BRCA1

Details:

UniProt Entry: P38398

Gene: BRCA1

Class: RING

Family: RING10

Protein length: 1863

Database confidence: 1.0

InterPro: InterPro Entry

Mode of Action: Standalone

AlphaFold Model: Link

PDB Structures: 1jm7, 1jnx, 1n5o, 1oqa, 1t15, 1t29, 1t2u, 1t2v, 1y98, 2ing, 3coj, 3k0h, 3k0k, 3k15, 3k16, 3pxa, 3pxb, 3pxc, 3pxd, 3pxe, 4ifi, 4igk, 4jlu, 4ofb, 4u4a, 4y18, 4y2g, 6g2i, 7jzv, 7lyb

Protein Sequence ▾

>P38398
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ
PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC
SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD
EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN
LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE
QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV
RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE
FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ
ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS
RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG
NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP
STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL
NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS
HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL
LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS
SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE
DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE
DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG
TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT
DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI
TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV
VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH
SHY

Domain Architecture (From InterPro) ▾

Protein functions ▾

Start	End	Type	Name	InterPro	Source
1	1858	Family	BRCA1-associated	IPR031099	PIRSF001734
1	112	Homologous_superfamily	Zinc finger, RING/FYVE/PHD-type	IPR013083	G3DSA:3.30.40.10
24	65	Domain	Zinc finger, RING-type	IPR001841	PS50089
24	64	Domain	Zinc finger, C3HC4 RING-type	IPR018957	PF00097
24	64	Domain	Zinc finger, RING-type	IPR001841	SM00184
39	48	Conserved_site	Zinc finger, RING-type, conserved site	IPR017907	PS00518
55	71	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
345	508	Domain	BRCA1, serine-rich domain	IPR025994	PF12820
564	1854	Family	BRCA1-associated	IPR031099	PTHR13763
760	780	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
1030	1047	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
1180	1200	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
1430	1446	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
1608	1753	Homologous_superfamily	BRCT domain superfamily	IPR036420	SSF52113
1632	1652	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
1642	1736	Domain	BRCT domain	IPR001357	PS50172
1644	1726	Domain	BRCT domain	IPR001357	SM00292
1646	1755	Homologous_superfamily	BRCT domain superfamily	IPR036420	G3DSA:3.40.50.10190
1658	1723	Domain	BRCT domain	IPR001357	PF00533
1699	1719	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493
1756	1855	Domain	BRCT domain	IPR001357	PS50172
1756	1859	Homologous_superfamily	BRCT domain superfamily	IPR036420	G3DSA:3.40.50.10190
1757	1841	Domain	BRCT domain	IPR001357	PF00533
1758	1845	Domain	BRCT domain	IPR001357	SM00292
1759	1857	Homologous_superfamily	BRCT domain superfamily	IPR036420	SSF52113
1771	1794	Family	Breast cancer type 1 susceptibility protein (BRCA1)	IPR011364	PR00493

GO term	Name	Ontology	Evidence	Reference
GO:0006281	DNA repair	Biological Process	IEA	GO_REF:0000120
GO:0006974	DNA damage response	Biological Process	IEA	GO_REF:0000120
GO:0006310	DNA recombination	Biological Process	IEA	GO_REF:0000043
GO:0006629	lipid metabolic process	Biological Process	IEA	GO_REF:0000043
GO:0006631	fatty acid metabolic process	Biological Process	IEA	GO_REF:0000043
GO:0006633	fatty acid biosynthetic process	Biological Process	IEA	GO_REF:0000043
GO:0051865	protein autoubiquitination	Biological Process	IEA	GO_REF:0000104
GO:0085020	protein K6-linked ubiquitination	Biological Process	IEA	GO_REF:0000104
GO:0051726	regulation of cell cycle	Biological Process	IDA	PMID:21102443
GO:0007098	centrosome cycle	Biological Process	IEA	GO_REF:0000107
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage	Biological Process	IDA	PMID:14654789
GO:0043009	chordate embryonic development	Biological Process	IEA	GO_REF:0000107
GO:0044818	mitotic G2/M transition checkpoint	Biological Process	IEA	GO_REF:0000107
GO:0060816	random inactivation of X chromosome	Biological Process	IEA	GO_REF:0000107
GO:0044027	negative regulation of gene expression via chromosomal CpG island methylation	Biological Process	IEA	GO_REF:0000107
GO:0000724	double-strand break repair via homologous recombination	Biological Process	IBA	GO_REF:0000033
GO:0006282	regulation of DNA repair	Biological Process	NAS	PMID:20656689
GO:0006301	postreplication repair	Biological Process	IDA	PMID:17349954
GO:0006302	double-strand break repair	Biological Process	IEA	GO_REF:0000107
GO:0006338	chromatin remodeling	Biological Process	TAS	PMID:35351360
GO:0006357	regulation of transcription by RNA polymerase II	Biological Process	TAS	PMID:10910365
GO:0007059	chromosome segregation	Biological Process	IMP	PMID:15965487
GO:0007095	mitotic G2 DNA damage checkpoint signaling	Biological Process	IBA	GO_REF:0000033
GO:0010212	response to ionizing radiation	Biological Process	IMP	PMID:17525340
GO:0010575	positive regulation of vascular endothelial growth factor production	Biological Process	IMP	PMID:23415688
GO:0010628	positive regulation of gene expression	Biological Process	IMP	PMID:23415688
GO:0016567	protein ubiquitination	Biological Process	IEA	GO_REF:0000041
GO:0030308	negative regulation of cell growth	Biological Process	IMP	PMID:10518542
GO:0033147	negative regulation of intracellular estrogen receptor signaling pathway	Biological Process	IMP	PMID:17505062
GO:0035825	homologous recombination	Biological Process	NAS	PMID:22369660
GO:0045717	negative regulation of fatty acid biosynthetic process	Biological Process	IMP	PMID:16326698
GO:0045739	positive regulation of DNA repair	Biological Process	IMP	PMID:17525340
GO:0045766	positive regulation of angiogenesis	Biological Process	IMP	PMID:23415688
GO:0045786	negative regulation of cell cycle	Biological Process	NAS	PMID:15159397
GO:0045892	negative regulation of DNA-templated transcription	Biological Process	IDA	PMID:16288014
GO:0045893	positive regulation of DNA-templated transcription	Biological Process	IMP	PMID:12080089
GO:0045944	positive regulation of transcription by RNA polymerase II	Biological Process	IBA	GO_REF:0000033
GO:0046600	negative regulation of centriole replication	Biological Process	NAS	PMID:12214252
GO:0071356	cellular response to tumor necrosis factor	Biological Process	IMP	PMID:23415688
GO:0071479	cellular response to ionizing radiation	Biological Process	IMP	PMID:14636569
GO:0071681	cellular response to indole-3-methanol	Biological Process	IDA	PMID:10868478
GO:0110025	DNA strand resection involved in replication fork processing	Biological Process	NAS	PMID:29709199
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	Biological Process	IMP	PMID:23415688
GO:2000001	regulation of DNA damage checkpoint	Biological Process	NAS	PMID:14636569
GO:2000378	negative regulation of reactive oxygen species metabolic process	Biological Process	IMP	PMID:23415688
GO:0005634	nucleus	Cellular Component	IEA	GO_REF:0000120
GO:0005654	nucleoplasm	Cellular Component	IEA	GO_REF:0000117
GO:0005694	chromosome	Cellular Component	IEA	GO_REF:0000120
GO:0005737	cytoplasm	Cellular Component	IEA	GO_REF:0000120
GO:0031436	BRCA1-BARD1 complex	Cellular Component	IEA	GO_REF:0000104
GO:0016020	membrane	Cellular Component	IEA	GO_REF:0000043
GO:0000793	condensed chromosome	Cellular Component	IEA	GO_REF:0000107
GO:0000794	condensed nuclear chromosome	Cellular Component	IEA	GO_REF:0000107
GO:0000800	lateral element	Cellular Component	IDA	PMID:9774970
GO:0001673	male germ cell nucleus	Cellular Component	IEA	GO_REF:0000107
GO:0001741	XY body	Cellular Component	IEA	GO_REF:0000107
GO:0005886	plasma membrane	Cellular Component	IDA	PMID:21282464
GO:0016604	nuclear body	Cellular Component	IDA	GO_REF:0000052
GO:0000151	ubiquitin ligase complex	Cellular Component	NAS	PMID:14976165
GO:0000152	nuclear ubiquitin ligase complex	Cellular Component	IDA	PMID:14636569
GO:0000931	gamma-tubulin ring complex	Cellular Component	NAS	PMID:12214252
GO:0032991	protein-containing complex	Cellular Component	IDA	PMID:9774970
GO:0070531	BRCA1-A complex	Cellular Component	IBA	GO_REF:0000033
GO:0070532	BRCA1-B complex	Cellular Component	IPI	PMID:16391231
GO:0070533	BRCA1-C complex	Cellular Component	IPI	PMID:16391231
GO:1990391	DNA repair complex	Cellular Component	IPI	PMID:19369211
GO:1990904	ribonucleoprotein complex	Cellular Component	IDA	PMID:18809582
GO:0005575	cellular_component	Cellular Component	ND	GO_REF:0000015
GO:0008270	zinc ion binding	Molecular Function	IEA	GO_REF:0000043
GO:0046872	metal ion binding	Molecular Function	IEA	GO_REF:0000120
GO:0003677	DNA binding	Molecular Function	IEA	GO_REF:0000002
GO:0004842	ubiquitin-protein transferase activity	Molecular Function	IEA	GO_REF:0000002
GO:0016740	transferase activity	Molecular Function	IEA	GO_REF:0000043
GO:0061630	ubiquitin protein ligase activity	Molecular Function	IEA	GO_REF:0000003
GO:0016746	acyltransferase activity	Molecular Function	IEA	GO_REF:0000043
GO:0016874	ligase activity	Molecular Function	IEA	GO_REF:0000043
GO:0000976	transcription cis-regulatory region binding	Molecular Function	IEA	GO_REF:0000107
GO:0002039	p53 binding	Molecular Function	IDA	PMID:15571721
GO:0003684	damaged DNA binding	Molecular Function	IEA	GO_REF:0000107
GO:0003713	transcription coactivator activity	Molecular Function	IEA	GO_REF:0000107
GO:0003723	RNA binding	Molecular Function	IDA	PMID:12419249
GO:0005515	protein binding	Molecular Function	IPI	PMID:10477523
GO:0015631	tubulin binding	Molecular Function	NAS	PMID:12214252
GO:0019899	enzyme binding	Molecular Function	IPI	PMID:15965487
GO:0031625	ubiquitin protein ligase binding	Molecular Function	IPI	PMID:17873885
GO:0042802	identical protein binding	Molecular Function	IPI	PMID:29656893
GO:0061649	ubiquitin-modified histone reader activity	Molecular Function	TAS	PMID:35351360
GO:0070063	RNA polymerase binding	Molecular Function	IDA	PMID:9662397
GO:0140863	histone H2AK127 ubiquitin ligase activity	Molecular Function	TAS	PMID:35351360
GO:0140864	histone H2AK129 ubiquitin ligase activity	Molecular Function	TAS	PMID:35351360
GO:0003674	molecular_function	Molecular Function	ND	GO_REF:0000015

Enzyme–Substrate Interactions ▾

Substrate	Name	Known ESI (UbiBrowser)	Known ESI (UbiNet)	PPI (IntAct direct) PSI-MI score ≥ 0.5	PPI (IntAct indirect) PSI-MI scores ≥ 0.5 for both PPIs	PubMed Ref.	IntAct Ref.	Substrate Specificity
P0DP91	ERPG3	Yes	Yes	No	No	—	No	E3-specific
Q13133	NR1H3	Yes	Yes	No	No	—	No	E3-specific
P30307	MPIP3	Yes	Yes	No	No	—	No	E3-specific
Q99728	BARD1	Yes	Yes	Yes	No	10477523, 29656893, 11573085, 28514442, 8944023, 17873885, 23680151, 19369211, 34591612, 22110403, 31270457, 24981860	EBI-1789920	E3-specific
O14818	PSA7	Yes	Yes	No	No	—	No	E3-specific
P14859	PO2F1	Yes	No	No	No	—	No	E3-specific
P23258	TBG1	Yes	Yes	No	No	—	No	E3-specific
Q9HAW4	CLSPN	Yes	Yes	No	No	—	No	E3-specific
P06401	PRGR	Yes	Yes	No	No	—	No	E3-specific

Small Molecule Interactions ▾

Type	ChEMBL Compound ID	Source	pChEMBL	PDB Compound ID	PDB Codes	SMILES
E3 Binder	CHEMBL1784786	ChEMBL	6.36	—	—	CC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](COP(=O)(O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(N)=O)[C@@H](C)O)[C@@H](C)O
E3 Binder	CHEMBL1784785	ChEMBL	6.7	—	—	CC(=O)N[C@@H](COP(=O)(O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)O)C(C)C
E3 Binder	CHEMBL1784784	ChEMBL	6.72	—	—	CC(=O)N[C@@H](COP(=O)(O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)O)[C@@H](C)O
E3 Binder	CHEMBL2017815	ChEMBL	6.89	—	—	CC(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](COP(=O)(O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)O)C(C)C
E3 Binder	CHEMBL2017814	ChEMBL	6.27	—	—	CC(=O)N[C@@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](COP(=O)(O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(N)=O)C(C)C
E3 Binder	CHEMBL2017822	ChEMBL	7.4	—	—	CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](COP(=O)(O)O)NC(=O)C/C=C/c1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
E3 Binder	CHEMBL2017817	ChEMBL	6.3	—	—	CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](COP(=O)(O)O)NC(=O)CCCc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
E3 Binder	CHEMBL2017816	ChEMBL	7.0	—	—	CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](COP(=O)(O)O)NC(=O)CCc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
E3 Binder	CHEMBL2017821	ChEMBL	7.1	—	—	CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](COP(=O)(O)O)NC(=O)c1cccc(-c2ccccc2)c1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
E3 Binder	CHEMBL1784787	ChEMBL	6.39	—	—	CC[C@H](C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](COP(=O)(O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O

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