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Conserved domains on  [gi|41281930|ref|NP_851798|]
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BRISC and BRCA1-A complex member 2 isoform III [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 ...
 6-314 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: 526.76  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   6 DIIFNAQYPELPPDFIFG-EDAEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRESSRLMFEYQTLLEE 84
Cdd:cd23664  60 EVIFDASYPELPPDFIFGdDDRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLEQYKEYQISLLESYSRLQFEYSSLLEQ 139

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930  85 PQYGENMEIYAGKKNNWtGEFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHA 164
Cdd:cd23664 140 NFSEDDIEVYVNRKNNW-GEGPVNFLIKLPVDFSNIPPYLTKD---NPGEDSALLLVSFPDPEGSRVTPQLYLSPRVEHA 215

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 165 LGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKDFCF 244
Cdd:cd23664 216 LGGSSSLRIPAFPSGGCLMDYVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHFGRSVLEYDAESFSKISLLLEWNDFFF 295

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 245 LVHIDLPLFFPRDQPTLTFQSVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAAF 314
Cdd:cd23664 296 ILHIELPLYFPQDQPTFTFQSIYHESN-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 ...
 6-314 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: 526.76  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   6 DIIFNAQYPELPPDFIFG-EDAEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRESSRLMFEYQTLLEE 84
Cdd:cd23664  60 EVIFDASYPELPPDFIFGdDDRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLEQYKEYQISLLESYSRLQFEYSSLLEQ 139

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930  85 PQYGENMEIYAGKKNNWtGEFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHA 164
Cdd:cd23664 140 NFSEDDIEVYVNRKNNW-GEGPVNFLIKLPVDFSNIPPYLTKD---NPGEDSALLLVSFPDPEGSRVTPQLYLSPRVEHA 215

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 165 LGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKDFCF 244
Cdd:cd23664 216 LGGSSSLRIPAFPSGGCLMDYVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHFGRSVLEYDAESFSKISLLLEWNDFFF 295

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 245 LVHIDLPLFFPRDQPTLTFQSVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAAF 314
Cdd:cd23664 296 ILHIELPLYFPQDQPTFTFQSIYHESN-GKPYSETVKDYPYSPRWSGNEMAERARAFILEYIPQFQEASV 364
BRE pfam06113
Brain and reproductive organ-expressed protein (BRE); This family consists of several ...
 6-269 1.60e-145

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: 412.60  E-value: 1.60e-145
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930     6 DIIFNAQYPELPPDFIF-GEDAEFLPDPSALH----NLASWNPSNPECLLLVVKELVQQYHQFQCGRL-RESSRLMFEYQ 79
Cdd:pfam06113  58 DVIFDSQYPEMPPDFIFnDESFLFDPDIDILStwvpSLTKWDPNNPEALLLVLSELLLYYKEHQIRLLgKEGSRLQFEYS 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930    80 TLLEEPQYG-ENMEIYAGKKNnwtgeFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLS 158
Cdd:pfam06113 138 TLVGETEIGeEDIEVILGGKP-----FEARFLIRLPVDYSRLPPYLNKD---DPGEDEALLLVTFYGPEWNRVIPQLYLS 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   159 PRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLM 238
Cdd:pfam06113 210 PTLEHALGGPEALHIPPFPPGGCLMDYVPQVKKFLENKINHVVQGYEKRREYIAALIVHFGGSILEYDAEEFTKLTLLLE 289

                         250       260       270
                  ....*....|....*....|....*....|.
gi 41281930   239 WKDFCFLVHIDLPLFFPRDQPTLTFQSVYHF 269
Cdd:pfam06113 290 WNDFHFLLHIDLPSFFPKDKPQLTLQSVYHM 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 ...
 6-314 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: 526.76  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   6 DIIFNAQYPELPPDFIFG-EDAEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRESSRLMFEYQTLLEE 84
Cdd:cd23664  60 EVIFDASYPELPPDFIFGdDDRDFVPDIEDIKSLVNWDPSNPDSLLLVVKELLEQYKEYQISLLESYSRLQFEYSSLLEQ 139

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930  85 PQYGENMEIYAGKKNNWtGEFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHA 164
Cdd:cd23664 140 NFSEDDIEVYVNRKNNW-GEGPVNFLIKLPVDFSNIPPYLTKD---NPGEDSALLLVSFPDPEGSRVTPQLYLSPRVEHA 215

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 165 LGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKDFCF 244
Cdd:cd23664 216 LGGSSSLRIPAFPSGGCLMDYVPAVCELLKNKVELVVQGYEKRKEYIAAFLSHFGRSVLEYDAESFSKISLLLEWNDFFF 295

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 245 LVHIDLPLFFPRDQPTLTFQSVYHFTNsGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAAF 314
Cdd:cd23664 296 ILHIELPLYFPQDQPTFTFQSIYHESN-GKPYSETVKDYPYSPRWSGNEMAERARAFILEYIPQFQEASV 364
BRE pfam06113
Brain and reproductive organ-expressed protein (BRE); This family consists of several ...
 6-269 1.60e-145

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: 412.60  E-value: 1.60e-145
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930     6 DIIFNAQYPELPPDFIF-GEDAEFLPDPSALH----NLASWNPSNPECLLLVVKELVQQYHQFQCGRL-RESSRLMFEYQ 79
Cdd:pfam06113  58 DVIFDSQYPEMPPDFIFnDESFLFDPDIDILStwvpSLTKWDPNNPEALLLVLSELLLYYKEHQIRLLgKEGSRLQFEYS 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930    80 TLLEEPQYG-ENMEIYAGKKNnwtgeFSARFLLKLPVDFSNIPTYLLKDvneDPGEDVALLSVSFEDTEATQVYPKLYLS 158
Cdd:pfam06113 138 TLVGETEIGeEDIEVILGGKP-----FEARFLIRLPVDYSRLPPYLNKD---DPGEDEALLLVTFYGPEWNRVIPQLYLS 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   159 PRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLM 238
Cdd:pfam06113 210 PTLEHALGGPEALHIPPFPPGGCLMDYVPQVKKFLENKINHVVQGYEKRREYIAALIVHFGGSILEYDAEEFTKLTLLLE 289

                         250       260       270
                  ....*....|....*....|....*....|.
gi 41281930   239 WKDFCFLVHIDLPLFFPRDQPTLTFQSVYHF 269
Cdd:pfam06113 290 WNDFHFLLHIDLPSFFPKDKPQLTLQSVYHM 320
BRE-like cd23520
BRCA1-A and BRISC complex subunit BRE and related proteins; BRCA1-A and BRISC complex subunit ...
 6-313 2.25e-140

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: 400.67  E-value: 2.25e-140
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   6 DIIFNAQYPELPPDFIFGEDaEFLPDPSALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRE-SSRLMFEYQTLLEE 84
Cdd:cd23520  57 DIIFNSQDPELPPDFIFHDD-FFLPDLTALTSLASWDPSDPNSLLKVLKELISMYQQHQRRRLERqNERIRFEYETLLAE 135

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930  85 PqYGENMEIYAGKKNNwtgeFSARFLLKLPVDFSNIPTYllkdvneDPGEDVALLSVSFEDTEATQVYPKLYL--SPRIE 162
Cdd:cd23520 136 P-YGEEMDISASVKND----LSEKVEFAIPVDFDNQPQG-------VNQDIVLLLQVQFLLSSADVRAPKLTLepSPSLF 203

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 163 HALGgSSALHIPAFPGGgCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLLLMWKDF 242
Cdd:cd23520 204 DALG-KLRLVPPETPHE-CLMEYVPRVKEHITEKVDKEIRSREKRREFIEALLSLFGDSLLEYDMENFRFISLLLKHEDF 281

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 41281930 243 CFLVHIDLPLFFPRDQPTLTFQSVYHFTNSGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQEAA 313
Cdd:cd23520 282 YFLVHIYLPLSFPKKQPTLTFQSVYHMTSSGKLYSREERNVPFSPRWEAERMAVEIAEFIYDEVPKFLTKA 352
BRE-like_insects cd23665
BRCA1-A and BRISC complex subunit BRE-like protein found in insects; BRCA1-A and BRISC complex ...
 6-311 2.95e-96

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: 288.71  E-value: 2.95e-96
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   6 DIIFNAQYPELPPDFIFGeDAEFLPDPSA------LHNLASWNPSNPECLLLVVKELVQQY--HQFQCGRLRESSRLMFE 77
Cdd:cd23665  52 EVIFDSEDPEFGPDFIFN-DDTFLADPDIdtisknVPSLAKWNPNDPKALLNVLNELLVLYkkHQIEKLQKQNYSRLQLE 130

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930  78 YQTLLEEPQYG-ENMEIYAGkkNNWTGEFSARFLLKLPVDFSNIPTYLLKDVNEDPGEDVALLSVSFEDTEATQVYPKLY 156
Cdd:cd23665 131 YSMLLTETEITpEDVEVILL--PNGSKPTEARFLIRLSVDFSQLPEYIQPIILLNPGNDTAMLLVTFSGPDWNRITPSLQ 208

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 157 LSPRIEHALGGSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLTLL 236
Cdd:cd23665 209 LSPRLEEILGGSTTLHLPPFPKDKTLMEYVPEVKKLIEEKINSIAQHFKKKKEFISALLSLQRGSIIEYDSINFSKITFL 288

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 41281930 237 LMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTnSGQLYSQAQKNYPYSPRWDGNEMAKRAKAYFKTFVPQFQE 311
Cdd:cd23665 289 LEVDDFHCLVHITLPPKFPQEKPKVTLQSIYHMT-SKKPYSEELDDYPYSPRWEPEMMVKKLLHILEEAVPKFKN 362
BRE-like_plant cd23666
BRCA1-A and BRISC complex subunit BRE-like protein found in plants; BRCA1-A and BRISC complex ...
 6-305 5.98e-42

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: 149.05  E-value: 5.98e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930   6 DIIFNAQYPELPPDFIFG-EDAEFLP------DP----SALHNLASWNPSNPECLLLVVKELVQQYHQFQCGRLRE--SS 72
Cdd:cd23666  52 DVIYNAQYPTVPPDVVFGaDDEDFQPllfmpeGPagkvSLWGILRDWNVKDPSRLLRLLLELRNLYLQYQRKRVEEldDD 131

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930  73 RLMFEYQTLLeePQYGENMEIYAGkknnwtGEFSARFLLKLP-VDFSNIPTYLLKDVNEDPGEDVaLLSVSFEDTEATQV 151
Cdd:cd23666 132 RVKFEISTIL--AREGLEMCLVTG------PDRPEEVKFAIPlVDVDLSNKLVLGCSPWKPQQKI-YLQVKFPVQRGQTS 202

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 152 YP-----KLYLSPRIEHALGgSSALHIPAFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVvEYD 226
Cdd:cd23666 203 LPsapqlKLVAPPALREVFD-VEDVKLPAWTDGMCLAEYLPNLEEQLKAQVVEAVASVGLRRRFIEALPPVFGRPL-EAD 280

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 41281930 227 AEGFTKLTLLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNSGQ-LYSQAQKNYPYSPRWDGNEMAKR-------A 298
Cdd:cd23666 281 TVYCRRASILASSGVFTFLVHFSLPTQFPKQQPTLTLQSSQHFDSQGVpIVSRLYDDYPWSPRWEPSEMVERifefiaeE 360


                ....*..
gi 41281930 299 KAYFKTF 305
Cdd:cd23666 361 ALAFKKY 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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