GREB1_HUMAN
ID GREB1_HUMAN Reviewed; 1949 AA.
AC Q4ZG55; A6NHD0; A6NKN0; B5MDA9; O60321; Q7Z5S2; Q9H2Q6; Q9H2Q7; Q9H2Q8;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Protein GREB1;
DE AltName: Full=Gene regulated in breast cancer 1 protein;
GN Name=GREB1; Synonyms=KIAA0575;
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] (ISOFORMS 2 AND 3), AND NUCLEOTIDE SEQUENCE
RP [MRNA] OF 1-1001 (ISOFORM 1).
RC TISSUE=Mammary carcinoma;
RX PubMed=11103799;
RA Ghosh M.G., Thompson D.A., Weigel R.J.;
RT "PDZK1 and GREB1 are estrogen-regulated genes expressed in hormone-
RT responsive breast cancer.";
RL Cancer Res. 60:6367-6375(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [3]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Ishikawa K.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS THR-77 AND
RP ASN-1687.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANTS THR-77 AND
RP ASN-1687.
RC TISSUE=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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP INDUCTION BY ESTROGEN.
RX PubMed=15345050; DOI=10.1186/gb-2004-5-9-r66;
RA Lin C.-Y., Stroem A., Vega V.B., Kong S.L., Yeo A.L., Thomsen J.S.,
RA Chan W.C., Doray B., Bangarusamy D.K., Ramasamy A., Vergara L.A., Tang S.,
RA Chong A., Bajic V.B., Miller L.D., Gustafsson J.-A., Liu E.T.;
RT "Discovery of estrogen receptor alpha target genes and response elements in
RT breast tumor cells.";
RL Genome Biol. 5:R66.1-R66.18(2004).
RN [8]
RP POSSIBLE FUNCTION, AND INDUCTION BY ESTROGEN.
RX PubMed=15986123; DOI=10.1007/s10549-005-1483-4;
RA Rae J.M., Johnson M.D., Scheys J.O., Cordero K.E., Larios J.M.,
RA Lippman M.E.;
RT "GREB 1 is a critical regulator of hormone dependent breast cancer
RT growth.";
RL Breast Cancer Res. Treat. 92:141-149(2005).
RN [9]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=16496412; DOI=10.1002/pros.20403;
RA Rae J.M., Johnson M.D., Cordero K.E., Scheys J.O., Larios J.M.,
RA Gottardis M.M., Pienta K.J., Lippman M.E.;
RT "GREB1 is a novel androgen-regulated gene required for prostate cancer
RT growth.";
RL Prostate 66:886-894(2006).
RN [10]
RP INDUCTION BY ESTROGEN.
RX PubMed=17463000; DOI=10.1074/jbc.c700030200;
RA Deschenes J., Bourdeau V., White J.H., Mader S.;
RT "Regulation of GREB1 transcription by estrogen receptor alpha through a
RT multipartite enhancer spread over 20 kb of upstream flanking sequences.";
RL J. Biol. Chem. 282:17335-17339(2007).
RN [11]
RP INDUCTION BY ESTROGEN.
RX PubMed=17666587; DOI=10.1210/me.2007-0082;
RA Sun J., Nawaz Z., Slingerland J.M.;
RT "Long-range activation of GREB1 by estrogen receptor via three distal
RT consensus estrogen-responsive elements in breast cancer cells.";
RL Mol. Endocrinol. 21:2651-2662(2007).
CC -!- FUNCTION: May play a role in estrogen-stimulated cell proliferation.
CC Acts as a regulator of hormone-dependent cancer growth in breast and
CC prostate cancers.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=GREB1a;
CC IsoId=Q4ZG55-1; Sequence=Displayed;
CC Name=2; Synonyms=GREB1b;
CC IsoId=Q4ZG55-2; Sequence=VSP_031760, VSP_031761;
CC Name=3; Synonyms=GREB1c;
CC IsoId=Q4ZG55-3; Sequence=VSP_031758, VSP_031759;
CC Name=4;
CC IsoId=Q4ZG55-4; Sequence=VSP_031757;
CC -!- TISSUE SPECIFICITY: Expressed in proliferating prostatic tissue and
CC prostate cancer. {ECO:0000269|PubMed:16496412}.
CC -!- INDUCTION: Estrogen-responsive; regulated by estrogen receptors.
CC Regulated by androgens. The regulatory region of the gene contains 3
CC estrogen-responsive elements. {ECO:0000269|PubMed:15345050,
CC ECO:0000269|PubMed:15986123, ECO:0000269|PubMed:16496412,
CC ECO:0000269|PubMed:17463000, ECO:0000269|PubMed:17666587}.
CC -!- SIMILARITY: Belongs to the GREB1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25501.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GREB1ID40751ch2p25.html";
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DR EMBL; AF245388; AAG39036.1; -; mRNA.
DR EMBL; AF245389; AAG39037.1; -; mRNA.
DR EMBL; AF245390; AAG39038.1; -; mRNA.
DR EMBL; AB011147; BAA25501.2; ALT_INIT; mRNA.
DR EMBL; AC011994; AAX88907.1; -; Genomic_DNA.
DR EMBL; AC110754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00927.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00928.1; -; Genomic_DNA.
DR EMBL; BC054502; AAH54502.1; -; mRNA.
DR CCDS; CCDS33146.1; -. [Q4ZG55-2]
DR CCDS; CCDS33147.1; -. [Q4ZG55-3]
DR CCDS; CCDS42655.1; -. [Q4ZG55-1]
DR PIR; T00340; T00340.
DR RefSeq; NP_055483.2; NM_014668.3. [Q4ZG55-1]
DR RefSeq; NP_149081.1; NM_033090.2. [Q4ZG55-2]
DR RefSeq; NP_683701.2; NM_148903.2. [Q4ZG55-3]
DR RefSeq; XP_005246249.1; XM_005246192.4. [Q4ZG55-1]
DR RefSeq; XP_011508725.1; XM_011510423.2. [Q4ZG55-2]
DR AlphaFoldDB; Q4ZG55; -.
DR BioGRID; 115040; 25.
DR IntAct; Q4ZG55; 16.
DR MINT; Q4ZG55; -.
DR STRING; 9606.ENSP00000370896; -.
DR iPTMnet; Q4ZG55; -.
DR PhosphoSitePlus; Q4ZG55; -.
DR BioMuta; GREB1; -.
DR DMDM; 74739248; -.
DR EPD; Q4ZG55; -.
DR MassIVE; Q4ZG55; -.
DR MaxQB; Q4ZG55; -.
DR PaxDb; Q4ZG55; -.
DR PeptideAtlas; Q4ZG55; -.
DR PRIDE; Q4ZG55; -.
DR ProteomicsDB; 62378; -. [Q4ZG55-1]
DR ProteomicsDB; 62379; -. [Q4ZG55-2]
DR ProteomicsDB; 62380; -. [Q4ZG55-3]
DR ProteomicsDB; 62381; -. [Q4ZG55-4]
DR Antibodypedia; 26843; 164 antibodies from 23 providers.
DR DNASU; 9687; -.
DR Ensembl; ENST00000234142.9; ENSP00000234142.5; ENSG00000196208.14. [Q4ZG55-1]
DR Ensembl; ENST00000263834.9; ENSP00000263834.5; ENSG00000196208.14. [Q4ZG55-3]
DR Ensembl; ENST00000381483.6; ENSP00000370892.2; ENSG00000196208.14. [Q4ZG55-2]
DR Ensembl; ENST00000381486.7; ENSP00000370896.2; ENSG00000196208.14. [Q4ZG55-1]
DR Ensembl; ENST00000396123.2; ENSP00000379429.1; ENSG00000196208.14. [Q4ZG55-4]
DR GeneID; 9687; -.
DR KEGG; hsa:9687; -.
DR MANE-Select; ENST00000381486.7; ENSP00000370896.2; NM_014668.4; NP_055483.2.
DR UCSC; uc002rbk.2; human. [Q4ZG55-1]
DR CTD; 9687; -.
DR DisGeNET; 9687; -.
DR GeneCards; GREB1; -.
DR HGNC; HGNC:24885; GREB1.
DR HPA; ENSG00000196208; Tissue enriched (ovary).
DR MIM; 611736; gene.
DR neXtProt; NX_Q4ZG55; -.
DR OpenTargets; ENSG00000196208; -.
DR PharmGKB; PA164747489; -.
DR VEuPathDB; HostDB:ENSG00000196208; -.
DR eggNOG; ENOG502QQXD; Eukaryota.
DR GeneTree; ENSGT00390000008041; -.
DR HOGENOM; CLU_237163_0_0_1; -.
DR InParanoid; Q4ZG55; -.
DR OMA; IFKGNCH; -.
DR OrthoDB; 70299at2759; -.
DR PhylomeDB; Q4ZG55; -.
DR TreeFam; TF329531; -.
DR PathwayCommons; Q4ZG55; -.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; Q4ZG55; -.
DR SIGNOR; Q4ZG55; -.
DR BioGRID-ORCS; 9687; 9 hits in 1075 CRISPR screens.
DR ChiTaRS; GREB1; human.
DR GenomeRNAi; 9687; -.
DR Pharos; Q4ZG55; Tbio.
DR PRO; PR:Q4ZG55; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q4ZG55; protein.
DR Bgee; ENSG00000196208; Expressed in left ovary and 159 other tissues.
DR ExpressionAtlas; Q4ZG55; baseline and differential.
DR Genevisible; Q4ZG55; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR InterPro; IPR028422; GREB1.
DR PANTHER; PTHR15720; PTHR15720; 1.
DR Pfam; PF15782; GREB1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1949
FT /note="Protein GREB1"
FT /id="PRO_0000320944"
FT TRANSMEM 1868..1888
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 52..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 302..334
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1085..1210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1085..1126
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1127..1155
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1183..1210
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..1002
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9628581"
FT /id="VSP_031757"
FT VAR_SEQ 387..409
FT /note="GHGNFPYLCGNLNDVVVSPLLYT -> VFVNGATQMVALGPAEPASPRSL
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11103799"
FT /id="VSP_031758"
FT VAR_SEQ 410..1949
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11103799"
FT /id="VSP_031759"
FT VAR_SEQ 450..457
FT /note="ADQVPLME -> HQIRNPDV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11103799"
FT /id="VSP_031760"
FT VAR_SEQ 458..1949
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11103799"
FT /id="VSP_031761"
FT VARIANT 77
FT /note="N -> T (in dbSNP:rs10929757)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_039313"
FT VARIANT 122
FT /note="V -> A (in dbSNP:rs4669751)"
FT /id="VAR_039314"
FT VARIANT 346
FT /note="V -> M (in dbSNP:rs6744817)"
FT /id="VAR_039315"
FT VARIANT 359
FT /note="F -> L (in dbSNP:rs35188552)"
FT /id="VAR_061654"
FT VARIANT 632
FT /note="A -> T (in dbSNP:rs36030386)"
FT /id="VAR_061655"
FT VARIANT 973
FT /note="R -> Q (in dbSNP:rs3762579)"
FT /id="VAR_039316"
FT VARIANT 1463
FT /note="Y -> C (in dbSNP:rs11695925)"
FT /id="VAR_039317"
FT VARIANT 1687
FT /note="D -> N (in dbSNP:rs2304402)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.5"
FT /id="VAR_039318"
FT VARIANT 1814
FT /note="L -> V (in dbSNP:rs34955282)"
FT /id="VAR_039319"
FT CONFLICT 829
FT /note="I -> S (in Ref. 1; AAG39036)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1949 AA; 216467 MW; BA12C0535B166BC4 CRC64;
MGNSYAGQLK TTRFEEVLHN SIEASLRSNN LVPRPIFSQL YLEAEQQLAA LEGGSRVDNE
EEEEEGEGGL ETNGPPNPFQ LHPLPEGCCT TDGFCQAGKD LRLVSISNEP MDVPAGFLLV
GVKSPSLPDH LLVCAVDKRF LPDDNGHNAL LGFSGNCVGC GKKGFCYFTE FSNHINLKLT
TQPKKQKHLK YYLVRNAQGT LTKGPLICWK GSEFRSRQIP ASTCSSSLFP ALESTAAFPS
EPVPGTNPSI LMGAQQAGPA SDHPSLNAAM GPAVFNGKDS PKCQQLAKNN LLALPRPSAL
GILSNSGPPK KRHKGWSPES PSAPDGGCPQ GGGNRAKYES AGMSCVPQVG LVGPASVTFP
VVASGEPVSV PDNLLKICKA KPVIFKGHGN FPYLCGNLND VVVSPLLYTC YQNSQSVSRA
YEQYGASAIQ PISEEMQLLL TVYYLVQLAA DQVPLMEDLE QIFLRSWRES HLTEIRQYQQ
APPQPFPPAP SAAAPVTSAQ LPWLASLAAS SCNDSVHVIE CAYSLAEGLS EMFRLLVEGK
LAKTNYVVII CACRSAAIDS CIAVTGKYQA RILSESLLTP AEYQKEVNYE LVTGKVDSLG
AFFSTLCPEG DIDILLDKFH QENQGHISSS LAASSVTKAA SLDVSGTPVC TSYNLEPHSI
RPFQLAVAQK LLSHVCSIAD SSTQNLDLGS FEKVDFLICI PPSEVTYQQT LLHVWHSGVL
LELGLKKEHM TKQRVEQYVL KLDTEAQTKF KAFLQNSFQN PHTLFVLIHD HAHWDLVSST
VHNLYSQSDP SVGLVDRLLN CREVKEAPNI VTLHVTSFPY ALQTQHTLIS PYNEIHWPAS
CSNGVDLYHE NKKYFGLSEF IESTLSGHSL PLLRYDSSFE AMVTALGKRF PRLHSAVIRT
FVLVQHYAAA LMAVSGLPQM KNYTSVETLE ITQNLLNSPK QCPCGHGLMV LLRVPCSPLA
VVAYERLAHV RARLALEEHF EIILGSPSSG VTVGKHFVKQ LRMWQKIEDV EWRPQTYLEL
EGLPCILIFS GMDPHGESLP RSLRYCDLRL INSSCLVRTA LEQELGLAAY FVSNEVPLEK
GARNEALESD AEKLSSTDNE DEELGTEGST SEKRSPMKRE RSRSHDSASS SLSSKASGSA
LGGESSAQPT ALPQGEHARS PQPRGPAEEG RAPGEKQRPR ASQGPPSAIS RHSPGPTPQP
DCSLRTGQRS VQVSVTSSCS QLSSSSGSSS SSVAPAAGTW VLQASQCSLT KACRQPPIVF
LPKLVYDMVV STDSSGLPKA ASLLPSPSVM WASSFRPLLS KTMTSTEQSL YYRQWTVPRP
SHMDYGNRAE GRVDGFHPRR LLLSGPPQIG KTGAYLQFLS VLSRMLVRLT EVDVYDEEEI
NINLREESDW HYLQLSDPWP DLELFKKLPF DYIIHDPKYE DASLICSHYQ GIKSEDRGMS
RKPEDLYVRR QTARMRLSKY AAYNTYHHCE QCHQYMGFHP RYQLYESTLH AFAFSYSMLG
EEIQLHFIIP KSKEHHFVFS QPGGQLESMR LPLVTDKSHE YIKSPTFTPT TGRHEHGLFN
LYHAMDGASH LHVLVVKEYE MAIYKKYWPN HIMLVLPSIF NSAGVGAAHF LIKELSYHNL
ELERNRQEEL GIKPQDIWPF IVISDDSCVM WNVVDVNSAG ERSREFSWSE RNVSLKHIMQ
HIEAAPDIMH YALLGLRKWS SKTRASEVQE PFSRCHVHNF IILNVDLTQN VQYNQNRFLC
DDVDFNLRVH SAGLLLCRFN RFSVMKKQIV VGGHRSFHIT SKVSDNSAAV VPAQYICAPD
SKHTFLAAPA QLLLEKFLQH HSHLFFPLSL KNHDHPVLSV DCYLNLGSQI SVCYVSSRPH
SLNISCSDLL FSGLLLYLCD SFVGASFLKK FHFLKGATLC VICQDRSSLR QTVVRLELED
EWQFRLRDEF QTANAREDRP LFFLTGRHI