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Basic Information Integrated Annotations

Tag Content
iUUCD ID IUUC-Hsa-046086
UUCD1 version UUC-HoS-00069
Ensembl Protein ID ENSP00000350283.3
UniProt Accession P38398; E9PFZ0; O15129; Q1RMC1; Q3LRJ0; Q3LRJ6; Q6IN79; Q7KYU9; BRCA1_HUMAN
Genbank Protein ID AAA73985.1; AAC37594.1; AAC00049.1; AAB61673.1; ABA29208.1; ABA29211.1; ABA29214.1; ABA29217.1; ABA29220.1; ABA29223.1; ABA29226.1; AAP12647.1; AAH72418.1; AAI15038.1
Protein Name Breast cancer type 1 susceptibility protein; RING finger protein 53; RING-type E3 ubiquitin transferase BRCA1
Genbank Nucleotide ID U14680; L78833; U64805; AF005068; DQ190450; DQ190451; DQ190452; DQ190453; DQ190454; DQ190455; DQ190456; AY273801; AC060780; BC115037
Gene Name BRCA1; RNF53
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000012048.20 ENST00000357654.7 ENSP00000350283.3
ENSG00000012048.20 ENST00000352993.7 ENSP00000312236.5
ENSG00000012048.20 ENST00000468300.5 ENSP00000417148.1
ENSG00000012048.20 ENST00000586385.5 ENSP00000465818.1
ENSG00000012048.20 ENST00000591849.5 ENSP00000465347.1
ENSG00000012048.20 ENST00000471181.6 ENSP00000418960.2
ENSG00000012048.20 ENST00000491747.6 ENSP00000420705.2
ENSG00000012048.20 ENST00000484087.5 ENSP00000419481.1
ENSG00000012048.20 ENST00000478531.5 ENSP00000420412.1
ENSG00000012048.20 ENST00000493919.5 ENSP00000418819.1
ENSG00000012048.20 ENST00000487825.5 ENSP00000418212.1
ENSG00000012048.20 ENST00000461574.1 ENSP00000417241.1
ENSG00000012048.20 ENST00000354071.7 ENSP00000326002.7
ENSG00000012048.20 ENST00000634433.1 ENSP00000489431.1
ENSG00000012048.20 ENST00000412061.3 ENSP00000397145.3
ENSG00000012048.20 ENST00000477152.5 ENSP00000419988.1
ENSG00000012048.20 ENST00000492859.5 ENSP00000420253.1
ENSG00000012048.20 ENST00000473961.5 ENSP00000420201.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
miRWalkTargetScanmiRecordsRepTar
SomamiRmiRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Protein 3D Structure
PDBMMDB
Disease-associated Information
ClinVarGWASdbOMIM
Post-translational Modifications (PTMs)
CPLMdbPAFPhosSNPPhosphositePlus
dbPTMHPRDPhospho.ELMUniProt
PHOSIDABioGRIDmUbiSiDa
DNA Methylation
MethyCancerTCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 activity/RING/RING RING 12431996; 19887647; 18388150; 19164445; 19261748; 17283126; 16818604; 25131202; 25355358
Classification
Family E-value Score Start End
E3 activity/RING/RING 8.30e-07 31.1 24 65
Active Site
Position(s) Description Evidence
N/A N/A N/A
Domain Profile

   E3 activity/RING/RING

   S: 1    CaiCledfkdgplvlpCgHvfhadClqkwpglknssskefrCPlCr 46
    C+iCle +k+ p+++ C H+f++ C k+ n++++ +CPlC+
   Q: 24 CPICLELIKE-PVSTKCDHIFCKFCMLKL---LNQKKGPSQCPLCK 65
    ********99.**************9666...68899********7 PP
   

Organism Homo sapiens
Functional Description
(View)

Functional Description



     E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator (PubMed:20160719).
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator (PubMed:20160719).
Protein Sequence
(Fasta)
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ 60
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD 120
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Protein Fasta Sequence



>IUUC-Hsa-046086|E3,RING|Homo sapiens
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Nucleotide Sequence
(Fasta)
AAAGCGTGGG AATTACAGAT AAATTAAAAC TGTGGAACCC CTTTCCTCGG CTGCCGCCAA 60
GGTGTTCGGT CCTTCCGAGG AAGCTAAGGC CGCGTTGGGG TGAGACCCTC ACTTCATCCG 120
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Nucleotide Fasta Sequence



>IUUC-Hsa-046086|E3,RING|Homo sapiens
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Sequence Source Ensembl
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0010--Activator
KW-0024--Alternative initiation
KW-0025--Alternative splicing
KW-0131--Cell cycle
KW-0158--Chromosome
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0903--Direct protein sequencing
KW-0225--Disease mutation
KW-0227--DNA damage
KW-0233--DNA recombination
KW-0234--DNA repair
KW-0238--DNA-binding
KW-0275--Fatty acid biosynthesis
KW-0276--Fatty acid metabolism
KW-1017--Isopeptide bond
KW-0444--Lipid biosynthesis
KW-0443--Lipid metabolism
KW-0479--Metal-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0677--Repeat
KW-0804--Transcription
KW-0805--Transcription regulation
KW-0808--Transferase
KW-0043--Tumor suppressor
KW-0832--Ubl conjugation
KW-0833--Ubl conjugation pathway
KW-0862--Zinc
KW-0863--Zinc-finger

Interpro

IPR011364--BRCA1
IPR031099--BRCA1-associated
IPR025994--BRCA1_serine_dom
IPR001357--BRCT_dom
IPR018957--Znf_C3HC4_RING-type
IPR001841--Znf_RING
IPR013083--Znf_RING/FYVE/PHD
IPR017907--Znf_RING_CS

PROSITE

PS50172--BRCT
PS00518--ZF_RING_1
PS50089--ZF_RING_2

Pfam

PF00533--BRCT
PF12820--BRCT_assoc
PF00097--zf-C3HC4

PRINTS

PR00493--BRSTCANCERI

SMART

SM00292--BRCT
SM00184--RING

Gene Ontology

GO:0070531--C:BRCA1-A complex
GO:0031436--C:BRCA1-BARD1 complex
GO:0005694--C:chromosome
GO:0005737--C:cytoplasm
GO:0008274--C:gamma-tubulin ring complex
GO:0030529--C:intracellular ribonucleoprotein complex
GO:0000800--C:lateral element
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0005886--C:plasma membrane
GO:0043234--C:protein complex
GO:0000151--C:ubiquitin ligase complex
GO:0050681--F:androgen receptor binding
GO:0003684--F:damaged DNA binding
GO:0003677--F:DNA binding
GO:0019899--F:enzyme binding
GO:0003723--F:RNA binding
GO:0003713--F:transcription coactivator activity
GO:0044212--F:transcription regulatory region DNA binding
GO:0015631--F:tubulin binding
GO:0031625--F:ubiquitin protein ligase binding
GO:0004842--F:ubiquitin-protein transferase activity
GO:0008270--F:zinc ion binding
GO:0030521--P:androgen receptor signaling pathway
GO:0006915--P:apoptotic process
GO:0006974--P:cellular response to DNA damage stimulus
GO:0071681--P:cellular response to indole-3-methanol
GO:0071356--P:cellular response to tumor necrosis factor
GO:0007098--P:centrosome cycle
GO:0043009--P:chordate embryonic development
GO:0007059--P:chromosome segregation
GO:0006978--P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0000729--P:DNA double-strand break processing
GO:0006260--P:DNA replication
GO:0000731--P:DNA synthesis involved in DNA repair
GO:0009048--P:dosage compensation by inactivation of X chromosome
GO:0006302--P:double-strand break repair
GO:0000724--P:double-strand break repair via homologous recombination
GO:0006303--P:double-strand break repair via nonhomologous end joining
GO:0006633--P:fatty acid biosynthetic process
GO:0031572--P:G2 DNA damage checkpoint
GO:0008630--P:intrinsic apoptotic signaling pathway in response to DNA damage
GO:0046600--P:negative regulation of centriole replication
GO:1902042--P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:0045717--P:negative regulation of fatty acid biosynthetic process
GO:0035067--P:negative regulation of histone acetylation
GO:0051572--P:negative regulation of histone H3-K4 methylation
GO:0051573--P:negative regulation of histone H3-K9 methylation
GO:0033147--P:negative regulation of intracellular estrogen receptor signaling pathway
GO:2000378--P:negative regulation of reactive oxygen species metabolic process
GO:0045892--P:negative regulation of transcription, DNA-templated
GO:0045766--P:positive regulation of angiogenesis
GO:0071158--P:positive regulation of cell cycle arrest
GO:0045739--P:positive regulation of DNA repair
GO:0010628--P:positive regulation of gene expression
GO:0035066--P:positive regulation of histone acetylation
GO:0051571--P:positive regulation of histone H3-K4 methylation
GO:2000617--P:positive regulation of histone H3-K9 acetylation
GO:0051574--P:positive regulation of histone H3-K9 methylation
GO:2000620--P:positive regulation of histone H4-K16 acetylation
GO:0070512--P:positive regulation of histone H4-K20 methylation
GO:0031398--P:positive regulation of protein ubiquitination
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0045893--P:positive regulation of transcription, DNA-templated
GO:0010575--P:positive regulation of vascular endothelial growth factor production
GO:0006301--P:postreplication repair
GO:0051865--P:protein autoubiquitination
GO:0016579--P:protein deubiquitination
GO:0085020--P:protein K6-linked ubiquitination
GO:0016567--P:protein ubiquitination
GO:0042981--P:regulation of apoptotic process
GO:0042127--P:regulation of cell proliferation
GO:0044030--P:regulation of DNA methylation
GO:0006349--P:regulation of gene expression by genetic imprinting
GO:1901796--P:regulation of signal transduction by p53 class mediator
GO:0006357--P:regulation of transcription from RNA polymerase II promoter
GO:0006359--P:regulation of transcription from RNA polymerase III promoter
GO:0043627--P:response to estrogen
GO:0010212--P:response to ionizing radiation
GO:0000732--P:strand displacement
GO:0006351--P:transcription, DNA-templated

KEGG hsa:672
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Aml-002388 Ailuropoda melanoleuca 75.03 0.00e+00 2676.00
IUUC-Apl-003252 Anas platyrhynchos 36.49 6.00e-132 466.00
IUUC-Aca-004526 Anolis carolinensis 54.55 7.00e-77 281.00
IUUC-Ame-011720 Astyanax mexicanus 47.78 9.00e-53 202.00
IUUC-Bta-013433 Bos taurus 71.83 0.00e+00 2516.00
IUUC-Cel-018208 Caenorhabditis elegans 33.66 9.00e-11 62.40
IUUC-Cja-019149 Callithrix jacchus 87.63 0.00e+00 3164.00
IUUC-Cfa-020322 Canis familiaris 74.04 0.00e+00 2605.00
IUUC-Cpo-021583 Cavia porcellus 47.04 0.00e+00 1365.00
IUUC-Csa-024227 Chlorocebus sabaeus 92.91 0.00e+00 682.00
IUUC-Cho-024530 Choloepus hoffmanni 68.63 0.00e+00 1205.00
IUUC-Cin-025364 Ciona intestinalis 33.59 1.00e-14 73.90
IUUC-Csv-026245 Ciona savignyi 38.46 2.00e-13 68.90
IUUC-Dno-029247 Dasypus novemcinctus 71.78 0.00e+00 2083.00
IUUC-Dme-032032 Drosophila melanogaster 54.35 8.00e-11 58.50
IUUC-Ete-032472 Echinops telfairi 56.28 0.00e+00 1734.00
IUUC-Eca-033446 Equus caballus 76.62 0.00e+00 2776.00
IUUC-Eeu-034858 Erinaceus europaeus 60.95 0.00e+00 983.00
IUUC-Fca-035991 Felis catus 75.39 0.00e+00 2702.00
IUUC-Fal-036803 Ficedula albicollis 30.83 3.00e-101 364.00
IUUC-Gmo-038782 Gadus morhua 45.31 2.00e-45 177.00
IUUC-Ggr-039833 Gaeumannomyces graminis 36.73 1.00e-07 51.60
IUUC-Gga-040969 Gallus gallus 62.98 1.00e-79 292.00
IUUC-Gac-042296 Gasterosteus aculeatus 44.98 1.00e-50 195.00
IUUC-Ggo-044740 Gorilla gorilla 93.51 0.00e+00 3314.00
IUUC-Itr-048512 Ictidomys tridecemlineatus 74.19 0.00e+00 2698.00
IUUC-Lch-049789 Latimeria chalumnae 37.80 2.00e-97 351.00
IUUC-Loc-051952 Lepisosteus oculatus 53.18 1.00e-68 255.00
IUUC-Laf-053648 Loxodonta africana 74.08 0.00e+00 2514.00
IUUC-Mcc-055210 Macaca mulatta 91.99 0.00e+00 3378.00
IUUC-Meu-056342 Macropus eugenii 38.29 1.00e-127 452.00
IUUC-Mor-057034 Magnaporthe oryzae 38.78 3.00e-08 53.50
IUUC-Mga-060163 Meleagris gallopavo 54.34 8.00e-83 303.00
IUUC-Mmr-061402 Microcebus murinus 72.66 0.00e+00 856.00
IUUC-Mdo-062209 Monodelphis domestica 45.42 0.00e+00 1271.00
IUUC-Mmu-064003 Mus musculus 55.93 0.00e+00 1837.00
IUUC-Mpu-065825 Mustela putorius furo 78.63 0.00e+00 815.00
IUUC-Mlu-068176 Myotis lucifugus 72.35 0.00e+00 2407.00
IUUC-Nle-069178 Nomascus leucogenys 95.92 0.00e+00 3459.00
IUUC-Opr-070574 Ochotona princeps 60.47 0.00e+00 1974.00
IUUC-Ont-072380 Oreochromis niloticus 48.06 1.00e-56 215.00
IUUC-Oan-073243 Ornithorhynchus anatinus 76.19 1.00e-34 138.00
IUUC-Ocu-074424 Oryctolagus cuniculus 69.42 0.00e+00 2374.00
IUUC-Ola-086863 Oryzias latipes 48.29 6.00e-54 206.00
IUUC-Oar-089938 Ovis aries 72.39 0.00e+00 2583.00
IUUC-Ptr-090960 Pan troglodytes 98.23 0.00e+00 3526.00
IUUC-Pan-092609 Papio anubis 92.46 0.00e+00 3002.00
IUUC-Psi-093889 Pelodiscus sinensis 30.93 4.00e-55 210.00
IUUC-Pfo-096328 Poecilia formosa 50.70 2.00e-59 224.00
IUUC-Pab-097982 Pongo abelii 96.83 0.00e+00 3504.00
IUUC-Pca-100698 Procavia capensis 64.89 0.00e+00 676.00
IUUC-Pva-102631 Pteropus vampyrus 77.70 0.00e+00 1181.00
IUUC-Rno-105879 Rattus norvegicus 55.98 0.00e+00 1802.00
IUUC-Sha-106701 Sarcophilus harrisii 38.94 0.00e+00 692.00
IUUC-Spo-108335 Schizosaccharomyces pombe 32.58 2.00e-09 57.40
IUUC-Sar-113047 Sorex araneus 64.29 0.00e+00 1535.00
IUUC-Ssc-115846 Sus scrofa 74.21 0.00e+00 2658.00
IUUC-Tgu-116785 Taeniopygia guttata 29.85 2.00e-91 331.00
IUUC-Tru-117895 Takifugu rubripes 40.70 2.00e-54 208.00
IUUC-Tsy-118885 Tarsius syrichta 60.97 0.00e+00 733.00
IUUC-Tni-119654 Tetraodon nigroviridis 45.63 7.00e-50 193.00
IUUC-Tbe-127421 Tupaia belangeri 63.33 1.00e-164 574.00
IUUC-Ttr-128685 Tursiops truncatus 75.98 0.00e+00 2558.00
IUUC-Vpa-130216 Vicugna pacos 71.94 0.00e+00 883.00
IUUC-Xtr-132398 Xenopus tropicalis 35.89 2.00e-63 238.00
IUUC-Xma-133651 Xiphophorus maculatus 52.35 3.00e-45 177.00
Created Date 25-Jun-2017

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