RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer's disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus, a genetic variant of RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759348  15 PITCHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16562   1 PISCHICLGKVRQPVICSNNHVFCSSCMDVWLKNNNQCPACRVPI 45

RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer's disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus, a genetic variant of RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759348  15 PITCHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16562   1 PISCHICLGKVRQPVICSNNHVFCSSCMDVWLKNNNQCPACRVPI 45

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 88759348    18 CHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVP 58
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAE 69

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348  91 RLELLHKEYEDEIDCLQKEVEELKSKNLSLESQIKTILDPLTLV------QGNQNEDKHLVtdnpskiNPETVAEWKKKL 164
Cdd:COG4942  66 ALARRIRALEQELAALEAELAELEKEIAELRAELEAQKEELAELlralyrLGRQPPLALLL-------SPEDFLDAVRRL 138

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348 165 RTANEIYEKVKDDVDKLKEANKKLKLENGGLVRENLRLKAEVDNRSPQKfgrfavAALQSKVEQYERETNRLKKALERSD 244
Cdd:COG4942 139 QYLKYLAPARREQAEELRADLAELAALRAELEAERAELEALLAELEEER------AALEALKAERQKLLARLEKELAELA 212

                       170       180
                ....*....|....*....|..
gi 88759348 245 KYIEELESQVAQLKNSSEEKEA 266
Cdd:COG4942 213 AELAELQQEAEELEALIARLEA 234

N1R/p28-like protein; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 88759348   18 CHICLGKVRQP--------VICINNHVFCSICIDLWLKNNSQCPACRVP 58
Cdd:PHA02929 177 CAICMEKVYDKeiknmyfgILSNCNHVFCIECIDIWKKEKNTCPVCRTP 225

Coiled-coil domain-containing protein 158; CCDC158 is a family of proteins found in eukaryotes. The function is not known.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348     95 LHKEYEDEIDCLQKEVEELKSKNLSLESQIKTILDpltLVQGNQNEDKHLVTDNPSKINPETVAEWK----KKLRTANEI 170
Cdd:pfam15921  466 LTAQLESTKEMLRKVVEELTAKKMTLESSERTVSD---LTASLQEKERAIEATNAEITKLRSRVDLKlqelQHLKNEGDH 542

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348    171 YEKVKDDVDKLkeankKLKLENGGLVRENLRLKAEVDNRSPQKFGRFAvAALQSKVEQYERETN-------RLKKALERS 243
Cdd:pfam15921  543 LRNVQTECEAL-----KLQMAEKDKVIEILRQQIENMTQLVGQHGRTA-GAMQVEKAQLEKEINdrrlelqEFKILKDKK 616

                          170
                   ....*....|....*
gi 88759348    244 DKYIEELESQVAQLK 258
Cdd:pfam15921  617 DAKIRELEARVSDLE 631

BRISC complex subunit Abraxas 2 found in insects; BRISC complex subunit Abraxas 2 is also known as ABRO1, FAM175B or KIAA0157. The BRISC complex consists of BRCC36, MERIT40, BRE, and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates; BRISC's catalytic subunit is the deubiquitinase (DUB) BRCC36. BRCC36 associates with pseudo-DUB protein Abraxas2, which lacks the essential Zn2+-coordinating residues required for DUB catalytic function. Higher-order association of BRCC36 and Abraxas2 into a dimer of heterodimers (superdimer) is required for BRCC36 DUB activity. In the BRISC complex, Abraxas 2 binds SHMT2a, a metabolic enzyme enabling cancer growth in hypoxic environments, which prevents the BRCC36 from binding and cleaving ubiquitin chains. BRCC36 in BRISC is activated by assembly due to interaction between Glu30 of BRCC36 and Asn164 in Abraxas 2 which structures the activation loop and positions the catalytic Glu33. The members in this subfamily include Camponotus floridanus KIAA0157 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348 164 LRTANEIYEKVKDDVDKLKEANKKLKLENG--------GLVREnlrLKAEVDNRSpqkfGRFAVAALQSKVEQYereTNR 235
Cdd:cd23525 152 LRYNRGMFEPIPLRINNLGEDATRYKGSDYkptpdtfnKIIKS---LNLDLKNTS----GVESITKIQKAAEEH---LDK 221

                        90       100       110
                ....*....|....*....|....*....|
gi 88759348 236 LKKALERSDKYIEELESQVAQLKNSSEEKE 265
Cdd:cd23525 222 LIPELAESEREVAELEKEIKELKNKIKLKK 251

RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer's disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus, a genetic variant of RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759348  15 PITCHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16562   1 PISCHICLGKVRQPVICSNNHVFCSSCMDVWLKNNNQCPACRVPI 45

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 88759348    16 ITCHICLGKVRQPVICIN---NHVFCSICIDLWLKNNSQCPACR 56
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVlpcGHHFHRECLDKWLRSSNTCPLCR 44

RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; RNF151 is a testis-specific RING finger protein that interacts with dysbindin, a synaptic and microtubular protein that binds brain snapin, a SNARE-binding protein that mediates intracellular membrane fusion in both neuronal and non-neuronal cells. Thus, it may be involved in acrosome formation of spermatids by interacting with multiple proteins participating in membrane biogenesis and microtubule organization. RNF151 contains a C3HC4-type RING finger domain, a putative nuclear localization signal (NLS), and a TNF receptor associated factor (TRAF)-type zinc finger domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 88759348  18 CHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPITP 61
Cdd:cd16547   6 CSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCRKEVKG 49

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 88759348  18 CHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16741  17 CAICQAEFRKPILLICQHVFCEECISLWFNREKTCPLCRTVI 58

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 88759348  18 CHICLGKVRQPVICINNHVFCSICIDLWLKN-NSQCPACRVPIT 60
Cdd:cd16509   6 CAICLDSLTNPVITPCAHVFCRRCICEVIQReKAKCPMCRAPLS 49

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 88759348  18 CHICLGKVRQPVICINNHVFCSICIDLWL---KNNSQCPACR 56
Cdd:cd16534   3 CNICLDTASDPVVTMCGHLFCWPCLYQWLetrPDRQTCPVCK 44

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 88759348  18 CHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPITPEN 63
Cdd:cd16535   4 CSICSELFIEAVTLNCSHSFCSYCITEWMKRKKECPICRKPITSKT 49

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759348  17 TCHICLGKVRQPVICIN--NHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16574   3 SCPICLDRFENEKAFLDgcFHAFCFTCILEWSKVKNECPLCKQPF 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 88759348    18 CHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVP 58
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAE 69

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348     90 TRLELLHKEYEDEIDCLQKEVEELKSKNLSLESQIKTILDPLTLVQGNQNEDKHLVTDNPSKIN--PETVAEWKKKLRTA 167
Cdd:TIGR02168  270 EELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDelAEELAELEEKLEEL 349

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348    168 NEIYEKVKDDVDKLKEANKKLKLENGGLVRENLRLKAEVDNRSPQkfgrfaVAALQSKVEQYERETNRLKKALERSDKYI 247
Cdd:TIGR02168  350 KEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQ------IASLNNEIERLEARLERLEDRRERLQQEI 423

                          170       180
                   ....*....|....*....|....*
gi 88759348    248 EEL-----ESQVAQLKNSSEEKEAM 267
Cdd:TIGR02168  424 EELlkkleEAELKELQAELEELEEE 448

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 88759348     18 CHICLGKVRQPVICIN-NHVFCSICIDLWLKN-NSQCPAC 55
Cdd:smart00184   1 CPICLEEYLKDPVILPcGHTFCRSCIRKWLESgNNTCPIC 40

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 88759348  17 TCHICLGKVRQPVICINNHVFCSICIDLWLK-NNSQCPAC 55
Cdd:cd16449   2 ECPICLERLKDPVLLPCGHVFCRECIRRLLEsGSIKCPIC 41

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348  18 CHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPitpenPCKEIIGGTSESEPML-SHTVrkhLRKTRLELLh 96
Cdd:COG5432  28 CRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCRED-----PCESRLRGSSGSREINeSHAR---NRDLLRKVL- 98

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 88759348  97 keyedEIDCLQKeveelKSKNLSLESQIKTILDPLTLVQGNQNEDKHLVTDNPSKINPETVAEWKKKLR 165
Cdd:COG5432  99 -----ESLCRLP-----RPIKEERPCRWETVIAQDSASGDEEWEDDLASNSSPASIAKKTSRDSKKRKR 157

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 88759348  16 ITCHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPITPE 62
Cdd:cd23147   5 LKCPICLSLFKSAANLSCNHCFCAGCIGESLKLSAICPVCKIPATRR 51

Zinc finger, C3HC4 type (RING finger);

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 88759348    18 CHICLGKVRQPVICIN-NHVFCSICIDLWLKNNSQCPAC 55
Cdd:pfam13923   2 CPICMDMLKDPSTTTPcGHVFCQDCILRALRAGNECPLC 40

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348  160 WKKKLRTANEIYEKVKDDVDKLKEANKKLKLENGGlvRENLRLKAEVDNRSPQKFGRFAvaALQSKVEQYERETNRLKKA 239
Cdd:PRK12704  29 AEAKIKEAEEEAKRILEEAKKEAEAIKKEALLEAK--EEIHKLRNEFEKELRERRNELQ--KLEKRLLQKEENLDRKLEL 104

                         90       100
                 ....*....|....*....|....*..
gi 88759348  240 LERSDKYIEELESQVAQLKNSSEEKEA 266
Cdd:PRK12704 105 LEKREEELEKKEKELEQKQQELEKKEE 131

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 88759348  12 LTLPITCHICLGKVRQPVICINNHVFCSICIDLW---LKNNSQCPACRVpITPENPCK 66
Cdd:cd16611   1 LTEELHCPLCLDFFRDPVMLSCGHNFCQSCITGFwelQAEDTTCPECRE-LCQYRNLT 57

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        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 88759348  16 ITCHICLGKVRQPVICIN-NHVFCSICIDLWLKNNS---QCPACRVPITPENPCKE 67
Cdd:cd16554   3 LTCPVCLDLYYDPYMCYPcGHIFCEPCLRQLAKSSPkntPCPLCRTTIRRVFFQEE 58

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM26 belongs the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 88759348  16 ITCHICLGKVRQPVICINNHVFCSICI----DLWLKNNS-QCPACRVPITPEN 63
Cdd:cd16598   5 VTCSICLDYLRDPVTIDCGHNFCRSCItdycPISGGHERpVCPLCRKPFKKEN 57

Possible nuclease of RNase H fold, RuvC/YqgF family [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348 149 PSKINPETVAEWKKKLRTANEIYEKVKD---DVDKLKEANKKLKLENGGLVRENLRLKAEVDN-RSPQKfgrfAVAALQS 224
Cdd:COG2433 390 LPEEEPEAEREKEHEERELTEEEEEIRRleeQVERLEAEVEELEAELEEKDERIERLERELSEaRSEER----REIRKDR 465

                        90       100       110
                ....*....|....*....|....*....|....*
gi 88759348 225 KVEQYERETNRLKKALERSDKYIEELESQVAQLKN 259
Cdd:COG2433 466 EISRLDREIERLERELEEERERIEELKRKLERLKE 500

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 88759348  17 TCHICLGKVRQPVICIN---NHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16454   1 TCAICLEEFKEGEKVRVlpcNHLFHKDCIDPWLEQHNTCPLCR 43

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348   83 VRKHLRKTRLELLHKEYEDEIDCLQKEVEELKSKNLSLESQIKTILDPLTLVQGNQNEDKHlvtdnpskinpETVAEWKK 162
Cdd:COG4913  277 LRAALRLWFAQRRLELLEAELEELRAELARLEAELERLEARLDALREELDELEAQIRGNGG-----------DRLEQLER 345

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348  163 KLRTANEIYEKVKDDVDKLKEANKKLKLENGGLVRENLRLKAEVDNRspqkfgrfaVAALQSKVEQYERETNRLKKALER 242
Cdd:COG4913  346 EIERLERELEERERRRARLEALLAALGLPLPASAEEFAALRAEAAAL---------LEALEEELEALEEALAEAEAALRD 416

                        170
                 ....*....|....*..
gi 88759348  243 SDKYIEELESQVAQLKN 259
Cdd:COG4913  417 LRRELRELEAEIASLER 433

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 88759348  16 ITCHICLGKVRQPVICINNHVFCSICIDLW---LKNNSQCPACRVPITPE 62
Cdd:cd23133   4 LTCSICQGIFMNPVYLRCGHKFCEACLLLFqedIKFPAYCPMCRQPFNQE 53

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
                ....*....|....*....|....*....|....*....|....*....|
gi 88759348  15 PITCHICLGKVRQPVICINNHVFCSICI-DLW--LKNNSQCPACRVPITP 61
Cdd:cd16543   3 QLTCSICLDLLKDPVTIPCGHSFCMNCItLLWdrKQGVPSCPQCRESFPP 52

RING finger found in polycomb group RING finger protein 5 (PCGF5) and similar proteins; PCGF5, also known as RING finger protein 159 (RNF159), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) and serves as the core component of a Polycomb repressive complex 1 (PRC1). Like other PCGF homologs, PCGF5 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. PCGF5 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 88759348  16 ITCHICLGKVRQP-VICINNHVFCSICIDLWLKNNSQCPACRVPITPENPCKEII 69
Cdd:cd16737  11 ITCRICKGYLIKPtTVTECLHTFCKSCIVQHFEDSNDCPECGIQVHETNPLEMLR 65

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity by modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. RNF6 also regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. It acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF12, also known as LIM domain-interacting RING finger protein, or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 88759348  17 TCHICLG------KVRQPViCInnHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16467   1 ECTICLGeyetgeKLRRLP-CS--HEFHSECVDRWLKENSSCPICR 43

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 88759348   5 VQNVTLSLTLPITCHICLGKVRQPVICINNHVFCSICIDLWLKNNS---QCPACRVPIT 60
Cdd:cd16498   6 VQEVISAMQKNLECPICLELLKEPVSTKCDHQFCRFCILKLLQKKKkpaPCPLCKKSVT 64

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
                ....*....|....*....|....*....|....*....|....
gi 88759348  17 TCHICLGKVRQPVICIN-NHVFCSICIDLWLKNNS-QCPACRVP 58
Cdd:cd16549   3 SCPICLEVYHKPVVITScGHTFCGECLQPCLQVASpLCPLCRMP 46

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 88759348  16 ITCHICLGKVRQPVICINNHVFCSICIDLWLKNN------SQCPACRVPITPEN 63
Cdd:cd16591   7 VTCPICLELLTEPLSLDCGHSFCQACITANHKESvnqegeSSCPVCRTSYQPEN 60

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759348 146 TDNPSKINPETVAEWKKKLRTANEIYEKVKDDVDKLKEANKK---LKLENGGLVRENLRLKAEVDNRSPQKFGRFAVAAL 222
Cdd:COG4717  62 QGRKPELNLKELKELEEELKEAEEKEEEYAELQEELEELEEEleeLEAELEELREELEKLEKLLQLLPLYQELEALEAEL 141

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 88759348 223 QSKVEQYERETNRLkKALERSDKYIEELESQVAQLKNSSEEKEAMNSI 270
Cdd:COG4717 142 AELPERLEELEERL-EELRELEEELEELEAELAELQEELEELLEQLSL 188

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 88759348  18 CHICLG------KVRQpVICInnHVFCSICIDLWLKNNSQCPACRV 57
Cdd:cd16474   3 CTICLSdfeegeDVRR-LPCM--HLFHQECVDQWLSTNKRCPICRV 45

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759348  16 ITCHICLGKVRQPVICINNHVFCSICIDLWLKNNSQCPACRVPIT 60
Cdd:cd16504   3 FLCPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNRCPKCNFYLT 47

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                        10        20
                ....*....|....*....|....*
gi 88759348  35 HVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16481  21 HIFHKECIKQWLKEQSTCPTCRVHV 45

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. RNF111 also regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, an NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 88759348  18 CHICL-----GKVRQPVICInnHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16681  13 CTICLsileeGEDVRRLPCM--HLFHQVCVDQWLITNKKCPICRVDI 57

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 88759348   18 CHICLGKVRQPVICINNHVFCSICIDLWL--KNNS--------------QCPACRVPIT 60
Cdd:PLN03208  21 CNICLDQVRDPVVTLCGHLFCWPCIHKWTyaSNNSrqrvdqydhkreppKCPVCKSDVS 79

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
                ....*....|....*....|....*....|....*....|....*....|..
gi 88759348  11 SLTLPITCHICLGKVRQPVICINNHVFCSICIDL---WLKNNS-QCPACRVP 58
Cdd:cd16597   1 DLEEELTCSICLELFKDPVTLPCGHNFCGVCIEKtwdSQHGSEySCPQCRAT 52

RING finger, HC subclass, found in RING finger protein 39 (RNF39) and similar proteins; RNF39, also called protein HZFw, may play a role in prolonged long term-potentiation (LTP) maintenance. It is involved in the etiology of Behcet's disease (BD). It may also be involved in HIV-1 replication. RNF39 acts as an E3 ubiquitin ligase that inhibits retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) pathways by mediating K48-linked ubiquitination and proteasomal degradation of DDX3X (DEAD-box RNA helicase 3, X-linked). RNF39 contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 88759348  17 TCHICLGKVRQPVICINNHVFCSICI-DLW----LKNNSQ----CPACRVPI 59
Cdd:cd16592   6 TCPICLGYFKDPVILDCEHSFCRACIaRHWgqeaMEGNGAegvfCPQCGEPC 57