Full text data of CUEDC2
CUEDC2
(C10orf66)
[Confidence: low (only semi-automatic identification from reviews)]
CUE domain-containing protein 2
Note: presumably soluble (membrane word is not in UniProt keywords or features)
CUE domain-containing protein 2
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9H467
ID CUED2_HUMAN Reviewed; 287 AA.
AC Q9H467; D3DR88; Q9BWG8;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 79.
DE RecName: Full=CUE domain-containing protein 2;
GN Name=CUEDC2; Synonyms=C10orf66; ORFNames=HOYS6;
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].
RC TISSUE=Osteocyte;
RA Ikeda A., Turitani K.;
RT "Molecular cloning of an osteocyte derived gene.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retinoblastoma;
RA Matsumoto K., Abiko S., Ariga H.;
RT "Nucleotide sequence of human CUEDC2 mRNA.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP FUNCTION, INTERACTION WITH PGR AND ESR1, AND SUBCELLULAR LOCATION.
RX PubMed=17347654; DOI=10.1038/sj.emboj.7601602;
RA Zhang P.-J., Zhao J., Li H.-Y., Man J.-H., He K., Zhou T., Pan X.,
RA Li A.-L., Gong W.-L., Jin B.-F., Xia Q., Yu M., Shen B.-F.,
RA Zhang X.-M.;
RT "CUE domain containing 2 regulates degradation of progesterone
RT receptor by ubiquitin-proteasome.";
RL EMBO J. 26:1831-1842(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, AND MASS
RP 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, INTERACTION WITH ESR1, AND ROLE IN BREAST CANCER RESISTANCE
RP TO TAMOXIFEN.
RX PubMed=21572428; DOI=10.1038/nm.2369;
RA Pan X., Zhou T., Tai Y.H., Wang C., Zhao J., Cao Y., Chen Y.,
RA Zhang P.J., Yu M., Zhen C., Mu R., Bai Z.F., Li H.Y., Li A.L.,
RA Liang B., Jian Z., Zhang W.N., Man J.H., Gao Y.F., Gong W.L.,
RA Wei L.X., Zhang X.M.;
RT "Elevated expression of CUEDC2 protein confers endocrine resistance in
RT breast cancer.";
RL Nat. Med. 17:708-714(2011).
CC -!- FUNCTION: Down-regulates ESR1 protein levels through the
CC ubiquitination-proteasome pathway, regardless of the presence of
CC 17 beta-estradiol. Also involved in 17 beta-estradiol-induced ESR1
CC degradation. Controls PGR protein levels through a similar
CC mechanism.
CC -!- SUBUNIT: Interacts with PGR. Interacts with ESR1 in the presence
CC or absence of 17 beta-estradiol.
CC -!- INTERACTION:
CC P03372:ESR1; NbExp=2; IntAct=EBI-1248228, EBI-78473;
CC P06401:PGR; NbExp=9; IntAct=EBI-1248228, EBI-78539;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Significantly up-regulated in breast tumor
CC tissues compared with matched adjacent normal tissues (at protein
CC level). Levels inversely correlate with ESR1 in breast cancers and
CC are lower in low-grade tumors compared to high-grade tumors.
CC -!- DOMAIN: The CUE domain mediates interaction with PGR and ESR1.
CC -!- DISEASE: Note=May predict the clinical outcome of tamoxifen
CC therapy of breast cancer patients. Patients with tumors that
CC highly express CUEDC2 do not respond to tamoxifen treatment as
CC effectively as those with tumors with low expression.
CC -!- SIMILARITY: Belongs to the CUEDC2 family.
CC -!- SIMILARITY: Contains 1 CUE domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH00262.1; Type=Erroneous termination; Positions=227; Note=Translated as Glu;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB025425; BAB87809.1; -; mRNA.
DR EMBL; AB232358; BAE19942.1; -; mRNA.
DR EMBL; AL121928; CAC08403.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49696.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49697.1; -; Genomic_DNA.
DR EMBL; BC000262; AAH00262.1; ALT_SEQ; mRNA.
DR RefSeq; NP_076945.2; NM_024040.2.
DR RefSeq; XP_005270204.1; XM_005270147.1.
DR UniGene; Hs.500874; -.
DR ProteinModelPortal; Q9H467; -.
DR IntAct; Q9H467; 3.
DR MINT; MINT-4787857; -.
DR STRING; 9606.ENSP00000358953; -.
DR PhosphoSite; Q9H467; -.
DR DMDM; 74752634; -.
DR PaxDb; Q9H467; -.
DR PRIDE; Q9H467; -.
DR Ensembl; ENST00000369937; ENSP00000358953; ENSG00000107874.
DR GeneID; 79004; -.
DR KEGG; hsa:79004; -.
DR UCSC; uc001kvn.2; human.
DR CTD; 79004; -.
DR GeneCards; GC10M104172; -.
DR HGNC; HGNC:28352; CUEDC2.
DR HPA; HPA036544; -.
DR MIM; 614142; gene.
DR neXtProt; NX_Q9H467; -.
DR PharmGKB; PA134871975; -.
DR eggNOG; NOG82697; -.
DR HOGENOM; HOG000044753; -.
DR HOVERGEN; HBG106839; -.
DR InParanoid; Q9H467; -.
DR OMA; GDTQDEA; -.
DR OrthoDB; EOG73JKW7; -.
DR PhylomeDB; Q9H467; -.
DR GenomeRNAi; 79004; -.
DR NextBio; 67629; -.
DR PRO; PR:Q9H467; -.
DR Bgee; Q9H467; -.
DR CleanEx; HS_CUEDC2; -.
DR Genevestigator; Q9H467; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR InterPro; IPR003892; CUE.
DR Pfam; PF02845; CUE; 1.
DR PROSITE; PS51140; CUE; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1 287 CUE domain-containing protein 2.
FT /FTId=PRO_0000282992.
FT DOMAIN 144 187 CUE.
FT MOD_RES 110 110 Phosphoserine.
FT CONFLICT 228 228 D -> Y (in Ref. 5; AAH00262).
SQ SEQUENCE 287 AA; 32009 MW; D092D9A6168E9C15 CRC64;
MELERIVSAA LLAFVQTHLP EADLSGLDEV IFSYVLGVLE DLGPSGPSEE NFDMEAFTEM
MEAYVPGFAH IPRGTIGDMM QKLSGQLSDA RNKENLQPQS SGVQGQVPIS PEPLQRPEML
KEETRSSAAA AADTQDEATG AEEELLPGVD VLLEVFPTCS VEQAQWVLAK ARGDLEEAVQ
MLVEGKEEGP AAWEGPNQDL PRRLRGPQKD ELKSFILQKY MMVDSAEDQK IHRPMAPKEA
PKKLIRYIDN QVVSTKGERF KDVRNPEAEE MKATYINLKP ARKYRFH
//
ID CUED2_HUMAN Reviewed; 287 AA.
AC Q9H467; D3DR88; Q9BWG8;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 79.
DE RecName: Full=CUE domain-containing protein 2;
GN Name=CUEDC2; Synonyms=C10orf66; ORFNames=HOYS6;
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].
RC TISSUE=Osteocyte;
RA Ikeda A., Turitani K.;
RT "Molecular cloning of an osteocyte derived gene.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retinoblastoma;
RA Matsumoto K., Abiko S., Ariga H.;
RT "Nucleotide sequence of human CUEDC2 mRNA.";
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP FUNCTION, INTERACTION WITH PGR AND ESR1, AND SUBCELLULAR LOCATION.
RX PubMed=17347654; DOI=10.1038/sj.emboj.7601602;
RA Zhang P.-J., Zhao J., Li H.-Y., Man J.-H., He K., Zhou T., Pan X.,
RA Li A.-L., Gong W.-L., Jin B.-F., Xia Q., Yu M., Shen B.-F.,
RA Zhang X.-M.;
RT "CUE domain containing 2 regulates degradation of progesterone
RT receptor by ubiquitin-proteasome.";
RL EMBO J. 26:1831-1842(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, AND MASS
RP 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP FUNCTION, INTERACTION WITH ESR1, AND ROLE IN BREAST CANCER RESISTANCE
RP TO TAMOXIFEN.
RX PubMed=21572428; DOI=10.1038/nm.2369;
RA Pan X., Zhou T., Tai Y.H., Wang C., Zhao J., Cao Y., Chen Y.,
RA Zhang P.J., Yu M., Zhen C., Mu R., Bai Z.F., Li H.Y., Li A.L.,
RA Liang B., Jian Z., Zhang W.N., Man J.H., Gao Y.F., Gong W.L.,
RA Wei L.X., Zhang X.M.;
RT "Elevated expression of CUEDC2 protein confers endocrine resistance in
RT breast cancer.";
RL Nat. Med. 17:708-714(2011).
CC -!- FUNCTION: Down-regulates ESR1 protein levels through the
CC ubiquitination-proteasome pathway, regardless of the presence of
CC 17 beta-estradiol. Also involved in 17 beta-estradiol-induced ESR1
CC degradation. Controls PGR protein levels through a similar
CC mechanism.
CC -!- SUBUNIT: Interacts with PGR. Interacts with ESR1 in the presence
CC or absence of 17 beta-estradiol.
CC -!- INTERACTION:
CC P03372:ESR1; NbExp=2; IntAct=EBI-1248228, EBI-78473;
CC P06401:PGR; NbExp=9; IntAct=EBI-1248228, EBI-78539;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- TISSUE SPECIFICITY: Significantly up-regulated in breast tumor
CC tissues compared with matched adjacent normal tissues (at protein
CC level). Levels inversely correlate with ESR1 in breast cancers and
CC are lower in low-grade tumors compared to high-grade tumors.
CC -!- DOMAIN: The CUE domain mediates interaction with PGR and ESR1.
CC -!- DISEASE: Note=May predict the clinical outcome of tamoxifen
CC therapy of breast cancer patients. Patients with tumors that
CC highly express CUEDC2 do not respond to tamoxifen treatment as
CC effectively as those with tumors with low expression.
CC -!- SIMILARITY: Belongs to the CUEDC2 family.
CC -!- SIMILARITY: Contains 1 CUE domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH00262.1; Type=Erroneous termination; Positions=227; Note=Translated as Glu;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AB025425; BAB87809.1; -; mRNA.
DR EMBL; AB232358; BAE19942.1; -; mRNA.
DR EMBL; AL121928; CAC08403.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49696.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49697.1; -; Genomic_DNA.
DR EMBL; BC000262; AAH00262.1; ALT_SEQ; mRNA.
DR RefSeq; NP_076945.2; NM_024040.2.
DR RefSeq; XP_005270204.1; XM_005270147.1.
DR UniGene; Hs.500874; -.
DR ProteinModelPortal; Q9H467; -.
DR IntAct; Q9H467; 3.
DR MINT; MINT-4787857; -.
DR STRING; 9606.ENSP00000358953; -.
DR PhosphoSite; Q9H467; -.
DR DMDM; 74752634; -.
DR PaxDb; Q9H467; -.
DR PRIDE; Q9H467; -.
DR Ensembl; ENST00000369937; ENSP00000358953; ENSG00000107874.
DR GeneID; 79004; -.
DR KEGG; hsa:79004; -.
DR UCSC; uc001kvn.2; human.
DR CTD; 79004; -.
DR GeneCards; GC10M104172; -.
DR HGNC; HGNC:28352; CUEDC2.
DR HPA; HPA036544; -.
DR MIM; 614142; gene.
DR neXtProt; NX_Q9H467; -.
DR PharmGKB; PA134871975; -.
DR eggNOG; NOG82697; -.
DR HOGENOM; HOG000044753; -.
DR HOVERGEN; HBG106839; -.
DR InParanoid; Q9H467; -.
DR OMA; GDTQDEA; -.
DR OrthoDB; EOG73JKW7; -.
DR PhylomeDB; Q9H467; -.
DR GenomeRNAi; 79004; -.
DR NextBio; 67629; -.
DR PRO; PR:Q9H467; -.
DR Bgee; Q9H467; -.
DR CleanEx; HS_CUEDC2; -.
DR Genevestigator; Q9H467; -.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR InterPro; IPR003892; CUE.
DR Pfam; PF02845; CUE; 1.
DR PROSITE; PS51140; CUE; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1 287 CUE domain-containing protein 2.
FT /FTId=PRO_0000282992.
FT DOMAIN 144 187 CUE.
FT MOD_RES 110 110 Phosphoserine.
FT CONFLICT 228 228 D -> Y (in Ref. 5; AAH00262).
SQ SEQUENCE 287 AA; 32009 MW; D092D9A6168E9C15 CRC64;
MELERIVSAA LLAFVQTHLP EADLSGLDEV IFSYVLGVLE DLGPSGPSEE NFDMEAFTEM
MEAYVPGFAH IPRGTIGDMM QKLSGQLSDA RNKENLQPQS SGVQGQVPIS PEPLQRPEML
KEETRSSAAA AADTQDEATG AEEELLPGVD VLLEVFPTCS VEQAQWVLAK ARGDLEEAVQ
MLVEGKEEGP AAWEGPNQDL PRRLRGPQKD ELKSFILQKY MMVDSAEDQK IHRPMAPKEA
PKKLIRYIDN QVVSTKGERF KDVRNPEAEE MKATYINLKP ARKYRFH
//
MIM
614142
*RECORD*
*FIELD* NO
614142
*FIELD* TI
*614142 CUE DOMAIN-CONTAINING PROTEIN 2; CUEDC2
*FIELD* TX
DESCRIPTION
CUEDC2 is involved in ubiquitin- and proteasome-mediated degradation of
read moreprogesterone receptor (PR, or PGR; 607311) and estrogen receptor
(ER)-alpha (ESR1; 133430) (Zhang et al., 2007; Pan et al., 2011).
CLONING
Using the N-terminal IF domain of PR as bait in a yeast 2-hybrid screen
of a human mammary cDNA library, followed by database analysis and PCR
of the same library, Zhang et al. (2007) cloned CUEDC2. The deduced
226-amino acid protein has a ubiquitin (see 191339)-binding CUE domain
in its C-terminal half.
GENE FUNCTION
Using coimmunoprecipitation analysis and protein pull-down assays, Zhang
et al. (2007) confirmed that CUEDC2 interacted with the PRB isoform of
PR. Mutation analysis revealed that the IF domain of PRB and the CUE
domain of CUEDC2 were required for the interaction. CUEDC2 reduced PRB
protein content and promoted progesterone-induced PRB degradation via
the ubiquitin-proteasome pathway. Knockdown of CUEDC2 via small
interfering RNA significantly reduced progesterone-induced PR
degradation. CUEDC2 promoted decreased sumoylation of PRB on lys388 and
simultaneously promoted ubiquitination of PRB on lys388. CUEDC2 also
repressed PR transactivation, inhibited the ability of PR to stimulate
rapid p42 (MAPK1; 176948)/p44 (MAPK3; 601795) activation, and impaired
the effect of progesterone on breast cancer cell growth.
Pan et al. (2011) showed that CUEDC2 modulated ER-alpha protein
stability through the ubiquitin-proteasome pathway. CUEDC2 interacted
with ER-alpha in the presence or absence of 17-beta-estradiol. Mutation
analysis revealed that an N-terminal domain of CUEDC2 was required for
interaction with ER-alpha, while the CUE domain was required for
ER-alpha ubiquitination and degradation. Pan et al. (2011) examined
breast cancer and matched adjacent normal tissue from 449 patients and
found a strong inverse correlation between CUEDC2 and ER-alpha protein
expression. Patients with high CUEDC2-expressing tumors had poor
responsiveness to tamoxifen treatment and high potential for relapse.
Ectopic CUEDC2 expression impaired the responsiveness of breast cancer
cells to tamoxifen.
MAPPING
Hartz (2011) mapped the CUEDC2 gene to chromosome 10q24.32 based on an
alignment of the CUEDC2 sequence (GenBank GENBANK BC000262) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 7/26/2011.
2. Pan, X.; Zhou, T.; Tai, Y.-H.; Wang, C.; Zhao, J.; Cao, Y.; Chen,
Y.; Zhang, P.-J.; Yu, M.; Zhen, C.; Mu, R.; Bai, Z.-F.; and 10 others
: Elevated expression of CUEDC2 protein confers endocrine resistance
in breast cancer. Nature Med. 17: 708-714, 2011.
3. Zhang, P.-J.; Zhao, J.; Li, H.-Y.; Man, J.-H.; He, K.; Zhou, T.;
Pan, X.; Li, A.-L.; Gong, W.-L.; Jin, B.-F.; Xia, Q.; Yu, M.; Shen,
B.-F.; Zhang, X.-M.: CUE domain containing 2 regulates degradation
of progesterone receptor by ubiquitin-proteasome. EMBO J. 26: 1831-1842,
2007.
*FIELD* CD
Patricia A. Hartz: 8/4/2011
*FIELD* ED
terry: 08/11/2011
mgross: 8/4/2011
*RECORD*
*FIELD* NO
614142
*FIELD* TI
*614142 CUE DOMAIN-CONTAINING PROTEIN 2; CUEDC2
*FIELD* TX
DESCRIPTION
CUEDC2 is involved in ubiquitin- and proteasome-mediated degradation of
read moreprogesterone receptor (PR, or PGR; 607311) and estrogen receptor
(ER)-alpha (ESR1; 133430) (Zhang et al., 2007; Pan et al., 2011).
CLONING
Using the N-terminal IF domain of PR as bait in a yeast 2-hybrid screen
of a human mammary cDNA library, followed by database analysis and PCR
of the same library, Zhang et al. (2007) cloned CUEDC2. The deduced
226-amino acid protein has a ubiquitin (see 191339)-binding CUE domain
in its C-terminal half.
GENE FUNCTION
Using coimmunoprecipitation analysis and protein pull-down assays, Zhang
et al. (2007) confirmed that CUEDC2 interacted with the PRB isoform of
PR. Mutation analysis revealed that the IF domain of PRB and the CUE
domain of CUEDC2 were required for the interaction. CUEDC2 reduced PRB
protein content and promoted progesterone-induced PRB degradation via
the ubiquitin-proteasome pathway. Knockdown of CUEDC2 via small
interfering RNA significantly reduced progesterone-induced PR
degradation. CUEDC2 promoted decreased sumoylation of PRB on lys388 and
simultaneously promoted ubiquitination of PRB on lys388. CUEDC2 also
repressed PR transactivation, inhibited the ability of PR to stimulate
rapid p42 (MAPK1; 176948)/p44 (MAPK3; 601795) activation, and impaired
the effect of progesterone on breast cancer cell growth.
Pan et al. (2011) showed that CUEDC2 modulated ER-alpha protein
stability through the ubiquitin-proteasome pathway. CUEDC2 interacted
with ER-alpha in the presence or absence of 17-beta-estradiol. Mutation
analysis revealed that an N-terminal domain of CUEDC2 was required for
interaction with ER-alpha, while the CUE domain was required for
ER-alpha ubiquitination and degradation. Pan et al. (2011) examined
breast cancer and matched adjacent normal tissue from 449 patients and
found a strong inverse correlation between CUEDC2 and ER-alpha protein
expression. Patients with high CUEDC2-expressing tumors had poor
responsiveness to tamoxifen treatment and high potential for relapse.
Ectopic CUEDC2 expression impaired the responsiveness of breast cancer
cells to tamoxifen.
MAPPING
Hartz (2011) mapped the CUEDC2 gene to chromosome 10q24.32 based on an
alignment of the CUEDC2 sequence (GenBank GENBANK BC000262) with the
genomic sequence (GRCh37).
*FIELD* RF
1. Hartz, P. A.: Personal Communication. Baltimore, Md. 7/26/2011.
2. Pan, X.; Zhou, T.; Tai, Y.-H.; Wang, C.; Zhao, J.; Cao, Y.; Chen,
Y.; Zhang, P.-J.; Yu, M.; Zhen, C.; Mu, R.; Bai, Z.-F.; and 10 others
: Elevated expression of CUEDC2 protein confers endocrine resistance
in breast cancer. Nature Med. 17: 708-714, 2011.
3. Zhang, P.-J.; Zhao, J.; Li, H.-Y.; Man, J.-H.; He, K.; Zhou, T.;
Pan, X.; Li, A.-L.; Gong, W.-L.; Jin, B.-F.; Xia, Q.; Yu, M.; Shen,
B.-F.; Zhang, X.-M.: CUE domain containing 2 regulates degradation
of progesterone receptor by ubiquitin-proteasome. EMBO J. 26: 1831-1842,
2007.
*FIELD* CD
Patricia A. Hartz: 8/4/2011
*FIELD* ED
terry: 08/11/2011
mgross: 8/4/2011