulates the efficiency of translation termination, resulting in the readthrough of all three types of nonsense codons UAA, UAG and UGA. ITT1 contains a typical C3HC4-type RING-HC finger.

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                ....*....|....*....|....*....|....
gi 19924163  23 CPICLEMFTKPVVI-LPCQHNLCRKCANDIFQAA 55
Cdd:cd23134   7 CGICFEEKKGSDFIkLPCGHVFCRECLQDYYTIH 40

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 19924163 122 CKEHEDEKINIYCLTCEVPTCSMCKVFGIHK 152
Cdd:cd19768   3 CPEHKDRPLELFCKTCKRCVCALCPILGQHR 33

RING finger, H2 subclass, found in p53-induced RING-H2 protein (Pirh2) and similar proteins; Pirh2, also known as RING finger and CHY zinc finger domain-containing protein 1 (Rchy1), androgen receptor N-terminal-interacting protein, CH-rich-interacting match with PLAG1, RING finger protein 199 (RNF199), or zinc finger protein 363 (ZNF363), is a p53 inducible E3 ubiquitin-protein ligase that functions as a negative regulator of p53. It preferably ubiquitylates the tetrameric form of p53 in vitro and in vivo, suggesting a role of Pirh2 in downregulating the transcriptionally active form of p53 in the cell. Moreover, Pirh2 inhibits the transcriptional activity of p73, a homolog of the tumor suppressor p53, by promoting its ubiquitination. It also monoubiquitinates DNA polymerase eta (PolH) to suppress translesion DNA synthesis. Furthermore, Pirh2 functions as a negative regulator of the cyclin-dependent kinase inhibitor p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation. Pirh2 enhances androgen receptor (AR) signaling through inhibition of histone deacetylase 1 (HDAC1) and is overexpressed in prostate cancer. It interacts with TIP60 and this association may regulate Pirh2 stability. In addition, the oncoprotein pleomorphic adenoma gene like 2 (PLAGL2) can bind to the Pirh2 dimer and therefore control the stability of Pirh2. Pirh2 contains a total of nine zinc-binding sites with six located at the N-terminal region, two in the C3H2C3-type RING-H2 domain, and one in the C-terminal region. Nine zinc binding sites comprise three different zinc coordination schemes, including RING type cross-brace zinc coordination, C4 zinc finger, and a novel left-handed beta-spiral zinc-binding motif formed by three recurrent CCHC sequence motifs. This subfamily also includes Drosophila melanogaster Deltex, a ubiquitously expressed cytoplasmic ubiquitin E3 ligase that mediates Notch activation in Drosophila. It selectively suppresses T-cell activation through degradation of a key signaling molecule, MAP kinase kinase kinase 1 (MEKK1). It also inhibits Jun-mediated transcription at the stage of Ras-dependent Jun N-terminal protein kinase (JNK) activation. Deltex contains N-terminal two Notch-binding WWE domains that physically interact with the Notch ankyrin domains, a proline-rich motif that shares homology with SH3-binding domains, and a RING finger at the C-terminus.

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                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 19924163  23 CPICLE-MFT--KPVVILPCQHNLCRKCANDIfqaanpywtsrgssvsMSGGRFRCPTCR 79
Cdd:cd16464   2 CPVCLEdLFTsrEPVHVLPCGHLMHSTCFEEY----------------LKSGNYRCPLCS 45

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, and TRIM64C, whose biological function remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of the target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members 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 as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. In RBCC region, they all have a C3HC4-type RING-HC finger.

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                ....*....|....*....|....*....|
gi 19924163  18 EKQLICPICLEMFTKPVVIlPCQHNLCRKC 47
Cdd:cd16603   2 QRELTCPICMNYFIDPVTI-DCGHSFCRPC 30

RING finger, HC subclass, found in really interesting new gene 2 protein (RING2) and similar proteins; RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. RING2 is a core component of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. The enzymatic activity of RING2 is enhanced by the interaction with BMI1/PCGF4, and it is dispensable for early embryonic development and much of the gene repression activity of PRC1. Moreover, RING2 plays a key role in terminating neural precursor cell (NPC)-mediated production of subcerebral projection neurons (SCPNs) during neocortical development. It also plays a critical role in nonhomologous end-joining (NHEJ)-mediated end-to-end chromosome fusions. Furthermore, RING2 is essential for expansion of hepatic stem/progenitor cells. It promotes hepatic stem/progenitor cell expansion through simultaneous suppression of cyclin-dependent kinase inhibitors (CDKIs) Cdkn1a and Cdkn2a, known negative regulators of cell proliferation. RING2 also negatively regulates p53 expression through directly binding with both p53 and MDM2 and promoting MDM2-mediated p53 ubiquitination in selective cancer cell types to stimulate tumor development. RING2 contains a C3HC4-type RING-HC finger.

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gi 19924163  16 NLEKQLICPICLEMFTKPVVILPCQHNLCRKCANDIFQAANPywtsrgssvsmsggrfRCPTCRHEVIMDR 86
Cdd:cd16740   8 SLHSELMCPICLDMLKNTMTTKECLHRFCADCIITALRSGNK----------------ECPTCRKKLVSKR 62