forkhead associated (FHA) domain 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. Specially, 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 FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348  18 WCLRRVGMS--AGWLLLEDGCEVTVGRGFGVTYQLVSkICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPL 95
Cdd:cd22663    1 WCLRRVGHGidPLVLLLEDGKEVTVGRGLGVTYQLVS-TCPLMISRNHCVLKKNDEGQWTIKDNKSLNGVWVNGERIEPL 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119624348  96 RVYSIHQGDYIQLGVPLENKENAEYEYEVTE 126
Cdd:cd22663   80 KPYPLNEGDLIQLGVPPENKEPAEYVFNLIK 110

Exopolysaccharide export protein/domain GumC/Wzc1 [Cell wall/membrane/envelope biogenesis];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348 233 EQKASNSSASQRSLQMFKvtmSRILRLKIQMQEKHEAVMNVKKQTQ--------KGNSKKVVQMEQELQDLQSQLcaeqA 304
Cdd:COG3206  164 QNLELRREEARKALEFLE---EQLPELRKELEEAEAALEEFRQKNGlvdlseeaKLLLQQLSELESQLAEARAEL----A 236

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348 305 QQQARVEQLEKTFQEEEQHLQGLEIAQGEKDLKQQLAQALQEhwaLMEELNRSKKDFEAIIQAKNkELEQTKEEKEKMQA 384
Cdd:COG3206  237 EAEARLAALRAQLGSGPDALPELLQSPVIQQLRAQLAELEAE---LAELSARYTPNHPDVIALRA-QIAALRAQLQQEAQ 312

                        170
                 ....*....|....*...
gi 119624348 385 QKEEVLSHMNDVLENELQ 402
Cdd:COG3206  313 RILASLEAELEALQAREA 330

forkhead associated (FHA) domain 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. Specially, 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 FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348  18 WCLRRVGMS--AGWLLLEDGCEVTVGRGFGVTYQLVSkICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPL 95
Cdd:cd22663    1 WCLRRVGHGidPLVLLLEDGKEVTVGRGLGVTYQLVS-TCPLMISRNHCVLKKNDEGQWTIKDNKSLNGVWVNGERIEPL 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119624348  96 RVYSIHQGDYIQLGVPLENKENAEYEYEVTE 126
Cdd:cd22663   80 KPYPLNEGDLIQLGVPPENKEPAEYVFNLIK 110

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119624348   38 VTVGRGFGVTYQLVSKicplMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPlRVYSIHQGDYIQL 108
Cdd:pfam00498   1 VTIGRSPDCDIVLDDP----SVSRRHAEIRYDGGGRFYLEDLGSTNGTFVNGQRLGP-EPVRLKDGDVIRL 66

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 119624348  399 NELQCIICSEYFIEAVTLNCAH-SFCSYCINEWMKRKIECPICRKDIKS 446
Cdd:pfam13920   1 EDLLCVICLDRPRNVVLLPCGHlCLCEECAERLLRKKKKCPICRQPIES 49

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 119624348  397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCR 67

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKD 443
Cdd:COG5432   22 LDSMLRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPFCPVCRED 68

phosphodiesterase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348 253 MSRILRLKI-QMQEKHEAVM-NVKKQTQKGNSKKVVQMEQELQDLQSQLCAEQAQQQARVEQLEKTFQEEEQHL-QGLEI 329
Cdd:PRK12704  25 RKKIAEAKIkEAEEEAKRILeEAKKEAEAIKKEALLEAKEEIHKLRNEFEKELRERRNELQKLEKRLLQKEENLdRKLEL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348 330 AqgeKDLKQQLAQALQEHWALMEELNRSKKDFEAIIQAKNKELEQ----TKEEKekmqaqKEEVLSHMNDVLENELQCII 405
Cdd:PRK12704 105 L---EKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERisglTAEEA------KEILLEKVEEEARHEAAVLI 175

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 119624348   231 HHEQKASNSSASQRSLQMfkvtMSRILRLKIQMQEKHEAVMNVKKQTQKGNSKKVVQmEQELQDLQsqlcAEQAQQQARV 310
Cdd:TIGR02168  728 ISALRKDLARLEAEVEQL----EERIAQLSKELTELEAEIEELEERLEEAEEELAEA-EAEIEELE----AQIEQLKEEL 798

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348   311 EQLEKTFQEEEQHLQGLEIAQGEKDLK-QQLAQALQEHWALMEELNRSKKDFEAIIQAKNKELEQTKEEKEKMQAQKEEV 389
Cdd:TIGR02168  799 KALREALDELRAELTLLNEEAANLRERlESLERRIAATERRLEDLEEQIEELSEDIESLAAEIEELEELIEELESELEAL 878

                   .
gi 119624348   390 L 390
Cdd:TIGR02168  879 L 879

HpsJ family protein; HpsJ (hormogornium polysaccharide J) is thought to be involved in the biosynthesis or secretion of an extracellular polysaccharide shared by many Cyanobacteria.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348 287 QMEQELQDLQSQLcaEQAQQQARVEQLEKTFQEEEQHLQGLEIAQGEKDLKQQLAQALQEHWALMEELNRSKkdfeaiiq 366
Cdd:NF038305 116 QAGQQETQLQQQL--NQLQAQTSPQQLNQLLKSEQKQGQALASGQLPEEQKEQLQQFKSNPQALDKFLAQQL-------- 185

                         90       100
                 ....*....|....*....|.
gi 119624348 367 aknKELEQTKEEKEKmQAQKE 387
Cdd:NF038305 186 ---TQIRTQAEEAEK-QARLE 202

HpsJ family protein; HpsJ (hormogornium polysaccharide J) is thought to be involved in the biosynthesis or secretion of an extracellular polysaccharide shared by many Cyanobacteria.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348 293 QDLQSQLCAEQAQQQARVEQLEKTFQEEEQHLQGLEIAQGEKDLKQQLA-QALQEhwALMEELNRSKKDFEAIIQAKNKE 371
Cdd:NF038305 107 TQALQQINQQAGQQETQLQQQLNQLQAQTSPQQLNQLLKSEQKQGQALAsGQLPE--EQKEQLQQFKSNPQALDKFLAQQ 184

                         90       100
                 ....*....|....*....|
gi 119624348 372 LEQTKEEKEKMQAQ-KEEVL 390
Cdd:NF038305 185 LTQIRTQAEEAEKQaRLEAL 204

forkhead associated (FHA) domain 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. Specially, 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 FHA domain, which is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348  18 WCLRRVGMS--AGWLLLEDGCEVTVGRGFGVTYQLVSkICPLMISRNHCVLKQNPEGQWTIMDNKSLNGVWLNRARLEPL 95
Cdd:cd22663    1 WCLRRVGHGidPLVLLLEDGKEVTVGRGLGVTYQLVS-TCPLMISRNHCVLKKNDEGQWTIKDNKSLNGVWVNGERIEPL 79

                         90       100       110
                 ....*....|....*....|....*....|.
gi 119624348  96 RVYSIHQGDYIQLGVPLENKENAEYEYEVTE 126
Cdd:cd22663   80 KPYPLNEGDLIQLGVPPENKEPAEYVFNLIK 110

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated (FHA) domain and a C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 119624348 399 NELQCIICSEYFIEAVTLN-CAHSFCSYCINEWM-KRKIECPICRKDIKS 446
Cdd:cd16503    1 ENLTCSICQDLLHDCVSLQpCMHNFCAACYSDWMeRSNTECPTCRATVQR 50

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 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINE-WMKRKIE---CPICRKDIKSK 447
Cdd:cd16597    2 LEEELTCSICLELFKDPVTLPCGHNFCGVCIEKtWDSQHGSeysCPQCRATFPRR 56

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        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 119624348 397 LENELQCIICSEYF-IEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIKSK 447
Cdd:cd16529    1 LDDLLRCPICFEYFnTAMMITQCSHNYCSLCIRRFLSYKTQCPTCRAAVTES 52

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 119624348 401 LQCIICSEYFIEAVTLNCAHSFCSYCINEWMK--RKIECPICRKDIKS 446
Cdd:cd16568    5 QECIICHEYLYEPMVTTCGHTYCYTCLNTWFKsnRSLSCPDCRTKITT 52

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 119624348 398 ENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRK----IECPICR 441
Cdd:cd16609    1 EEELTCSICLGLYQDPVTLPCQHSFCRACIEDHWRQKdegsFSCPECR 48

RING finger, HC subclass, found in Equid alphaherpesvirus 1 (Equine herpesvirus 1/EHV-1) regulatory protein and similar proteins; EHV-1 regulatory protein belongs to the Vmw110 (IPC0) protein family. It contains a typical C3HC4-type RING-HC finger and binds zinc stably.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 119624348 402 QCIIC-SEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIKS 446
Cdd:cd23130    2 VCPIClDDPEDEAITLPCLHQFCYTCILRWLQTSPTCPLCKTPVTS 47

RING finger, HC subclass, found in Ret finger protein-like 4B (RFPL4B) and similar proteins; RFPL4B, also called RING finger protein 211 (RNF211), is an uncharacterized RING finger protein containing a typical C3HC4-type RING-HC finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 119624348 393 MNDVLENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRK----IECPICRKDIK 445
Cdd:cd16623    1 MANRLEMEATCPICLDFFSHPISLSCAHIFCFDCIQKWMTKRedsiLTCPLCRKEQK 57

forkhead associated (FHA) domain found in Saccharomyces cerevisiae defective in mitotic arrest protein 1 (DMA1), 2 (DMA2) and similar proteins; DMA1 (also known as checkpoint forkhead associated with RING domains-containing protein 1, or CHF1) and DMA2 (also known as checkpoint forkhead associated with RING domains-containing protein 2, or CHF2) are E3 ubiquitin-protein ligases which function in cell cycle retarding in conjunction with the UBC4 and UBC13/MMS2 complex, two E2 ubiquitin conjugating enzymes. They are involved in nutritional control of the cell cycle and required for proper spindle positioning, likely regulating septin ring deposition at the bud neck. DMA1 targets the degradation of G1 cyclin PCL1. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 119624348  58 MISRNHCVLKQNpEGQWTIMDNKSLNGVWLNRARLEPL----RVYSIHQGDYIQLG 109
Cdd:cd22692   62 VVSRTHGCIKVD-EGNWYIKDVKSSSGTFLNHQRLSPAsrtsKPYPLRDGDILQLG 116

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        40
                 ....*....|....*....|....*....|....*....|
gi 119624348 402 QCIICSEYFIEaVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:cd16545    2 ECCICMDRKAD-LILPCAHSYCQKCIDKWSDRHRTCPICR 40

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 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRK-----IECPICRKDIK 445
Cdd:cd16598    1 LEEEVTCSICLDYLRDPVTIDCGHNFCRSCITDYCPISggherPVCPLCRKPFK 54

first forkhead associated (FHA) domain found in Mycobacterium tuberculosis ABC transporter ATP-binding/permease protein Rv1747 and similar proteins; Rv1747 is a putative ATP-binding cassette (ABC) transporter involved in the translocation of an unknown substrate across the membrane. It is required for normal virulent infection by M. tuberculosis. Rv1747 has a cytoplasmic regulatory module consisting of two pThr-interacting forkhead-associated (FHA) domains connected by a conformationally disordered linker with two phospho-acceptor threonines (pThr). Recruitment and phosphorylation of Rv1747 depend on the interaction between its two non-redundant FHA domains and the autophosphorylated form of serine/threonine protein kinase PknF. This model corresponds to the first FHA domain. The FHA domain is a small phosphopeptide recognition module.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119624348  27 AGWLLLEDGCEVTVGRGFGVTYQLVSkicPLmISRNHCVLKQNPEGqWTIMDNKSLNGVWLNRARLEPLRVYSihqGDYI 106
Cdd:cd22694    7 GGELRFDPGSSVRIGRDPDADVRLDD---PR-VSRRHALLEFDGDG-WVYTDLGSRNGTYLNGRRVQQVKLSD---GTRV 78

                         90
                 ....*....|
gi 119624348 107 QLGVPLENKE 116
Cdd:cd22694   79 RLGDPTDGPA 88

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 119624348 398 ENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIK 445
Cdd:cd16547    1 DDDLICSICHGVLRCPVRLSCSHIFCKKCILQWLKRQETCPCCRKEVK 48

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
                 ....*....|....*....|....*....|....*....|....*....
gi 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIE---CPICRK 442
Cdd:cd16611    1 LTEELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEdttCPECRE 49

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

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                 ....*....|....*....|....*....|....*....|....*....
gi 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINE-WMKR--KIECPICRK 442
Cdd:cd16594    2 LQEELTCPICLDYFTDPVTLDCGHSFCRACIARcWEEPetSASCPQCRE 50

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.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 119624348 400 ELQCIICSEYFIEAVTL-NCAHSFCSYCINEWMKR-KIECPICRKDIKSK 447
Cdd:cd16531    1 ELMCPICLGIIKNTMTVkECLHRFCAECIEKALRLgNKECPTCRKHLPSR 50

RING finger, HC subclass, found in bifunctional apoptosis regulator (BAR); BAR, also known as RING finger protein 47, was originally identified as an inhibitor of Bax-induced apoptosis. It participates in the block of apoptosis induced by TNF-family death receptors (extrinsic pathway) and mitochondria-dependent apoptosis (intrinsic pathway). BAR is predominantly expressed by neurons in the central nervous system and is involved in the regulation of neuronal survival. It is an endoplasmic reticulum (ER)-associated RING-type E3 ubiquitin ligase that interacts with BI-1 protein and post-translationally regulates its stability, as well as functioning in ER stress. BAR contains an N-terminal C3HC4-type RING-HC finger, a SAM domain, a coiled-coil domain, and a C-terminal transmembrane (TM) domain. This model corresponds to the RING-HC finger responsible for the binding of ubiquitin conjugating enzymes (E2s).

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                 ....*....|....*....|....*....|....*....|....*
gi 119624348 400 ELQCIICSEYFIEAVTLNCAHSFCSYCINEWMK--RKIECPICRK 442
Cdd:cd16497    1 EFLCHCCYDLLVNPTTLNCGHSFCRHCLALWWKssKKTECPECRQ 45

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRK---IECPICRKDI 444
Cdd:cd16498   13 MQKNLECPICLELLKEPVSTKCDHQFCRFCILKLLQKKkkpAPCPLCKKSV 63

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.

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                 ....*....|....*....|....*....|....*....|..
gi 119624348 400 ELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:cd16637    1 DLTCHICLQPLVEPLDTPCGHTFCYKCLTNYLKIQQCCPLDR 42

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

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                 ....*....|....*....|....*....|....*....|..
gi 119624348 400 ELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:cd23135    3 KLSCSICFSEIRSGAILKCGHFFCLSCIASWLREKSTCPLCK 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).

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                 ....*....|....*....|....*....|....*....|.
gi 119624348 403 CIICSEYFIE--AVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:cd16574    4 CPICLDRFENekAFLDGCFHAFCFTCILEWSKVKNECPLCK 44

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.

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                 ....*....|....*....|....*....|....*....|....*
gi 119624348 400 ELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDI 444
Cdd:cd16514    1 DLECSLCLRLLYEPVTTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 119624348 398 ENELQCIICSEYFIEAVTLNCAHSFCSYCINE-WmkrKIECPICRKDIKSKTY 449
Cdd:cd16602    1 QEEAVCAICLDYFKDPVSIGCGHNFCRVCVTQlW---GFTCPQCRKSFPRRSF 50

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

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                 ....*....|....*....|....*....|....*....|....*....|
gi 119624348 399 NELQCIICSEYFIEAVTLNCAH-SFCSYCI-NEWMKRKIECPICRKDIKS 446
Cdd:cd16620    2 DELKCPICKDLMKDAVLTPCCGnSFCDECIrTALLEEDFTCPTCKEPDVS 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]

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                  ....*....|....*....|....*....|....*....|....*
gi 119624348  397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCR 67

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.

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                 ....*....|....*....|....*....|....*....|..
gi 119624348 403 CIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDI 444
Cdd:cd16741   17 CAICQAEFRKPILLICQHVFCEECISLWFNREKTCPLCRTVI 58

RING finger found in polycomb group RING finger protein 2 (PCGF2) and similar proteins; PCGF2, also known as DNA-binding protein Mel-18, RING finger protein 110 (RNF110), or zinc finger protein 144 (ZNF144), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR). It serves as the core component of a canonical Polycomb repressive complex 1 (PRC1), which is composed of a chromodomain-containing protein (CBX2, CBX4, CBX6, CBX7 or CBX8) and a Polyhomeotic protein (PHC1, PHC2, or PHC3). Like other PCGF homologs, PCGF2 associates with ring finger protein 2 (RNF2) to form a RNF2-PCGF heterodimer, which is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. Moreover, PCGF2 uniquely regulates PRC1 to specify mesoderm cell fate in embryonic stem cells. It is required for PRC1 stability and maintenance of gene repression in embryonic stem cells (ESCs) and essential for ESC differentiation into early cardiac-mesoderm precursors. PCGF2 also plays a significant role in the angiogenic function of endothelial cells (ECs) by regulating endothelial gene expression. Furthermore, PCGF2 is a SUMO-dependent regulator of hormone receptors. It facilitates the deSUMOylation process by inhibiting PCGF4/BMI1-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). It is also a novel negative regulator of breast cancer stem cells (CSCs) that inhibits the stem cell population and in vitro and in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling. PCGF2 contains a C3HC4-type RING-HC finger.

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gi 119624348 397 LENELQCIICSEYFIEAVTL-NCAHSFCSYCINEWMKRKIECPIC 440
Cdd:cd16734   11 LNPHLMCALCGGYFIDAATIvECLHSFCKTCIVRYLETNKYCPMC 55

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.

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gi 119624348 403 CIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIK 445
Cdd:cd16539    8 CFICRKPFKNPVVTKCGHYFCEKCALKHYRKSKKCFVCGKQTN 50

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

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gi 119624348 402 QCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICRKDIK 445
Cdd:cd16527    2 KCSLCLEERRHPTATPCGHLFCWSCITEWCNEKPECPLCREPFQ 45

RING finger, HC subclass, found in Arabidopsis thaliana proteolysis 1 protein (PRT1) and similar proteins; PRT1, also called RING-type E3 ubiquitin transferase PRT1, is an E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. It functions in the N-end rule pathway of protein degradation, where it specifically recognizes and ubiquitinates proteins with an N-terminal bulky aromatic amino acid (Phe). It does not act on aliphatic hydrophobic and basic N-terminal residues (Arg or Leu) containing proteins. PRT1 contains a typical C3HC4-type RING-HC finger.

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gi 119624348 400 ELQCIICSEYFIEAVTLNCAHSFCSYCINEWMK--RKIECPICRKD 443
Cdd:cd23132    2 EFLCCICLDLLYKPVVLECGHVFCFWCVHRCMNgyDESHCPLCRRP 47

RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 (AtBARD1) and similar proteins; AtBARD1, also called protein REPRESSOR OF WUSCHEL 1, binds specifically to H3K4me3 regions of target gene (e.g. WUS and WOX5) promoters to repress their transcription via chromatin remodeling. It is required for the shoot apical meristem (SAM) organization and maintenance, by confining WUS expression to the organizing center, and for the quiescent center (QC) development in the root apical meristem (RAM), by repressing WOX5 expression in the root proximal meristem. AtBARD1 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). AtBARD1 contains a typical C3HC4-type RING-HC finger.

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                 ....*....|....*....|....*....|....*....|....*
gi 119624348 397 LENELQCIICSEYFIEAVTLNCAHSFCSYCINEWMKRKIECPICR 441
Cdd:cd23146    1 MELELKCPICLKLLNRPVLLPCDHIFCSSCITDSTKVGSDCPVCK 45