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Conserved domains on  [gi|41281924|ref|NP_851796|]
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BRISC and BRCA1-A complex member 2 isoform I [Mus musculus]

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 ...
 81-415 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: 581.84  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924  81 CTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-EDAEFLPDPSALHNLASWNPSNPECLLLVVKELVQ 159
Cdd:cd23664  34 CPSLTKGPNCDRFKLVIPYAGQSLTWEVIFDASYPELPPDFIFGdDDRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLE 113

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 160 QYHQFQCGRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWtGEFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVAL 239
Cdd:cd23664 114 QYKEYQISLLESYSRLQFEYSSLLEQNFSEDDIEVYVNRKNNW-GEGPVNFLIKLPVDFSNIPPYLTKD---NPGEDSAL 189

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 240 LSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHF 319
Cdd:cd23664 190 LLVSFPDPEGSRVTPQLYLSPRVEHALGGSSSLRIPAFPSGGCLMDYVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHF 269

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 320 GTGVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRA 399
Cdd:cd23664 270 GRSVLEYDAESFSKISLLLEWNDFFFILHIELPLYFPQDQPTFTFQSIYHESN-GKPYSETVKDYPYSPRWSGNEMAERA 348

                       330
                ....*....|....*.
gi 41281924 400 KAYFKTFVPQFQEAAF 415
Cdd:cd23664 349 RAFILEYIPQFQEASV 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 ...
 81-415 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: 581.84  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924  81 CTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-EDAEFLPDPSALHNLASWNPSNPECLLLVVKELVQ 159
Cdd:cd23664  34 CPSLTKGPNCDRFKLVIPYAGQSLTWEVIFDASYPELPPDFIFGdDDRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLE 113

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 160 QYHQFQCGRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWtGEFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVAL 239
Cdd:cd23664 114 QYKEYQISLLESYSRLQFEYSSLLEQNFSEDDIEVYVNRKNNW-GEGPVNFLIKLPVDFSNIPPYLTKD---NPGEDSAL 189

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 240 LSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHF 319
Cdd:cd23664 190 LLVSFPDPEGSRVTPQLYLSPRVEHALGGSSSLRIPAFPSGGCLMDYVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHF 269

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 320 GTGVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRA 399
Cdd:cd23664 270 GRSVLEYDAESFSKISLLLEWNDFFFILHIELPLYFPQDQPTFTFQSIYHESN-GKPYSETVKDYPYSPRWSGNEMAERA 348

                       330
                ....*....|....*.
gi 41281924 400 KAYFKTFVPQFQEAAF 415
Cdd:cd23664 349 RAFILEYIPQFQEASV 364
BRE pfam06113
Brain and reproductive organ-expressed protein (BRE); This family consists of several ...
 8-370 3.29e-164

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: 464.22  E-value: 3.29e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924     8 NRISPMLSPFISSVVRNGKihekgpsqklsfkscsyhLPMCacnewYGVPDLEKAsylwrkkenhlplekGQNCTSltpg 87
Cdd:pfam06113   1 NTISPMIEPLIKSVLQTGK------------------LGLC-----YGNLRLDDV---------------KSGCNK---- 38

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924    88 PNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIF-GEDAEFLPDPSALH----NLASWNPSNPECLLLVVKELVQQYH 162
Cdd:pfam06113  39 PKNDRFKLHIPYAGEHLKWDVIFDSQYPEMPPDFIFnDESFLFDPDIDILStwvpSLTKWDPNNPEALLLVLSELLLYYK 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924   163 QFQCGRL-RESSRLMFEYQTLLEEPQYG-ENMEIYAGKKNnwtgeFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALL 240
Cdd:pfam06113 119 EHQIRLLgKEGSRLQFEYSTLVGETEIGeEDIEVILGGKP-----FEARFLIRLPVDYSRLPPYLNKD---DPGEDEALL 190

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924   241 SVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFG 320
Cdd:pfam06113 191 LVTFYGPEWNRVIPQLYLSPTLEHALGGPEALHIPPFPPGGCLMDYVPQVKKFLENKINHVVQGYEKRREYIAALIVHFG 270

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 41281924   321 TGVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHF 370
Cdd:pfam06113 271 GSILEYDAEEFTKLTLLLEWNDFHFLLHIDLPSFFPKDKPQLTLQSVYHM 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 ...
 81-415 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: 581.84  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924  81 CTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-EDAEFLPDPSALHNLASWNPSNPECLLLVVKELVQ 159
Cdd:cd23664  34 CPSLTKGPNCDRFKLVIPYAGQSLTWEVIFDASYPELPPDFIFGdDDRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLE 113

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 160 QYHQFQCGRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWtGEFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVAL 239
Cdd:cd23664 114 QYKEYQISLLESYSRLQFEYSSLLEQNFSEDDIEVYVNRKNNW-GEGPVNFLIKLPVDFSNIPPYLTKD---NPGEDSAL 189

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 240 LSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHF 319
Cdd:cd23664 190 LLVSFPDPEGSRVTPQLYLSPRVEHALGGSSSLRIPAFPSGGCLMDYVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHF 269

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 320 GTGVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRA 399
Cdd:cd23664 270 GRSVLEYDAESFSKISLLLEWNDFFFILHIELPLYFPQDQPTFTFQSIYHESN-GKPYSETVKDYPYSPRWSGNEMAERA 348

                       330
                ....*....|....*.
gi 41281924 400 KAYFKTFVPQFQEAAF 415
Cdd:cd23664 349 RAFILEYIPQFQEASV 364
BRE pfam06113
Brain and reproductive organ-expressed protein (BRE); This family consists of several ...
 8-370 3.29e-164

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: 464.22  E-value: 3.29e-164
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924     8 NRISPMLSPFISSVVRNGKihekgpsqklsfkscsyhLPMCacnewYGVPDLEKAsylwrkkenhlplekGQNCTSltpg 87
Cdd:pfam06113   1 NTISPMIEPLIKSVLQTGK------------------LGLC-----YGNLRLDDV---------------KSGCNK---- 38

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924    88 PNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIF-GEDAEFLPDPSALH----NLASWNPSNPECLLLVVKELVQQYH 162
Cdd:pfam06113  39 PKNDRFKLHIPYAGEHLKWDVIFDSQYPEMPPDFIFnDESFLFDPDIDILStwvpSLTKWDPNNPEALLLVLSELLLYYK 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924   163 QFQCGRL-RESSRLMFEYQTLLEEPQYG-ENMEIYAGKKNnwtgeFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALL 240
Cdd:pfam06113 119 EHQIRLLgKEGSRLQFEYSTLVGETEIGeEDIEVILGGKP-----FEARFLIRLPVDYSRLPPYLNKD---DPGEDEALL 190

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924   241 SVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFG 320
Cdd:pfam06113 191 LVTFYGPEWNRVIPQLYLSPTLEHALGGPEALHIPPFPPGGCLMDYVPQVKKFLENKINHVVQGYEKRREYIAALIVHFG 270

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 41281924   321 TGVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHF 370
Cdd:pfam06113 271 GSILEYDAEEFTKLTLLLEWNDFHFLLHIDLPSFFPKDKPQLTLQSVYHM 320
BRE-like cd23520
BRCA1-A and BRISC complex subunit BRE and related proteins; BRCA1-A and BRISC complex subunit ...
 80-414 1.07e-156

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: 446.12  E-value: 1.07e-156
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924  80 NCTSLTPGPNCDRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFGEDaEFLPDPSALHNLASWNPSNPECLLLVVKELVQ 159
Cdd:cd23520  30 GCGQLEGTPKADRFKLSIPYAGESVDWDIIFNSQDPELPPDFIFHDD-FFLPDLTALTSLASWDPSDPNSLLKVLKELIS 108

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 160 QYHQFQCGRLRE-SSRLMFEYQTLLEEPqYGENMEIYAGKKNNwtgeFSARFLLKLPVDFSNIPTYllkdvneDPGEDVA 238
Cdd:cd23520 109 MYQQHQRRRLERqNERIRFEYETLLAEP-YGEEMDISASVKND----LSEKVEFAIPVDFDNQPQG-------VNQDIVL 176

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 239 LLSVSFEDTEATQVYPKLYL--SPRIEHALGgSSALHIPAFPGGgCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFL 316
Cdd:cd23520 177 LLQVQFLLSSADVRAPKLTLepSPSLFDALG-KLRLVPPETPHE-CLMEYVPRVKEHITEKVDKEIRSREKRREFIEALL 254

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 317 SHFGTGVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNSGQLYSQAQKNYPYSPRWDGNEMA 396
Cdd:cd23520 255 SLFGDSLLEYDMENFRFISLLLKHEDFYFLVHIYLPLSFPKKQPTLTFQSVYHMTSSGKLYSREERNVPFSPRWEAERMA 334

                       330
                ....*....|....*...
gi 41281924 397 KRAKAYFKTFVPQFQEAA 414
Cdd:cd23520 335 VEIAEFIYDEVPKFLTKA 352
BRE-like_insects cd23665
BRCA1-A and BRISC complex subunit BRE-like protein found in insects; BRCA1-A and BRISC complex ...
 91-412 5.90e-107

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: 319.92  E-value: 5.90e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924  91 DRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFGeDAEFLPDPSA------LHNLASWNPSNPECLLLVVKELVQQY--H 162
Cdd:cd23665  36 DRFKLSIPYAGKNLNWEVIFDSEDPEFGPDFIFN-DDTFLADPDIdtisknVPSLAKWNPNDPKALLNVLNELLVLYkkH 114

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 163 QFQCGRLRESSRLMFEYQTLLEEPQYG-ENMEIYAGkkNNWTGEFSARFLLKLPVDFSNIPTYLLKDVNEDPGEDVALLS 241
Cdd:cd23665 115 QIEKLQKQNYSRLQLEYSMLLTETEITpEDVEVILL--PNGSKPTEARFLIRLSVDFSQLPEYIQPIILLNPGNDTAMLL 192

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 242 VSFEDTEATQVYPKLYLSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGT 321
Cdd:cd23665 193 VTFSGPDWNRITPSLQLSPRLEEILGGSTTLHLPPFPKDKTLMEYVPEVKKLIEEKINSIAQHFKKKKEFISALLSLQRG 272

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 322 GVVEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTnSGQLYSQAQKNYPYSPRWDGNEMAKRAKA 401
Cdd:cd23665 273 SIIEYDSINFSKITFLLEVDDFHCLVHITLPPKFPQEKPKVTLQSIYHMT-SKKPYSEELDDYPYSPRWEPEMMVKKLLH 351

                       330
                ....*....|.
gi 41281924 402 YFKTFVPQFQE 412
Cdd:cd23665 352 ILEEAVPKFKN 362
BRE-like_plant cd23666
BRCA1-A and BRISC complex subunit BRE-like protein found in plants; BRCA1-A and BRISC complex ...
 91-406 2.10e-50

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: 174.09  E-value: 2.10e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924  91 DRFKLHIPYAGETLKWDIIFNAQYPELPPDFIFG-EDAEFLP------DP----SALHNLASWNPSNPECLLLVVKELVQ 159
Cdd:cd23666  36 DRFTLLIPCCLEYIKWDVIYNAQYPTVPPDVVFGaDDEDFQPllfmpeGPagkvSLWGILRDWNVKDPSRLLRLLLELRN 115

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 160 QYHQFQCGRLRE--SSRLMFEYQTLLeePQYGENMEIYAGkknnwtGEFSARFLLKLP-VDFSNIPTYLLKDVNEDPGED 236
Cdd:cd23666 116 LYLQYQRKRVEEldDDRVKFEISTIL--AREGLEMCLVTG------PDRPEEVKFAIPlVDVDLSNKLVLGCSPWKPQQK 187

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 237 VaLLSVSFEDTEATQVYP-----KLYLSPRIEHALGgSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREY 311
Cdd:cd23666 188 I-YLQVKFPVQRGQTSLPsapqlKLVAPPALREVFD-VEDVKLPAWTDGMCLAEYLPNLEEQLKAQVVEAVASVGLRRRF 265

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281924 312 IAAFLSHFGTGVvEYDAEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNSGQ-LYSQAQKNYPYSPRW 390
Cdd:cd23666 266 IEALPPVFGRPL-EADTVYCRRASILASSGVFTFLVHFSLPTQFPKQQPTLTLQSSQHFDSQGVpIVSRLYDDYPWSPRW 344

                       330       340
                ....*....|....*....|...
gi 41281924 391 DGNEMAKR-------AKAYFKTF 406
Cdd:cd23666 345 EPSEMVERifefiaeEALAFKKY 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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