BRAP_MOUSE
ID BRAP_MOUSE Reviewed; 591 AA.
AC Q99MP8; Q8CC00; Q8CHX1; Q99MP7; Q9CXX8;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=BRCA1-associated protein;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q7Z569};
DE AltName: Full=BRAP2;
DE AltName: Full=Impedes mitogenic signal propagation;
DE Short=IMP;
DE AltName: Full=RING-type E3 ubiquitin transferase BRAP2 {ECO:0000305};
GN Name=Brap {ECO:0000312|MGI:MGI:1919649};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAK28079.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY.
RC STRAIN=ICR {ECO:0000312|EMBL:AAK28079.1};
RC TISSUE=Testis {ECO:0000312|EMBL:AAK28079.1};
RX PubMed=14607334; DOI=10.1016/s0304-3835(03)00443-9;
RA Nakajima A., Kataoka K., Hong M., Sakaguchi M., Huh N.-H.;
RT "BRPK, a novel protein kinase showing increased expression in mouse cancer
RT cell lines with higher metastatic potential.";
RL Cancer Lett. 201:195-201(2003).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH38490.1}; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 102-591 (ISOFORMS 1/2).
RC STRAIN=C57BL/6J; TISSUE=Diencephalon, and Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
CC -!- FUNCTION: Negatively regulates MAP kinase activation by limiting the
CC formation of Raf/MEK complexes probably by inactivation of the KSR1
CC scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase
CC that, on activation of Ras, is modified by auto-polyubiquitination
CC resulting in the release of inhibition of Raf/MEK complex formation.
CC May also act as a cytoplasmic retention protein with a role in
CC regulating nuclear transport (By similarity).
CC {ECO:0000250|UniProtKB:Q7Z569}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q7Z569};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with the nuclear localization signal of BRCA1 and
CC with the N-terminal of KSR1. The C-terminal portion of BRCA1 interacts
CC with DDB1. {ECO:0000250|UniProtKB:Q7Z569}.
CC -!- INTERACTION:
CC Q99MP8; O88987: Akap3; NbExp=3; IntAct=EBI-10818333, EBI-9033539;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q7Z569}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:14607334}; Synonyms=alpha
CC {ECO:0000269|PubMed:14607334};
CC IsoId=Q99MP8-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:14607334}; Synonyms=beta
CC {ECO:0000269|PubMed:14607334};
CC IsoId=Q99MP8-2; Sequence=VSP_050761;
CC Name=3 {ECO:0000305};
CC IsoId=Q99MP8-3; Sequence=VSP_050762;
CC -!- TISSUE SPECIFICITY: Isoform 2 is highly expressed in testis, lower
CC levels in brain, heart, lung, stomach, colon, uterus, liver and kidney.
CC Isoform 1 is only expressed in the testis. Isoform 2 is predominant
CC over isoform 1 in both fetal and adult testis.
CC {ECO:0000269|PubMed:14607334}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB29036.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF321920; AAK28079.1; -; mRNA.
DR EMBL; AF321921; AAK28080.1; -; mRNA.
DR EMBL; BC038490; AAH38490.1; -; mRNA.
DR EMBL; AK013885; BAB29036.1; ALT_INIT; mRNA.
DR EMBL; AK034212; BAC28633.1; -; mRNA.
DR CCDS; CCDS19640.1; -. [Q99MP8-1]
DR CCDS; CCDS80389.1; -. [Q99MP8-2]
DR RefSeq; NP_001276473.1; NM_001289544.1. [Q99MP8-2]
DR RefSeq; NP_082503.2; NM_028227.3. [Q99MP8-1]
DR RefSeq; XP_006530532.1; XM_006530469.1.
DR AlphaFoldDB; Q99MP8; -.
DR SMR; Q99MP8; -.
DR BioGRID; 215356; 16.
DR IntAct; Q99MP8; 3.
DR STRING; 10090.ENSMUSP00000031414; -.
DR iPTMnet; Q99MP8; -.
DR PhosphoSitePlus; Q99MP8; -.
DR EPD; Q99MP8; -.
DR MaxQB; Q99MP8; -.
DR PaxDb; Q99MP8; -.
DR PeptideAtlas; Q99MP8; -.
DR PRIDE; Q99MP8; -.
DR ProteomicsDB; 273796; -. [Q99MP8-1]
DR ProteomicsDB; 273797; -. [Q99MP8-2]
DR ProteomicsDB; 273798; -. [Q99MP8-3]
DR Antibodypedia; 31107; 195 antibodies from 30 providers.
DR DNASU; 72399; -.
DR Ensembl; ENSMUST00000031414; ENSMUSP00000031414; ENSMUSG00000029458. [Q99MP8-1]
DR Ensembl; ENSMUST00000111765; ENSMUSP00000107395; ENSMUSG00000029458. [Q99MP8-2]
DR GeneID; 72399; -.
DR KEGG; mmu:72399; -.
DR UCSC; uc008zkc.2; mouse. [Q99MP8-1]
DR CTD; 8315; -.
DR MGI; MGI:1919649; Brap.
DR VEuPathDB; HostDB:ENSMUSG00000029458; -.
DR eggNOG; KOG0804; Eukaryota.
DR GeneTree; ENSGT00500000044909; -.
DR HOGENOM; CLU_009969_3_0_1; -.
DR InParanoid; Q99MP8; -.
DR OMA; GIIHLYK; -.
DR OrthoDB; 659103at2759; -.
DR PhylomeDB; Q99MP8; -.
DR TreeFam; TF313622; -.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 72399; 18 hits in 74 CRISPR screens.
DR ChiTaRS; Brap; mouse.
DR PRO; PR:Q99MP8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q99MP8; protein.
DR Bgee; ENSMUSG00000029458; Expressed in spermatid and 257 other tissues.
DR ExpressionAtlas; Q99MP8; baseline and differential.
DR Genevisible; Q99MP8; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008139; F:nuclear localization sequence binding; ISO:MGI.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; ISO:MGI.
DR CDD; cd12718; RRM_BRAP2; 1.
DR Gene3D; 3.30.40.10; -; 2.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR011422; BRAP2.
DR InterPro; IPR034932; BRAP2_RRM.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF07576; BRAP2; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Metal-binding;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..591
FT /note="BRCA1-associated protein"
FT /id="PRO_0000055826"
FT ZN_FING 263..303
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175,
FT ECO:0000305"
FT ZN_FING 300..392
FT /note="UBP-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 82..124
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..591
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 430..536
FT /evidence="ECO:0000255"
FT COMPBIAS 99..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 328
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 336
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 343
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 347
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z569"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z569"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7Z569"
FT VAR_SEQ 1..217
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050762"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14607334"
FT /id="VSP_050761"
FT CONFLICT 111
FT /note="N -> I (in Ref. 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 591 AA; 66991 MW; DF925A28C0388E72 CRC64;
MSVSLVVIRL ELAGHSPVPT DFGFSAAAGE MSDEEIKKKT LASAVACLEG KSAGEKAAII
HQHLGRREMT DVIIETMKAR ADEVRDTVEE KKPSAAPVSA QRSREQSESV NTAPESPSKQ
LPDQISFFSG NPSVEIVHGI MHLYKTNKMT SLKEDVRRSA MLCVLTVPAT MTSHDLMKFV
APFNDVIEQM KIIRDSTPNQ YMVLIKFSAQ ADADSFYMAC NGRQFNSIED DVCQLVYVER
AEVLKSEDGA SLPVMDLTEL PKCTVCLERM DESVNGILTT LCNHSFHSQC LQRWDDTTCP
VCRYCQTPEP VEENKCFECG VQENLWICLI CGHIGCGRYV SRHAYKHFEE TQHTYAMQLT
NHRVWDYAGD NYVHRLVASK TDGKIVQYEC EGDTCQEEKI DALQLEYSYL LTSQLESQRI
YWENKIVRIE KDTAEEINNM KTKFKETIEK CDSLELRLSD LLKEKQSVER KCTQLNTRVA
KLSTELQEEQ ELNKCLRANQ LVLQNQLKEE EKLLKETCAQ KDLQITEIQE QLRDVMFYLE
TQQQISHLPA ETRQEIQEGQ INIAMASAPN PPSSGAGGKL QSRKGRSKRG K
