second (C-terminal) BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the second BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 635 LFDGCYFFLGGNFKHH-PKEDLLKLIAAAGGRILSRKPKPDSDVTQTINTVAYhAKPDSDQRFCTQYIVYEDLFNCHPER 713
Cdd:cd17720     1 LFDGCHFYFHGTFKPPtTKDDLEQLVKAGGGTVLSREPKPDSDVTQTINTVAY-ARPDSDLANCTHYIIYDKLNDKKPAK 79

                          90       100
                  ....*....|....*....|..
gi 1958803878 714 VRQGKVWMAPSTWLISCVMAFE 735
Cdd:cd17720    80 VRQGKVRVVPVSWLLDCISQFK 101

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 405 LSSGIPARKRNHRGETLLHIAsikheaCSHGHLKIVELLLQHNALVNTTGYHNDSPLHDAAKNGHIDIVKVLLSHGASRN 484
Cdd:COG0666   140 LEAGADVNAQDNDGNTPLHLA------AANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVN 213

                          90       100
                  ....*....|....*....|....
gi 1958803878 485 AVNIFGERPVDYTDAENIRSLLLL 508
Cdd:COG0666   214 AKDNDGKTALDLAAENGNLEIVKL 237

second (C-terminal) BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the second BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 635 LFDGCYFFLGGNFKHH-PKEDLLKLIAAAGGRILSRKPKPDSDVTQTINTVAYhAKPDSDQRFCTQYIVYEDLFNCHPER 713
Cdd:cd17720     1 LFDGCHFYFHGTFKPPtTKDDLEQLVKAGGGTVLSREPKPDSDVTQTINTVAY-ARPDSDLANCTHYIIYDKLNDKKPAK 79

                          90       100
                  ....*....|....*....|..
gi 1958803878 714 VRQGKVWMAPSTWLISCVMAFE 735
Cdd:cd17720    80 VRQGKVRVVPVSWLLDCISQFK 101

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 534 LVLIGSGLSSQQQKLLSKLETVLKAKKCAEFDNTVTHVIVPDEE---AQSTLKCMLGILNGCWVLKFDWVKACLDSQERE 610
Cdd:cd17734     1 LVLLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADErgvCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 400 PSTVK--LSSGIPARKRNHRGETLLHIAsikheaCSHGHLKIVELLLQHNALVNTTgyHNDSPLHDAAKNGHIDIVKVLL 477
Cdd:pfam12796  10 LELVKllLENGADANLQDKNGRTALHLA------AKNGHLEIVKLLLEHADVNLKD--NGRTALHYAARSGHLEIVKLLL 81

                          90
                  ....*....|
gi 1958803878 478 SHGASRNAVN 487
Cdd:pfam12796  82 EKGADINVKD 91

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958803878  545 QQKLLSKLETVLKAKKCAEFDN----TVTHVIVPDEEaQSTLKCMLGILNGCWVLKFDWVKACL 604
Cdd:smart00292  16 DKEERDELKELIEALGGKVTSSlsskTTTHVIVGSPE-GGKLELLKAIALGIPIVKEEWLLDCL 78

ankyrin repeats; Ankyrin repeats are about 33 amino acids long and occur in at least four consecutive copies. They are involved in protein-protein interactions. The core of the repeat seems to be an helix-loop-helix structure.

                           10        20        30
                   ....*....|....*....|....*....|
gi 1958803878  456 HNDSPLHDAAKNGHIDIVKVLLSHGASRNA 485
Cdd:smart00248   1 DGRTPLHLAAENGNLEVVKLLLDKGADINA 30

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878  34 ALARLEKLLRCSRCANILREPvCLGGCEHIFCSGCISDCVGS--GCPVCHTPAWILDLKINRQLDSMIQLYSKLQNLLHD 111
Cdd:COG5432    18 SLKGLDSMLRCRICDCRISIP-CETTCGHTFCSLCIRRHLGTqpFCPVCREDPCESRLRGSSGSREINESHARNRDLLRK 96

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 1958803878   44 CSRCANILREPVCLGGCEHIFCSGCISDCVGSG---CPVC 80
Cdd:smart00184   1 CPICLEEYLKDPVILPCGHTFCRSCIRKWLESGnntCPIC 40

BRCT domain, a BRCA1 C-terminus domain; This BRCT domain, a BRCA1 C-terminus region, is found on many RAP1 proteins, usually at the very N-terminus. The function in human at least of a BRCT is to contribute to the heterogeneity of the telomere DNA length, but that may not be its general function, which remains unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 632 LPKLFDGCYFFLGGnFKHHPKEDLLKLIAAAGGRILSRKPKPDSDVTQTINTVAYHAKPDSDQRFCTQYIvyedlFNChp 711
Cdd:pfam16589   1 LPNLFEPLRFYINA-IPSPSRSKLKRLIEANGGTVVDNINPAVYIVIAPYNKTDKLAENTKLGVVSPQWI-----FDC-- 72

                  ....*...
gi 1958803878 712 erVRQGKV 719
Cdd:pfam16589  73 --VKKGKL 78

second (C-terminal) BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the second BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 635 LFDGCYFFLGGNFKHH-PKEDLLKLIAAAGGRILSRKPKPDSDVTQTINTVAYhAKPDSDQRFCTQYIVYEDLFNCHPER 713
Cdd:cd17720     1 LFDGCHFYFHGTFKPPtTKDDLEQLVKAGGGTVLSREPKPDSDVTQTINTVAY-ARPDSDLANCTHYIIYDKLNDKKPAK 79

                          90       100
                  ....*....|....*....|..
gi 1958803878 714 VRQGKVWMAPSTWLISCVMAFE 735
Cdd:cd17720    80 VRQGKVRVVPVSWLLDCISQFK 101

first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; Bard1, also termed BARD-1, or RING-type E3 ubiquitin transferase BARD1, is a critical factor in BRCA1-mediated tumor suppression and may also serve as a target for tumorigenic lesions in some human cancers. It associates with BRCA1 (breast cancer-1) to form a heterodimeric BRCA1/BARD1 complex that is responsible for maintaining genomic stability through nuclear functions involving DNA damage signaling and repair, transcriptional regulation, and cell cycle control. The BRCA1/BARD1 complex catalyzes autoubiquitination of BRCA1 and trans ubiquitination of other protein substrates. Its E3 ligase activity is dramatically reduced in the presence of UBX domain protein 1 (UBXN1). BARD-1 contains an N-terminal C3HC4-type RING-HC finger that binds BRCA1, and a C-terminal region with three ankyrin repeats and tandem BRCT domains that bind CstF-50 (cleavage stimulation factor) to modulate mRNA processing and RNAP II stability in response to DNA damage. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 534 LVLIGSGLSSQQQKLLSKLETVLKAKKCAEFDNTVTHVIVPDEE---AQSTLKCMLGILNGCWVLKFDWVKACLDSQERE 610
Cdd:cd17734     1 LVLLGSGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADErgvCPRTMKYLMGILAGKWIVSFEWVEACLKAKKLV 80

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 405 LSSGIPARKRNHRGETLLHIAsikheaCSHGHLKIVELLLQHNALVNTTGYHNDSPLHDAAKNGHIDIVKVLLSHGASRN 484
Cdd:COG0666   107 LEAGADVNARDKDGETPLHLA------AYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVN 180

                          90       100
                  ....*....|....*....|....*.
gi 1958803878 485 AVNIFGERP----VDYTDAENIRSLL 506
Cdd:COG0666   181 ARDNDGETPlhlaAENGHLEIVKLLL 206

Ankyrin repeats (3 copies);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 400 PSTVK--LSSGIPARKRNHRGETLLHIAsikheaCSHGHLKIVELLLQHNALVNTTgyHNDSPLHDAAKNGHIDIVKVLL 477
Cdd:pfam12796  10 LELVKllLENGADANLQDKNGRTALHLA------AKNGHLEIVKLLLEHADVNLKD--NGRTALHYAARSGHLEIVKLLL 81

                          90
                  ....*....|
gi 1958803878 478 SHGASRNAVN 487
Cdd:pfam12796  82 EKGADINVKD 91

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene 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. The family corresponds to the first BRCT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 536 LIGSGLSSQQQKLLSKLETVLKAKKCAEFDNTVTHVIV-PDEE--AQSTLKCMLGILNGCWVLKFDWVKACLDSQEREQE 612
Cdd:cd17735     3 MVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMkTDAElvCERTLKYFLGIAGRKWVVSYQWITQSIKEGKILPE 82

                  ....*..
gi 1958803878 613 EKYEVPG 619
Cdd:cd17735    83 HDFEVRG 89

C-terminal domain of the breast cancer suppressor protein (BRCA1) and related domains; The BRCT (BRCA1 C-terminus) domain is found within many DNA damage repair and cell cycle checkpoint proteins. BRCT domains interact with each other forming homo/hetero BRCT multimers, but are also involved in BRCT-non-BRCT interactions and interactions within DNA strand breaks. BRCT tandem repeats bind to phosphopeptides; it has been shown that the repeats in human BRCA1 bind specifically to pS-X-X-F motifs, mediating the interaction between BRCA1 and the DNA helicase BACH1, or BRCA1 and CtIP, a transcriptional corepressor. It is assumed that BRCT repeats play similar roles in many signaling pathways associated with the response to DNA damage.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 534 LVLIGSGLSSQQQKLLSKLETVLKAKKCAEFDNTVTHVIVPDEEaqSTLKCMLGILNGCWVLKFDWVKAC 603
Cdd:cd00027     1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSPS--GEKYYLAALAWGIPIVSPEWLLDC 68

second BRCT domain of microcephalin and similar proteins; Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1. It has been implicated in chromosome condensation and DNA damage induced cellular responses. It may play a role in neurogenesis and regulation of the size of the cerebral cortex. Microcephalin contains three BRCT repeats. This family corresponds to the second repeat.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 542 SSQQQKLLSKLETVLKAKKCAEFDNTVTHVIVpdEEAQSTLKCMLGILNGCWVLKFDWVkacLDSQEREQ 611
Cdd:cd17736    10 SEEQELLESVVKKLGGFRVEDSVTEKTTHVVV--GSPRRTLNVLLGIARGCWILSPDWV---LESLEAGK 74

Ankyrin repeats (many copies);

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958803878 443 LLQH-NALVNTTGYHNDSPLHDAAKNGHIDIVKVLLSHGASRNAVNIFGERPVDY 496
Cdd:pfam13857   1 LLEHgPIDLNRLDGEGYTPLHVAAKYGALEIVRVLLAYGVDLNLKDEEGLTALDL 55

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 405 LSSGIPARKRNHRGETLLHIAsIKHeacshGHLKIVELLLQHNALVNTTGYHNDSPLHDAAKNGHIDIVKVLLSHGASRN 484
Cdd:PHA02874  111 LDCGIDVNIKDAELKTFLHYA-IKK-----GDLESIKMLFEYGADVNIEDDNGCYPIHIAIKHNFFDIIKLLLEKGAYAN 184

                          90       100
                  ....*....|....*....|....*.
gi 1958803878 485 AVNIFGERP----VDYTDAENIRSLL 506
Cdd:PHA02874  185 VKDNNGESPlhnaAEYGDYACIKLLI 210

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1958803878  38 LEKLLRCSRCANILREPVCLGgCEHIFCSGCISDC--VGSGCPVCHTP 83
Cdd:cd23146     1 MELELKCPICLKLLNRPVLLP-CDHIFCSSCITDStkVGSDCPVCKLP 47

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878  33 AALARLEKLLRCSRCANILREPVcLGGCEHIFCSGCISDC--VGSGCPVCHTPAWILDLKINRQLDSMIQLYSKLQNLLH 110
Cdd:TIGR00599  18 PSLYPLDTSLRCHICKDFFDVPV-LTSCSHTFCSLCIRRClsNQPKCPLCRAEDQESKLRSNWLVSEIVESFKNLRPSLL 96

                  .
gi 1958803878 111 D 111
Cdd:TIGR00599  97 E 97

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878  34 ALARLEKLLRCSRCANILREPVCLGgCEHIFCSGCISDC---VGSGCPVCHTPAWILDLKINRQLDSMIQ 100
Cdd:cd16596     2 RLTMMWEEVTCPICLDPFVEPVSIE-CGHSFCQECISQVgkgGGSVCPVCRQRFLLKNLRPNRQLANMVN 70

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958803878 403 VKLSSGIPARKRNHRGETLLHIAsikheaCSHGHLKIVELLLQHNALVNTTGYHNDSPLHDAAKNGHIDIVKVLLSH 479
Cdd:PTZ00322  100 ILLTGGADPNCRDYDGRTPLHIA------CANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFREVVQLLSRH 170

seventh BRCT domain of DNA topoisomerase 2-binding protein 1; TopBP1, also termed DNA topoisomerase II-beta-binding protein 1, or DNA topoisomerase II-binding protein 1, functions in DNA replication and damage response. It binds double-stranded DNA breaks and nicks as well as single-stranded DNA. TopBP1 contains six copies of BRCT domain. The family corresponds to the seventh BRCT domain. The Trp-X-X-X-Cys/Ser signature motif of the BRCT family is missing in this group.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958803878 539 SGLSSQQQKLLSKLETVLKAKKC--AEFDNTVTHVIVpdEEAQSTLKCMLGILNGCWVLKFDWVKACLDSQ 607
Cdd:cd17738     7 SGFSEDEKKELISIIEKLGGKVLdsDEFDPKCTHLIC--GKPSRSEKFLAACAAGKWILHPSYIEASAKAG 75

Ankyrin repeats (many copies);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1958803878 457 NDSPLHDAAKNGHIDIVKVLLSHGASRNAVNIFGERPVDY 496
Cdd:pfam13637   1 ELTALHAAAASGHLELLRLLLEKGADINAVDGNGETALHF 40

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 399 KPSTVK--LSSGIPARKRNHRGETLLHIASIKHEACSHGhLKIVELLLQHNALVNTTGYHNDSPLHDAA--KNGHIDIVK 474
Cdd:PHA03100   47 NIDVVKilLDNGADINSSTKNNSTPLHYLSNIKYNLTDV-KEIVKLLLEYGANVNAPDNNGITPLLYAIskKSNSYSIVE 125

                          90       100
                  ....*....|....*....|..
gi 1958803878 475 VLLSHGASRNAVNIFGERPVDY 496
Cdd:PHA03100  126 YLLDNGANVNIKNSDGENLLHL 147

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958803878  42 LRCSRCANILREPVCLGGCEHIFCSGCISDCVGSG---CPVCHTP 83
Cdd:cd16531     2 LMCPICLGIIKNTMTVKECLHRFCAECIEKALRLGnkeCPTCRKH 46

ankyrin repeat protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878 419 ETLLHIASIKhEACSHGHLKIVELLLQHNALVNTTGYHNDSPLHDAAKNGHIDIVKVLLSHGASRNAVNIFGERPVDYT- 497
Cdd:PHA02876  141 ESIEYMKLIK-ERIQQDELLIAEMLLEGGADVNAKDIYCITPIHYAAERGNAKMVNLLLSYGADVNIIALDDLSVLECAv 219

                  ....*...
gi 1958803878 498 DAENIRSL 505
Cdd:PHA02876  220 DSKNIDTI 227

breast cancer carboxy-terminal domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878  633 PKLFDGCYFFLGGNFKHHPKEDLLKLIAAAGGRILSRKPKPDsdvtqtintvayhakpdsdqrfcTQYIVYEDLFN--CH 710
Cdd:smart00292   1 PKLFKGKTFYITGSFDKEERDELKELIEALGGKVTSSLSSKT-----------------------TTHVIVGSPEGgkLE 57

                           90       100
                   ....*....|....*....|.
gi 1958803878  711 PERVRQGKVWMAPSTWLISCV 731
Cdd:smart00292  58 LLKAIALGIPIVKEEWLLDCL 78

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1958803878  42 LRCSRCANILREPVCLGgCEHIFCSGCISDCVGSG---CPVC 80
Cdd:cd16449     1 LECPICLERLKDPVLLP-CGHVFCRECIRRLLESGsikCPIC 41

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 1958803878  34 ALARLEKLLRCSRCANILREPVCLgGCEHIFCSGCISDCVGSG-----CPVCHTP 83
Cdd:cd16498     9 VISAMQKNLECPICLELLKEPVST-KCDHQFCRFCILKLLQKKkkpapCPLCKKS 62

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958803878  42 LRCSRCANILREPVCLGGCEHIFCSGCISDCVGSG---CPVCHTP 83
Cdd:cd16620     4 LKCPICKDLMKDAVLTPCCGNSFCDECIRTALLEEdftCPTCKEP 48

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
                  ....*....|....*....|....*....|....*....|....*
gi 1958803878  42 LRCSRCANILREPVCLGGCEHIFCSGCISDCVGSG---CPVCHTP 83
Cdd:cd16503     3 LTCSICQDLLHDCVSLQPCMHNFCAACYSDWMERSnteCPTCRAT 47

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958803878  42 LRCSRCANILREPVCLGGCEHIFCSGCISDCVGSG---CPVCHTPAWIL-----DLKINRQLDSMIQLYSKLQNLLHDNK 113
Cdd:COG5222   275 LKCPLCHCLLRNPMKTPCCGHTFCDECIGTALLDSdfkCPNCSRKDVLLdgltpDIDKKLEVEKALKKQRKKVGTSDDNN 354

                          90
                  ....*....|....*...
gi 1958803878 114 GSDSK-----DDTSRASL 126
Cdd:COG5222   355 TPMSEkrkreDPNSSAVF 372

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1958803878  39 EKLLRCSRCANILREPVcLGGCEHIFCSGCISDC--VGSGCPVCHTP 83
Cdd:cd23148     1 DHALRCHICKDLLKAPM-RTPCNHTFCSFCIRTHlnNDARCPLCKAE 46

Ankyrin repeats (3 copies);

                          10        20        30
                  ....*....|....*....|....*....|...
gi 1958803878 461 LHDAAKNGHIDIVKVLLSHGASRNAVNIFGERP 493
Cdd:pfam12796   1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTA 33

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1958803878  38 LEKLLRCSRCANILREPVCLGgCEHIFCSGCI--SDCVGSGCPVCHTPA 84
Cdd:cd23147     1 LGKELKCPICLSLFKSAANLS-CNHCFCAGCIgeSLKLSAICPVCKIPA 48