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Conserved domains on  [gi|2250232332|ref|NP_001394872|]
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breast cancer type 1 susceptibility protein isoform 69 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
BRCT_assoc pfam12820
Serine-rich domain associated with BRCT; This domain is found on BRCA1 proteins.
 297-460 4.30e-94

Serine-rich domain associated with BRCT; This domain is found on BRCA1 proteins.


:

Pssm-ID: 463719  Cd Length: 164  Bit Score: 300.92  E-value: 4.30e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  297 DPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSG 376
Cdd:pfam12820    1 DPLCGRKELPKQKPPCPETPRDTQDVSWITLNSSIQKVNEWFSRSDEILTSDDSHDRRSESNAEVAGALEVPNEVDGYSG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  377 SSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKR 456
Cdd:pfam12820   81 SSEKIDLMADDPHGALICESERVHSKPVENNIEDKIFGKTYRRKASLPNLSHITERLILGAFAKEPQITQEHPLTNKLKR 160


                   ....
gi 2250232332  457 KRRP 460
Cdd:pfam12820  161 KRRT 164
BRCT_BRCA1_rpt1 cd17735
first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; ...
 1602-1698 4.26e-61

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling, and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus. The family corresponds to the first BRCT domain.


:

Pssm-ID: 349367  Cd Length: 97  Bit Score: 203.73  E-value: 4.26e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332 1602 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1681
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 2250232332 1682 NEHDFEVRGDVVNGRNH 1698
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97
RING_Ubox super family cl17238
RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger ...
 1-52 1.11e-20

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.


The actual alignment was detected with superfamily member cd16498:

Pssm-ID: 473075 [Multi-domain]  Cd Length: 94  Bit Score: 88.12  E-value: 1.11e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2250232332    1 MLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGL 52
Cdd:cd16498     43 ILKLLQKKKKPAPCPLCKKSVTKRSLQESTRFKQLVEAVKKLIDAFELDTGL 94
BRCT super family cl00038
C-terminal domain of the breast cancer suppressor protein (BRCA1) and related domains; The ...
 1710-1730 6.72e-05

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


The actual alignment was detected with superfamily member cd17721:

Pssm-ID: 469589  Cd Length: 98  Bit Score: 43.41  E-value: 6.72e-05
                           10        20
                   ....*....|....*....|.
gi 2250232332 1710 RKIFRGLEICCYGPFTNMPTG 1730
Cdd:cd17721      1 KLLFRGFEICCYGPFTNMTKD 21
 
Name Accession Description Interval E-value
BRCT_assoc pfam12820
Serine-rich domain associated with BRCT; This domain is found on BRCA1 proteins.
 297-460 4.30e-94

Serine-rich domain associated with BRCT; This domain is found on BRCA1 proteins.


Pssm-ID: 463719  Cd Length: 164  Bit Score: 300.92  E-value: 4.30e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  297 DPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSG 376
Cdd:pfam12820    1 DPLCGRKELPKQKPPCPETPRDTQDVSWITLNSSIQKVNEWFSRSDEILTSDDSHDRRSESNAEVAGALEVPNEVDGYSG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  377 SSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKR 456
Cdd:pfam12820   81 SSEKIDLMADDPHGALICESERVHSKPVENNIEDKIFGKTYRRKASLPNLSHITERLILGAFAKEPQITQEHPLTNKLKR 160


                   ....
gi 2250232332  457 KRRP 460
Cdd:pfam12820  161 KRRT 164
BRCT_BRCA1_rpt1 cd17735
first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; ...
 1602-1698 4.26e-61

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling, and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus. The family corresponds to the first BRCT domain.


Pssm-ID: 349367  Cd Length: 97  Bit Score: 203.73  E-value: 4.26e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332 1602 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1681
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 2250232332 1682 NEHDFEVRGDVVNGRNH 1698
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97
RING-HC_BRCA1 cd16498
RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and ...
 1-52 1.11e-20

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.


Pssm-ID: 438161 [Multi-domain]  Cd Length: 94  Bit Score: 88.12  E-value: 1.11e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2250232332    1 MLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGL 52
Cdd:cd16498     43 ILKLLQKKKKPAPCPLCKKSVTKRSLQESTRFKQLVEAVKKLIDAFELDTGL 94
BRCT pfam00533
BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in ...
 1596-1675 4.46e-08

BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilized head-to-tail BRCT-BRCT oligomerization mode. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants.


Pssm-ID: 425736 [Multi-domain]  Cd Length: 75  Bit Score: 51.91  E-value: 4.46e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332 1596 ERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVmktdaefVCERTLKYFLGIAGGKWVVSYFWVTQSI 1675
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI-------VEARTKKYLKAKELGIPIVTEEWLLDCI 75
BRCT_BRCA1_rpt2 cd17721
second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and ...
 1710-1730 6.72e-05

second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling, and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT repeats at the C-terminus. The family corresponds to the second BRCT domain.


Pssm-ID: 349353  Cd Length: 98  Bit Score: 43.41  E-value: 6.72e-05
                           10        20
                   ....*....|....*....|.
gi 2250232332 1710 RKIFRGLEICCYGPFTNMPTG 1730
Cdd:cd17721      1 KLLFRGFEICCYGPFTNMTKD 21
BRCT smart00292
breast cancer carboxy-terminal domain;
1614-1675 5.43e-03

breast cancer carboxy-terminal domain;


Pssm-ID: 214602 [Multi-domain]  Cd Length: 78  Bit Score: 37.35  E-value: 5.43e-03
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  1614 FMLVYKFARKHHITLTNLITE----ETTHVVMKTDAEFVCE----RTLKYFLGIAGGKWVVSYFWVTQSI 1675
Cdd:smart00292    9 FYITGSFDKEERDELKELIEAlggkVTSSLSSKTTTHVIVGspegGKLELLKAIALGIPIVKEEWLLDCL 78
 
Name Accession Description Interval E-value
BRCT_assoc pfam12820
Serine-rich domain associated with BRCT; This domain is found on BRCA1 proteins.
 297-460 4.30e-94

Serine-rich domain associated with BRCT; This domain is found on BRCA1 proteins.


Pssm-ID: 463719  Cd Length: 164  Bit Score: 300.92  E-value: 4.30e-94
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  297 DPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSG 376
Cdd:pfam12820    1 DPLCGRKELPKQKPPCPETPRDTQDVSWITLNSSIQKVNEWFSRSDEILTSDDSHDRRSESNAEVAGALEVPNEVDGYSG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  377 SSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKR 456
Cdd:pfam12820   81 SSEKIDLMADDPHGALICESERVHSKPVENNIEDKIFGKTYRRKASLPNLSHITERLILGAFAKEPQITQEHPLTNKLKR 160


                   ....
gi 2250232332  457 KRRP 460
Cdd:pfam12820  161 KRRT 164
BRCT_BRCA1_rpt1 cd17735
first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; ...
 1602-1698 4.26e-61

first BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling, and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus. The family corresponds to the first BRCT domain.


Pssm-ID: 349367  Cd Length: 97  Bit Score: 203.73  E-value: 4.26e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332 1602 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1681
Cdd:cd17735      1 MSMVASGLTPEELMLVQKFARKTGSTLTSQFTEETTHVIMKTDAELVCERTLKYFLGIAGRKWVVSYQWITQSIKEGKIL 80

                           90
                   ....*....|....*..
gi 2250232332 1682 NEHDFEVRGDVVNGRNH 1698
Cdd:cd17735     81 PEHDFEVRGDVVNGRNH 97
BRCT_Bard1_rpt1 cd17734
first BRCT domain of BRCA1-associated RING domain protein 1 (Bard1) and similar proteins; ...
 1607-1679 1.11e-20

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


Pssm-ID: 349366  Cd Length: 80  Bit Score: 87.66  E-value: 1.11e-20
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2250232332 1607 SGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERK 1679
Cdd:cd17734      6 SGLSSEQKKLLEKLAQLLKAKVVTEFSPEVTHVVVPADERGVCPRTMKYLMGILAGKWIVSFEWVEACLKAKK 78
RING-HC_BRCA1 cd16498
RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and ...
 1-52 1.11e-20

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.


Pssm-ID: 438161 [Multi-domain]  Cd Length: 94  Bit Score: 88.12  E-value: 1.11e-20
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2250232332    1 MLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGL 52
Cdd:cd16498     43 ILKLLQKKKKPAPCPLCKKSVTKRSLQESTRFKQLVEAVKKLIDAFELDTGL 94
BRCT_microcephalin_rpt2 cd17736
second BRCT domain of microcephalin and similar proteins; Microcephalin is a DNA damage ...
 1602-1681 1.23e-12

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


Pssm-ID: 349368 [Multi-domain]  Cd Length: 76  Bit Score: 64.53  E-value: 1.23e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332 1602 MSMVVSGLTPEEFMLVYKFARKH-HITLTNLITEETTHVVMKTDAefvceRTLKYFLGIAGGKWVVSYFWVTQSIKERKM 1680
Cdd:cd17736      1 RTLVMTSVHSEEQELLESVVKKLgGFRVEDSVTEKTTHVVVGSPR-----RTLNVLLGIARGCWILSPDWVLESLEAGKW 75


                   .
gi 2250232332 1681 L 1681
Cdd:cd17736     76 L 76
BRCT cd00027
C-terminal domain of the breast cancer suppressor protein (BRCA1) and related domains; The ...
 1602-1674 1.35e-10

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


Pssm-ID: 349339 [Multi-domain]  Cd Length: 68  Bit Score: 58.53  E-value: 1.35e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2250232332 1602 MSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDaefvcERTLKYFLGIAGGKWVVSYFWVTQS 1674
Cdd:cd00027      1 LVICFSGLDDEEREELKKLIEALGGKVSESLSSKVTHLIAKSP-----SGEKYYLAALAWGIPIVSPEWLLDC 68
BRCT pfam00533
BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in ...
 1596-1675 4.46e-08

BRCA1 C Terminus (BRCT) domain; The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilized head-to-tail BRCT-BRCT oligomerization mode. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants.


Pssm-ID: 425736 [Multi-domain]  Cd Length: 75  Bit Score: 51.91  E-value: 4.46e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332 1596 ERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVmktdaefVCERTLKYFLGIAGGKWVVSYFWVTQSI 1675
Cdd:pfam00533    3 EKLFSGKTFVITGLDGLERDELKELIEKLGGKVTDSLSKKTTHVI-------VEARTKKYLKAKELGIPIVTEEWLLDCI 75
BRCT_BRCA1_rpt2 cd17721
second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and ...
 1710-1730 6.72e-05

second (C-terminal) BRCT domain of breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also termed RING finger protein 53 (RNF53), is a RING finger protein encoded by BRCA1, a tumor suppressor gene that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling, and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT repeats at the C-terminus. The family corresponds to the second BRCT domain.


Pssm-ID: 349353  Cd Length: 98  Bit Score: 43.41  E-value: 6.72e-05
                           10        20
                   ....*....|....*....|.
gi 2250232332 1710 RKIFRGLEICCYGPFTNMPTG 1730
Cdd:cd17721      1 KLLFRGFEICCYGPFTNMTKD 21
BRCT smart00292
breast cancer carboxy-terminal domain;
1614-1675 5.43e-03

breast cancer carboxy-terminal domain;


Pssm-ID: 214602 [Multi-domain]  Cd Length: 78  Bit Score: 37.35  E-value: 5.43e-03
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2250232332  1614 FMLVYKFARKHHITLTNLITE----ETTHVVMKTDAEFVCE----RTLKYFLGIAGGKWVVSYFWVTQSI 1675
Cdd:smart00292    9 FYITGSFDKEERDELKELIEAlggkVTSSLSSKTTTHVIVGspegGKLELLKAIALGIPIVKEEWLLDCL 78
BRCT_MDC1_rpt1 cd17744
first BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins; ...
 1634-1681 8.69e-03

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


Pssm-ID: 349375 [Multi-domain]  Cd Length: 72  Bit Score: 36.83  E-value: 8.69e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2250232332 1634 EETTHVVmkTDAEfvcERTLKYFLGIAGGKWVVSYFWVTQSIKERKML 1681
Cdd:cd17744     30 EDCTHLV--TDKV---RRTVKFLCALARGIPIVSPDWLEASIKANKFL 72
 
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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