Q5U5Q9 (UIMC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
BRCA1-A complex subunit RAP80

Alternative name(s):
Receptor-associated protein 80
Ubiquitin interaction motif-containing protein 1

Gene names

Name:	Uimc1
Synonyms:	Rap80, Rip110, Rxrip110

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	727 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1 By similarity.
Subunit structure	Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with FAM175A/Abraxas. Interacts with ESR1 and UBE2I By similarity. Interacts with NR6A1 and TSP57. Ref.3 Ref.4
Subcellular location	Nucleus By similarity. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs) By similarity.
Domain	The UIM-linker region between the 2 UIM repeats determines the selectivity for 'Lys-63'-linked ubiquitin. The length of the linker is important. The linker reduces the flexibility between the UIM repeats and promotes high-affinity and linkage-selective interactions By similarity. The Abraxas-interacting region (AIR) mediates the interaction with FAM175A/Abraxas By similarity.
Post-translational modification	Sumoylated By similarity. Phosphorylated upon DNA damage by ATM or ATR By similarity.
Sequence similarities	Belongs to the RAP80 family. Contains 2 UIM (ubiquitin-interacting motif) repeats.
Sequence caution	The sequence AAH37092.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	DNA damage DNA repair Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Chromatin regulator
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G2 DNA damage checkpoint Inferred from sequence or structural similarity. Source: UniProtKB double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB histone H2A K63-linked deubiquitination Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity PubMed 12080054. Source: HGNC positive regulation of DNA repair Inferred from sequence or structural similarity. Source: UniProtKB response to ionizing radiation Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	BRCA1-A complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	K63-linked polyubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB histone binding Inferred from sequence or structural similarity. Source: UniProtKB retinoid X receptor binding Inferred from direct assay Ref.3. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q5U5Q9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q5U5Q9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     401-406: SSQGLF → HCSFDQ
     407-727: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q5U5Q9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     120-400: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 727

727

BRCA1-A complex subunit RAP80

PRO_0000097548

Regions

Repeat

79 – 96

18

UIM 1

Repeat

104 – 124

21

UIM 2

Region

1 – 101

101

Necessary for transcriptional repression By similarity

Region

97 – 103

7

UIM-linker

Region

100 – 200

101

Necessary for interaction with NR6A1 N-terminus By similarity

Region

270 – 400

131

AIR

Region

400 – 508

109

Necessary for interaction with NR6A1 C-terminus By similarity

Region

513 – 590

78

Zinc-finger-like region

Motif

60 – 78

19

LR motif

Compositional bias

81 – 108

28

Glu-rich

Amino acid modifications

Modified residue

44

1

Phosphoserine By similarity

Modified residue

46

1

Phosphoserine By similarity

Modified residue

140

1

Phosphoserine By similarity

Modified residue

205

1

Phosphoserine By similarity

Modified residue

402

1

Phosphoserine By similarity

Modified residue

637

1

Phosphoserine By similarity

Modified residue

665

1

Phosphoserine By similarity

Modified residue

689

1

Phosphoserine By similarity

Natural variations

Alternative sequence

120 – 400

281

Missing in isoform 3.

VSP_037266

Alternative sequence

401 – 406

6

SSQGLF → HCSFDQ in isoform 2.

VSP_037267

Alternative sequence

407 – 727

321

Missing in isoform 2.

VSP_037268

Experimental info

Sequence conflict

377

1

Q → R in BAC38875. Ref.1

Sequence conflict

450

1

I → T in BAC35106. Ref.1

Sequence conflict

450

1

I → T in BAC38875. Ref.1

Sequence conflict

450

1

I → T in BAE36094. Ref.1

Sequence conflict

554

1

D → G in AAH40808. Ref.2

Sequence conflict

722

1

G → E in AAC52167. Ref.3

Secondary structure

1

.

.

.

727

Helix Strand Turn

Details...

Helix

81 – 119

39

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 5, 2009. Version 2. Checksum: B753BF61180D63ED	FASTA	727	81,478
	10 20 30 40 50 60 MPRRKKKIKE ASESQNLEKK DLETSSCVSI KKKRRLEDLL IVISDSDGEE TKEENGLQKT 70 80 90 100 110 120 KTKQSNRSKC LAKRKVAHMS EEEQFALALK MSEQEAREVN NQEEKEEELL RKAIAESLNS 130 140 150 160 170 180 CWSSAASATR SRPLAAELSS HSHQENTKDS GTTEGVWQLV PPSLCKGSHV SQGNEAEQRK 190 200 210 220 230 240 EPWDHNENTE EEPVSGSSGS WDQSSQPVFE NENVKCFDRC TGHLAEHTQC GKPQESTGSG 250 260 270 280 290 300 YAFSKAVQGR GDTSRQCLPI PADTKGLQDT GGTVHYYWGI PFCPAGVDPN QYTNVILCQL 310 320 330 340 350 360 EVYQKSLKMA QRQLVKKRGF GEPVLPRPPF LIQNECGQED QTSDKNEGIS EDMGDEAKEE 370 380 390 400 410 420 RQESRASVWH SETKDFQKSP IKSLKQKLLL EEEPTTSRGQ SSQGLFVEET SEEGLKSSEG 430 440 450 460 470 480 DNSVPTTQSI AALTSKRSLV LMPESSAEEI TVCPETQLSF LEPLDLNRED SPDSRELPIE 490 500 510 520 530 540 VRMAVGDKQV ANREDCMKEN PPPAVSSSTR VSCPLCNQDF PPTKIEQHAM YCNGLMEQET 550 560 570 580 590 600 VLTRRRREAK NKSDGRTAAQ PALDANRKEK CYLCKSLVPL GEYQCHVEAC LQLAKVDRED 610 620 630 640 650 660 GIEGTRRPRV CAPVEGKQQQ RLKKSKDKGH SQGRLLSLLE QSEHRTTGVE KKPKYSEVRT 670 680 690 700 710 720 FRMPSPEVEE ASCSREMQST LSQLNLNESP IKSFVPVSEA TNCLVDFKEQ FAFRSRTKSG RGRRRKS
	Isoform 2 [UniParc]. Checksum: 904F4FDD0F27ECB0	FASTA	406	45,575
	10 20 30 40 50 60 MPRRKKKIKE ASESQNLEKK DLETSSCVSI KKKRRLEDLL IVISDSDGEE TKEENGLQKT 70 80 90 100 110 120 KTKQSNRSKC LAKRKVAHMS EEEQFALALK MSEQEAREVN NQEEKEEELL RKAIAESLNS 130 140 150 160 170 180 CWSSAASATR SRPLAAELSS HSHQENTKDS GTTEGVWQLV PPSLCKGSHV SQGNEAEQRK 190 200 210 220 230 240 EPWDHNENTE EEPVSGSSGS WDQSSQPVFE NENVKCFDRC TGHLAEHTQC GKPQESTGSG 250 260 270 280 290 300 YAFSKAVQGR GDTSRQCLPI PADTKGLQDT GGTVHYYWGI PFCPAGVDPN QYTNVILCQL 310 320 330 340 350 360 EVYQKSLKMA QRQLVKKRGF GEPVLPRPPF LIQNECGQED QTSDKNEGIS EDMGDEAKEE 370 380 390 400 RQESRASVWH SETKDFQKSP IKSLKQKLLL EEEPTTSRGQ HCSFDQ
	Isoform 3 [UniParc]. Checksum: 4E76F9B20CF84D80	FASTA	446	50,382
	10 20 30 40 50 60 MPRRKKKIKE ASESQNLEKK DLETSSCVSI KKKRRLEDLL IVISDSDGEE TKEENGLQKT 70 80 90 100 110 120 KTKQSNRSKC LAKRKVAHMS EEEQFALALK MSEQEAREVN NQEEKEEELL RKAIAESLNS 130 140 150 160 170 180 SQGLFVEETS EEGLKSSEGD NSVPTTQSIA ALTSKRSLVL MPESSAEEIT VCPETQLSFL 190 200 210 220 230 240 EPLDLNREDS PDSRELPIEV RMAVGDKQVA NREDCMKENP PPAVSSSTRV SCPLCNQDFP 250 260 270 280 290 300 PTKIEQHAMY CNGLMEQETV LTRRRREAKN KSDGRTAAQP ALDANRKEKC YLCKSLVPLG 310 320 330 340 350 360 EYQCHVEACL QLAKVDREDG IEGTRRPRVC APVEGKQQQR LKKSKDKGHS QGRLLSLLEQ 370 380 390 400 410 420 SEHRTTGVEK KPKYSEVRTF RMPSPEVEEA SCSREMQSTL SQLNLNESPI KSFVPVSEAT 430 440 NCLVDFKEQF AFRSRTKSGR GRRRKS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Strain: C57BL/6J. Tissue: Extraembryonic tissue, Kidney, Placenta and Thymus.
[2]	"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] (ISOFORMS 1 AND 2). Strain: C57BL/6J and FVB/N. Tissue: Mammary cancer and Mammary tumor.
[3]	"Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors." Seol W., Choi H.S., Moore D.D. Mol. Endocrinol. 9:72-85(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 148-727 (ISOFORM 1), INTERACTION WITH NR6A1. Tissue: Liver.
[4]	"Tsp57: a novel gene induced during a specific stage of spermatogenesis." Kim Y.-S., Nakanishi G., Oudes A.J., Kim K.H., Wang H., Kilpatrick D.L., Jetten A.M. Biol. Reprod. 70:106-113(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TSP57.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AK052704 mRNA. Translation: BAC35106.1.
AK083342 mRNA. Translation: BAC38875.1.
AK160926 mRNA. Translation: BAE36094.1.
BC037092 mRNA. Translation: AAH37092.1. Different initiation.
BC040808 mRNA. Translation: AAH40808.1.
U22015 mRNA. Translation: AAC52167.1.

IPI

IPI00169849.
IPI00652794.
IPI00874501.

RefSeq

NP_035437.1. NM_011307.2.

UniGene

Mm.259301.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3A1Q	X-ray	2.20	C/F	80-120	[»]

ProteinModelPortal

Q5U5Q9.

SMR

Q5U5Q9. Positions 80-120.

ModBase

Search...

PTM databases

PhosphoSite

Q5U5Q9.

Proteomic databases

PaxDb

Q5U5Q9.

PRIDE

Q5U5Q9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000026997; ENSMUSP00000026997; ENSMUSG00000025878.
ENSMUST00000099496; ENSMUSP00000097095; ENSMUSG00000025878.

GeneID

20184.

KEGG

mmu:20184.

UCSC

uc007qpv.1. mouse.
uc007qpw.1. mouse.

Organism-specific databases

CTD

51720.

MGI

MGI:103185. Uimc1.

Phylogenomic databases

eggNOG

NOG72551.

GeneTree

ENSGT00390000007635.

HOGENOM

HOG000154772.

HOVERGEN

HBG056783.

InParanoid

Q8C3Z8.

Gene expression databases

ArrayExpress

Q5U5Q9.

Bgee

Q5U5Q9.

CleanEx

MM_UIMC1.

Genevestigator

Q5U5Q9.

GermOnline

ENSMUSG00000025878. Mus musculus.

Family and domain databases

InterPro

IPR003903. Ubiquitin-int_motif.
[Graphical view]

SMART

SM00726. UIM. 2 hits.
[Graphical view]

PROSITE

PS50330. UIM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q5U5Q9.

NextBio

297717.

SOURCE

Search...

Entry information

Entry name

UIMC1_MOUSE

Accession

Primary (citable) accession number: Q5U5Q9
Secondary accession number(s): Q3TU77 , Q60811, Q8C3Z8, Q8C719, Q8K1X7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	May 5, 2009
Last modified:	May 1, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program