CUED2_HUMAN
ID CUED2_HUMAN Reviewed; 287 AA.
AC Q9H467; D3DR88; Q9BWG8;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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., Zhang X.-M.;
RT "CUE domain containing 2 regulates degradation of progesterone receptor by
RT ubiquitin-proteasome.";
RL EMBO J. 26:1831-1842(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., Buerckstuemmer T.,
RA 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 TO
RP 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., Zhang P.J.,
RA Yu M., Zhen C., Mu R., Bai Z.F., Li H.Y., Li A.L., Liang B., Jian Z.,
RA Zhang W.N., Man J.H., Gao Y.F., Gong W.L., 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).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Down-regulates ESR1 protein levels through the
CC ubiquitination-proteasome pathway, regardless of the presence of 17
CC beta-estradiol. Also involved in 17 beta-estradiol-induced ESR1
CC degradation. Controls PGR protein levels through a similar mechanism.
CC {ECO:0000269|PubMed:17347654, ECO:0000269|PubMed:21572428}.
CC -!- SUBUNIT: Interacts with PGR. Interacts with ESR1 in the presence or
CC absence of 17 beta-estradiol. {ECO:0000269|PubMed:17347654,
CC ECO:0000269|PubMed:21572428}.
CC -!- INTERACTION:
CC Q9H467; P03372: ESR1; NbExp=2; IntAct=EBI-1248228, EBI-78473;
CC Q9H467; P06401: PGR; NbExp=9; IntAct=EBI-1248228, EBI-78539;
CC Q9H467; Q32MN6: TBP; NbExp=3; IntAct=EBI-1248228, EBI-10239991;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17347654}. Nucleus
CC {ECO:0000269|PubMed:17347654}.
CC -!- TISSUE SPECIFICITY: Significantly up-regulated in breast tumor tissues
CC compared with matched adjacent normal tissues (at protein level).
CC Levels inversely correlate with ESR1 in breast cancers and are lower in
CC 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 therapy of
CC breast cancer patients. Patients with tumors that highly express CUEDC2
CC do not respond to tamoxifen treatment as effectively as those with
CC tumors with low expression.
CC -!- SIMILARITY: Belongs to the CUEDC2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH00262.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB025425; BAB87809.1; -; mRNA.
DR EMBL; AB232358; BAE19942.1; -; mRNA.
DR EMBL; AL121928; -; NOT_ANNOTATED_CDS; 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 CCDS; CCDS41566.1; -.
DR RefSeq; NP_076945.2; NM_024040.2.
DR AlphaFoldDB; Q9H467; -.
DR BioGRID; 122475; 36.
DR IntAct; Q9H467; 12.
DR MINT; Q9H467; -.
DR STRING; 9606.ENSP00000358953; -.
DR iPTMnet; Q9H467; -.
DR PhosphoSitePlus; Q9H467; -.
DR BioMuta; CUEDC2; -.
DR DMDM; 74752634; -.
DR EPD; Q9H467; -.
DR jPOST; Q9H467; -.
DR MassIVE; Q9H467; -.
DR MaxQB; Q9H467; -.
DR PaxDb; Q9H467; -.
DR PeptideAtlas; Q9H467; -.
DR PRIDE; Q9H467; -.
DR ProteomicsDB; 80788; -.
DR Antibodypedia; 31442; 316 antibodies from 36 providers.
DR DNASU; 79004; -.
DR Ensembl; ENST00000369937.5; ENSP00000358953.4; ENSG00000107874.11.
DR GeneID; 79004; -.
DR KEGG; hsa:79004; -.
DR MANE-Select; ENST00000369937.5; ENSP00000358953.4; NM_024040.3; NP_076945.2.
DR UCSC; uc001kvn.3; human.
DR CTD; 79004; -.
DR DisGeNET; 79004; -.
DR GeneCards; CUEDC2; -.
DR HGNC; HGNC:28352; CUEDC2.
DR HPA; ENSG00000107874; Low tissue specificity.
DR MIM; 614142; gene.
DR neXtProt; NX_Q9H467; -.
DR OpenTargets; ENSG00000107874; -.
DR PharmGKB; PA134871975; -.
DR VEuPathDB; HostDB:ENSG00000107874; -.
DR eggNOG; ENOG502RZII; Eukaryota.
DR GeneTree; ENSGT00390000014513; -.
DR HOGENOM; CLU_048031_0_0_1; -.
DR InParanoid; Q9H467; -.
DR OMA; VICEWIY; -.
DR OrthoDB; 1410219at2759; -.
DR PhylomeDB; Q9H467; -.
DR TreeFam; TF324328; -.
DR PathwayCommons; Q9H467; -.
DR SignaLink; Q9H467; -.
DR BioGRID-ORCS; 79004; 11 hits in 1083 CRISPR screens.
DR ChiTaRS; CUEDC2; human.
DR GenomeRNAi; 79004; -.
DR Pharos; Q9H467; Tbio.
DR PRO; PR:Q9H467; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9H467; protein.
DR Bgee; ENSG00000107874; Expressed in olfactory bulb and 196 other tissues.
DR Genevisible; Q9H467; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IMP:MGI.
DR GO; GO:0010936; P:negative regulation of macrophage cytokine production; IMP:MGI.
DR CDD; cd14367; CUE_CUED2; 1.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR039805; CUE_CUED2.
DR InterPro; IPR039784; CUEDC2.
DR PANTHER; PTHR12493; PTHR12493; 1.
DR PROSITE; PS51140; CUE; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..287
FT /note="CUE domain-containing protein 2"
FT /id="PRO_0000282992"
FT DOMAIN 144..187
FT /note="CUE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468"
FT REGION 92..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 92..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT CONFLICT 228
FT /note="D -> Y (in Ref. 5; AAH00262)"
FT /evidence="ECO:0000305"
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
