AGR3_HUMAN
ID AGR3_HUMAN Reviewed; 166 AA.
AC Q8TD06; A4D120;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Anterior gradient protein 3;
DE Short=AG-3;
DE Short=AG3;
DE Short=hAG-3;
DE AltName: Full=Anterior gradient 3 homolog {ECO:0000312|HGNC:HGNC:24167};
DE AltName: Full=Breast cancer membrane protein 11 {ECO:0000312|HGNC:HGNC:24167};
DE AltName: Full=Protein disulfide isomerase family A, member 18 {ECO:0000312|HGNC:HGNC:24167};
DE Flags: Precursor;
GN Name=AGR3; Synonyms=BCMP11, PDIA18; ORFNames=UNQ642/PRO1272;
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].
RX PubMed=12477722; DOI=10.1074/jbc.m210184200;
RA Adam P.J., Boyd R., Tyson K.L., Fletcher G.C., Stamps A., Hudson L.,
RA Poyser H.R., Redpath N., Griffiths M., Steers G., Harris A.L., Patel S.,
RA Berry J., Loader J.A., Townsend R.R., Daviet L., Legrain P., Parekh R.,
RA Terrett J.A.;
RT "Comprehensive proteomic analysis of breast cancer cell membranes reveals
RT unique proteins with potential roles in clinical cancer.";
RL J. Biol. Chem. 278:6482-6489(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 PROTEIN SEQUENCE OF 22-36.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP INTERACTION WITH LYPD3 AND DAG1.
RX PubMed=12592373; DOI=10.1038/sj.bjc.6600740;
RA Fletcher G.C., Patel S., Tyson K., Adam P.J., Schenker M., Loader J.A.,
RA Daviet L., Legrain P., Parekh R., Harris A.L., Terrett J.A.;
RT "hAG-2 and hAG-3, human homologues of genes involved in differentiation,
RT are associated with oestrogen receptor-positive breast tumours and interact
RT with metastasis gene C4.4a and dystroglycan.";
RL Br. J. Cancer 88:579-585(2003).
RN [8]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 163-GLN--LEU-166.
RX PubMed=18086916; DOI=10.1083/jcb.200705180;
RA Raykhel I., Alanen H., Salo K., Jurvansuu J., Nguyen V.D., Latva-Ranta M.,
RA Ruddock L.;
RT "A molecular specificity code for the three mammalian KDEL receptors.";
RL J. Cell Biol. 179:1193-1204(2007).
RN [9]
RP INDUCTION.
RX PubMed=22361111; DOI=10.1016/j.jim.2012.01.013;
RA Gray T.A., MacLaine N.J., Michie C.O., Bouchalova P., Murray E., Howie J.,
RA Hrstka R., Maslon M.M., Nenutil R., Vojtesek B., Langdon S., Hayward L.,
RA Gourley C., Hupp T.R.;
RT "Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates
RT cisplatin resistance in xenograft models.";
RL J. Immunol. Methods 378:20-32(2012).
RN [10]
RP INDUCTION.
RX PubMed=23294566; DOI=10.1111/febs.12118;
RA Bu H., Schweiger M.R., Manke T., Wunderlich A., Timmermann B., Kerick M.,
RA Pasqualini L., Shehu E., Fuchsberger C., Cato A.C., Klocker H.;
RT "Anterior gradient 2 and 3--two prototype androgen-responsive genes
RT transcriptionally upregulated by androgens and by oestrogens in prostate
RT cancer cells.";
RL FEBS J. 280:1249-1266(2013).
RN [11]
RP TISSUE SPECIFICITY, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25751668; DOI=10.1165/rcmb.2014-0318oc;
RA Bonser L.R., Schroeder B.W., Ostrin L.A., Baumlin N., Olson J.L.,
RA Salathe M., Erle D.J.;
RT "The ER resident protein AGR3 is required for regulation of ciliary beat
RT frequency in the airway.";
RL Am. J. Respir. Cell Mol. Biol. 53:536-543(2015).
RN [12]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=26170690; DOI=10.2147/ott.s82235;
RA Obacz J., Brychtova V., Podhorec J., Fabian P., Dobes P., Vojtesek B.,
RA Hrstka R.;
RT "Anterior gradient protein 3 is associated with less aggressive tumors and
RT better outcome of breast cancer patients.";
RL Onco Targets Ther. 8:1523-1532(2015).
RN [13] {ECO:0007744|PDB:3PH9}
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 24-166.
RA Nguyen V.D., Ruddock L.W., Salin M., Wierenga R.K.;
RT "Crystal structure of the human anterior gradient protein 3.";
RL Submitted (NOV-2010) to the PDB data bank.
CC -!- FUNCTION: Required for calcium-mediated regulation of ciliary beat
CC frequency and mucociliary clearance in the airway. Might be involved in
CC the regulation of intracellular calcium in tracheal epithelial cells.
CC {ECO:0000250|UniProtKB:Q8R3W7}.
CC -!- SUBUNIT: Interacts with LYPD3 and DAG1 (alphaDAG1).
CC {ECO:0000269|PubMed:12592373}.
CC -!- INTERACTION:
CC Q8TD06; Q10567-3: AP1B1; NbExp=3; IntAct=EBI-3925742, EBI-11978055;
CC Q8TD06; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-3925742, EBI-744545;
CC Q8TD06; P15529-3: CD46; NbExp=3; IntAct=EBI-3925742, EBI-13046140;
CC Q8TD06; Q99675: CGRRF1; NbExp=3; IntAct=EBI-3925742, EBI-2130213;
CC Q8TD06; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-3925742, EBI-741032;
CC Q8TD06; Q6ICB0: DESI1; NbExp=3; IntAct=EBI-3925742, EBI-2806959;
CC Q8TD06; Q9HAV5: EDA2R; NbExp=3; IntAct=EBI-3925742, EBI-526033;
CC Q8TD06; O75477: ERLIN1; NbExp=6; IntAct=EBI-3925742, EBI-359299;
CC Q8TD06; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-3925742, EBI-12175685;
CC Q8TD06; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-3925742, EBI-1052037;
CC Q8TD06; Q9H400: LIME1; NbExp=3; IntAct=EBI-3925742, EBI-2830566;
CC Q8TD06; O15116: LSM1; NbExp=3; IntAct=EBI-3925742, EBI-347619;
CC Q8TD06; Q8N4V1: MMGT1; NbExp=3; IntAct=EBI-3925742, EBI-6163737;
CC Q8TD06; Q8IXM6: NRM; NbExp=3; IntAct=EBI-3925742, EBI-10262547;
CC Q8TD06; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-3925742, EBI-741158;
CC Q8TD06; P37198: NUP62; NbExp=6; IntAct=EBI-3925742, EBI-347978;
CC Q8TD06; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-3925742, EBI-716063;
CC Q8TD06; O60831: PRAF2; NbExp=3; IntAct=EBI-3925742, EBI-2506064;
CC Q8TD06; A0A0S2Z4U3: SDC3; NbExp=3; IntAct=EBI-3925742, EBI-10204280;
CC Q8TD06; O43765: SGTA; NbExp=6; IntAct=EBI-3925742, EBI-347996;
CC Q8TD06; Q96EQ0: SGTB; NbExp=8; IntAct=EBI-3925742, EBI-744081;
CC Q8TD06; O43278-2: SPINT1; NbExp=3; IntAct=EBI-3925742, EBI-12078338;
CC Q8TD06; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-3925742, EBI-6268651;
CC Q8TD06; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-3925742, EBI-8638294;
CC Q8TD06; Q9UMX0: UBQLN1; NbExp=4; IntAct=EBI-3925742, EBI-741480;
CC Q8TD06; Q9UMX0-2: UBQLN1; NbExp=3; IntAct=EBI-3925742, EBI-10173939;
CC Q8TD06; Q9UHD9: UBQLN2; NbExp=6; IntAct=EBI-3925742, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:18086916, ECO:0000269|PubMed:25751668}. Note=Found
CC in the cytoplasm, which could include the endoplasmic reticulum.
CC {ECO:0000305|PubMed:26170690}.
CC -!- TISSUE SPECIFICITY: Expressed in the lung, in the ciliated cells of the
CC airway epithelium (PubMed:25751668). Expression increased with
CC differentiation of airway epithelial cells (PubMed:25751668). Not
CC detected in the mucous cells (PubMed:25751668). Expressed in ciliated
CC cells in the oviduct (PubMed:26170690). Also detected in stomach,
CC colon, prostate and liver (PubMed:25751668). Expressed in breast,
CC ovary, prostate and liver cancer (PubMed:26170690). Expression is
CC associated with the level of differentiation of breast cancer (at
CC protein level) (PubMed:26170690). {ECO:0000269|PubMed:25751668,
CC ECO:0000269|PubMed:26170690}.
CC -!- INDUCTION: Not induced as part of the cellular response to endoplasmic
CC reticulum stress (PubMed:25751668). Up-regulated by androgens and by
CC estrogens in prostate cancer cells (PubMed:23294566) Up-regulated by a
CC hormone (estrogen-receptor alpha) independent mechanism in ovarian
CC cancer (PubMed:22361111). {ECO:0000269|PubMed:22361111,
CC ECO:0000269|PubMed:23294566, ECO:0000269|PubMed:25751668}.
CC -!- SIMILARITY: Belongs to the AGR family. {ECO:0000305}.
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DR EMBL; AY069977; AAL55402.1; -; mRNA.
DR EMBL; AY359065; AAQ89424.1; -; mRNA.
DR EMBL; CH236948; EAL24282.1; -; Genomic_DNA.
DR EMBL; CH471073; EAW93685.1; -; Genomic_DNA.
DR EMBL; BC058284; AAH58284.1; -; mRNA.
DR CCDS; CCDS5365.1; -.
DR RefSeq; NP_789783.1; NM_176813.4.
DR RefSeq; XP_005249684.1; XM_005249627.2.
DR PDB; 3PH9; X-ray; 1.83 A; A/B=24-166.
DR PDBsum; 3PH9; -.
DR AlphaFoldDB; Q8TD06; -.
DR SMR; Q8TD06; -.
DR BioGRID; 127586; 39.
DR IntAct; Q8TD06; 34.
DR MINT; Q8TD06; -.
DR STRING; 9606.ENSP00000308606; -.
DR GlyGen; Q8TD06; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; Q8TD06; -.
DR PhosphoSitePlus; Q8TD06; -.
DR BioMuta; AGR3; -.
DR DMDM; 66774045; -.
DR jPOST; Q8TD06; -.
DR MassIVE; Q8TD06; -.
DR MaxQB; Q8TD06; -.
DR PaxDb; Q8TD06; -.
DR PeptideAtlas; Q8TD06; -.
DR PRIDE; Q8TD06; -.
DR ProteomicsDB; 74205; -.
DR Antibodypedia; 25286; 300 antibodies from 34 providers.
DR DNASU; 155465; -.
DR Ensembl; ENST00000310398.7; ENSP00000308606.2; ENSG00000173467.9.
DR GeneID; 155465; -.
DR KEGG; hsa:155465; -.
DR MANE-Select; ENST00000310398.7; ENSP00000308606.2; NM_176813.5; NP_789783.1.
DR UCSC; uc003sts.4; human.
DR CTD; 155465; -.
DR DisGeNET; 155465; -.
DR GeneCards; AGR3; -.
DR HGNC; HGNC:24167; AGR3.
DR HPA; ENSG00000173467; Tissue enhanced (fallopian tube, intestine, lung).
DR MIM; 609482; gene.
DR neXtProt; NX_Q8TD06; -.
DR OpenTargets; ENSG00000173467; -.
DR PharmGKB; PA162375917; -.
DR VEuPathDB; HostDB:ENSG00000173467; -.
DR eggNOG; ENOG502R72A; Eukaryota.
DR GeneTree; ENSGT00530000063273; -.
DR HOGENOM; CLU_088048_1_0_1; -.
DR InParanoid; Q8TD06; -.
DR OMA; NMAPDGY; -.
DR OrthoDB; 1382017at2759; -.
DR PhylomeDB; Q8TD06; -.
DR TreeFam; TF321449; -.
DR PathwayCommons; Q8TD06; -.
DR SignaLink; Q8TD06; -.
DR BioGRID-ORCS; 155465; 42 hits in 1026 CRISPR screens.
DR ChiTaRS; AGR3; human.
DR GeneWiki; AGR3; -.
DR GenomeRNAi; 155465; -.
DR Pharos; Q8TD06; Tbio.
DR PRO; PR:Q8TD06; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q8TD06; protein.
DR Bgee; ENSG00000173467; Expressed in bronchial epithelial cell and 128 other tissues.
DR ExpressionAtlas; Q8TD06; baseline and differential.
DR Genevisible; Q8TD06; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0002162; F:dystroglycan binding; IDA:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR SUPFAM; SSF52833; SSF52833; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum;
KW Reference proteome; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 22..166
FT /note="Anterior gradient protein 3"
FT /id="PRO_0000001040"
FT MOTIF 163..166
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000269|PubMed:18086916"
FT MUTAGEN 163..166
FT /note="Missing: Leads to Golgi localization;."
FT /evidence="ECO:0000269|PubMed:18086916"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:3PH9"
FT HELIX 48..58
FT /evidence="ECO:0007829|PDB:3PH9"
FT STRAND 62..66
FT /evidence="ECO:0007829|PDB:3PH9"
FT HELIX 72..83
FT /evidence="ECO:0007829|PDB:3PH9"
FT HELIX 85..93
FT /evidence="ECO:0007829|PDB:3PH9"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:3PH9"
FT HELIX 107..109
FT /evidence="ECO:0007829|PDB:3PH9"
FT STRAND 116..122
FT /evidence="ECO:0007829|PDB:3PH9"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:3PH9"
FT HELIX 148..159
FT /evidence="ECO:0007829|PDB:3PH9"
SQ SEQUENCE 166 AA; 19171 MW; B1A4804B47705D65 CRC64;
MMLHSALGLC LLLVTVSSNL AIAIKKEKRP PQTLSRGWGD DITWVQTYEE GLFYAQKSKK
PLMVIHHLED CQYSQALKKV FAQNEEIQEM AQNKFIMLNL MHETTDKNLS PDGQYVPRIM
FVDPSLTVRA DIAGRYSNRL YTYEPRDLPL LIENMKKALR LIQSEL
