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Conserved domains on  [gi|81885356|sp|Q6P7Q1|]
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RecName: Full=BRISC and BRCA1-A complex member 2; AltName: Full=BRCA1-A complex subunit BRE; AltName: Full=BRCA1/BRCA2-containing complex subunit 45; AltName: Full=Brain and reproductive organ-expressed protein

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
BRE cd23664
BRCA1-A and BRISC complex subunit BRE; BRCA1-A and BRISC complex subunit BRE (also known as ...
10-378 0e+00

BRCA1-A and BRISC complex subunit BRE; BRCA1-A and BRISC complex subunit BRE (also known as BRISC and BRCA1 A complex member 2; BRCC4; BRCC45) is a core component of both the BRCA1-A and BRISC complexes. BRCA1-A and BRISC are separate complexes with diverging function; they use the same core of subunits to perform very distinct biological tasks, and are found in all vertebrates. The BRCA1-A complex consists of BRE, Abraxas-1, BRCC36, MERIT40 and RAP80, and specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSB)s. This complex also possesses deubiquitinase (DUB) activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In BRCA1-A, two heteropentamers, composed of BRCC36, ABRAXAS, BRE and MERIT40, form an arc-shaped complex; the two half-arcs contact each other through BRCC36 and its scaffold partner ABRAXAS. BRCC36 is connected to this arc via the ABRAXAS MPN domain. BRE forms the central bridge between the ABRAXAS-BRCC36 MPN domain dimer and MERIT40. BRE's N-terminal ubiquitin-conjugating enzyme variants domain (UEV-N) binds the ABRAXAS MPN, and BRE's C-terminal UEV domain (UEV-C) holds MERIT40 at the extremity of the arc. Loss of BRE significantly impairs BRCA1-A function, resulting in DNA repair defects and loss of cancer suppression. The BRISC complex consists of BRE, BRCC36, MERIT40 and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. The BRISC core has the same 2-fold symmetrical arc shape and is structurally similar to BRCA1-A; however, the conformation of BRE UEV-C and MERIT40 differs markedly. BRE has different functionality in the BRCA1-A and BRISC complexes: in BRCA1, it is involved in RAP80 integration, BRCA1 sequestration and ubiquitin binding, while in BRISC, it is involved in dimerization, SHMT2 recruitment, DUB inhibition and ubiquitin binding. A BRISC complex (containing of BRE/BRCC45, BRCC36, MERIT40, and Abraxas 2/KIAA0157) has been found in insects (Camponotus floridanus) and shown to efficiently degrade 'Lys-63'-linked chains. Homologs of genes encoding components of BRCA1-A and BRISC complexes have been found in plant genomes, including for BRE/BRCC45; plant homologs of BRCC36 have been shown to be involved in DNA repair; BRCC36-Abraxas 2 complexes have been found in Arabidopsis.


:

Pssm-ID: 467821  Cd Length: 364  Bit Score: 614.97  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  10 ISPMLSPFISSVVRNGKVGLDAtNCLRITDLKSGCTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-E 88
Cdd:cd23664   1 FAPHIRKFVEALLRNGKIGLCG-GSLRITDPKSGCPSLTKGPNCDRFKLVIPYAGQSLTWEVIFDASYPELPPDFIFGdD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  89 DAEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWtGE 168
Cdd:cd23664  80 DRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLEQYKEYQISLLESYSRLQFEYSSLLEQNFSEDDIEVYVNRKNNW-GE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 169 FSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLID 248
Cdd:cd23664 159 GPVNFLIKLPVDFSNIPPYLTKD---NPGEDSALLLVSFPDPEGSRVTPQLYLSPRVEHALGGSSSLRIPAFPSGGCLMD 235
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 249 YVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPRDQPTLTFQ 328
Cdd:cd23664 236 YVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHFGRSVLEYDAESFSKISLLLEWNDFFFILHIELPLYFPQDQPTFTFQ 315
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|
gi 81885356 329 SVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAAF 378
Cdd:cd23664 316 SIYHESN-GKPYSETVKDYPYSPRWSGNEMAERARAFILEYIPQFQEASV 364
 
Name Accession Description Interval E-value
BRE cd23664
BRCA1-A and BRISC complex subunit BRE; BRCA1-A and BRISC complex subunit BRE (also known as ...
10-378 0e+00

BRCA1-A and BRISC complex subunit BRE; BRCA1-A and BRISC complex subunit BRE (also known as BRISC and BRCA1 A complex member 2; BRCC4; BRCC45) is a core component of both the BRCA1-A and BRISC complexes. BRCA1-A and BRISC are separate complexes with diverging function; they use the same core of subunits to perform very distinct biological tasks, and are found in all vertebrates. The BRCA1-A complex consists of BRE, Abraxas-1, BRCC36, MERIT40 and RAP80, and specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSB)s. This complex also possesses deubiquitinase (DUB) activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In BRCA1-A, two heteropentamers, composed of BRCC36, ABRAXAS, BRE and MERIT40, form an arc-shaped complex; the two half-arcs contact each other through BRCC36 and its scaffold partner ABRAXAS. BRCC36 is connected to this arc via the ABRAXAS MPN domain. BRE forms the central bridge between the ABRAXAS-BRCC36 MPN domain dimer and MERIT40. BRE's N-terminal ubiquitin-conjugating enzyme variants domain (UEV-N) binds the ABRAXAS MPN, and BRE's C-terminal UEV domain (UEV-C) holds MERIT40 at the extremity of the arc. Loss of BRE significantly impairs BRCA1-A function, resulting in DNA repair defects and loss of cancer suppression. The BRISC complex consists of BRE, BRCC36, MERIT40 and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. The BRISC core has the same 2-fold symmetrical arc shape and is structurally similar to BRCA1-A; however, the conformation of BRE UEV-C and MERIT40 differs markedly. BRE has different functionality in the BRCA1-A and BRISC complexes: in BRCA1, it is involved in RAP80 integration, BRCA1 sequestration and ubiquitin binding, while in BRISC, it is involved in dimerization, SHMT2 recruitment, DUB inhibition and ubiquitin binding. A BRISC complex (containing of BRE/BRCC45, BRCC36, MERIT40, and Abraxas 2/KIAA0157) has been found in insects (Camponotus floridanus) and shown to efficiently degrade 'Lys-63'-linked chains. Homologs of genes encoding components of BRCA1-A and BRISC complexes have been found in plant genomes, including for BRE/BRCC45; plant homologs of BRCC36 have been shown to be involved in DNA repair; BRCC36-Abraxas 2 complexes have been found in Arabidopsis.


Pssm-ID: 467821  Cd Length: 364  Bit Score: 614.97  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  10 ISPMLSPFISSVVRNGKVGLDAtNCLRITDLKSGCTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-E 88
Cdd:cd23664   1 FAPHIRKFVEALLRNGKIGLCG-GSLRITDPKSGCPSLTKGPNCDRFKLVIPYAGQSLTWEVIFDASYPELPPDFIFGdD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  89 DAEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWtGE 168
Cdd:cd23664  80 DRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLEQYKEYQISLLESYSRLQFEYSSLLEQNFSEDDIEVYVNRKNNW-GE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 169 FSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLID 248
Cdd:cd23664 159 GPVNFLIKLPVDFSNIPPYLTKD---NPGEDSALLLVSFPDPEGSRVTPQLYLSPRVEHALGGSSSLRIPAFPSGGCLMD 235
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 249 YVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPRDQPTLTFQ 328
Cdd:cd23664 236 YVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHFGRSVLEYDAESFSKISLLLEWNDFFFILHIELPLYFPQDQPTFTFQ 315
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|
gi 81885356 329 SVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAAF 378
Cdd:cd23664 316 SIYHESN-GKPYSETVKDYPYSPRWSGNEMAERARAFILEYIPQFQEASV 364
BRE pfam06113
Brain and reproductive organ-expressed protein (BRE); This family consists of several ...
8-333 6.38e-178

Brain and reproductive organ-expressed protein (BRE); This family consists of several eukaryotic brain and reproductive organ-expressed (BRE) proteins. BRE is a putative stress-modulating gene, found able to down-regulate TNF-alpha-induced-NF-kappaB activation upon over expression. A total of six isoforms are produced by alternative splicing predominantly at either end of the gene.Compared to normal cells, immortalized human cell lines uniformly express higher levels of BRE. Peripheral blood monocytes respond to LPS by down-regulating the expression of all the BRE isoforms.It is thought that the function of BRE and its isoforms is to regulate peroxisomal activities.


Pssm-ID: 461832  Cd Length: 320  Bit Score: 497.35  E-value: 6.38e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356     8 NRISPMLSPFISSVVRNGKVGLDATNcLRITDLKSGCTSltpgPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIF- 86
Cdd:pfam06113   1 NTISPMIEPLIKSVLQTGKLGLCYGN-LRLDDVKSGCNK----PKNDRFKLHIPYAGEHLKWDVIFDSQYPEMPPDFIFn 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356    87 GEDAEFLPDPSALH----NLASWNPSNPECLLLVVKELVQQYHQFQCGRL-RESSRLMFEYQTLLEEPQYG-ENMEIYAG 160
Cdd:pfam06113  76 DESFLFDPDIDILStwvpSLTKWDPNNPEALLLVLSELLLYYKEHQIRLLgKEGSRLQFEYSTLVGETEIGeEDIEVILG 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356   161 KKNnwtgeFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAF 240
Cdd:pfam06113 156 GKP-----FEARFLIRLPVDYSRLPPYLNKD---DPGEDEALLLVTFYGPEWNRVIPQLYLSPTLEHALGGPEALHIPPF 227
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356   241 PGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPR 320
Cdd:pfam06113 228 PPGGCLMDYVPQVKKFLENKINHVVQGYEKRREYIAALIVHFGGSILEYDAEEFTKLTLLLEWNDFHFLLHIDLPSFFPK 307
                         330
                  ....*....|...
gi 81885356   321 DQPTLTFQSVYHF 333
Cdd:pfam06113 308 DKPQLTLQSVYHM 320
 
Name Accession Description Interval E-value
BRE cd23664
BRCA1-A and BRISC complex subunit BRE; BRCA1-A and BRISC complex subunit BRE (also known as ...
10-378 0e+00

BRCA1-A and BRISC complex subunit BRE; BRCA1-A and BRISC complex subunit BRE (also known as BRISC and BRCA1 A complex member 2; BRCC4; BRCC45) is a core component of both the BRCA1-A and BRISC complexes. BRCA1-A and BRISC are separate complexes with diverging function; they use the same core of subunits to perform very distinct biological tasks, and are found in all vertebrates. The BRCA1-A complex consists of BRE, Abraxas-1, BRCC36, MERIT40 and RAP80, and specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSB)s. This complex also possesses deubiquitinase (DUB) activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In BRCA1-A, two heteropentamers, composed of BRCC36, ABRAXAS, BRE and MERIT40, form an arc-shaped complex; the two half-arcs contact each other through BRCC36 and its scaffold partner ABRAXAS. BRCC36 is connected to this arc via the ABRAXAS MPN domain. BRE forms the central bridge between the ABRAXAS-BRCC36 MPN domain dimer and MERIT40. BRE's N-terminal ubiquitin-conjugating enzyme variants domain (UEV-N) binds the ABRAXAS MPN, and BRE's C-terminal UEV domain (UEV-C) holds MERIT40 at the extremity of the arc. Loss of BRE significantly impairs BRCA1-A function, resulting in DNA repair defects and loss of cancer suppression. The BRISC complex consists of BRE, BRCC36, MERIT40 and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. The BRISC core has the same 2-fold symmetrical arc shape and is structurally similar to BRCA1-A; however, the conformation of BRE UEV-C and MERIT40 differs markedly. BRE has different functionality in the BRCA1-A and BRISC complexes: in BRCA1, it is involved in RAP80 integration, BRCA1 sequestration and ubiquitin binding, while in BRISC, it is involved in dimerization, SHMT2 recruitment, DUB inhibition and ubiquitin binding. A BRISC complex (containing of BRE/BRCC45, BRCC36, MERIT40, and Abraxas 2/KIAA0157) has been found in insects (Camponotus floridanus) and shown to efficiently degrade 'Lys-63'-linked chains. Homologs of genes encoding components of BRCA1-A and BRISC complexes have been found in plant genomes, including for BRE/BRCC45; plant homologs of BRCC36 have been shown to be involved in DNA repair; BRCC36-Abraxas 2 complexes have been found in Arabidopsis.


Pssm-ID: 467821  Cd Length: 364  Bit Score: 614.97  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  10 ISPMLSPFISSVVRNGKVGLDAtNCLRITDLKSGCTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-E 88
Cdd:cd23664   1 FAPHIRKFVEALLRNGKIGLCG-GSLRITDPKSGCPSLTKGPNCDRFKLVIPYAGQSLTWEVIFDASYPELPPDFIFGdD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  89 DAEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWtGE 168
Cdd:cd23664  80 DRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLEQYKEYQISLLESYSRLQFEYSSLLEQNFSEDDIEVYVNRKNNW-GE 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 169 FSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLID 248
Cdd:cd23664 159 GPVNFLIKLPVDFSNIPPYLTKD---NPGEDSALLLVSFPDPEGSRVTPQLYLSPRVEHALGGSSSLRIPAFPSGGCLMD 235
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 249 YVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPRDQPTLTFQ 328
Cdd:cd23664 236 YVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHFGRSVLEYDAESFSKISLLLEWNDFFFILHIELPLYFPQDQPTFTFQ 315
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|
gi 81885356 329 SVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAAF 378
Cdd:cd23664 316 SIYHESN-GKPYSETVKDYPYSPRWSGNEMAERARAFILEYIPQFQEASV 364
BRE pfam06113
Brain and reproductive organ-expressed protein (BRE); This family consists of several ...
8-333 6.38e-178

Brain and reproductive organ-expressed protein (BRE); This family consists of several eukaryotic brain and reproductive organ-expressed (BRE) proteins. BRE is a putative stress-modulating gene, found able to down-regulate TNF-alpha-induced-NF-kappaB activation upon over expression. A total of six isoforms are produced by alternative splicing predominantly at either end of the gene.Compared to normal cells, immortalized human cell lines uniformly express higher levels of BRE. Peripheral blood monocytes respond to LPS by down-regulating the expression of all the BRE isoforms.It is thought that the function of BRE and its isoforms is to regulate peroxisomal activities.


Pssm-ID: 461832  Cd Length: 320  Bit Score: 497.35  E-value: 6.38e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356     8 NRISPMLSPFISSVVRNGKVGLDATNcLRITDLKSGCTSltpgPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIF- 86
Cdd:pfam06113   1 NTISPMIEPLIKSVLQTGKLGLCYGN-LRLDDVKSGCNK----PKNDRFKLHIPYAGEHLKWDVIFDSQYPEMPPDFIFn 75
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356    87 GEDAEFLPDPSALH----NLASWNPSNPECLLLVVKELVQQYHQFQCGRL-RESSRLMFEYQTLLEEPQYG-ENMEIYAG 160
Cdd:pfam06113  76 DESFLFDPDIDILStwvpSLTKWDPNNPEALLLVLSELLLYYKEHQIRLLgKEGSRLQFEYSTLVGETEIGeEDIEVILG 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356   161 KKNnwtgeFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAF 240
Cdd:pfam06113 156 GKP-----FEARFLIRLPVDYSRLPPYLNKD---DPGEDEALLLVTFYGPEWNRVIPQLYLSPTLEHALGGPEALHIPPF 227
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356   241 PGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPR 320
Cdd:pfam06113 228 PPGGCLMDYVPQVKKFLENKINHVVQGYEKRREYIAALIVHFGGSILEYDAEEFTKLTLLLEWNDFHFLLHIDLPSFFPK 307
                         330
                  ....*....|...
gi 81885356   321 DQPTLTFQSVYHF 333
Cdd:pfam06113 308 DKPQLTLQSVYHM 320
BRE-like cd23520
BRCA1-A and BRISC complex subunit BRE and related proteins; BRCA1-A and BRISC complex subunit ...
14-377 1.10e-166

BRCA1-A and BRISC complex subunit BRE and related proteins; BRCA1-A and BRISC complex subunit BRE (also known as BRISC and BRCA1 A complex member 2; BRCC4; BRCC45) is a core component of both the BRCA1-A and BRISC complexes. BRCA1-A and BRISC are separate complexes with diverging function; they use the same core of subunits to perform very distinct biological tasks, and are found in all vertebrates. The BRCA1-A complex consists of BRE, Abraxas-1, BRCC36, MERIT40 and RAP80, and specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSB)s. This complex also possesses deubiquitinase (DUB) activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In BRCA1-A, two heteropentamers, composed of BRCC36, ABRAXAS, BRE and MERIT40, form an arc-shaped complex; the two half-arcs contact each other through BRCC36 and its scaffold partner ABRAXAS. BRCC36 is connected to this arc via the ABRAXAS MPN domain. BRE forms the central bridge between the ABRAXAS-BRCC36 MPN domain dimer and MERIT40. BRE's N-terminal ubiquitin-conjugating enzyme variants domain (UEV-N) binds the ABRAXAS MPN, and BRE's C-terminal UEV domain (UEV-C) holds MERIT40 at the extremity of the arc. Loss of BRE significantly impairs BRCA1-A function, resulting in DNA repair defects and loss of cancer suppression. The BRISC complex consists of BRE, BRCC36, MERIT40 and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. The BRISC core has the same 2-fold symmetrical arc shape and is structurally similar to BRCA1-A; however, the conformation of BRE UEV-C and MERIT40 differs markedly. BRE has different functionality in the BRCA1-A and BRISC complexes: in BRCA1, it is involved in RAP80 integration, BRCA1 sequestration and ubiquitin binding, while in BRISC, it is involved in dimerization, SHMT2 recruitment, DUB inhibition and ubiquitin binding. A BRISC complex (consisting of BRE/BRCC45, BRCC36, MERIT40 and Abraxas 2/KIAA0157) has been found in insects (Camponotus floridanus) and shown to efficiently degrade 'Lys-63'-linked chains. Homologs of genes encoding components of BRCA1-A and BRISC complexes have been found in plant genomes, including for BRE/BRCC45; plant homologs of BRCC36 have been shown to be involved in DNA repair; BRCC36-Abraxas 2 complexes have been found in Arabidopsis.


Pssm-ID: 467820  Cd Length: 352  Bit Score: 470.01  E-value: 1.10e-166
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  14 LSPFISSVVRNgKVGLDAT-NCLRITDLKSGCTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFGEDaEF 92
Cdd:cd23520   1 LPPPLDLVQRL-YLSTHAFmQLLRIESLKSGCGQLEGTPKADRFKLSIPYAGESVDWDIIFNSQDPELPPDFIFHDD-FF 78
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  93 LPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRE-SSRLMFEYQTLLEEPqYGENMEIYAGKKNNwtgeFSA 171
Cdd:cd23520  79 LPDLTALTSLASWDPSDPNSLLKVLKELISMYQQHQRRRLERqNERIRFEYETLLAEP-YGEEMDISASVKND----LSE 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 172 RFLLKLPVDFSNIPTYllkdvneDPGEDVALLSVSFEDTEATQVYPKLYL--SPRIEHALGgSSALHIPAFPGGgCLIDY 249
Cdd:cd23520 154 KVEFAIPVDFDNQPQG-------VNQDIVLLLQVQFLLSSADVRAPKLTLepSPSLFDALG-KLRLVPPETPHE-CLMEY 224
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 250 VPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPRDQPTLTFQS 329
Cdd:cd23520 225 VPRVKEHITEKVDKEIRSREKRREFIEALLSLFGDSLLEYDMENFRFISLLLKHEDFYFLVHIYLPLSFPKKQPTLTFQS 304
                       330       340       350       360
                ....*....|....*....|....*....|....*....|....*...
gi 81885356 330 VYHFTNSGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAA 377
Cdd:cd23520 305 VYHMTSSGKLYSREERNVPFSPRWEAERMAVEIAEFIYDEVPKFLTKA 352
BRE-like_insects cd23665
BRCA1-A and BRISC complex subunit BRE-like protein found in insects; BRCA1-A and BRISC complex ...
14-375 1.01e-110

BRCA1-A and BRISC complex subunit BRE-like protein found in insects; BRCA1-A and BRISC complex subunit BRE (also known as BRISC and BRCA1 A complex member 2; BRCC4; BRCC45) is a core component of both the BRCA1-A and BRISC complexes. BRCA1-A and BRISC are separate complexes with diverging function; they use the same core of subunits to perform very distinct biological tasks, and are found in all vertebrates. The BRCA1-A complex consists of BRE, Abraxas-1, BRCC36, MERIT40 and RAP80, and specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSB)s. This complex also possesses deubiquitinase (DUB) activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In BRCA1-A, two heteropentamers, composed of BRCC36, ABRAXAS, BRE and MERIT40, form an arc-shaped complex; the two half-arcs contact each other through BRCC36 and its scaffold partner ABRAXAS. BRCC36 is connected to this arc via the ABRAXAS MPN domain. BRE forms the central bridge between the ABRAXAS-BRCC36 MPN domain dimer and MERIT40. BRE's N-terminal ubiquitin-conjugating enzyme variants domain (UEV-N) binds the ABRAXAS MPN, and BRE's C-terminal UEV domain (UEV-C) holds MERIT40 at the extremity of the arc. Loss of BRE significantly impairs BRCA1-A function, resulting in DNA repair defects and loss of cancer suppression. The BRISC complex consists of BRE, BRCC36, MERIT40 and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. The BRISC core has the same 2-fold symmetrical arc shape and is structurally similar to BRCA1-A; however, the conformation of BRE UEV-C and MERIT40 differs markedly. BRE has different functionality in the BRCA1-A and BRISC complexes: in BRCA1, it is involved in RAP80 integration, BRCA1 sequestration and ubiquitin binding; in BRISC, it is involved in dimerization, SHMT2 recruitment, DUB inhibition and ubiquitin binding. A BRISC complex (containing of BRE/BRCC45, BRCC36, MERIT40, and Abraxas 2/KIAA0157) has been found in insects (Camponotus floridanus) and shown to efficiently degrade 'Lys-63'-linked chains. This model contains the BRE domain of BRISC complexes found in insects.


Pssm-ID: 467822  Cd Length: 364  Bit Score: 328.39  E-value: 1.01e-110
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  14 LSPFISSVVRNGKVGLdatnCLRITDLKSGCTSLTPGPNcDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFGeDAEFL 93
Cdd:cd23665   1 LRPLLKELLLTDKIGL----SCGLIEIDSISSSCGKSKG-DRFKLSIPYAGKNLNWEVIFDSEDPEFGPDFIFN-DDTFL 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  94 PDPSA------LHNLASWNPSNPECLLLVVKELVQQY--HQFQCGRLRESSRLMFEYQTLLEEPQYG-ENMEIYAGkkNN 164
Cdd:cd23665  75 ADPDIdtisknVPSLAKWNPNDPKALLNVLNELLVLYkkHQIEKLQKQNYSRLQLEYSMLLTETEITpEDVEVILL--PN 152
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 165 WTGEFSARFLLKLPVDFSNIPTYLLKDVNEDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGG 244
Cdd:cd23665 153 GSKPTEARFLIRLSVDFSQLPEYIQPIILLNPGNDTAMLLVTFSGPDWNRITPSLQLSPRLEEILGGSTTLHLPPFPKDK 232
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 245 CLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPRDQPT 324
Cdd:cd23665 233 TLMEYVPEVKKLIEEKINSIAQHFKKKKEFISALLSLQRGSIIEYDSINFSKITFLLEVDDFHCLVHITLPPKFPQEKPK 312
                       330       340       350       360       370
                ....*....|....*....|....*....|....*....|....*....|.
gi 81885356 325 LTFQSVYHFTnSGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQE 375
Cdd:cd23665 313 VTLQSIYHMT-SKKPYSEELDDYPYSPRWEPEMMVKKLLHILEEAVPKFKN 362
BRE-like_plant cd23666
BRCA1-A and BRISC complex subunit BRE-like protein found in plants; BRCA1-A and BRISC complex ...
35-369 1.23e-52

BRCA1-A and BRISC complex subunit BRE-like protein found in plants; BRCA1-A and BRISC complex subunit BRE (also known as BRISC and BRCA1 A complex member 2; BRCC4; BRCC45) is a core component of both the BRCA1-A and BRISC complexes. BRCA1-A and BRISC are separate complexes with diverging function; they use the same core of subunits to perform very distinct biological tasks, and are found in all vertebrates. The BRCA1-A complex consists of BRE, Abraxas-1, BRCC36, MERIT40, and RAP80 and specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSB)s. This complex also possesses deubiquitinase (DUB) activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In BRCA1-A, two heteropentamers composed of BRCC36, ABRAXAS, BRE, and MERIT40 form an arc-shaped complex; the two half-arcs contact each other through BRCC36 and its scaffold partner ABRAXAS. BRCC36 is connected to this arc via the ABRAXAS MPN domain. BRE forms the central bridge between the ABRAXAS-BRCC36 MPN domain dimer and MERIT40. BRE's N-terminal ubiquitin-conjugating enzyme variants domain (UEV-N) binds the ABRAXAS MPN, and BRE's C-terminal UEV domain (UEV-C) holds MERIT40 at the extremity of the arc. Loss of BRE significantly impairs BRCA1-A function, resulting in DNA repair defects and loss of cancer suppression. The BRISC complex consists of BRE, BRCC36, MERIT40, and Abraxas 2, and serves cellular stress response and immune signaling functions; it specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. The BRISC core has the same 2-fold symmetrical arc shape and is structurally similar to BRCA1-A, however the conformation of BRE UEV-C and MERIT40 differs markedly. BRE has different functionality in the BRCA1-A and BRISC complexes: in BRCA1 it is involved in RAP80 integration, BRCA1 sequestration, and ubiquitin binding; in BRISC it is involved in dimerization, SHMT2 recruitment, DUB inhibition, and ubiquitin binding. Homologs of genes encoding components of BRCA1-A and BRISC complexes have been found in plant genomes, including for BRE/BRCC45; plant homologs of BRCC36 have been shown to be involved in DNA repair, and BRCC36-Abraxas 2 complexes have been found in Arabidopsis. This model contains the BRE domain of BRISC complexes found in plants.


Pssm-ID: 467823  Cd Length: 370  Bit Score: 179.10  E-value: 1.23e-52
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356  35 LRITDLKSGCTSltpGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-EDAEFLP------DP----SALHNLA 103
Cdd:cd23666  20 IKIEQIRSGSRN---AKYADRFTLLIPCCLEYIKWDVIYNAQYPTVPPDVVFGaDDEDFQPllfmpeGPagkvSLWGILR 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 104 SWNPSNPECLLLVVKELVQQYHQFQCGRLRE--SSRLMFEYQTLLeePQYGENMEIYAGkknnwtGEFSARFLLKLP-VD 180
Cdd:cd23666  97 DWNVKDPSRLLRLLLELRNLYLQYQRKRVEEldDDRVKFEISTIL--AREGLEMCLVTG------PDRPEEVKFAIPlVD 168
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 181 FSNIPTYLLKDVNEDPGEDVaLLSVSFEDTEATQVYP-----KLYLSPRIEHALGgSSALHIPAFPGGGCLIDYVPQVCH 255
Cdd:cd23666 169 VDLSNKLVLGCSPWKPQQKI-YLQVKFPVQRGQTSLPsapqlKLVAPPALREVFD-VEDVKLPAWTDGMCLAEYLPNLEE 246
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81885356 256 LLTNKVQYVIQGYHKRREYIAAFLSHFGTGVvEYDAEGFTKLTLLLMWKEFCFLVHIDLPLFFPRDQPTLTFQSVYHFTN 335
Cdd:cd23666 247 QLKAQVVEAVASVGLRRRFIEALPPVFGRPL-EADTVYCRRASILASSGVFTFLVHFSLPTQFPKQQPTLTLQSSQHFDS 325
                       330       340       350       360
                ....*....|....*....|....*....|....*....|..
gi 81885356 336 SGQ-LYSQAQKNYPYSPRWDGNEMAKR-------AKAYFKTF 369
Cdd:cd23666 326 QGVpIVSRLYDDYPWSPRWEPSEMVERifefiaeEALAFKKY 367
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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