BRMS1_HUMAN
ID BRMS1_HUMAN Reviewed; 246 AA.
AC Q9HCU9; Q6IAI2;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Breast cancer metastasis-suppressor 1;
GN Name=BRMS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=10850410;
RA Seraj M.J., Samant R.S., Verderame M.F., Welch D.R.;
RT "Functional evidence for a novel human breast carcinoma metastasis
RT suppressor, BRMS1, encoded at chromosome 11q13.";
RL Cancer Res. 60:2764-2769(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Welch D.R., Samant R.S., Debies M.T., Seraj M.J., Verderame M.F.;
RT "Genomic structure and chromosomal localization of the breast metastasis
RT suppressor gene, BRMS1.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [6]
RP TISSUE SPECIFICITY, AND POSSIBLE INVOLVEMENT IN INVASION/MIGRATION OF
RP TROPHOBLAST CELLS.
RX PubMed=12414911; DOI=10.1210/jc.2002-021093;
RA Janneau J.-L., Maldonado-Estrada J., Tachdjian G., Miran I., Motte N.,
RA Saulnier P., Sabourin J.-C., Cote J.-F., Simon B., Frydman R., Chaouat G.,
RA Bellet D.;
RT "Transcriptional expression of genes involved in cell invasion and
RT migration by normal and tumoral trophoblast cells.";
RL J. Clin. Endocrinol. Metab. 87:5336-5339(2002).
RN [7]
RP FUNCTION, INTERACTION WITH ARID4A, AND IDENTIFICATION IN A COMPLEX WITH
RP SIN3A; SIN3B; HDAC1; HDAC2; SAP30; SUDS3; RBBP4 AND RBBP7.
RX PubMed=14581478; DOI=10.1074/jbc.m307969200;
RA Meehan W.J., Samant R.S., Hopper J.E., Carrozza M.J., Shevde L.A.,
RA Workman J.L., Eckert K.A., Verderame M.F., Welch D.R.;
RT "Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with
RT retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase
RT complex and represses transcription.";
RL J. Biol. Chem. 279:1562-1569(2004).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HDAC1 AND RELA.
RX PubMed=17000776; DOI=10.1128/mcb.00940-06;
RA Liu Y., Smith P.W., Jones D.R.;
RT "Breast cancer metastasis suppressor 1 functions as a corepressor by
RT enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and
RT promoting apoptosis.";
RL Mol. Cell. Biol. 26:8683-8696(2006).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SNX6.
RX PubMed=20830743; DOI=10.1002/jcb.22874;
RA Rivera J., Megias D., Bravo J.;
RT "Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and
RT promotes transcriptional repression.";
RL J. Cell. Biochem. 111:1464-1472(2010).
RN [10]
RP UBIQUITINATION, SUBCELLULAR LOCATION, INTERACTION WITH SPOP, AND
RP IDENTIFICATION IN A COMPLEX WITH CUL3 AND SPOP.
RX PubMed=22085717; DOI=10.1016/j.bbrc.2011.10.154;
RA Kim B., Nam H.J., Pyo K.E., Jang M.J., Kim I.S., Kim D., Boo K., Lee S.H.,
RA Yoon J.B., Baek S.H., Kim J.H.;
RT "Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-
RT SPOP E3 ubiquitin ligase complex.";
RL Biochem. Biophys. Res. Commun. 415:720-726(2011).
RN [11]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-184, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 51-98, COILED-COIL DOMAIN, AND
RP SUBUNIT.
RX PubMed=21777593; DOI=10.1016/j.jmb.2011.07.006;
RA Spinola-Amilibia M., Rivera J., Ortiz-Lombardia M., Romero A., Neira J.L.,
RA Bravo J.;
RT "The structure of BRMS1 nuclear export signal and SNX6 interacting region
RT reveals a hexamer formed by antiparallel coiled coils.";
RL J. Mol. Biol. 411:1114-1127(2011).
CC -!- FUNCTION: Transcriptional repressor. Down-regulates transcription
CC activation by NF-kappa-B by promoting the deacetylation of RELA at
CC 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates
CC expression of anti-apoptotic genes that are controlled by NF-kappa-B.
CC Promotes apoptosis in cells that have inadequate adherence to a
CC substrate, a process called anoikis, and may thereby inhibit
CC metastasis. May be a mediator of metastasis suppression in breast
CC carcinoma. {ECO:0000269|PubMed:14581478, ECO:0000269|PubMed:17000776,
CC ECO:0000269|PubMed:20830743}.
CC -!- SUBUNIT: Homohexamer (Potential). Interacts with SNX6, HDAC1 and RELA.
CC Interacts with ARID4A. Identified in mSin3A corepressor complexes
CC together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, SUDS3, ARID4A, HDAC1
CC and HDAC2. Interacts with SPOP; this recruits the protein to a
CC ubiquitin ligase complex containing SPOP and CUL3.
CC {ECO:0000269|PubMed:14581478, ECO:0000269|PubMed:17000776,
CC ECO:0000269|PubMed:20830743, ECO:0000269|PubMed:21777593,
CC ECO:0000269|PubMed:22085717, ECO:0000305}.
CC -!- INTERACTION:
CC Q9HCU9; Q8NHQ1: CEP70; NbExp=4; IntAct=EBI-714781, EBI-739624;
CC Q9HCU9; O75190: DNAJB6; NbExp=2; IntAct=EBI-714781, EBI-1053164;
CC Q9HCU9; Q13547: HDAC1; NbExp=5; IntAct=EBI-714781, EBI-301834;
CC Q9HCU9; Q92769: HDAC2; NbExp=4; IntAct=EBI-714781, EBI-301821;
CC Q9HCU9; P56524: HDAC4; NbExp=2; IntAct=EBI-714781, EBI-308629;
CC Q9HCU9; Q9UQL6: HDAC5; NbExp=2; IntAct=EBI-714781, EBI-715576;
CC Q9HCU9; Q9UBN7: HDAC6; NbExp=2; IntAct=EBI-714781, EBI-301697;
CC Q9HCU9; Q96EZ8: MCRS1; NbExp=3; IntAct=EBI-714781, EBI-348259;
CC Q9HCU9; Q13287: NMI; NbExp=7; IntAct=EBI-714781, EBI-372942;
CC Q9HCU9; Q969G3: SMARCE1; NbExp=3; IntAct=EBI-714781, EBI-455078;
CC Q9HCU9; Q9H7L9: SUDS3; NbExp=2; IntAct=EBI-714781, EBI-540496;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Predominantly nuclear.
CC -!- TISSUE SPECIFICITY: Expression levels are higher in term placentas than
CC in early placentas. Low levels of expression observed in normal
CC pregnancies and in molar pregnancies. {ECO:0000269|PubMed:12414911}.
CC -!- DOMAIN: Contains an N-terminal anti-parallel coiled coil formed by two
CC BRMS1 chains; this region can form homohexamers.
CC -!- PTM: Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3
CC ubiquitin-protein ligase complex containing SPOP, leading to
CC proteasomal degradation. {ECO:0000269|PubMed:22085717}.
CC -!- SIMILARITY: Belongs to the BRMS1 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BRMS1ID841ch11q13.html";
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DR EMBL; AF159141; AAG00075.1; -; mRNA.
DR EMBL; AF281036; AAK69131.1; -; Genomic_DNA.
DR EMBL; CR457173; CAG33454.1; -; mRNA.
DR EMBL; AK313773; BAG36511.1; -; mRNA.
DR EMBL; BC009834; AAH09834.1; -; mRNA.
DR CCDS; CCDS8135.1; -.
DR RefSeq; NP_056214.1; NM_015399.3.
DR PDB; 2XUS; X-ray; 1.91 A; A/B=51-98.
DR PDB; 4AUV; X-ray; 2.00 A; A/B/C/D/E/F/G/H=51-84.
DR PDBsum; 2XUS; -.
DR PDBsum; 4AUV; -.
DR AlphaFoldDB; Q9HCU9; -.
DR SMR; Q9HCU9; -.
DR BioGRID; 117379; 119.
DR ComplexPortal; CPX-3321; SIN3A histone deacetylase complex.
DR ComplexPortal; CPX-3322; SIN3B histone deacetylase complex.
DR ComplexPortal; CPX-3323; SIN3A histone deacetylase complex, ES cell-specific variant.
DR CORUM; Q9HCU9; -.
DR DIP; DIP-24250N; -.
DR IntAct; Q9HCU9; 53.
DR MINT; Q9HCU9; -.
DR STRING; 9606.ENSP00000396052; -.
DR iPTMnet; Q9HCU9; -.
DR PhosphoSitePlus; Q9HCU9; -.
DR BioMuta; BRMS1; -.
DR DMDM; 18202959; -.
DR EPD; Q9HCU9; -.
DR jPOST; Q9HCU9; -.
DR MassIVE; Q9HCU9; -.
DR MaxQB; Q9HCU9; -.
DR PaxDb; Q9HCU9; -.
DR PeptideAtlas; Q9HCU9; -.
DR PRIDE; Q9HCU9; -.
DR ProteomicsDB; 81803; -.
DR Antibodypedia; 4414; 303 antibodies from 32 providers.
DR DNASU; 25855; -.
DR Ensembl; ENST00000359957.8; ENSP00000353042.3; ENSG00000174744.14.
DR GeneID; 25855; -.
DR KEGG; hsa:25855; -.
DR MANE-Select; ENST00000359957.8; ENSP00000353042.3; NM_015399.4; NP_056214.1.
DR UCSC; uc001ohp.2; human.
DR CTD; 25855; -.
DR DisGeNET; 25855; -.
DR GeneCards; BRMS1; -.
DR HGNC; HGNC:17262; BRMS1.
DR HPA; ENSG00000174744; Low tissue specificity.
DR MIM; 606259; gene.
DR neXtProt; NX_Q9HCU9; -.
DR OpenTargets; ENSG00000174744; -.
DR PharmGKB; PA164741342; -.
DR VEuPathDB; HostDB:ENSG00000174744; -.
DR eggNOG; KOG4466; Eukaryota.
DR GeneTree; ENSGT00940000161779; -.
DR InParanoid; Q9HCU9; -.
DR OMA; SEKHMAV; -.
DR OrthoDB; 1456563at2759; -.
DR PhylomeDB; Q9HCU9; -.
DR PathwayCommons; Q9HCU9; -.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR SignaLink; Q9HCU9; -.
DR SIGNOR; Q9HCU9; -.
DR BioGRID-ORCS; 25855; 82 hits in 1084 CRISPR screens.
DR ChiTaRS; BRMS1; human.
DR EvolutionaryTrace; Q9HCU9; -.
DR GeneWiki; BRMS1; -.
DR GenomeRNAi; 25855; -.
DR Pharos; Q9HCU9; Tbio.
DR PRO; PR:Q9HCU9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9HCU9; protein.
DR Bgee; ENSG00000174744; Expressed in granulocyte and 165 other tissues.
DR ExpressionAtlas; Q9HCU9; baseline and differential.
DR Genevisible; Q9HCU9; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016580; C:Sin3 complex; IC:ComplexPortal.
DR GO; GO:0070822; C:Sin3-type complex; IBA:GO_Central.
DR GO; GO:0042826; F:histone deacetylase binding; IBA:GO_Central.
DR GO; GO:0051059; F:NF-kappaB binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0016575; P:histone deacetylation; IBA:GO_Central.
DR GO; GO:0030336; P:negative regulation of cell migration; IC:ComplexPortal.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1902455; P:negative regulation of stem cell population maintenance; IC:ComplexPortal.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IC:ComplexPortal.
DR GO; GO:2000210; P:positive regulation of anoikis; IMP:UniProtKB.
DR GO; GO:0090312; P:positive regulation of protein deacetylation; IDA:UniProtKB.
DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; IC:ComplexPortal.
DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB.
DR IDEAL; IID00501; -.
DR InterPro; IPR013907; Sds3.
DR PANTHER; PTHR21964; PTHR21964; 1.
DR Pfam; PF08598; Sds3; 1.
DR SMART; SM01401; Sds3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Coiled coil; Cytoplasm; Isopeptide bond; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Tumor suppressor; Ubl conjugation.
FT CHAIN 1..246
FT /note="Breast cancer metastasis-suppressor 1"
FT /id="PRO_0000064988"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 51..98
FT /evidence="ECO:0000269|PubMed:21777593"
FT COMPBIAS 15..49
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 184
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 242
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV4"
FT HELIX 55..93
FT /evidence="ECO:0007829|PDB:2XUS"
SQ SEQUENCE 246 AA; 28461 MW; 89FB59FB96ECD4DB CRC64;
MPVQPPSKDT EEMEAEGDSA AEMNGEEEES EEERSGSQTE SEEESSEMDD EDYERRRSEC
VSEMLDLEKQ FSELKEKLFR ERLSQLRLRL EEVGAERAPE YTEPLGGLQR SLKIRIQVAG
IYKGFCLDVI RNKYECELQG AKQHLESEKL LLYDTLQGEL QERIQRLEED RQSLDLSSEW
WDDKLHARGS SRSWDSLPPS KRKKAPLVSG PYIVYMLQEI DILEDWTAIK KARAAVSPQK
RKSDGP
