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Anterior gradient protein 3 (AG-3) (AG3) (hAG-3) (Anterior gradient 3 homolog) (Breast cancer membrane protein 11) (Protein disulfide isomerase family A, member 18)

 AGR3_HUMAN              Reviewed;         166 AA.
Q8TD06; A4D120;
10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
01-JUN-2002, sequence version 1.
18-JUL-2018, entry version 114.
RecName: Full=Anterior gradient protein 3;
Short=AG-3;
Short=AG3;
Short=hAG-3;
AltName: Full=Anterior gradient 3 homolog {ECO:0000312|HGNC:HGNC:24167};
AltName: Full=Breast cancer membrane protein 11 {ECO:0000312|HGNC:HGNC:24167};
AltName: Full=Protein disulfide isomerase family A, member 18 {ECO:0000312|HGNC:HGNC:24167};
Flags: Precursor;
Name=AGR3; Synonyms=BCMP11, PDIA18; ORFNames=UNQ642/PRO1272;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=12477722; DOI=10.1074/jbc.M210184200;
Adam P.J., Boyd R., Tyson K.L., Fletcher G.C., Stamps A., Hudson L.,
Poyser H.R., Redpath N., Griffiths M., Steers G., Harris A.L.,
Patel S., Berry J., Loader J.A., Townsend R.R., Daviet L., Legrain P.,
Parekh R., Terrett J.A.;
"Comprehensive proteomic analysis of breast cancer cell membranes
reveals unique proteins with potential roles in clinical cancer.";
J. Biol. Chem. 278:6482-6489(2003).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12690205; DOI=10.1126/science.1083423;
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
Mural R.J., Adams M.D., Tsui L.-C.;
"Human chromosome 7: DNA sequence and biology.";
Science 300:767-772(2003).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PROTEIN SEQUENCE OF 22-36.
PubMed=15340161; DOI=10.1110/ps.04682504;
Zhang Z., Henzel W.J.;
"Signal peptide prediction based on analysis of experimentally
verified cleavage sites.";
Protein Sci. 13:2819-2824(2004).
[7]
INTERACTION WITH LYPD3 AND DAG1.
PubMed=12592373; DOI=10.1038/sj.bjc.6600740;
Fletcher G.C., Patel S., Tyson K., Adam P.J., Schenker M.,
Loader J.A., Daviet L., Legrain P., Parekh R., Harris A.L.,
Terrett J.A.;
"hAG-2 and hAG-3, human homologues of genes involved in
differentiation, are associated with oestrogen receptor-positive
breast tumours and interact with metastasis gene C4.4a and
dystroglycan.";
Br. J. Cancer 88:579-585(2003).
[8]
SUBCELLULAR LOCATION, AND MUTAGENESIS OF 163-GLN--LEU-166.
PubMed=18086916; DOI=10.1083/jcb.200705180;
Raykhel I., Alanen H., Salo K., Jurvansuu J., Nguyen V.D.,
Latva-Ranta M., Ruddock L.;
"A molecular specificity code for the three mammalian KDEL
receptors.";
J. Cell Biol. 179:1193-1204(2007).
[9]
INDUCTION.
PubMed=22361111; DOI=10.1016/j.jim.2012.01.013;
Gray T.A., MacLaine N.J., Michie C.O., Bouchalova P., Murray E.,
Howie J., Hrstka R., Maslon M.M., Nenutil R., Vojtesek B., Langdon S.,
Hayward L., Gourley C., Hupp T.R.;
"Anterior Gradient-3: a novel biomarker for ovarian cancer that
mediates cisplatin resistance in xenograft models.";
J. Immunol. Methods 378:20-32(2012).
[10]
INDUCTION.
PubMed=23294566; DOI=10.1111/febs.12118;
Bu H., Schweiger M.R., Manke T., Wunderlich A., Timmermann B.,
Kerick M., Pasqualini L., Shehu E., Fuchsberger C., Cato A.C.,
Klocker H.;
"Anterior gradient 2 and 3--two prototype androgen-responsive genes
transcriptionally upregulated by androgens and by oestrogens in
prostate cancer cells.";
FEBS J. 280:1249-1266(2013).
[11]
TISSUE SPECIFICITY, INDUCTION, AND SUBCELLULAR LOCATION.
PubMed=25751668; DOI=10.1165/rcmb.2014-0318OC;
Bonser L.R., Schroeder B.W., Ostrin L.A., Baumlin N., Olson J.L.,
Salathe M., Erle D.J.;
"The ER resident protein AGR3 is required for regulation of ciliary
beat frequency in the airway.";
Am. J. Respir. Cell Mol. Biol. 53:536-543(2015).
[12]
TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
PubMed=26170690; DOI=10.2147/OTT.S82235;
Obacz J., Brychtova V., Podhorec J., Fabian P., Dobes P., Vojtesek B.,
Hrstka R.;
"Anterior gradient protein 3 is associated with less aggressive tumors
and better outcome of breast cancer patients.";
Onco Targets Ther. 8:1523-1532(2015).
[13] {ECO:0000244|PDB:3PH9}
X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 24-166.
Nguyen V.D., Ruddock L.W., Salin M., Wierenga R.K.;
"Crystal structure of the human anterior gradient protein 3.";
Submitted (NOV-2010) to the PDB data bank.
-!- FUNCTION: Required for calcium-mediated regulation of ciliary beat
frequency and mucociliary clearance in the airway. Might be
involved in the regulation of intracellular calcium in tracheal
epithelial cells. {ECO:0000250|UniProtKB:Q8R3W7}.
-!- SUBUNIT: Interacts with LYPD3 and DAG1 (alphaDAG1).
{ECO:0000269|PubMed:12592373}.
-!- INTERACTION:
O75477:ERLIN1; NbExp=5; IntAct=EBI-3925742, EBI-359299;
P37198:NUP62; NbExp=5; IntAct=EBI-3925742, EBI-347978;
O43765:SGTA; NbExp=5; IntAct=EBI-3925742, EBI-347996;
Q96EQ0:SGTB; NbExp=4; IntAct=EBI-3925742, EBI-744081;
Q9UMX0:UBQLN1; NbExp=3; IntAct=EBI-3925742, EBI-741480;
Q9UMX0-2:UBQLN1; NbExp=3; IntAct=EBI-3925742, EBI-10173939;
Q9UHD9:UBQLN2; NbExp=4; IntAct=EBI-3925742, EBI-947187;
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum
{ECO:0000269|PubMed:18086916, ECO:0000269|PubMed:25751668}.
Note=Found in the cytoplasm, which could include the endoplasmic
reticulum. {ECO:0000305|PubMed:26170690}.
-!- TISSUE SPECIFICITY: Expressed in the lung, in the ciliated cells
of the airway epithelium (PubMed:25751668). Expression increased
with differentiation of airway epithelial cells (PubMed:25751668).
Not detected in the mucous cells (PubMed:25751668). Expressed in
ciliated cells in the oviduct (PubMed:26170690). Also detected in
stomach, colon, prostate and liver (PubMed:25751668). Expressed in
breast, ovary, prostate and liver cancer (PubMed:26170690).
Expression is associated with the level of differentiation of
breast cancer (at protein level) (PubMed:26170690).
{ECO:0000269|PubMed:25751668, ECO:0000269|PubMed:26170690}.
-!- INDUCTION: Not induced as part of the cellular response to
endoplasmic reticulum stress (PubMed:25751668). Up-regulated by
androgens and by estrogens in prostate cancer cells
(PubMed:23294566) Up-regulated by a hormone (estrogen-receptor
alpha) independent mechanism in ovarian cancer (PubMed:22361111).
{ECO:0000269|PubMed:22361111, ECO:0000269|PubMed:23294566,
ECO:0000269|PubMed:25751668}.
-!- SIMILARITY: Belongs to the AGR family. {ECO:0000305}.
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EMBL; AY069977; AAL55402.1; -; mRNA.
EMBL; AY359065; AAQ89424.1; -; mRNA.
EMBL; CH236948; EAL24282.1; -; Genomic_DNA.
EMBL; CH471073; EAW93685.1; -; Genomic_DNA.
EMBL; BC058284; AAH58284.1; -; mRNA.
CCDS; CCDS5365.1; -.
RefSeq; NP_789783.1; NM_176813.4.
RefSeq; XP_005249684.1; XM_005249627.2.
UniGene; Hs.100686; -.
PDB; 3PH9; X-ray; 1.83 A; A/B=24-166.
PDBsum; 3PH9; -.
ProteinModelPortal; Q8TD06; -.
SMR; Q8TD06; -.
BioGrid; 127586; 17.
IntAct; Q8TD06; 29.
MINT; Q8TD06; -.
STRING; 9606.ENSP00000308606; -.
iPTMnet; Q8TD06; -.
PhosphoSitePlus; Q8TD06; -.
BioMuta; AGR3; -.
DMDM; 66774045; -.
MaxQB; Q8TD06; -.
PaxDb; Q8TD06; -.
PeptideAtlas; Q8TD06; -.
PRIDE; Q8TD06; -.
ProteomicsDB; 74205; -.
DNASU; 155465; -.
Ensembl; ENST00000310398; ENSP00000308606; ENSG00000173467.
GeneID; 155465; -.
KEGG; hsa:155465; -.
UCSC; uc003sts.4; human.
CTD; 155465; -.
DisGeNET; 155465; -.
EuPathDB; HostDB:ENSG00000173467.8; -.
GeneCards; AGR3; -.
HGNC; HGNC:24167; AGR3.
HPA; HPA053942; -.
MIM; 609482; gene.
neXtProt; NX_Q8TD06; -.
OpenTargets; ENSG00000173467; -.
PharmGKB; PA162375917; -.
eggNOG; ENOG410IWAH; Eukaryota.
eggNOG; ENOG4111K70; LUCA.
GeneTree; ENSGT00530000063273; -.
HOGENOM; HOG000231100; -.
HOVERGEN; HBG006516; -.
InParanoid; Q8TD06; -.
KO; K20357; -.
OMA; AQNNFIM; -.
OrthoDB; EOG091G0RHV; -.
PhylomeDB; Q8TD06; -.
TreeFam; TF321449; -.
GeneWiki; AGR3; -.
GenomeRNAi; 155465; -.
PRO; PR:Q8TD06; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000173467; -.
CleanEx; HS_AGR3; -.
ExpressionAtlas; Q8TD06; baseline and differential.
Genevisible; Q8TD06; HS.
GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
GO; GO:0002162; F:dystroglycan binding; IDA:UniProtKB.
GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
GO; GO:0060548; P:negative regulation of cell death; IBA:GO_Central.
InterPro; IPR036249; Thioredoxin-like_sf.
SUPFAM; SSF52833; SSF52833; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Direct protein sequencing;
Endoplasmic reticulum; Reference proteome; Signal.
SIGNAL 1 21 {ECO:0000269|PubMed:15340161}.
CHAIN 22 166 Anterior gradient protein 3.
/FTId=PRO_0000001040.
MOTIF 163 166 Prevents secretion from ER.
{ECO:0000269|PubMed:18086916}.
MUTAGEN 163 166 Missing: Leads to Golgi localization;.
{ECO:0000269|PubMed:18086916}.
STRAND 33 35 {ECO:0000244|PDB:3PH9}.
HELIX 48 58 {ECO:0000244|PDB:3PH9}.
STRAND 62 66 {ECO:0000244|PDB:3PH9}.
HELIX 72 83 {ECO:0000244|PDB:3PH9}.
HELIX 85 93 {ECO:0000244|PDB:3PH9}.
STRAND 96 102 {ECO:0000244|PDB:3PH9}.
HELIX 107 109 {ECO:0000244|PDB:3PH9}.
STRAND 116 122 {ECO:0000244|PDB:3PH9}.
HELIX 145 147 {ECO:0000244|PDB:3PH9}.
HELIX 148 159 {ECO:0000244|PDB:3PH9}.
SEQUENCE 166 AA; 19171 MW; B1A4804B47705D65 CRC64;
MMLHSALGLC LLLVTVSSNL AIAIKKEKRP PQTLSRGWGD DITWVQTYEE GLFYAQKSKK
PLMVIHHLED CQYSQALKKV FAQNEEIQEM AQNKFIMLNL MHETTDKNLS PDGQYVPRIM
FVDPSLTVRA DIAGRYSNRL YTYEPRDLPL LIENMKKALR LIQSEL


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