Anterior gradient protein
From Proteopedia
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== Anterior Gradient Protein 2 == | == Anterior Gradient Protein 2 == | ||
<StructureSection load='2LNS' size='350' side='right' caption='residues 41-175 of AGR2 in dimer form (PDB entry [[2lns]])' scene='87/872187/Agr2_full/1'> | <StructureSection load='2LNS' size='350' side='right' caption='residues 41-175 of AGR2 in dimer form (PDB entry [[2lns]])' scene='87/872187/Agr2_full/1'> | ||
| + | __TOC__ | ||
| + | ==Function== | ||
[https://www.uniprot.org/uniprot/AGR2_HUMAN AGR2_HUMAN] | [https://www.uniprot.org/uniprot/AGR2_HUMAN AGR2_HUMAN] | ||
Originally discovered in Xenopus laevis as a cement gland differentiation regulator <ref>PMID: 31644305</ref>, <scene name='87/872187/Agr2_full/1'>Anterior Gradient Protein 2</scene> (AGR2) in humans is a protein chaperone ([[chaperones]]) involved in '''proteostasis''', mainly for proteins expressed in epithelial cells, such as in the esophagus or lungs<ref>PMID:33005802</ref>. AGR2, composed of 175 amino acids, belongs to the protein disulfide isomerase family ([https://www.uniprot.org/uniprot/P07237 PDI]). | Originally discovered in Xenopus laevis as a cement gland differentiation regulator <ref>PMID: 31644305</ref>, <scene name='87/872187/Agr2_full/1'>Anterior Gradient Protein 2</scene> (AGR2) in humans is a protein chaperone ([[chaperones]]) involved in '''proteostasis''', mainly for proteins expressed in epithelial cells, such as in the esophagus or lungs<ref>PMID:33005802</ref>. AGR2, composed of 175 amino acids, belongs to the protein disulfide isomerase family ([https://www.uniprot.org/uniprot/P07237 PDI]). | ||
== Structural highlights == | == Structural highlights == | ||
This protein contains various remarkable domains which can be visualized in the interactive model<ref>PMID:33005802</ref>. | This protein contains various remarkable domains which can be visualized in the interactive model<ref>PMID:33005802</ref>. | ||
| - | + | '''- an unfolded NH2 terminal sequence with a peptide signal from the first to the 21st amino acid.''' | |
| - | + | '''- an active pseudo-thioredoxin domain (CXXS) from the <scene name='87/872187/Agr2_cxxs/2'>81st to the 84th amino acid</scene>. | |
Called “pseudo” because there is only one active cysteine residue (<scene name='87/872187/Agr2_c81/2'>C81</scene>) | Called “pseudo” because there is only one active cysteine residue (<scene name='87/872187/Agr2_c81/2'>C81</scene>) | ||
| - | + | ''' - a terminal COOH sequence with a KTEL motif from the <scene name='87/872187/Agr2_cter/1'>172nd to the last amino acid.</scene>''''' | |
Moreover, this protein can be found as a monomer or a dimer, thanks to a specific motif which is '''EALYK''' between the <scene name='87/872187/Agr2_dim/1'>60th and the 64th amino acids</scene>. There are intermolecular [[salt bridges]] involving E60 and K64, in order to fix the second monomer. The''' CXXS domain''' is on the opposite side to avoid any disulfide exchange. Nevertheless, the dimeric structure is oxidation-dependent which means that C81 is necessary<ref>PMID: 31644305</ref>. | Moreover, this protein can be found as a monomer or a dimer, thanks to a specific motif which is '''EALYK''' between the <scene name='87/872187/Agr2_dim/1'>60th and the 64th amino acids</scene>. There are intermolecular [[salt bridges]] involving E60 and K64, in order to fix the second monomer. The''' CXXS domain''' is on the opposite side to avoid any disulfide exchange. Nevertheless, the dimeric structure is oxidation-dependent which means that C81 is necessary<ref>PMID: 31644305</ref>. | ||
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The AGR2 protein can form complexes with [https://www.uniprot.org/uniprot/Q9Y230 Reptin] ([[2cqa]]) which is recognized as an '''anti-oncogene'''. However, it binds more easily when the protein is in dimeric form. Thus, a mutation on (<scene name='87/872187/Agr2_e60/2'>E60</scene>) site, giving the protein a monomeric form, would reduce cancer repression by Reptin. | The AGR2 protein can form complexes with [https://www.uniprot.org/uniprot/Q9Y230 Reptin] ([[2cqa]]) which is recognized as an '''anti-oncogene'''. However, it binds more easily when the protein is in dimeric form. Thus, a mutation on (<scene name='87/872187/Agr2_e60/2'>E60</scene>) site, giving the protein a monomeric form, would reduce cancer repression by Reptin. | ||
Finally, the expression of AGR2 in breast cancer patients confers chemoresistance to cancer cell growth inhibitors such as Tamoxifen, the mechanism is still unclear.<ref>PMID: 25937245</ref> | Finally, the expression of AGR2 in breast cancer patients confers chemoresistance to cancer cell growth inhibitors such as Tamoxifen, the mechanism is still unclear.<ref>PMID: 25937245</ref> | ||
| - | </StructureSection> | ||
| + | == 3D Structures of anterior gradient protein == | ||
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| + | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
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| + | [[2lns]] - hAGR2 - human - NMR<br /> | ||
| + | [[2lnt]] - hAGR2 (mutant) - NMR<br /> | ||
| + | [[3ph9]] - hAGR3<br /> | ||
== References == | == References == | ||
<references/> | <references/> | ||
| + | </StructureSection> | ||
| + | [[Category:Topic Page]] | ||
Current revision
Anterior Gradient Protein 2
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Loane Schertzer, Michal Harel, Marion Ottinger, Léa Moyon, Jaime Prilusky
