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 88759344     90 TRLELLHREYEDEIDCLQKEVEELKSKNLSLESQIKTILDPLALMQGSQNEDKHPLADNPSKMDPD--SVVEWKKKLRTA 167
Cdd:TIGR02168  270 EELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDELaeELAELEEKLEEL 349

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344    168 NEIYEKVKDDVDKLKEANKKLKLENGGLLRENLRLKAEVDNRSPQkfgrftVAALQSKVEQYERETNRLKKALERSDKYI 247
Cdd:TIGR02168  350 KEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQ------IASLNNEIERLEARLERLEDRRERLQQEI 423

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 88759344    248 EELESQVAHLKHSE-------------EAKEDVDALCQRAPSADskgpngsDELGPPKNQSDSARKQAGSASA 307
Cdd:TIGR02168  424 EELLKKLEEAELKElqaeleeleeeleELQEELERLEEALEELR-------EELEEAEQALDAAERELAQLQA 489

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 88759344    16 ITCHICLGKVRQPVVCTN---NHVFCSICIDLWLKNNSQCPACR 56
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVlpcGHHFHRECLDKWLRSSNTCPLCR 44

N1R/p28-like protein; Provisional

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 88759344   18 CHICLGKVRQP--------VVCTNNHVFCSICIDLWLKNNSQCPACRVP 58
Cdd:PHA02929 177 CAICMEKVYDKeiknmyfgILSNCNHVFCIECIDIWKKEKNTCPVCRTP 225

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 88759344    18 CHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVP 58
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAE 69

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344  96 HREYEDEIDCLQKEV------EELKS---KNLSLESQI-KTILDPLALMQGSQNEDKHPLADNPSKMDP-----DSVVEw 160
Cdd:COG2433 345 YDAYKNKFERVEKKVppdvdrDEVKArviRGLSIEEALeELIEKELPEEEPEAEREKEHEERELTEEEEeirrlEEQVE- 423

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344 161 kkKLRTANEiyeKVKDDVDKLKEANKKLKLENGgLLRENLRLKAEVDNrspqkfgrftvaalqsKVEQYERETNRLKKAL 240
Cdd:COG2433 424 --RLEAEVE---ELEAELEEKDERIERLERELS-EARSEERREIRKDR----------------EISRLDREIERLEREL 481

                       170
                ....*....|....*....
gi 88759344 241 ERSDKYIEELESQVAHLKH 259
Cdd:COG2433 482 EEERERIEELKRKLERLKE 500

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 88759344     95 LHREYEDEIDCLQKEVEELKSKNLSLESQIKTILDplaLMQGSQNEDKHPLADNPSKMDPDSVVEWK----KKLRTANEI 170
Cdd:pfam15921  466 LTAQLESTKEMLRKVVEELTAKKMTLESSERTVSD---LTASLQEKERAIEATNAEITKLRSRVDLKlqelQHLKNEGDH 542

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344    171 YEKVKDDVDKLkeankKLKLENGGLLRENLRLKAEVDNRSPQKFGRfTVAALQSKVEQYERETN-------RLKKALERS 243
Cdd:pfam15921  543 LRNVQTECEAL-----KLQMAEKDKVIEILRQQIENMTQLVGQHGR-TAGAMQVEKAQLEKEINdrrlelqEFKILKDKK 616

                          170
                   ....*....|....*
gi 88759344    244 DKYIEELESQVAHLK 258
Cdd:pfam15921  617 DAKIRELEARVSDLE 631

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 88759344  18 CHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVPITPEN 63
Cdd:cd16561   5 CSICLEDLNDPVKLPCDHVFCEECIRQWLPGQMSCPLCRTELPDDF 50

RING finger, HC subclass, found in Saccharomyces cerevisiae radiation sensitivity protein 18 (RAD18) and similar proteins; RAD18, also called RING-type E3 ubiquitin transferase RAD18, acts as a postreplication repair E3 ubiquitin-protein ligase that associates with the E2 ubiquitin conjugating enzyme UBC2/RAD6 to form the UBC2-RAD18 ubiquitin ligase complex involved in postreplicative repair (PRR) of damaged DNA. The UBC2-RAD18 complex cooperates with RAD5 and the UBC13-MMS2 dimer to attach mono-ubiquitin chains on 'Lys-164' of POL30, which is necessary for PRR. The UBC2-RAD18 complex is also involved in prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine. RAD18 is an E3 RING-finger protein belonging to the UBC2/RAD6 epistasis group. It contains a typical C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759344  16 ITCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVPIT 60
Cdd:cd23148   4 LRCHICKDLLKAPMRTPCNHTFCSFCIRTHLNNDARCPLCKAEVT 48

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 88759344    16 ITCHICLGKVRQPVVCTN---NHVFCSICIDLWLKNNSQCPACR 56
Cdd:pfam13639   1 DECPICLEEFEEGDKVVVlpcGHHFHRECLDKWLRSSNTCPLCR 44

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 88759344     90 TRLELLHREYEDEIDCLQKEVEELKSKNLSLESQIKTILDPLALMQGSQNEDKHPLADNPSKMDPD--SVVEWKKKLRTA 167
Cdd:TIGR02168  270 EELRLEVSELEEEIEELQKELYALANEISRLEQQKQILRERLANLERQLEELEAQLEELESKLDELaeELAELEEKLEEL 349

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344    168 NEIYEKVKDDVDKLKEANKKLKLENGGLLRENLRLKAEVDNRSPQkfgrftVAALQSKVEQYERETNRLKKALERSDKYI 247
Cdd:TIGR02168  350 KEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQ------IASLNNEIERLEARLERLEDRRERLQQEI 423

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 88759344    248 EELESQVAHLKHSE-------------EAKEDVDALCQRAPSADskgpngsDELGPPKNQSDSARKQAGSASA 307
Cdd:TIGR02168  424 EELLKKLEEAELKElqaeleeleeeleELQEELERLEEALEELR-------EELEEAEQALDAAERELAQLQA 489

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 88759344  17 TCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16532   2 ICPICQDEFKDPVVLRCKHIFCEDCVSEWFERERTCPLCR 41

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. 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. Both RING1 and RING2 are core components 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. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 88759344  15 PITCHICLGKVRQPVV---CTnnHVFCSICIDLWLKN-NSQCPACRVPI 59
Cdd:cd16531   1 ELMCPICLGIIKNTMTvkeCL--HRFCAECIEKALRLgNKECPTCRKHL 47

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 88759344  18 CHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVPIT 60
Cdd:cd16742  16 CAICQAEFREPLILICQHVFCEECLCLWFDRERTCPLCRSVVV 58

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 88759344  17 TCHICLGKVRQPVVCTNNHVFCSICIDLWLK-NNSQCPAC 55
Cdd:cd16449   2 ECPICLERLKDPVLLPCGHVFCRECIRRLLEsGSIKCPIC 41

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 88759344  18 CHICLG------KVRQPVVCtnNHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16461   2 CAICLSdyengeELRRLPEC--KHAFHKECIDEWLKSNSTCPLCR 44

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 88759344  17 TCHICLGKVRQPVVCTN--NHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16574   3 SCPICLDRFENEKAFLDgcFHAFCFTCILEWSKVKNECPLCKQPF 47

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 88759344  16 ITCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVPITPE 62
Cdd:cd23147   5 LKCPICLSLFKSAANLSCNHCFCAGCIGESLKLSAICPVCKIPATRR 51

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 88759344    18 CHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVP 58
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAE 69

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

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 88759344  18 CHICLGKVRQPVVCTN-NHVFCSICIDLWLKNNSQCPACRVPIT 60
Cdd:cd16529   7 CPICFEYFNTAMMITQcSHNYCSLCIRRFLSYKTQCPTCRAAVT 50

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 88759344  15 PITCHICLGKVRQPVVCTNNHVFCSICIDLWLK--NNSQCPACRVPITPEN 63
Cdd:cd16568   4 TQECIICHEYLYEPMVTTCGHTYCYTCLNTWFKsnRSLSCPDCRTKITTQP 54

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 88759344  16 ITCHICLGKVRQPVVCTN-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 88759344  16 ITCHICLGKVRQPVVCTNNHVFCSICI----DLWLKNNS-QCPACRVPITPEN 63
Cdd:cd16598   5 VTCSICLDYLRDPVTIDCGHNFCRSCItdycPISGGHERpVCPLCRKPFKKEN 57

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 88759344  18 CHICLGKvRQPVVCTNNHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16545   3 CCICMDR-KADLILPCAHSYCQKCIDKWSDRHRTCPICR 40

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 88759344  16 ITCHICLGKVRQPVVCTN-NHVFCSICIDLWLKNNSQCPACRVPITPENPCKEII 69
Cdd:cd16737  11 ITCRICKGYLIKPTTVTEcLHTFCKSCIVQHFEDSNDCPECGIQVHETNPLEMLR 65

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

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 88759344  17 TCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCP 53
Cdd:cd16637   3 TCHICLQPLVEPLDTPCGHTFCYKCLTNYLKIQQCCP 39

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 88759344  16 ITCHICLGKVRQPVVCTNNHVFCSICIDLW---LKNNSQCPACRVPITPE 62
Cdd:cd23133   4 LTCSICQGIFMNPVYLRCGHKFCEACLLLFqedIKFPAYCPMCRQPFNQE 53

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 88759344  17 TCHICLGKVRQPVVCTN---NHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16454   1 TCAICLEEFKEGEKVRVlpcNHLFHKDCIDPWLEQHNTCPLCR 43

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 88759344  16 ITCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVPIT 60
Cdd:cd16504   3 FLCPICFDIIKEAFVTKCGHSFCYKCIVKHLEQKNRCPKCNFYLT 47

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344  160 WKKKLRTANEIYEKVKDDVDKLKEANKKLKLENGGllRENLRLKAEVDNRSPQKfgRFTVAALQSKVEQYERETNRLKKA 239
Cdd:PRK12704  29 AEAKIKEAEEEAKRILEEAKKEAEAIKKEALLEAK--EEIHKLRNEFEKELRER--RNELQKLEKRLLQKEENLDRKLEL 104

                         90       100       110
                 ....*....|....*....|....*....|..
gi 88759344  240 LERSDKYIEELESQVAHLKHS-EEAKEDVDAL 270
Cdd:PRK12704 105 LEKREEELEKKEKELEQKQQElEKKEEELEEL 136

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 88759344   5 VQNVTLSLTLPITCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNS---QCPACRVPIT 60
Cdd:cd16498   6 VQEVISAMQKNLECPICLELLKEPVSTKCDHQFCRFCILKLLQKKKkpaPCPLCKKSVT 64

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 88759344  84 RKHLRKTRLELLH--REYEDEIDCLQKEVEELKSKNLSLESQIKTILDPLALMQGSQNEDKHPLAD-----------NPS 150
Cdd:COG4942  43 LAALKKEEKALLKqlAALERRIAALARRIRALEQELAALEAELAELEKEIAELRAELEAQKEELAEllralyrlgrqPPL 122

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344 151 KM--DPDSVVEWKKKLRTANEIYEKVKDDVDKLKEANKKLKLENGGLLRENLRLKAEVDNRSPQKfgrftvAALQSKVEQ 228
Cdd:COG4942 123 ALllSPEDFLDAVRRLQYLKYLAPARREQAEELRADLAELAALRAELEAERAELEALLAELEEER------AALEALKAE 196

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 88759344 229 YERETNRLKKALERSDKYIEELESQVAHLKHS-EEAKEDVDALCQRAPSADSKGPNGS 285
Cdd:COG4942 197 RQKLLARLEKELAELAAELAELQQEAEELEALiARLEAEAAAAAERTPAAGFAALKGK 254

second RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the second RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 88759344  18 CHICLGKVRQPVVCTNNHVFCSICIDLWLKNNSQCPACRVPI 59
Cdd:cd16514   4 CSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

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 88759344  17 TCHICLG------KVRQPVvCTnnHVFCSICIDLWLKNNSQCPACR 56
Cdd:cd16467   1 ECTICLGeyetgeKLRRLP-CS--HEFHSECVDRWLKENSSCPICR 43

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 88759344  18 CHICL--GKVRQPVVCTN-NHVFCSICIDLWLKN-NSQCPACR 56
Cdd:cd16448   1 CVICLeeFEEGDVVRLLPcGHVFHLACILRWLESgNNTCPLCR 43

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 88759344  16 ITCHICLGKVRQPVVCTNNHVFCSICIDLWLKNN------SQCPACRVPITPEN 63
Cdd:cd16591   7 VTCPICLELLTEPLSLDCGHSFCQACITANHKESvnqegeSSCPVCRTSYQPEN 60

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 88759344     95 LHREYEDEIDCLQKEVEELKSKNLSLESQIKTILDplaLMQGSQNEDKHPLADNPSKMDPDSVVEWK----KKLRTANEI 170
Cdd:pfam15921  466 LTAQLESTKEMLRKVVEELTAKKMTLESSERTVSD---LTASLQEKERAIEATNAEITKLRSRVDLKlqelQHLKNEGDH 542

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344    171 YEKVKDDVDKLkeankKLKLENGGLLRENLRLKAEVDNRSPQKFGRfTVAALQSKVEQYERETN-------RLKKALERS 243
Cdd:pfam15921  543 LRNVQTECEAL-----KLQMAEKDKVIEILRQQIENMTQLVGQHGR-TAGAMQVEKAQLEKEINdrrlelqEFKILKDKK 616

                          170
                   ....*....|....*
gi 88759344    244 DKYIEELESQVAHLK 258
Cdd:pfam15921  617 DAKIRELEARVSDLE 631

RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; RNF170, also known as putative LAG1-interacting protein, is an endoplasmic reticulum (ER) membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate (IP3) receptors (ITPR1) via the endoplasmic-reticulum-associated protein degradation (ERAD) pathway. A point mutation (arginine to cysteine at position 199) in the RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. RNF170 contains a C3HC4-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 88759344  15 PITCHICLGKVRQPVVCTNNHVFCSICIDLWLKNNS-----QCPACRVPIT 60
Cdd:cd16553   1 DMECPICLQDARFPVETNCGHLFCGPCIITYWRHGSwlgavSCPVCRQTVT 51

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 88759344  17 TCHICLGKVRQPVVCTN-NHVFCSICIDLWLKNNS-QCPACRVP 58
Cdd:cd16549   3 SCPICLEVYHKPVVITScGHTFCGECLQPCLQVASpLCPLCRMP 46

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344  85 KHLRKTRLELlhREYEDEIDCLQKEVEELKSKNLSLESQIKtILDPLALMQGSQNEdkhpLADNPSKMDpdsvvEWKKKL 164
Cdd:COG4717  88 EEYAELQEEL--EELEEELEELEAELEELREELEKLEKLLQ-LLPLYQELEALEAE----LAELPERLE-----ELEERL 155

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 88759344 165 RTaneiYEKVKDDVDKLKEANKKLKlenggllRENLRLKAEVDNRSPQKFGRF--TVAALQSKVEQYERETNRLKKALER 242
Cdd:COG4717 156 EE----LRELEEELEELEAELAELQ-------EELEELLEQLSLATEEELQDLaeELEELQQRLAELEEELEEAQEELEE 224

                       170       180
                ....*....|....*....|...
gi 88759344 243 SDKYIEELESQVAHLKHSEEAKE 265
Cdd:COG4717 225 LEEELEQLENELEAAALEERLKE 247