Cysteine rich domain with multizinc binding regions; This is a cysteine rich domain which contains four zinc-binding regions (binding five zinc ions). Family members include human CHFR which interacts with Poly(ADP-ribose) (PAR) through a 20-amino acid PAR binding zinc finger region (PBZ) found at the C-terminal end of this cysteine-rich domain (i.e. the 4th region towards the C-terminal). CHFR lacking PBZ does not co-localize with nuclear PAR foci in interphase cells and cannot rescue antephase checkpoint function despite retaining autoubiquitination activity. Hence it has been suggested that the CHFR-PAR interaction is an important part of the antephase checkpoint and could form part of the checkpoint sensor for cellular stress and microtubule poisons or be required for proper localization of CHFR. The PBZ region of CHFR contains two adenine binding sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 441 TTAPQEFRCPPQASHLICTCCLQPMPDRRfehlpPQVSPQHCLVCQKPFCHVYW-GCPRIGCHGCLARFSElNLNDKCLD 519
Cdd:pfam17979   5 GTAIGGFQCPPQTQHLQCTCCGGMMPDRR-----DAGVPQQCLLCKRPFCGLYWgGCPRAGCQGCLKPFSE-NLISKIPD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 520 GVFNGNQYESEVLQNYLSCRGMSWRHLLQDSLQALQQGLYH-------LSDYRITANSFLCYCCGLRTFRELAYKYRERI 592
Cdd:pfam17979  79 NVFNGNQYEQDILQDYLAQKGKTLQDVISEWLQKLDNGEIDrtrkplnLSDYIITADTPLCNDCALKLFSFLLYKYRISI 158

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 1040690151 273 ESLTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSS-FCPTCRCPVERIRKNH 326
Cdd:cd16503     1 ENLTCSICQDLLHDCVSLQPCMHNFCAACYSDWMERSNtECPTCRATVQRVNKNH 55

Cysteine rich domain with multizinc binding regions; This is a cysteine rich domain which contains four zinc-binding regions (binding five zinc ions). Family members include human CHFR which interacts with Poly(ADP-ribose) (PAR) through a 20-amino acid PAR binding zinc finger region (PBZ) found at the C-terminal end of this cysteine-rich domain (i.e. the 4th region towards the C-terminal). CHFR lacking PBZ does not co-localize with nuclear PAR foci in interphase cells and cannot rescue antephase checkpoint function despite retaining autoubiquitination activity. Hence it has been suggested that the CHFR-PAR interaction is an important part of the antephase checkpoint and could form part of the checkpoint sensor for cellular stress and microtubule poisons or be required for proper localization of CHFR. The PBZ region of CHFR contains two adenine binding sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 441 TTAPQEFRCPPQASHLICTCCLQPMPDRRfehlpPQVSPQHCLVCQKPFCHVYW-GCPRIGCHGCLARFSElNLNDKCLD 519
Cdd:pfam17979   5 GTAIGGFQCPPQTQHLQCTCCGGMMPDRR-----DAGVPQQCLLCKRPFCGLYWgGCPRAGCQGCLKPFSE-NLISKIPD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 520 GVFNGNQYESEVLQNYLSCRGMSWRHLLQDSLQALQQGLYH-------LSDYRITANSFLCYCCGLRTFRELAYKYRERI 592
Cdd:pfam17979  79 NVFNGNQYEQDILQDYLAQKGKTLQDVISEWLQKLDNGEIDrtrkplnLSDYIITADTPLCNDCALKLFSFLLYKYRISI 158

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 1040690151 273 ESLTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSS-FCPTCRCPVERIRKNH 326
Cdd:cd16503     1 ENLTCSICQDLLHDCVSLQPCMHNFCAACYSDWMERSNtECPTCRATVQRVNKNH 55

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1040690151  31 CTVGRKKDCDLSFPaNKLVSGNHCKITHDqNSGKVWLEDM-STNGTVINmSKVVKKQTHLLQNGDVIYF 98
Cdd:pfam00498   1 VTIGRSPDCDIVLD-DPSVSRRHAEIRYD-GGGRFYLEDLgSTNGTFVN-GQRLGPEPVRLKDGDVIRL 66

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1040690151 271 MEESLTCIICQDLlYDCISVQPCMHTFCAACYSGWMERSSFCPTCRCPVE--RIRKNHILNNLVEAY 335
Cdd:TIGR00599  23 LDTSLRCHICKDF-FDVPVLTSCSHTFCSLCIRRCLSNQPKCPLCRAEDQesKLRSNWLVSEIVESF 88

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1040690151  277 CIICQDLLYDCISVQPCMHTFCAACYSGWMERSSF-CPTC 315
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGNNtCPIC 40

Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 1040690151   32 TVGR-KKDCDLSFPaNKLVSGNHCKITHDQNsGKVWLEDM-STNGTVIN 78
Cdd:smart00240   2 TIGRsSEDCDIQLD-GPSISRRHAVIVYDGG-GRFYLIDLgSTNGTFVN 48

Cysteine rich domain with multizinc binding regions; This is a cysteine rich domain which contains four zinc-binding regions (binding five zinc ions). Family members include human CHFR which interacts with Poly(ADP-ribose) (PAR) through a 20-amino acid PAR binding zinc finger region (PBZ) found at the C-terminal end of this cysteine-rich domain (i.e. the 4th region towards the C-terminal). CHFR lacking PBZ does not co-localize with nuclear PAR foci in interphase cells and cannot rescue antephase checkpoint function despite retaining autoubiquitination activity. Hence it has been suggested that the CHFR-PAR interaction is an important part of the antephase checkpoint and could form part of the checkpoint sensor for cellular stress and microtubule poisons or be required for proper localization of CHFR. The PBZ region of CHFR contains two adenine binding sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 441 TTAPQEFRCPPQASHLICTCCLQPMPDRRfehlpPQVSPQHCLVCQKPFCHVYW-GCPRIGCHGCLARFSElNLNDKCLD 519
Cdd:pfam17979   5 GTAIGGFQCPPQTQHLQCTCCGGMMPDRR-----DAGVPQQCLLCKRPFCGLYWgGCPRAGCQGCLKPFSE-NLISKIPD 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 520 GVFNGNQYESEVLQNYLSCRGMSWRHLLQDSLQALQQGLYH-------LSDYRITANSFLCYCCGLRTFRELAYKYRERI 592
Cdd:pfam17979  79 NVFNGNQYEQDILQDYLAQKGKTLQDVISEWLQKLDNGEIDrtrkplnLSDYIITADTPLCNDCALKLFSFLLYKYRISI 158

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 1040690151 273 ESLTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSS-FCPTCRCPVERIRKNH 326
Cdd:cd16503     1 ENLTCSICQDLLHDCVSLQPCMHNFCAACYSDWMERSNtECPTCRATVQRVNKNH 55

forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  17 DASPGSEIVLINSECTVGRKKDCDLSFPaNKLVSGNHCKITHDqnSGKVWLEDM-STNGTVINMSKVVKKqtHLLQNGDV 95
Cdd:cd00060     7 GDGGGREFPLTKGVVTIGRSPDCDIVLD-DPSVSRRHARIEVD--GGGVYLEDLgSTNGTFVNGKRITPP--VPLQDGDV 81

                  ...
gi 1040690151  96 IYF 98
Cdd:cd00060    82 IRL 84

forkhead associated (FHA) domain found in checkpoint kinase 2 (Chk2) and similar proteins; Chk2, also called Hucds1, Cds1 homolog, or serine/threonine-protein kinase Chk2, plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  10 WGKLVKVDASpGSEIVLINSECTVGRKKDCDLSFPANKL--------VSGNHCKITHDQNSGK---VWLEDMSTNGTVIN 78
Cdd:cd22666     1 WGRLFPLGSG-FSSLDLVKDEYTFGRDKSCDYCFDSPALkktsyyrtYSKKHFRIFREKGSKNtypVFLEDHSSNGTFVN 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1040690151  79 MSKVVKKQTHLLQNGDVIYFVYRKNEpeqniAYVYQSI 116
Cdd:cd22666    80 GEKIGKGKKRPLNNNDEIALSLPKNK-----VFVFMDL 112

forkhead associated (FHA) domain found in Saccharomyces cerevisiae meiosis-specific serine/threonine-protein kinase MEK1 and similar proteins; MEK1 (EC 2.7.11.1), also known as MRE4, is a meiosis-specific protein kinase required for chromosome synapsis and meiotic recombination. The recruitment and activation of MEK1 require the phosphorylation of the chromosome axis protein Hop1 at Thr318 (pT318), which is necessary for recognition by the MEK1 FHA domain. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  11 GKLVKVDASPGSEIVLI--NSECTVGRKKDCDLSFPaNKLVSGNHCKITH---DQNSG-KVWLEDMSTNGTVINMSKVVK 84
Cdd:cd22670     2 GKLEVSSPGSTDIVLPIykNQVITIGRSPSCDIVIN-DPFVSRTHCRIYSvqfDESSApLVYVEDLSSNGTYLNGKLIGR 80

                          90
                  ....*....|....
gi 1040690151  85 KQTHLLQNGDVIYF 98
Cdd:cd22670    81 NNTVLLSDGDVIEI 94

forkhead associated (FHA) domain found in proliferation marker protein Ki-67 and similar proteins; Ki-67, also called antigen identified by monoclonal antibody Ki-67, antigen KI-67, or antigen Ki67, acts as a biological surfactant to disperse mitotic chromosomes. It is required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly. Ki-67 binds DNA with a preference for supercoiled DNA and AT-rich DNA. It may also play a role in chromatin organization. Ki-67 contains an FHA domain at its N-terminus. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  11 GKLV--KVDASPGSEIVLINSECTVGRKKDCD--LSFPAnklVSGNHCKITHDQNsGKVWLEDMS-TNGTVINMSKVVKK 85
Cdd:cd22673     1 GKLVviKKDGTDGSRFPLTKKSCTFGRDLSCDirIQLPG---VSREHCRIEVDEN-GKAYLENLStTNPTLVNGKAIEKS 76

                          90
                  ....*....|.
gi 1040690151  86 qtHLLQNGDVI 96
Cdd:cd22673    77 --AELKDGDVI 85

forkhead associated (FHA) domain found in Myxococcus xanthus EspA and similar proteins; EspA is a histidine protein kinase with a fork head-associated (FHA) domain at the N-terminus and a receiver domain at the C-terminus. It functions as an inhibitor of sporulation during early fruiting body development while cells are aggregating into raised mounds. EspA is part of a two-component signal transduction system that regulates the timing of sporulation initiation. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1040690151  21 GSEIVLINSECTVGRKKDCDLSFPANKlVSGNHCKITHdqNSGKVWLEDM-STNGTVINMSKVvkkQTHLLQNGDVI 96
Cdd:cd22698    13 GKDYELDQDEFTIGRSSNNDIRLNDHS-VSRHHARIVR--QGDKCNLTDLgSTNGTFLNGIRV---GTHELKHGDRI 83

first forkhead associated (FHA) domain found in Saccharomyces cerevisiae Serine/threonine-protein kinase RAD53 and similar proteins; RAD53, also called CHEK2 homolog, or serine-protein kinase 1 (Spk1), is a nuclear protein kinase that phosphorylates proteins on serine, threonine, and tyrosine. It controls S-phase checkpoint as well as G1 and G2 DNA damage checkpoints and prevents entry into anaphase and mitotic exit after DNA damage via regulation of the Polo kinase CDC5. It may be involved in the phosphorylation of RPH1. RAD53 contains two FHA domains. This model corresponds to the first one. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1040690151  32 TVGRKKDCDLSFpANKLVSGNHCKIT---HDQNSGKVWLEDMSTNGTVINMSKVVKKQTHLLQNGDVIY 97
Cdd:cd22689    48 TFGRHPACDYHL-GNSRLSNKHFQILlgeSDPSDGNVLLNDISSNGTWLNGQRLEKNSNQLLSQGDEIT 115

type VI secretion system FHA domain protein; Members of this protein family are FHA (forkhead-associated) domain-containing proteins that are part of type VI secretion loci in a considerable number of bacteria, most of which are known pathogens. Species include Pseudomonas aeruginosa PAO1, Aeromonas hydrophila, Yersinia pestis, Burkholderia mallei, etc. [Protein fate, Protein and peptide secretion and trafficking, Cellular processes, Pathogenesis]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  32 TVGRKKDCDLSFP-ANKLVSGNHCKITHDqnSGKVWLEDMSTNGTVINMS--KVVKKQTHLLQNGDVIY---FVYRknep 105
Cdd:TIGR03354  27 TIGRSEDCDWVLPdPERHVSGRHARIRYR--DGAYLLTDLSTNGVFLNGSgsPLGRGNPVRLEQGDRLRlgdYEIR---- 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1040690151 106 eqniAYVYQSITPQEsASHDVEDAGREEDSdlteTESEPAPVEPVIVKPLPQSGHEDPQPS 166
Cdd:TIGR03354 101 ----VSLGDPLVSRQ-ASESRADTSLPTAG----GPPTPDPAPLAQLDPLKALDQEPLSAA 152

forkhead associated (FHA) domain found in the centrosomal protein of 170 kDa protein (Cep170) family; The Cep170 family includes Cep170 and Cep170B. Cep170, also called Cep170A, KARP-1-binding protein, or KARP1-binding protein, is a protein that localizes to centrosomes as well as spindle microtubules and plays a role in microtubule organization and microtubule assembly. It is required for centriole subdistal appendage assembly. Cep170 is phosphorylated during M phase and interacts with Polo-like kinase 1 (Plk1). Cep170B, also called centrosomal protein 170B, plays a role in microtubule organization. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  33 VGRKkDCDLSFpANKLVSGNHCKITHDQNSGKVWLEDM-STNGTVINMSKvVKKQTHL-LQNGDVIYFVY 100
Cdd:cd22704    21 VGRE-DCDLIL-QSRSVDKQHAVITYDQIDNEFKIKDLgSLNGTFVNDSR-IPEQTYItLKLGDSIRFGY 87

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1040690151 276 TCIICQDLLY--DCISVQPCMHTFCAACYSGWMERSSFCPTCR 316
Cdd:pfam13639   2 ECPICLEEFEegDKVVVLPCGHHFHRECLDKWLRSSNTCPLCR 44

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1040690151 273 ESLTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSSF-CPTCRCPVERIRK 324
Cdd:cd16544     1 AELTCPVCQEVLKDPVELPPCRHIFCKACILLALRSSGArCPLCRGPVGKTER 53

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        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151 270 KMEESLTCIICQDLLYDCISVQpCMHTFCAACYSGWMERSS---FCPTCRCPVER--IRKNHILNNLVEA 334
Cdd:cd16498    12 AMQKNLECPICLELLKEPVSTK-CDHQFCRFCILKLLQKKKkpaPCPLCKKSVTKrsLQESTRFKQLVEA 80

forkhead associated (FHA) domain found in nibrin and similar proteins; Nibrin (NBN), also called cell cycle regulatory protein p95, or Nijmegen breakage syndrome protein 1 (NBS1), is a novel DNA double-strand break repair protein that is mutated in Nijmegen breakage syndrome. It is a component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity. Nibrin modulates the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to the DNA damage sites and activating their functions. It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX. Nibrin also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation. Nibrin is a major player in the control of intra-S-phase checkpoint. This subfamily also includes Schizosaccharomyces pombe DNA repair and telomere maintenance protein Nbs1 and Arabidopsis thaliana AtNbs1. SpNbs1 is an FHA domain-containing protein required for DNA damage repair and S-phase DNA damage checkpoint. It is involved in telomere length maintenance and maintenance of chromatin structure. AtNbs1 is a component of MRN complex. It also functions in the very early stages of meiosis. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1040690151  32 TVGRKkDCDLSFPANKLVSGNHCKIT---------HDQNSGKVWLEDMSTNGTVINMSKVVKKQTHLLQNGDVIYF 98
Cdd:cd22667    23 TVGRK-DCDIIIVDDSSISRKHATLTvlhpeanlsDPDTRPELTLKDLSKYGTFVNGEKLKGGSEVTLKDGDVITF 97

forkhead associated (FHA) domain found in mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins; MDC1, also called nuclear factor with BRCT domains 1 (NFBD1), is a nuclear chromatin-associated protein that is required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S and G2/M phases of the cell cycle. It directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. MDC1 contains a forkhead-associated (FHA) domain and two BRCT domains, as well as an internal 41-amino acid repeat sequence. The FHA domain is a small phosphopeptide recognition module.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1040690151  11 GKLVKVDASPGSEI--VLINSECTVGRKKDCDLSFPANKlVSGNHCKITHDqnSGKVWLEDM-STNGTVINMSKVVK-KQ 86
Cdd:cd22665     1 GRLKVFSQAHGPEKdfPLYEGENVIGRDPSCSVVLPDKS-VSKQHACIEVD--GGTHLIEDLgSTNGTRIGNKVRLKpNV 77

                          90
                  ....*....|..
gi 1040690151  87 THLLQNGDVIYF 98
Cdd:cd22665    78 RYELIDGDLLLF 89

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 1040690151 275 LTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSSF-CPTCRCPV 319
Cdd:cd16531     2 LMCPICLGIIKNTMTVKECLHRFCAECIEKALRLGNKeCPTCRKHL 47

RING finger, HC subclass, found in Polycomb Group RING finger homologs (PCGF1, 2, 3, 4, 5 and 6), and similar proteins; This subfamily includes six Polycomb Group (PcG) RING finger homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) that use epigenetic mechanisms to maintain or repress expression of their target genes. They were first discovered in fruit flies and are well known for silencing Hox genes through modulation of chromatin structure during embryonic development. PCGF homologs play important roles in cell proliferation, differentiation, and tumorigenesis. They all have been found to associate with ring finger protein 2 (RNF2). The RNF2-PCGF heterodimer is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. Moreover, PCGF homologs are critical components in the assembly of distinct Polycomb Repression Complex 1 (PRC1) related complexes which is involved in the maintenance of gene repression and which target different genes through distinct mechanisms. The Drosophila PRC1 core complex is formed by the Polycomb (Pc), Polyhomeotic (Ph), Posterior sex combs (Psc), and Sex combs extra (Sce, also known as Ring) subunits. In mammals, the composition of PRC1 is much more diverse and varies depending on the cellular context. All PRC1 complexes contain homologs of the Drosophila Ring protein. Ring1A/RNF1 and Ring1B/RNF2 are E3 ubiquitin ligases that mark lysine 119 of histone H2A with a single ubiquitin group (H2AK119ub). Mammalian homologs of the Drosophila Psc protein, such as PCGF2/Mel-18 or PCGF4/BMI1, regulate PRC1 enzymatic activity. PRC1 complexes can be divided into at least two classes according to the presence or absence of CBX proteins, which are homologs of Drosophila Pc. Canonical PRC1 complexes contain CBX proteins that recognize and bind H3K27me3, the mark deposited by PRC2. Therefore, canonical PRC1 complexes and PRC2 can act together to repress gene transcription and maintain this repression through cell division. Non-canonical PRC1 complexes, containing RYBP (together with additional proteins, such as L3mbtl2 or Kdm2b) rather than the CBX proteins have recently been described in mammals. PCGF homologs contain a C3HC4-type RING-HC finger.

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gi 1040690151 275 LTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSSFCPTCR 316
Cdd:cd16525     1 LTCSLCKGYLIDATTITECLHSFCKSCIVRHLETSKNCPVCD 42

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 1040690151 275 LTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSSFCPTCRC------PVERIRKNHILNNLV 332
Cdd:cd16734    15 LMCALCGGYFIDAATIVECLHSFCKTCIVRYLETNKYCPMCDVqvhktrPLLSIRSDKTLQDIV 78

forkhead associated (FHA) domain found in kanadaptin and similar proteins; Kanadaptin, also called human lung cancer oncogene 3 protein (HLC-3), kidney anion exchanger adapter protein, or solute carrier family 4 anion exchanger member 1 adapter protein (SLC4A1AP), is a nuclear protein widely expressed in mammalian tissues. It was originally isolated as a kidney Cl-/HCO3- anion exchanger 1 (kAE1)-binding protein. It is a highly mobile nucleocytoplasmic shuttling and multilocalizing protein. Its role in mammalian cells remains unclear. It contains an FHA domain, which is a small phosphopeptide recognition module.

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gi 1040690151  32 TVGRKKDCDLSF--PAnklVSGNHCKITH----DQNSGKVWLEDM-STNGTVINMSKVVKKQTHLLQNGDVIYF 98
Cdd:cd22677    25 VFGRLPGCDVVLehPS---ISRYHAVLQYrgdaDDHDGGFYLYDLgSTHGTFLNKQRIPPKQYYRLRVGHVLKF 95

Inner membrane component of T3SS, cytoplasmic domain; Yop-YscD-cpl is the cytoplasmic domain of Yop proteins like YscD from Proteobacteria. YscD forms part of the inner membrane component of the bacterial type III secretion injectosome apparatus.

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gi 1040690151  21 GSEIVLINSECTVGRKKDCDLSFpANKLVSGNHCKITHDQNSgkVWLEDM-STNGTVINmSKVVKKQTHLLQNGDVI 96
Cdd:pfam16697   9 GAEFPLEGGRYRIGSDPDCDIVL-SDKEVSRVHLKLEVDDEG--WRLDDLgSGNGTLVN-GQRVTELGIALRPGDRI 81

RING finger found in polycomb group RING finger protein 4 (PCGF4) and similar proteins; PCGF4, also known as polycomb complex protein BMI-1 (B cell-specific Moloney murine leukemia virus integration site 1) or RING finger protein 51 (RNF51), 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), and plays important roles in chromatin compaction and H2AK119 monoubiquitination. PCGF4 associates with the Runx1/CBFbeta transcription factor complex to silence target genes in a PRC2-independent manner. Moreover, PCGF4 is expressed in the hair cells and supporting cells. It can regulate cell survival by controlling mitochondrial function and reactive oxygen species (ROS) level in thymocytes and neurons, thus having an important role in the survival and sensitivity to ototoxic drug of auditory hair cells. Furthermore, PCGF4 controls memory CD4 T-cell survival through direct repression of Noxa gene in an Ink4a- and Arf-independent manner. It is required in neurons to suppress p53-induced apoptosis via regulating the antioxidant defensive response, and also involved in the tumorigenesis of various cancer types. PCGF4 contains a C3HC4-type RING-HC finger.

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gi 1040690151 270 KMEESLTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSSFCPTCRCPVERIR 323
Cdd:cd16736     7 ELNPHLMCVLCGGYFIDATTIIECLHSFCKTCIVRYLETSKYCPICDVQVHKTR 60

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 1040690151 274 SLTCIICQDLLYDCIsVQPCMHTFCAACYSGWMERSSFCPTCRCPV 319
Cdd:cd16514     1 DLECSLCLRLLYEPV-TTPCGHTFCRACLERCLDHSPKCPLCRTSL 45

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

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gi 1040690151 272 EESLTCIICQDLLYDCISVqPCMHTFCAACYSGWMER--SSFCPTCR--CPVERIRKNHILNNLVE 333
Cdd:cd16599     2 KEELLCPICYEPFREAVTL-RCGHNFCKGCVSRSWERqpRAPCPVCKeaSSSDDLRTNHTLNNLVE 66

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatorial component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.

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gi 1040690151 277 CIICQDLL--YDCISVQPCMHTFCAACYSGWMERSSFCPTCRCPV 319
Cdd:cd16460     3 CVICHEAFsdGDRLLVLPCAHKFHTQCIGPWLDGQQTCPTCRLHV 47

forkhead associated (FHA) domain found in Mycobacterium tuberculosis FHA domain-containing protein FhaA and similar proteins; FhaA regulates cell growth and peptidoglycan synthesis by binding to MviN. It may inhibit the late stages of peptidoglycan synthesis. It contains an FHA domain, which is a small phosphopeptide recognition module.

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gi 1040690151  32 TVGRKKDCDLSFPaNKLVSGNHCKITHDqnSGKVWLEDM-STNGTVINMSKVvkKQTHLLQNGDVIYF 98
Cdd:cd22668    21 IIGRGSDADFRLP-DTGVSRRHAEIRWD--GQVAHLTDLgSTNGTTVNNAPV--TPEWRLADGDVITL 83

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.

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gi 1040690151 273 ESLTCIICQDLLYDCISVQpCMHTFCAACYSGWMERS---SFCPTCR--CPVERIRKN 325
Cdd:cd16611     3 EELHCPLCLDFFRDPVMLS-CGHNFCQSCITGFWELQaedTTCPECRelCQYRNLTPN 59

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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.

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gi 1040690151 269 DKMEESLTCIICQDLLYDCISVQpCMHTFCAACYSG-WMERSSFCPTCRCP--VERIRKNHILNNLVE 333
Cdd:cd16596     4 TMMWEEVTCPICLDPFVEPVSIE-CGHSFCQECISQvGKGGGSVCPVCRQRflLKNLRPNRQLANMVN 70

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.

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gi 1040690151 275 LTCIICQDLLYDCISVQPCMHTFCAACYSGWMERSSFCPTCRC------PVERIRKNHILNNLV 332
Cdd:cd16737    11 ITCRICKGYLIKPTTVTECLHTFCKSCIVQHFEDSNDCPECGIqvhetnPLEMLRLDNTLEEII 74

Forkhead associated domain; Found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain.

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gi 1040690151   32 TVGR-KKDCDLSFPaNKLVSGNHCKITHDQNsGKVWLEDM-STNGTVIN 78
Cdd:smart00240   2 TIGRsSEDCDIQLD-GPSISRRHAVIVYDGG-GRFYLIDLgSTNGTFVN 48

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.

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gi 1040690151 272 EESLTCIICQDLLYDCISVQpCMHTFCAACYSGWMERSSF---CPTCRCPV 319
Cdd:cd23133     1 EETLTCSICQGIFMNPVYLR-CGHKFCEACLLLFQEDIKFpayCPMCRQPF 50