Full text data of UIMC1
UIMC1
(RAP80, RXRIP110)
[Confidence: low (only semi-automatic identification from reviews)]
BRCA1-A complex subunit RAP80 (Receptor-associated protein 80; Retinoid X receptor-interacting protein 110; Ubiquitin interaction motif-containing protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
BRCA1-A complex subunit RAP80 (Receptor-associated protein 80; Retinoid X receptor-interacting protein 110; Ubiquitin interaction motif-containing protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96RL1
ID UIMC1_HUMAN Reviewed; 719 AA.
AC Q96RL1; A8MSA1; B3KMZ1; B4E3N2; Q5XKQ1; Q7Z3W7; Q8N5B9; Q9BZR1;
read moreAC Q9BZR5; Q9UHX7;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 2.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=BRCA1-A complex subunit RAP80;
DE AltName: Full=Receptor-associated protein 80;
DE AltName: Full=Retinoid X receptor-interacting protein 110;
DE AltName: Full=Ubiquitin interaction motif-containing protein 1;
GN Name=UIMC1; Synonyms=RAP80, RXRIP110;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN TRANSCRIPTIONAL
RP REPRESSION, INTERACTION WITH NR6A1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12080054; DOI=10.1074/jbc.M203475200;
RA Yan Z., Kim Y.-S., Jetten A.M.;
RT "RAP80: a novel nuclear protein that interacts with the retinoid-
RT related testis-associated receptor.";
RL J. Biol. Chem. 277:32379-32388(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Hypothalamus;
RA Peng Y., Gu Y., Gu J., Huang Q., Fu S., Wu T., Dong H., Jin W., Fu G.,
RA Han Z., Chen Z., Wang Y.;
RT "A novel gene expressed in the human hypothalamus.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Hypothalamus;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Teratocarcinoma, and Uterus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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] (ISOFORM 1).
RC TISSUE=Esophageal carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ovary, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-46, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [9]
RP SUMOYLATION, INTERACTION WITH UBE2I, AND MUTAGENESIS OF LYS-9; LYS-19;
RP LYS-31; LYS-52 AND LYS-61.
RX PubMed=17698038; DOI=10.1016/j.bbrc.2007.07.158;
RA Yan J., Yang X.-P., Kim Y.-S., Joo J.H., Jetten A.M.;
RT "RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel
RT target for sumoylation.";
RL Biochem. Biophys. Res. Commun. 362:132-138(2007).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ALA-88 AND ALA-113, AND
RP PHOSPHORYLATION AT SER-205 AND SER-402.
RX PubMed=17621610; DOI=10.1158/0008-5472.CAN-07-0924;
RA Yan J., Kim Y.S., Yang X.-P., Li L.-P., Liao G., Xia F., Jetten A.M.;
RT "The ubiquitin-interacting motif containing protein RAP80 interacts
RT with BRCA1 and functions in DNA damage repair response.";
RL Cancer Res. 67:6647-6656(2007).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FAM175A.
RX PubMed=17643121; DOI=10.1038/nsmb1279;
RA Liu Z., Wu J., Yu X.;
RT "CCDC98 targets BRCA1 to DNA damage sites.";
RL Nat. Struct. Mol. Biol. 14:716-720(2007).
RN [12]
RP INTERACTION WITH FAM175A.
RX PubMed=17643122; DOI=10.1038/nsmb1277;
RA Kim H., Huang J., Chen J.;
RT "CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA
RT damage response.";
RL Nat. Struct. Mol. Biol. 14:710-715(2007).
RN [13]
RP INTERACTION WITH ESR1.
RX PubMed=17311814; DOI=10.1093/nar/gkl1112;
RA Yan J., Kim Y.S., Yang X.-P., Albers M., Koegl M., Jetten A.M.;
RT "Ubiquitin-interaction motifs of RAP80 are critical in its regulation
RT of estrogen receptor alpha.";
RL Nucleic Acids Res. 35:1673-1686(2007).
RN [14]
RP INTERACTION WITH FAM175A.
RX PubMed=18077395; DOI=10.1073/pnas.0710061104;
RA Wang B., Elledge S.J.;
RT "Ubc13/Rnf8 ubiquitin ligases control foci formation of the
RT Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20759-20763(2007).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140; SER-402
RP AND SER-419, AND MUTAGENESIS OF ALA-88; SER-92; ALA-113 AND SER-117.
RX PubMed=17525340; DOI=10.1126/science.1139476;
RA Wang B., Matsuoka S., Ballif B.A., Zhang D., Smogorzewska A., Giyi S.,
RA Elledge S.J.;
RT "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA
RT damage response.";
RL Science 316:1194-1198(2007).
RN [17]
RP FUNCTION, IDENTIFICATION IN THE BRCA1-A COMPLEX, SUBCELLULAR LOCATION,
RP UBIQUITIN-BINDING, AND PHOSPHORYLATION AT SER-101.
RX PubMed=17525341; DOI=10.1126/science.1139516;
RA Sobhian B., Shao G., Lilli D.R., Culhane A.C., Moreau L.A., Xia B.,
RA Livingston D.M., Greenberg R.A.;
RT "RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage
RT sites.";
RL Science 316:1198-1202(2007).
RN [18]
RP FUNCTION, IDENTIFICATION IN THE BRCA1-A COMPLEX, SUBCELLULAR LOCATION,
RP UBIQUITIN-BINDING, PHOSPHORYLATION AT SER-101, AND MUTAGENESIS OF
RP ALA-88; SER-92; ALA-113 AND SER-117.
RX PubMed=17525342; DOI=10.1126/science.1139621;
RA Kim H., Chen J., Yu X.;
RT "Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage
RT response.";
RL Science 316:1202-1205(2007).
RN [19]
RP PHOSPHORYLATION AT SER-205, AND MUTAGENESIS OF SER-205.
RX PubMed=18519686; DOI=10.1158/0008-5472.CAN-07-5950;
RA Yan J., Yang X.-P., Kim Y.-S., Jetten A.M.;
RT "RAP80 responds to DNA damage induced by both ionizing radiation and
RT UV irradiation and is phosphorylated at Ser 205.";
RL Cancer Res. 68:4269-4276(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-627; SER-653 AND
RP SER-677, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261746; DOI=10.1101/gad.1739609;
RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N.,
RA Wang Y., Greenberg R.A.;
RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA
RT double-strand breaks.";
RL Genes Dev. 23:740-754(2009).
RN [22]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX, UBIQUITIN-BINDING, AND
RP INTERACTION WITH FAM175A.
RX PubMed=19261749; DOI=10.1101/gad.1770309;
RA Wang B., Hurov K., Hofmann K., Elledge S.J.;
RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage
RT resistance and checkpoint control.";
RL Genes Dev. 23:729-739(2009).
RN [23]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE
RP BRCA1-A COMPLEX, AND INTERACTION WITH FAM175A.
RX PubMed=19261748; DOI=10.1101/gad.1770609;
RA Feng L., Huang J., Chen J.;
RT "MERIT40 facilitates BRCA1 localization and DNA damage repair.";
RL Genes Dev. 23:719-728(2009).
RN [24]
RP UBIQUITIN-BINDING, DOMAIN UIM-LINKER, AND MUTAGENESIS OF
RP 97-ARG--GLU-103 AND SER-101.
RX PubMed=19328070; DOI=10.1016/j.molcel.2009.02.011;
RA Sims J.J., Cohen R.E.;
RT "Linkage-specific avidity defines the lysine 63-linked polyubiquitin-
RT binding preference of rap80.";
RL Mol. Cell 33:775-783(2009).
RN [25]
RP FUNCTION, AND MUTAGENESIS OF CYS-508.
RX PubMed=19015238; DOI=10.1128/MCB.01302-08;
RA Wu J., Huen M.S.Y., Lu L.-Y., Ye L., Dou Y., Ljungman M., Chen J.,
RA Yu X.;
RT "Histone ubiquitination associates with BRCA1-dependent DNA damage
RT response.";
RL Mol. Cell. Biol. 29:849-860(2009).
RN [26]
RP FUNCTION.
RX PubMed=19202061; DOI=10.1073/pnas.0807485106;
RA Shao G., Lilli D.R., Patterson-Fortin J., Coleman K.A.,
RA Morrissey D.E., Greenberg R.A.;
RT "The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-
RT Ubc13-dependent ubiquitination events at DNA double strand breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-46, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-46 AND SER-677,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-677, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP UBIQUITIN-BINDING, AND LR MOTIF.
RX PubMed=22742833; DOI=10.1016/j.molcel.2012.05.045;
RA Panier S., Ichijima Y., Fradet-Turcotte A., Leung C.C., Kaustov L.,
RA Arrowsmith C.H., Durocher D.;
RT "Tandem protein interaction modules organize the ubiquitin-dependent
RT response to DNA double-strand breaks.";
RL Mol. Cell 47:383-395(2012).
RN [31]
RP VARIANTS TRP-15; THR-353; LEU-435 AND ARG-511.
RX PubMed=18695986; DOI=10.1007/s10549-008-0134-y;
RA Novak D.J., Sabbaghian N., Maillet P., Chappuis P.O., Foulkes W.D.,
RA Tischkowitz M.;
RT "Analysis of the genes coding for the BRCA1-interacting proteins,
RT RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic
RT breast cancer cases.";
RL Breast Cancer Res. Treat. 117:453-459(2009).
CC -!- FUNCTION: Ubiquitin-binding protein that specifically recognizes
CC and binds 'Lys-63'-linked ubiquitin. Plays a central role in the
CC BRCA1-A complex by specifically binding 'Lys-63'-linked
CC ubiquitinated histones H2A and H2AX at DNA lesions sites, leading
CC to target the BRCA1-BARD1 heterodimer to sites of DNA damage at
CC double-strand breaks (DSBs). The BRCA1-A complex also possesses
CC deubiquitinase activity that specifically removes 'Lys-63'-linked
CC ubiquitin on histones H2A and H2AX. Also weakly binds
CC monoubiquitin but with much less affinity than 'Lys-63'-linked
CC ubiquitin. May interact with monoubiquitinated histones H2A and
CC H2B; the relevance of such results is however unclear in vivo.
CC Does not bind Lys-48'-linked ubiquitin. May indirectly act as a
CC transcriptional repressor by inhibiting the interaction of NR6A1
CC with the corepressor NCOR1.
CC -!- SUBUNIT: Interacts with TSP57 (By similarity). Component of the
CC BRCA1-A complex, at least composed of the BRCA1, BARD1,
CC UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and
CC BABAM1/NBA1. In the BRCA1-A complex, interacts directly with
CC FAM175A/Abraxas. Interacts with ESR1, NR6A1 and UBE2I.
CC -!- INTERACTION:
CC P54132:BLM; NbExp=2; IntAct=EBI-725300, EBI-621372;
CC P38398:BRCA1; NbExp=9; IntAct=EBI-725300, EBI-349905;
CC Q6UWZ7:FAM175A; NbExp=9; IntAct=EBI-725300, EBI-1263451;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Localizes at sites of DNA
CC damage at double-strand breaks (DSBs).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q96RL1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RL1-2; Sequence=VSP_012935;
CC Name=3; Synonyms=XHRIP110;
CC IsoId=Q96RL1-3; Sequence=VSP_012932;
CC Name=4; Synonyms=X2HRIP110;
CC IsoId=Q96RL1-4; Sequence=VSP_012933, VSP_012934;
CC Name=5;
CC IsoId=Q96RL1-5; Sequence=VSP_037264, VSP_037265;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in testis, ovary, thymus and heart.
CC Expressed in germ cells of the testis.
CC -!- DOMAIN: The UIM-linker region between the 2 UIM repeats determines
CC the selectivity for 'Lys-63'-linked ubiquitin. The length of the
CC linker is important. The linker reduces the flexibility between
CC the UIM repeats and promotes high-affinity and linkage-selective
CC interactions.
CC -!- DOMAIN: The Abraxas-interacting region (AIR) mediates the
CC interaction with FAM175A/Abraxas.
CC -!- PTM: Sumoylated.
CC -!- PTM: Phosphorylated upon DNA damage by ATM or ATR.
CC -!- SIMILARITY: Belongs to the RAP80 family.
CC -!- SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06078.1; Type=Erroneous termination; Positions=386; Note=Translated as Glu;
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DR EMBL; AF349313; AAK61871.1; -; mRNA.
DR EMBL; AF113538; AAF14875.1; -; mRNA.
DR EMBL; AF284749; AAG59851.1; -; mRNA.
DR EMBL; AF284753; AAG59855.1; -; mRNA.
DR EMBL; AK023044; BAG51153.1; -; mRNA.
DR EMBL; AK304794; BAG65544.1; -; mRNA.
DR EMBL; BX537376; CAD97618.1; -; mRNA.
DR EMBL; AC027318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006078; AAH06078.1; ALT_TERM; mRNA.
DR EMBL; BC032561; AAH32561.1; -; mRNA.
DR RefSeq; NP_001186226.1; NM_001199297.1.
DR RefSeq; NP_001186227.1; NM_001199298.1.
DR RefSeq; NP_057374.3; NM_016290.4.
DR RefSeq; XP_005265987.1; XM_005265930.1.
DR RefSeq; XP_005265993.1; XM_005265936.1.
DR UniGene; Hs.232721; -.
DR PDB; 2RR9; NMR; -; C=79-124.
DR PDBsum; 2RR9; -.
DR ProteinModelPortal; Q96RL1; -.
DR SMR; Q96RL1; 79-124.
DR DIP; DIP-29936N; -.
DR IntAct; Q96RL1; 46.
DR MINT; MINT-1197441; -.
DR PhosphoSite; Q96RL1; -.
DR DMDM; 60390957; -.
DR PaxDb; Q96RL1; -.
DR PRIDE; Q96RL1; -.
DR DNASU; 51720; -.
DR Ensembl; ENST00000377227; ENSP00000366434; ENSG00000087206.
DR Ensembl; ENST00000506128; ENSP00000427480; ENSG00000087206.
DR Ensembl; ENST00000511320; ENSP00000421926; ENSG00000087206.
DR GeneID; 51720; -.
DR KEGG; hsa:51720; -.
DR UCSC; uc021yil.1; human.
DR CTD; 51720; -.
DR GeneCards; GC05M176265; -.
DR H-InvDB; HIX0005450; -.
DR HGNC; HGNC:30298; UIMC1.
DR HPA; HPA037503; -.
DR HPA; HPA037504; -.
DR MIM; 609433; gene.
DR neXtProt; NX_Q96RL1; -.
DR PharmGKB; PA162408624; -.
DR eggNOG; NOG72551; -.
DR HOVERGEN; HBG056783; -.
DR OrthoDB; EOG74XS6K; -.
DR PhylomeDB; Q96RL1; -.
DR ChiTaRS; UIMC1; human.
DR EvolutionaryTrace; Q96RL1; -.
DR GeneWiki; UIMC1; -.
DR GenomeRNAi; 51720; -.
DR NextBio; 55772; -.
DR PRO; PR:Q96RL1; -.
DR ArrayExpress; Q96RL1; -.
DR Bgee; Q96RL1; -.
DR CleanEx; HS_UIMC1; -.
DR Genevestigator; Q96RL1; -.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin binding; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:HGNC.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR SMART; SM00726; UIM; 2.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator;
KW Complete proteome; DNA damage; DNA repair; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 719 BRCA1-A complex subunit RAP80.
FT /FTId=PRO_0000097547.
FT REPEAT 79 96 UIM 1.
FT REPEAT 104 124 UIM 2.
FT REGION 1 101 Necessary for transcriptional repression.
FT REGION 97 103 UIM-linker.
FT REGION 100 200 Necessary for interaction with NR6A1 N-
FT terminus.
FT REGION 270 400 AIR.
FT REGION 400 500 Necessary for interaction with NR6A1 C-
FT terminus.
FT REGION 505 582 Zinc-finger-like region.
FT MOTIF 60 78 LR motif.
FT COMPBIAS 81 108 Glu-rich.
FT MOD_RES 44 44 Phosphoserine.
FT MOD_RES 46 46 Phosphoserine.
FT MOD_RES 101 101 Phosphoserine.
FT MOD_RES 140 140 Phosphoserine.
FT MOD_RES 205 205 Phosphoserine.
FT MOD_RES 402 402 Phosphoserine.
FT MOD_RES 419 419 Phosphoserine.
FT MOD_RES 627 627 Phosphoserine.
FT MOD_RES 653 653 Phosphoserine.
FT MOD_RES 677 677 Phosphoserine.
FT VAR_SEQ 1 370 Missing (in isoform 4).
FT /FTId=VSP_012933.
FT VAR_SEQ 1 78 Missing (in isoform 3).
FT /FTId=VSP_012932.
FT VAR_SEQ 120 152 SCRPSDASATRSRPLATGPSSQSHQEKTTDSGL -> VNMP
FT CCKSLWRLISYIFDFCGVVVALGTSCSHL (in isoform
FT 5).
FT /FTId=VSP_037264.
FT VAR_SEQ 153 719 Missing (in isoform 5).
FT /FTId=VSP_037265.
FT VAR_SEQ 234 399 Missing (in isoform 2).
FT /FTId=VSP_012935.
FT VAR_SEQ 371 400 SKTKDFQESSIKSLKEKLLLEEEPTTSHGQ -> MLPLPDL
FT DLWPLDRLPSPIKRKPQTLGSLK (in isoform 4).
FT /FTId=VSP_012934.
FT VARIANT 15 15 R -> W (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs13167812).
FT /FTId=VAR_051469.
FT VARIANT 353 353 M -> T (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs143282828).
FT /FTId=VAR_055328.
FT VARIANT 435 435 P -> L (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs3733876).
FT /FTId=VAR_051470.
FT VARIANT 511 511 C -> R (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs13360277).
FT /FTId=VAR_051471.
FT VARIANT 596 596 G -> E (in dbSNP:rs10475633).
FT /FTId=VAR_051472.
FT MUTAGEN 9 9 K->A: Does not affect symoylation; when
FT associated with A-19; A-31; A-52 and A-
FT 61.
FT MUTAGEN 19 19 K->A: Does not affect symoylation; when
FT associated with A-9; A-31; A-52 and A-61.
FT MUTAGEN 31 31 K->A: Does not affect symoylation; when
FT associated with A-9; A-19; A-52 and A-61.
FT MUTAGEN 52 52 K->A: Does not affect symoylation; when
FT associated with A-9; A-19; A-31 and A-61.
FT MUTAGEN 61 61 K->A: Does not affect symoylation; when
FT associated with A-9; A-19; A-31 and A-52.
FT MUTAGEN 88 88 A->G,S: Impairs localization to DNA
FT damages sites; when associated with A-92;
FT S-113 and A-117.
FT MUTAGEN 92 92 S->A: Impairs localization to DNA damages
FT sites; when associated with S-88; S-113
FT and A-117.
FT MUTAGEN 97 103 REVNSQE->AA: Impairs the selectivity for
FT 'K-63'-linked ubiquitin.
FT MUTAGEN 97 103 REVNSQE->AAAAAAA: Increases the
FT selectivity for 'K-63'-linked ubiquitin.
FT MUTAGEN 97 103 REVNSQE->AAAAAAAAA: Impairs the
FT selectivity for 'K-63'-linked ubiquitin.
FT MUTAGEN 101 101 S->A,E: Slightly impairs the selectivity
FT for 'K-63'-linked ubiquitin.
FT MUTAGEN 113 113 A->G,S: Impairs ubiquitin-binding and
FT localization to DNA damages sites; when
FT associated with S-88; A-92 and A-117.
FT MUTAGEN 117 117 S->A: Impairs ubiquitin-binding and
FT localization to DNA damages sites; when
FT associated with S-88; A-92 and S-113.
FT MUTAGEN 205 205 S->G: Abolishes phosphorylation at this
FT position.
FT MUTAGEN 508 508 C->A: Abolishes interaction with histone
FT monoubiquitinated H2B without affecting
FT the interaction with H2A.
FT CONFLICT 187 187 E -> K (in Ref. 7; AAH06078).
FT CONFLICT 192 192 E -> G (in Ref. 4; BAG51153).
FT CONFLICT 247 247 V -> C (in Ref. 3; AAG59851).
FT CONFLICT 347 347 E -> G (in Ref. 1; AAK61871).
FT CONFLICT 518 518 E -> G (in Ref. 1; AAK61871).
FT CONFLICT 634 634 H -> R (in Ref. 3; AAG59855).
FT CONFLICT 638 638 D -> N (in Ref. 4; BAG51153).
FT CONFLICT 694 694 D -> V (in Ref. 3; AAG59855).
FT HELIX 82 119
SQ SEQUENCE 719 AA; 79727 MW; 56B7699E42395861 CRC64;
MPRRKKKVKE VSESRNLEKK DVETTSSVSV KRKRRLEDAF IVISDSDGEE PKEENGLQKT
KTKQSNRAKC LAKRKIAQMT EEEQFALALK MSEQEAREVN SQEEEEEELL RKAIAESLNS
CRPSDASATR SRPLATGPSS QSHQEKTTDS GLTEGIWQLV PPSLFKGSHI SQGNEAEERE
EPWDHTEKTE EEPVSGSSGS WDQSSQPVFE NVNVKSFDRC TGHSAEHTQC GKPQESTGRG
SAFLKAVQGS GDTSRHCLPT LADAKGLQDT GGTVNYFWGI PFCPDGVDPN QYTKVILCQL
EVYQKSLKMA QRQLLNKKGF GEPVLPRPPS LIQNECGQGE QASEKNECIS EDMGDEDKEE
RQESRASDWH SKTKDFQESS IKSLKEKLLL EEEPTTSHGQ SSQGIVEETS EEGNSVPASQ
SVAALTSKRS LVLMPESSAE EITVCPETQL SSSETFDLER EVSPGSRDIL DGVRIIMADK
EVGNKEDAEK EVAISTFSSS NQVSCPLCDQ CFPPTKIERH AMYCNGLMEE DTVLTRRQKE
AKTKSDSGTA AQTSLDIDKN EKCYLCKSLV PFREYQCHVD SCLQLAKADQ GDGPEGSGRA
CSTVEGKWQQ RLKNPKEKGH SEGRLLSFLE QSEHKTSDAD IKSSETGAFR VPSPGMEEAG
CSREMQSSFT RRDLNESPVK SFVSISEATD CLVDFKKQVT VQPGSRTRTK AGRGRRRKF
//
ID UIMC1_HUMAN Reviewed; 719 AA.
AC Q96RL1; A8MSA1; B3KMZ1; B4E3N2; Q5XKQ1; Q7Z3W7; Q8N5B9; Q9BZR1;
read moreAC Q9BZR5; Q9UHX7;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 2.
DT 22-JAN-2014, entry version 100.
DE RecName: Full=BRCA1-A complex subunit RAP80;
DE AltName: Full=Receptor-associated protein 80;
DE AltName: Full=Retinoid X receptor-interacting protein 110;
DE AltName: Full=Ubiquitin interaction motif-containing protein 1;
GN Name=UIMC1; Synonyms=RAP80, RXRIP110;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN TRANSCRIPTIONAL
RP REPRESSION, INTERACTION WITH NR6A1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=12080054; DOI=10.1074/jbc.M203475200;
RA Yan Z., Kim Y.-S., Jetten A.M.;
RT "RAP80: a novel nuclear protein that interacts with the retinoid-
RT related testis-associated receptor.";
RL J. Biol. Chem. 277:32379-32388(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
RC TISSUE=Hypothalamus;
RA Peng Y., Gu Y., Gu J., Huang Q., Fu S., Wu T., Dong H., Jin W., Fu G.,
RA Han Z., Chen Z., Wang Y.;
RT "A novel gene expressed in the human hypothalamus.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Hypothalamus;
RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Teratocarcinoma, and Uterus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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] (ISOFORM 1).
RC TISSUE=Esophageal carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Ovary, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-46, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [9]
RP SUMOYLATION, INTERACTION WITH UBE2I, AND MUTAGENESIS OF LYS-9; LYS-19;
RP LYS-31; LYS-52 AND LYS-61.
RX PubMed=17698038; DOI=10.1016/j.bbrc.2007.07.158;
RA Yan J., Yang X.-P., Kim Y.-S., Joo J.H., Jetten A.M.;
RT "RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel
RT target for sumoylation.";
RL Biochem. Biophys. Res. Commun. 362:132-138(2007).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ALA-88 AND ALA-113, AND
RP PHOSPHORYLATION AT SER-205 AND SER-402.
RX PubMed=17621610; DOI=10.1158/0008-5472.CAN-07-0924;
RA Yan J., Kim Y.S., Yang X.-P., Li L.-P., Liao G., Xia F., Jetten A.M.;
RT "The ubiquitin-interacting motif containing protein RAP80 interacts
RT with BRCA1 and functions in DNA damage repair response.";
RL Cancer Res. 67:6647-6656(2007).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FAM175A.
RX PubMed=17643121; DOI=10.1038/nsmb1279;
RA Liu Z., Wu J., Yu X.;
RT "CCDC98 targets BRCA1 to DNA damage sites.";
RL Nat. Struct. Mol. Biol. 14:716-720(2007).
RN [12]
RP INTERACTION WITH FAM175A.
RX PubMed=17643122; DOI=10.1038/nsmb1277;
RA Kim H., Huang J., Chen J.;
RT "CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA
RT damage response.";
RL Nat. Struct. Mol. Biol. 14:710-715(2007).
RN [13]
RP INTERACTION WITH ESR1.
RX PubMed=17311814; DOI=10.1093/nar/gkl1112;
RA Yan J., Kim Y.S., Yang X.-P., Albers M., Koegl M., Jetten A.M.;
RT "Ubiquitin-interaction motifs of RAP80 are critical in its regulation
RT of estrogen receptor alpha.";
RL Nucleic Acids Res. 35:1673-1686(2007).
RN [14]
RP INTERACTION WITH FAM175A.
RX PubMed=18077395; DOI=10.1073/pnas.0710061104;
RA Wang B., Elledge S.J.;
RT "Ubc13/Rnf8 ubiquitin ligases control foci formation of the
RT Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20759-20763(2007).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-140; SER-402
RP AND SER-419, AND MUTAGENESIS OF ALA-88; SER-92; ALA-113 AND SER-117.
RX PubMed=17525340; DOI=10.1126/science.1139476;
RA Wang B., Matsuoka S., Ballif B.A., Zhang D., Smogorzewska A., Giyi S.,
RA Elledge S.J.;
RT "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA
RT damage response.";
RL Science 316:1194-1198(2007).
RN [17]
RP FUNCTION, IDENTIFICATION IN THE BRCA1-A COMPLEX, SUBCELLULAR LOCATION,
RP UBIQUITIN-BINDING, AND PHOSPHORYLATION AT SER-101.
RX PubMed=17525341; DOI=10.1126/science.1139516;
RA Sobhian B., Shao G., Lilli D.R., Culhane A.C., Moreau L.A., Xia B.,
RA Livingston D.M., Greenberg R.A.;
RT "RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage
RT sites.";
RL Science 316:1198-1202(2007).
RN [18]
RP FUNCTION, IDENTIFICATION IN THE BRCA1-A COMPLEX, SUBCELLULAR LOCATION,
RP UBIQUITIN-BINDING, PHOSPHORYLATION AT SER-101, AND MUTAGENESIS OF
RP ALA-88; SER-92; ALA-113 AND SER-117.
RX PubMed=17525342; DOI=10.1126/science.1139621;
RA Kim H., Chen J., Yu X.;
RT "Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage
RT response.";
RL Science 316:1202-1205(2007).
RN [19]
RP PHOSPHORYLATION AT SER-205, AND MUTAGENESIS OF SER-205.
RX PubMed=18519686; DOI=10.1158/0008-5472.CAN-07-5950;
RA Yan J., Yang X.-P., Kim Y.-S., Jetten A.M.;
RT "RAP80 responds to DNA damage induced by both ionizing radiation and
RT UV irradiation and is phosphorylated at Ser 205.";
RL Cancer Res. 68:4269-4276(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-627; SER-653 AND
RP SER-677, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261746; DOI=10.1101/gad.1739609;
RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N.,
RA Wang Y., Greenberg R.A.;
RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA
RT double-strand breaks.";
RL Genes Dev. 23:740-754(2009).
RN [22]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX, UBIQUITIN-BINDING, AND
RP INTERACTION WITH FAM175A.
RX PubMed=19261749; DOI=10.1101/gad.1770309;
RA Wang B., Hurov K., Hofmann K., Elledge S.J.;
RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage
RT resistance and checkpoint control.";
RL Genes Dev. 23:729-739(2009).
RN [23]
RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE
RP BRCA1-A COMPLEX, AND INTERACTION WITH FAM175A.
RX PubMed=19261748; DOI=10.1101/gad.1770609;
RA Feng L., Huang J., Chen J.;
RT "MERIT40 facilitates BRCA1 localization and DNA damage repair.";
RL Genes Dev. 23:719-728(2009).
RN [24]
RP UBIQUITIN-BINDING, DOMAIN UIM-LINKER, AND MUTAGENESIS OF
RP 97-ARG--GLU-103 AND SER-101.
RX PubMed=19328070; DOI=10.1016/j.molcel.2009.02.011;
RA Sims J.J., Cohen R.E.;
RT "Linkage-specific avidity defines the lysine 63-linked polyubiquitin-
RT binding preference of rap80.";
RL Mol. Cell 33:775-783(2009).
RN [25]
RP FUNCTION, AND MUTAGENESIS OF CYS-508.
RX PubMed=19015238; DOI=10.1128/MCB.01302-08;
RA Wu J., Huen M.S.Y., Lu L.-Y., Ye L., Dou Y., Ljungman M., Chen J.,
RA Yu X.;
RT "Histone ubiquitination associates with BRCA1-dependent DNA damage
RT response.";
RL Mol. Cell. Biol. 29:849-860(2009).
RN [26]
RP FUNCTION.
RX PubMed=19202061; DOI=10.1073/pnas.0807485106;
RA Shao G., Lilli D.R., Patterson-Fortin J., Coleman K.A.,
RA Morrissey D.E., Greenberg R.A.;
RT "The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-
RT Ubc13-dependent ubiquitination events at DNA double strand breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44 AND SER-46, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44; SER-46 AND SER-677,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-677, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [30]
RP UBIQUITIN-BINDING, AND LR MOTIF.
RX PubMed=22742833; DOI=10.1016/j.molcel.2012.05.045;
RA Panier S., Ichijima Y., Fradet-Turcotte A., Leung C.C., Kaustov L.,
RA Arrowsmith C.H., Durocher D.;
RT "Tandem protein interaction modules organize the ubiquitin-dependent
RT response to DNA double-strand breaks.";
RL Mol. Cell 47:383-395(2012).
RN [31]
RP VARIANTS TRP-15; THR-353; LEU-435 AND ARG-511.
RX PubMed=18695986; DOI=10.1007/s10549-008-0134-y;
RA Novak D.J., Sabbaghian N., Maillet P., Chappuis P.O., Foulkes W.D.,
RA Tischkowitz M.;
RT "Analysis of the genes coding for the BRCA1-interacting proteins,
RT RAP80 and Abraxas (CCDC98), in high-risk, non-BRCA1/2, multiethnic
RT breast cancer cases.";
RL Breast Cancer Res. Treat. 117:453-459(2009).
CC -!- FUNCTION: Ubiquitin-binding protein that specifically recognizes
CC and binds 'Lys-63'-linked ubiquitin. Plays a central role in the
CC BRCA1-A complex by specifically binding 'Lys-63'-linked
CC ubiquitinated histones H2A and H2AX at DNA lesions sites, leading
CC to target the BRCA1-BARD1 heterodimer to sites of DNA damage at
CC double-strand breaks (DSBs). The BRCA1-A complex also possesses
CC deubiquitinase activity that specifically removes 'Lys-63'-linked
CC ubiquitin on histones H2A and H2AX. Also weakly binds
CC monoubiquitin but with much less affinity than 'Lys-63'-linked
CC ubiquitin. May interact with monoubiquitinated histones H2A and
CC H2B; the relevance of such results is however unclear in vivo.
CC Does not bind Lys-48'-linked ubiquitin. May indirectly act as a
CC transcriptional repressor by inhibiting the interaction of NR6A1
CC with the corepressor NCOR1.
CC -!- SUBUNIT: Interacts with TSP57 (By similarity). Component of the
CC BRCA1-A complex, at least composed of the BRCA1, BARD1,
CC UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and
CC BABAM1/NBA1. In the BRCA1-A complex, interacts directly with
CC FAM175A/Abraxas. Interacts with ESR1, NR6A1 and UBE2I.
CC -!- INTERACTION:
CC P54132:BLM; NbExp=2; IntAct=EBI-725300, EBI-621372;
CC P38398:BRCA1; NbExp=9; IntAct=EBI-725300, EBI-349905;
CC Q6UWZ7:FAM175A; NbExp=9; IntAct=EBI-725300, EBI-1263451;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Localizes at sites of DNA
CC damage at double-strand breaks (DSBs).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q96RL1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96RL1-2; Sequence=VSP_012935;
CC Name=3; Synonyms=XHRIP110;
CC IsoId=Q96RL1-3; Sequence=VSP_012932;
CC Name=4; Synonyms=X2HRIP110;
CC IsoId=Q96RL1-4; Sequence=VSP_012933, VSP_012934;
CC Name=5;
CC IsoId=Q96RL1-5; Sequence=VSP_037264, VSP_037265;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in testis, ovary, thymus and heart.
CC Expressed in germ cells of the testis.
CC -!- DOMAIN: The UIM-linker region between the 2 UIM repeats determines
CC the selectivity for 'Lys-63'-linked ubiquitin. The length of the
CC linker is important. The linker reduces the flexibility between
CC the UIM repeats and promotes high-affinity and linkage-selective
CC interactions.
CC -!- DOMAIN: The Abraxas-interacting region (AIR) mediates the
CC interaction with FAM175A/Abraxas.
CC -!- PTM: Sumoylated.
CC -!- PTM: Phosphorylated upon DNA damage by ATM or ATR.
CC -!- SIMILARITY: Belongs to the RAP80 family.
CC -!- SIMILARITY: Contains 2 UIM (ubiquitin-interacting motif) repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH06078.1; Type=Erroneous termination; Positions=386; Note=Translated as Glu;
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DR EMBL; AF349313; AAK61871.1; -; mRNA.
DR EMBL; AF113538; AAF14875.1; -; mRNA.
DR EMBL; AF284749; AAG59851.1; -; mRNA.
DR EMBL; AF284753; AAG59855.1; -; mRNA.
DR EMBL; AK023044; BAG51153.1; -; mRNA.
DR EMBL; AK304794; BAG65544.1; -; mRNA.
DR EMBL; BX537376; CAD97618.1; -; mRNA.
DR EMBL; AC027318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006078; AAH06078.1; ALT_TERM; mRNA.
DR EMBL; BC032561; AAH32561.1; -; mRNA.
DR RefSeq; NP_001186226.1; NM_001199297.1.
DR RefSeq; NP_001186227.1; NM_001199298.1.
DR RefSeq; NP_057374.3; NM_016290.4.
DR RefSeq; XP_005265987.1; XM_005265930.1.
DR RefSeq; XP_005265993.1; XM_005265936.1.
DR UniGene; Hs.232721; -.
DR PDB; 2RR9; NMR; -; C=79-124.
DR PDBsum; 2RR9; -.
DR ProteinModelPortal; Q96RL1; -.
DR SMR; Q96RL1; 79-124.
DR DIP; DIP-29936N; -.
DR IntAct; Q96RL1; 46.
DR MINT; MINT-1197441; -.
DR PhosphoSite; Q96RL1; -.
DR DMDM; 60390957; -.
DR PaxDb; Q96RL1; -.
DR PRIDE; Q96RL1; -.
DR DNASU; 51720; -.
DR Ensembl; ENST00000377227; ENSP00000366434; ENSG00000087206.
DR Ensembl; ENST00000506128; ENSP00000427480; ENSG00000087206.
DR Ensembl; ENST00000511320; ENSP00000421926; ENSG00000087206.
DR GeneID; 51720; -.
DR KEGG; hsa:51720; -.
DR UCSC; uc021yil.1; human.
DR CTD; 51720; -.
DR GeneCards; GC05M176265; -.
DR H-InvDB; HIX0005450; -.
DR HGNC; HGNC:30298; UIMC1.
DR HPA; HPA037503; -.
DR HPA; HPA037504; -.
DR MIM; 609433; gene.
DR neXtProt; NX_Q96RL1; -.
DR PharmGKB; PA162408624; -.
DR eggNOG; NOG72551; -.
DR HOVERGEN; HBG056783; -.
DR OrthoDB; EOG74XS6K; -.
DR PhylomeDB; Q96RL1; -.
DR ChiTaRS; UIMC1; human.
DR EvolutionaryTrace; Q96RL1; -.
DR GeneWiki; UIMC1; -.
DR GenomeRNAi; 51720; -.
DR NextBio; 55772; -.
DR PRO; PR:Q96RL1; -.
DR ArrayExpress; Q96RL1; -.
DR Bgee; Q96RL1; -.
DR CleanEx; HS_UIMC1; -.
DR Genevestigator; Q96RL1; -.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin binding; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:HGNC.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR SMART; SM00726; UIM; 2.
DR PROSITE; PS50330; UIM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromatin regulator;
KW Complete proteome; DNA damage; DNA repair; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 719 BRCA1-A complex subunit RAP80.
FT /FTId=PRO_0000097547.
FT REPEAT 79 96 UIM 1.
FT REPEAT 104 124 UIM 2.
FT REGION 1 101 Necessary for transcriptional repression.
FT REGION 97 103 UIM-linker.
FT REGION 100 200 Necessary for interaction with NR6A1 N-
FT terminus.
FT REGION 270 400 AIR.
FT REGION 400 500 Necessary for interaction with NR6A1 C-
FT terminus.
FT REGION 505 582 Zinc-finger-like region.
FT MOTIF 60 78 LR motif.
FT COMPBIAS 81 108 Glu-rich.
FT MOD_RES 44 44 Phosphoserine.
FT MOD_RES 46 46 Phosphoserine.
FT MOD_RES 101 101 Phosphoserine.
FT MOD_RES 140 140 Phosphoserine.
FT MOD_RES 205 205 Phosphoserine.
FT MOD_RES 402 402 Phosphoserine.
FT MOD_RES 419 419 Phosphoserine.
FT MOD_RES 627 627 Phosphoserine.
FT MOD_RES 653 653 Phosphoserine.
FT MOD_RES 677 677 Phosphoserine.
FT VAR_SEQ 1 370 Missing (in isoform 4).
FT /FTId=VSP_012933.
FT VAR_SEQ 1 78 Missing (in isoform 3).
FT /FTId=VSP_012932.
FT VAR_SEQ 120 152 SCRPSDASATRSRPLATGPSSQSHQEKTTDSGL -> VNMP
FT CCKSLWRLISYIFDFCGVVVALGTSCSHL (in isoform
FT 5).
FT /FTId=VSP_037264.
FT VAR_SEQ 153 719 Missing (in isoform 5).
FT /FTId=VSP_037265.
FT VAR_SEQ 234 399 Missing (in isoform 2).
FT /FTId=VSP_012935.
FT VAR_SEQ 371 400 SKTKDFQESSIKSLKEKLLLEEEPTTSHGQ -> MLPLPDL
FT DLWPLDRLPSPIKRKPQTLGSLK (in isoform 4).
FT /FTId=VSP_012934.
FT VARIANT 15 15 R -> W (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs13167812).
FT /FTId=VAR_051469.
FT VARIANT 353 353 M -> T (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs143282828).
FT /FTId=VAR_055328.
FT VARIANT 435 435 P -> L (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs3733876).
FT /FTId=VAR_051470.
FT VARIANT 511 511 C -> R (common polymorphism not
FT associated with susceptibility to breast
FT cancer; dbSNP:rs13360277).
FT /FTId=VAR_051471.
FT VARIANT 596 596 G -> E (in dbSNP:rs10475633).
FT /FTId=VAR_051472.
FT MUTAGEN 9 9 K->A: Does not affect symoylation; when
FT associated with A-19; A-31; A-52 and A-
FT 61.
FT MUTAGEN 19 19 K->A: Does not affect symoylation; when
FT associated with A-9; A-31; A-52 and A-61.
FT MUTAGEN 31 31 K->A: Does not affect symoylation; when
FT associated with A-9; A-19; A-52 and A-61.
FT MUTAGEN 52 52 K->A: Does not affect symoylation; when
FT associated with A-9; A-19; A-31 and A-61.
FT MUTAGEN 61 61 K->A: Does not affect symoylation; when
FT associated with A-9; A-19; A-31 and A-52.
FT MUTAGEN 88 88 A->G,S: Impairs localization to DNA
FT damages sites; when associated with A-92;
FT S-113 and A-117.
FT MUTAGEN 92 92 S->A: Impairs localization to DNA damages
FT sites; when associated with S-88; S-113
FT and A-117.
FT MUTAGEN 97 103 REVNSQE->AA: Impairs the selectivity for
FT 'K-63'-linked ubiquitin.
FT MUTAGEN 97 103 REVNSQE->AAAAAAA: Increases the
FT selectivity for 'K-63'-linked ubiquitin.
FT MUTAGEN 97 103 REVNSQE->AAAAAAAAA: Impairs the
FT selectivity for 'K-63'-linked ubiquitin.
FT MUTAGEN 101 101 S->A,E: Slightly impairs the selectivity
FT for 'K-63'-linked ubiquitin.
FT MUTAGEN 113 113 A->G,S: Impairs ubiquitin-binding and
FT localization to DNA damages sites; when
FT associated with S-88; A-92 and A-117.
FT MUTAGEN 117 117 S->A: Impairs ubiquitin-binding and
FT localization to DNA damages sites; when
FT associated with S-88; A-92 and S-113.
FT MUTAGEN 205 205 S->G: Abolishes phosphorylation at this
FT position.
FT MUTAGEN 508 508 C->A: Abolishes interaction with histone
FT monoubiquitinated H2B without affecting
FT the interaction with H2A.
FT CONFLICT 187 187 E -> K (in Ref. 7; AAH06078).
FT CONFLICT 192 192 E -> G (in Ref. 4; BAG51153).
FT CONFLICT 247 247 V -> C (in Ref. 3; AAG59851).
FT CONFLICT 347 347 E -> G (in Ref. 1; AAK61871).
FT CONFLICT 518 518 E -> G (in Ref. 1; AAK61871).
FT CONFLICT 634 634 H -> R (in Ref. 3; AAG59855).
FT CONFLICT 638 638 D -> N (in Ref. 4; BAG51153).
FT CONFLICT 694 694 D -> V (in Ref. 3; AAG59855).
FT HELIX 82 119
SQ SEQUENCE 719 AA; 79727 MW; 56B7699E42395861 CRC64;
MPRRKKKVKE VSESRNLEKK DVETTSSVSV KRKRRLEDAF IVISDSDGEE PKEENGLQKT
KTKQSNRAKC LAKRKIAQMT EEEQFALALK MSEQEAREVN SQEEEEEELL RKAIAESLNS
CRPSDASATR SRPLATGPSS QSHQEKTTDS GLTEGIWQLV PPSLFKGSHI SQGNEAEERE
EPWDHTEKTE EEPVSGSSGS WDQSSQPVFE NVNVKSFDRC TGHSAEHTQC GKPQESTGRG
SAFLKAVQGS GDTSRHCLPT LADAKGLQDT GGTVNYFWGI PFCPDGVDPN QYTKVILCQL
EVYQKSLKMA QRQLLNKKGF GEPVLPRPPS LIQNECGQGE QASEKNECIS EDMGDEDKEE
RQESRASDWH SKTKDFQESS IKSLKEKLLL EEEPTTSHGQ SSQGIVEETS EEGNSVPASQ
SVAALTSKRS LVLMPESSAE EITVCPETQL SSSETFDLER EVSPGSRDIL DGVRIIMADK
EVGNKEDAEK EVAISTFSSS NQVSCPLCDQ CFPPTKIERH AMYCNGLMEE DTVLTRRQKE
AKTKSDSGTA AQTSLDIDKN EKCYLCKSLV PFREYQCHVD SCLQLAKADQ GDGPEGSGRA
CSTVEGKWQQ RLKNPKEKGH SEGRLLSFLE QSEHKTSDAD IKSSETGAFR VPSPGMEEAG
CSREMQSSFT RRDLNESPVK SFVSISEATD CLVDFKKQVT VQPGSRTRTK AGRGRRRKF
//
MIM
609433
*RECORD*
*FIELD* NO
609433
*FIELD* TI
*609433 UBIQUITIN INTERACTION MOTIF-CONTAINING PROTEIN 1; UIMC1
;;RECEPTOR-ASSOCIATED PROTEIN, 80-KD; RAP80
read more*FIELD* TX
CLONING
By differential display of RNA expressed by young proliferating and
senescent normal human epidermal keratinocytes, followed by screening a
testis cDNA library, Yan et al. (2002) cloned RAP80. The deduced
719-amino acid protein has a calculated molecular mass of 79.6 kD. The
N-terminal half of RAP80 contains 2 nuclear localization signals and a
putative ubiquitin interaction motif. The C-terminal half contains a
potential PEST sequence, 2 zinc fingers, and a third nuclear
localization signal. Northern blot analysis detected a major 2.6-kb
transcript expressed highly in testis and moderately in ovary, thymus,
and heart. In situ hybridization of mouse testis detected Rap80
associated with germ cells, with little expression in surrounding Leydig
cells. No significant differences in the level of Rap80 were found
between developmental subpopulations of germ cells, suggesting that
Rap80 expression is not developmentally regulated. Immunofluorescence
localization detected RAP80 in a speckled nuclear distribution in a
transfected monkey kidney cell line, and mutation analysis indicated
that the second nuclear localization signal directed intracellular
localization.
GENE FUNCTION
Yan et al. (2002) found that RAP80 decreased basal transcription of a
reporter gene in transfected Chinese hamster ovary and monkey kidney
cell lines. Yeast 2-hybrid analysis indicated that RAP80 could interact
with the retinoid-related testis-associated receptor (RTR; 602778), but
not with retinoid receptors (see RXRA; 180245) or other nuclear
receptors tested. Cotransfection experiments showed that RAP80 and RTR
interacted with each other in a dose-dependent manner. Mutation analysis
indicated that several regions of RAP80 were important for optimal
interaction with RTR. RAP80 inhibited the interaction of NCOR (600849)
with RTR in a concentration-dependent manner, and RAP80 and NCOR
appeared to compete with each other for RTR binding.
Wang et al. (2007) showed that Abraxas (ABRA1; 611143), a protein that
binds BRCA1 (113705), recruits the ubiquitin-interacting motif
(UIM)-containing protein RAP80 to the BRCA1 complex. Both Abraxas and
RAP80 were required for DNA damage resistance, G2/M checkpoint control,
and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on
damaged DNA (foci) in response to ionizing radiation, and the UIM
domains alone were capable of foci formation. Wang et al. (2007)
concluded that the RAP80-Abraxas complex may help recruit BRCA1 to DNA
damage sites in part through recognition of ubiquitinated proteins.
Sobhian et al. (2007) reported the interaction of the BRCT (BRCA1
C-terminal) BRCA1 domain with the ubiquitin-binding protein RAP80. RAP80
targets a complex containing the BRCA1-BARD1 (601593) E3 ligase and the
deubiquitinating enzyme BRCC36 (300617) to MDC1 (607593)-gamma-H2AX
(601772)-dependent lys6- and lys63-linked ubiquitin polymers at
double-strand breaks. Sobhian et al. (2007) stated that these events are
required for cell cycle checkpoint and repair responses to ionizing
radiation, implicating ubiquitin chain recognition and turnover in the
BRCA1-mediated repair of double-strand breaks.
Kim et al. (2007) independently reported the identification of AP80 as a
BRCA1-interacting protein in humans. RAP80 contains a tandem UIM domain,
which is required for its binding with ubiquitin in vitro and its
damage-induced foci formation in vivo. Moreover, Kim et al. (2007)
showed that RAP80 specifically recruits BRCA1 to DNA damage sites and
functions with BRCA1 in G2/M checkpoint control. Kim et al. (2007)
concluded that taken together, their results suggested the existence of
a ubiquitination-dependent signaling pathway involved in the DNA damage
response.
GENE STRUCTURE
Yan et al. (2002) determined that the RAP80 gene contains 15 exons and
spans more than 90 kb.
MAPPING
By FISH, Yan et al. (2002) mapped the UIMC1 gene to chromosome 5q35.
*FIELD* RF
1. Kim, H.; Chen, J.; Yu, X.: Ubiquitin-binding protein RAP80 mediates
BRCA1-dependent DNA damage response. Science 316: 1202-1205, 2007.
2. Sobhian, B.; Shao, G.; Lilli, D. R.; Culhane, A. C.; Moreau, L.
A.; Xia, B.; Livingston, D. M.; Greenberg, R. A.: RAP80 targets BRCA1
to specific ubiquitin structures at DNA damage sites. Science 316:
1198-1202, 2007.
3. Wang, B.; Matsuoka, S.; Ballif, B. A.; Zhang, D.; Smogorzewska,
A.; Gygi, S. P.; Elledge, S. J.: Abraxas and RAP80 form a BRCA1 protein
complex required for the DNA damage response. Science 316: 1194-1198,
2007.
4. Yan, Z.; Kim, Y.-S.; Jetten, A. M.: RAP80, a novel nuclear protein
that interacts with the retinoid-related testis-associated receptor. J.
Biol. Chem. 277: 32379-32388, 2002.
*FIELD* CN
Ada Hamosh - updated: 6/20/2007
*FIELD* CD
Patricia A. Hartz: 6/21/2005
*FIELD* ED
alopez: 06/27/2007
terry: 6/20/2007
mgross: 6/21/2005
*RECORD*
*FIELD* NO
609433
*FIELD* TI
*609433 UBIQUITIN INTERACTION MOTIF-CONTAINING PROTEIN 1; UIMC1
;;RECEPTOR-ASSOCIATED PROTEIN, 80-KD; RAP80
read more*FIELD* TX
CLONING
By differential display of RNA expressed by young proliferating and
senescent normal human epidermal keratinocytes, followed by screening a
testis cDNA library, Yan et al. (2002) cloned RAP80. The deduced
719-amino acid protein has a calculated molecular mass of 79.6 kD. The
N-terminal half of RAP80 contains 2 nuclear localization signals and a
putative ubiquitin interaction motif. The C-terminal half contains a
potential PEST sequence, 2 zinc fingers, and a third nuclear
localization signal. Northern blot analysis detected a major 2.6-kb
transcript expressed highly in testis and moderately in ovary, thymus,
and heart. In situ hybridization of mouse testis detected Rap80
associated with germ cells, with little expression in surrounding Leydig
cells. No significant differences in the level of Rap80 were found
between developmental subpopulations of germ cells, suggesting that
Rap80 expression is not developmentally regulated. Immunofluorescence
localization detected RAP80 in a speckled nuclear distribution in a
transfected monkey kidney cell line, and mutation analysis indicated
that the second nuclear localization signal directed intracellular
localization.
GENE FUNCTION
Yan et al. (2002) found that RAP80 decreased basal transcription of a
reporter gene in transfected Chinese hamster ovary and monkey kidney
cell lines. Yeast 2-hybrid analysis indicated that RAP80 could interact
with the retinoid-related testis-associated receptor (RTR; 602778), but
not with retinoid receptors (see RXRA; 180245) or other nuclear
receptors tested. Cotransfection experiments showed that RAP80 and RTR
interacted with each other in a dose-dependent manner. Mutation analysis
indicated that several regions of RAP80 were important for optimal
interaction with RTR. RAP80 inhibited the interaction of NCOR (600849)
with RTR in a concentration-dependent manner, and RAP80 and NCOR
appeared to compete with each other for RTR binding.
Wang et al. (2007) showed that Abraxas (ABRA1; 611143), a protein that
binds BRCA1 (113705), recruits the ubiquitin-interacting motif
(UIM)-containing protein RAP80 to the BRCA1 complex. Both Abraxas and
RAP80 were required for DNA damage resistance, G2/M checkpoint control,
and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on
damaged DNA (foci) in response to ionizing radiation, and the UIM
domains alone were capable of foci formation. Wang et al. (2007)
concluded that the RAP80-Abraxas complex may help recruit BRCA1 to DNA
damage sites in part through recognition of ubiquitinated proteins.
Sobhian et al. (2007) reported the interaction of the BRCT (BRCA1
C-terminal) BRCA1 domain with the ubiquitin-binding protein RAP80. RAP80
targets a complex containing the BRCA1-BARD1 (601593) E3 ligase and the
deubiquitinating enzyme BRCC36 (300617) to MDC1 (607593)-gamma-H2AX
(601772)-dependent lys6- and lys63-linked ubiquitin polymers at
double-strand breaks. Sobhian et al. (2007) stated that these events are
required for cell cycle checkpoint and repair responses to ionizing
radiation, implicating ubiquitin chain recognition and turnover in the
BRCA1-mediated repair of double-strand breaks.
Kim et al. (2007) independently reported the identification of AP80 as a
BRCA1-interacting protein in humans. RAP80 contains a tandem UIM domain,
which is required for its binding with ubiquitin in vitro and its
damage-induced foci formation in vivo. Moreover, Kim et al. (2007)
showed that RAP80 specifically recruits BRCA1 to DNA damage sites and
functions with BRCA1 in G2/M checkpoint control. Kim et al. (2007)
concluded that taken together, their results suggested the existence of
a ubiquitination-dependent signaling pathway involved in the DNA damage
response.
GENE STRUCTURE
Yan et al. (2002) determined that the RAP80 gene contains 15 exons and
spans more than 90 kb.
MAPPING
By FISH, Yan et al. (2002) mapped the UIMC1 gene to chromosome 5q35.
*FIELD* RF
1. Kim, H.; Chen, J.; Yu, X.: Ubiquitin-binding protein RAP80 mediates
BRCA1-dependent DNA damage response. Science 316: 1202-1205, 2007.
2. Sobhian, B.; Shao, G.; Lilli, D. R.; Culhane, A. C.; Moreau, L.
A.; Xia, B.; Livingston, D. M.; Greenberg, R. A.: RAP80 targets BRCA1
to specific ubiquitin structures at DNA damage sites. Science 316:
1198-1202, 2007.
3. Wang, B.; Matsuoka, S.; Ballif, B. A.; Zhang, D.; Smogorzewska,
A.; Gygi, S. P.; Elledge, S. J.: Abraxas and RAP80 form a BRCA1 protein
complex required for the DNA damage response. Science 316: 1194-1198,
2007.
4. Yan, Z.; Kim, Y.-S.; Jetten, A. M.: RAP80, a novel nuclear protein
that interacts with the retinoid-related testis-associated receptor. J.
Biol. Chem. 277: 32379-32388, 2002.
*FIELD* CN
Ada Hamosh - updated: 6/20/2007
*FIELD* CD
Patricia A. Hartz: 6/21/2005
*FIELD* ED
alopez: 06/27/2007
terry: 6/20/2007
mgross: 6/21/2005