Q9HCU9 (BRMS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Breast cancer metastasis-suppressor 1

Gene names

Name:

BRMS1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	246 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma. Ref.7 Ref.8 Ref.9
Subunit structure	Homohexamer Potential. Interacts with SNX6, HDAC1 and RELA. Interacts with ARID4A. Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, SUDS3, ARID4A, HDAC1 and HDAC2. Interacts with SPOP; this recruits the protein to a ubiquitin ligase complex containing SPOP and CUL3. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Subcellular location	Nucleus. Cytoplasm. Note: Predominantly nuclear. Ref.8 Ref.9 Ref.10
Tissue specificity	Expression levels are higher in term placentas than in early placentas. Low levels of expression observed in normal pregnancies and in molar pregnancies. Ref.6
Domain	Contains an N-terminal anti-parallel coiled coil formed by two BRMS1 chains; this region can form homohexamers. Ref.11
Post-translational modification	Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing SPOP, leading to proteasomal degradation. Ref.10
Sequence similarities	Belongs to the BRMS1 family.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Disease	Tumor suppressor
Domain	Coiled coil
Molecular function	Repressor
PTM	Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.8. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.9. Source: UniProtKB positive regulation of anoikis Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of protein deacetylation Inferred from direct assay Ref.8. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay Ref.8Ref.9. Source: UniProtKB
Molecular_function	NF-kappaB binding Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DNAJB6	O75190	2	EBI-714781,EBI-1053164
HDAC1	Q13547	3	EBI-714781,EBI-301834
HDAC2	Q92769	3	EBI-714781,EBI-301821
HDAC4	P56524	2	EBI-714781,EBI-308629
HDAC5	Q9UQL6	2	EBI-714781,EBI-715576
HDAC6	Q9UBN7	2	EBI-714781,EBI-301697
NMI	Q13287	2	EBI-714781,EBI-372942
SMARCE1	Q969G3	2	EBI-714781,EBI-455078
SUDS3	Q9H7L9	2	EBI-714781,EBI-540496

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 246

246

Breast cancer metastasis-suppressor 1

PRO_0000064988

Regions

Coiled coil

51 – 98

48

Ref.11

Secondary structure

1

.

.

.

246

Helix Strand Turn

Details...

Helix

55 – 93

39

Sequences

	Sequence		Length	Mass (Da)
	Q9HCU9 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 89FB59FB96ECD4DB	FASTA	246	28,461
	10 20 30 40 50 60 MPVQPPSKDT EEMEAEGDSA AEMNGEEEES EEERSGSQTE SEEESSEMDD EDYERRRSEC 70 80 90 100 110 120 VSEMLDLEKQ FSELKEKLFR ERLSQLRLRL EEVGAERAPE YTEPLGGLQR SLKIRIQVAG 130 140 150 160 170 180 IYKGFCLDVI RNKYECELQG AKQHLESEKL LLYDTLQGEL QERIQRLEED RQSLDLSSEW 190 200 210 220 230 240 WDDKLHARGS SRSWDSLPPS KRKKAPLVSG PYIVYMLQEI DILEDWTAIK KARAAVSPQK RKSDGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13." Seraj M.J., Samant R.S., Verderame M.F., Welch D.R. Cancer Res. 60:2764-2769(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	"Genomic structure and chromosomal localization of the breast metastasis suppressor gene, BRMS1." Welch D.R., Samant R.S., Debies M.T., Seraj M.J., Verderame M.F. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells." Janneau J.-L., Maldonado-Estrada J., Tachdjian G., Miran I., Motte N., Saulnier P., Sabourin J.-C., Cote J.-F., Simon B., Frydman R., Chaouat G., Bellet D. J. Clin. Endocrinol. Metab. 87:5336-5339(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, POSSIBLE INVOLVEMENT IN INVASION/MIGRATION OF TROPHOBLAST CELLS.
[7]	"Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription." Meehan W.J., Samant R.S., Hopper J.E., Carrozza M.J., Shevde L.A., Workman J.L., Eckert K.A., Verderame M.F., Welch D.R. J. Biol. Chem. 279:1562-1569(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ARID4A, IDENTIFICATION IN A COMPLEX WITH SIN3A; SIN3B; HDAC1; HDAC2; SAP30; SUDS3; RBBP4 AND RBBP7.
[8]	"Breast cancer metastasis suppressor 1 functions as a corepressor by enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and promoting apoptosis." Liu Y., Smith P.W., Jones D.R. Mol. Cell. Biol. 26:8683-8696(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH HDAC1 AND RELA.
[9]	"Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression." Rivera J., Megias D., Bravo J. J. Cell. Biochem. 111:1464-1472(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SNX6.
[10]	"Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3-SPOP E3 ubiquitin ligase complex." Kim B., Nam H.J., Pyo K.E., Jang M.J., Kim I.S., Kim D., Boo K., Lee S.H., Yoon J.B., Baek S.H., Kim J.H. Biochem. Biophys. Res. Commun. 415:720-726(2011) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, SUBCELLULAR LOCATION, INTERACTION WITH SPOP, IDENTIFICATION IN A COMPLEX WITH CUL3 AND SPOP.
[11]	"The structure of BRMS1 nuclear export signal and SNX6 interacting region reveals a hexamer formed by antiparallel coiled coils." Spinola-Amilibia M., Rivera J., Ortiz-Lombardia M., Romero A., Neira J.L., Bravo J. J. Mol. Biol. 411:1114-1127(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 51-98, DOMAIN, COILED COIL, SUBUNIT.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF159141 mRNA. Translation: AAG00075.1.
AF281036 Genomic DNA. Translation: AAK69131.1.
CR457173 mRNA. Translation: CAG33454.1.
AK313773 mRNA. Translation: BAG36511.1.
BC009834 mRNA. Translation: AAH09834.1.

IPI

IPI00018017.

RefSeq

NP_056214.1. NM_015399.3.

UniGene

Hs.100426.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2XUS	X-ray	1.91	A/B	51-98	[»]

ProteinModelPortal

Q9HCU9.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24250N.

IntAct

Q9HCU9. 21 interactions.

MINT

MINT-1389009.

STRING

9606.ENSP00000396052.

PTM databases

PhosphoSite

Q9HCU9.

Polymorphism databases

DMDM

18202959.

Proteomic databases

PaxDb

Q9HCU9.

PRIDE

Q9HCU9.

Protocols and materials databases

DNASU

25855.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359957; ENSP00000353042; ENSG00000174744.

GeneID

25855.

KEGG

hsa:25855.

UCSC

uc001oho.1. human.

Organism-specific databases

CTD

25855.

GeneCards

GC11M066104.

HGNC

HGNC:17262. BRMS1.

HPA

HPA019637.

MIM

606259. gene.

neXtProt

NX_Q9HCU9.

PharmGKB

PA164741342.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG260250.

HOGENOM

HOG000007483.

HOVERGEN

HBG050734.

InParanoid

Q9HCU9.

OrthoDB

EOG4T784C.

PhylomeDB

Q9HCU9.

Gene expression databases

ArrayExpress

Q9HCU9.

Bgee

Q9HCU9.

CleanEx

HS_BRMS1.

Genevestigator

Q9HCU9.

GermOnline

ENSG00000174744. Homo sapiens.

Family and domain databases

InterPro

IPR013907. Sds3.
[Graphical view]

Pfam

PF08598. Sds3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9HCU9.

GenomeRNAi

25855.

NextBio

47213.

SOURCE

Search...

Entry information

Entry name

BRMS1_HUMAN

Accession

Primary (citable) accession number: Q9HCU9
Secondary accession number(s): Q6IAI2

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.