Aminopeptidazni regulator tipa 1 receptorskog faktora tumorske necroze, znan i kao endoplazmatskoretikulumska aminopeptidaza 1 (ARTS-1), jest protein koji je kod ljudi kodiran genom ARTS-1.[5]
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Zatvori
Endoplazmatskoretikulumska aminopeptidaza 1 je aktivna u endoplazmatskom retikulumu, koji je uključen u obradu i transport proteina. Ovaj protein je aminopeptidaza, enzim koji cijepa peptide na N-terminalu na manje fragmente koji se nazivaju aminokiseline.
ARTS1 je takođe poznat kao:
- ER aminopeptidaza 1 (ERAP1), naziv gena koji je prihvatio Odbor za nomenklaturu Hugo[6]
- ER aminopeptidaza povezana s obradom antigena (ERAAP) kod miševa [7]
- Leucin-aminopeptidaza izvedena iz adipocita (ALAP)
- Puromicin neosjetljiva leucin-aminopeptidaza (PILS-AP)
Dužina polipeptidnog lanca je 941 aminokiselina, а molekulska težina 107.235 Da.[8]
| 10 | | 20 | | 30 | | 40 | | 50 |
|---|
| MVFLPLKWSL | | ATMSFLLSSL | | LALLTVSTPS | | WCQSTEASPK | | RSDGTPFPWN |
| KIRLPEYVIP | | VHYDLLIHAN | | LTTLTFWGTT | | KVEITASQPT | | STIILHSHHL |
| QISRATLRKG | | AGERLSEEPL | | QVLEHPRQEQ | | IALLAPEPLL | | VGLPYTVVIH |
| YAGNLSETFH | | GFYKSTYRTK | | EGELRILAST | | QFEPTAARMA | | FPCFDEPAFK |
| ASFSIKIRRE | | PRHLAISNMP | | LVKSVTVAEG | | LIEDHFDVTV | | KMSTYLVAFI |
| ISDFESVSKI | | TKSGVKVSVY | | AVPDKINQAD | | YALDAAVTLL | | EFYEDYFSIP |
| YPLPKQDLAA | | IPDFQSGAME | | NWGLTTYRES | | ALLFDAEKSS | | ASSKLGITMT |
| VAHELAHQWF | | GNLVTMEWWN | | DLWLNEGFAK | | FMEFVSVSVT | | HPELKVGDYF |
| FGKCFDAMEV | | DALNSSHPVS | | TPVENPAQIR | | EMFDDVSYDK | | GACILNMLRE |
| YLSADAFKSG | | IVQYLQKHSY | | KNTKNEDLWD | | SMASICPTDG | | VKGMDGFCSR |
| SQHSSSSSHW | | HQEGVDVKTM | | MNTWTLQKGF | | PLITITVRGR | | NVHMKQEHYM |
| KGSDGAPDTG | | YLWHVPLTFI | | TSKSDMVHRF | | LLKTKTDVLI | | LPEEVEWIKF |
| NVGMNGYYIV | | HYEDDGWDSL | | TGLLKGTHTA | | VSSNDRASLI | | NNAFQLVSIG |
| KLSIEKALDL | | SLYLKHETEI | | MPVFQGLNEL | | IPMYKLMEKR | | DMNEVETQFK |
| AFLIRLLRDL | | IDKQTWTDEG | | SVSERMLRSQ | | LLLLACVHNY | | QPCVQRAEGY |
| FRKWKESNGN | | LSLPVDVTLA | | VFAVGAQSTE | | GWDFLYSKYQ | | FSLSSTEKSQ |
| IEFALCRTQN | | KEKLQWLLDE | | SFKGDKIKTQ | | EFPQILTLIG | | RNPVGYPLAW |
| QFLRKNWNKL | | VQKFELGSSS | | IAHMVMGTTN | | QFSTRTRLEE | | VKGFFSSLKE |
| NGSQLRCVQQ | | TIETIEENIG | | WMDKNFDKIR | | VWLQSEKLER | | M |
ERAP1 ima dvije glavne funkcije u imunskom sistemu:
- Prvo, ERAP1 cijepa nekoliko proteina koji se nazivaju citokinskim receptorima na površini ćelija. Cijepanje ovih receptora smanjuje njihovu sposobnost da prenose hemijske signale u ćeliju, što utiče na proces upale.
- Drugo, ERAP1 skračuje peptide unutar endoplazmatskog retikuluma, tako da se mogu učitati u glavni kompleks histokompatibilnosti (MHC) klase I. Ovi peptidi su vezani za MHC klasu I u endoplazmatskom retikulumu i eksportirani na ćelijsku površinu, gdje se prezentiraju u imunskom sistemu. Ako imunski sistem prepozna peptide kao strane (kao što su virusni ili bakterijski peptidi), reagira aktiviranjem zaražene ćelije na samouništenje.[9]
ARTS-1 je član M1 cinkove porodice metaloproteinaza koji djeluje kao aminopeptidaza za razgradnju oligopeptida, cijepanjem počevši od N-terminala. Jedna od funkcija aminopeptidaza je razgradnja potencijalno toksičnih peptida u citosolu.[5]
ARTS-1 je transmembranski protein koji je lokaliziran na endoplazmatski retikulum. Bio je uključen u sljedeće funkcije:
Aminopeptidaze imaju ulogu u metabolizmu nekoliko peptida koji mogu biti uključeni u krvni pritisak i patopatogenezu esencijalne hipertenzije.[5] Mutacije u ARTS-1 povezane su s povećanim rizikom od ankilozantnog spondilitisa, ali samo u HLA-B27 pozitivnih pacijenata.[11]
Protein kodiran ovim genom je aminopeptidaza uključena u podrezivanje prekursora za vezivanje HLA klase I, tako da se mogu prezentirati na molekulama MHC klase I. Kodirani protein djeluje kao monomer ili kao heterodimer ERAP2. Ovaj protein također može biti uključen u regulaciju krvnog pritiska, inaktivacijom angiotenzina II. Za ovaj gen su pronađene tri varijante transkripta koje kodiraju dvije različite izoforme.[5]
"HGNC". HGNC. Arhivirano s originala, 11. 4. 2015. Pristupljeno 27. 3. 2014.
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- Tsujimoto M, Hattori A (2005). "The oxytocinase subfamily of M1 aminopeptidases". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1751 (1): 9–18. doi:10.1016/j.bbapap.2004.09.011. PMID 16054015.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5′-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (1998). "Prediction of the Coding Sequences of Unidentified Human Genes. IX. The Complete Sequences of 100 New cDNA Clones from Brain Which Can Code for Large Proteins in vitro". DNA Research. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581.
- Hattori A, Matsumoto H, Mizutani S, Tsujimoto M (1999). "Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase". Journal of Biochemistry. 125 (5): 931–8. doi:10.1093/oxfordjournals.jbchem.a022371. PMID 10220586.
- Hattori A, Kitatani K, Matsumoto H, Miyazawa S, Rogi T, Tsuruoka N, Mizutani S, Natori Y, Tsujimoto M (2000). "Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells". Journal of Biochemistry. 128 (5): 755–62. doi:10.1093/oxfordjournals.jbchem.a022812. PMID 11056387.
- Hattori A, Matsumoto K, Mizutani S, Tsujimoto M (2001). "Genomic organization of the human adipocyte-derived leucine aminopeptidase gene and its relationship to the placental leucine aminopeptidase/oxytocinase gene". Journal of Biochemistry. 130 (2): 235–41. doi:10.1093/oxfordjournals.jbchem.a002977. PMID 11481040.
- Yamamoto N, Nakayama J, Yamakawa-Kobayashi K, Hamaguchi H, Miyazaki R, Arinami T (2002). "Identification of 33 polymorphisms in the adipocyte-derived leucine aminopeptidase (ALAP) gene and possible association with hypertension". Human Mutation. 19 (3): 251–7. doi:10.1002/humu.10047. PMID 11857741. S2CID 23459237.
- Cui X, Hawari F, Alsaaty S, Lawrence M, Combs CA, Geng W, Rouhani FN, Miskinis D, Levine SJ (2002). "Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding". Journal of Clinical Investigation. 110 (4): 515–26. doi:10.1172/JCI13847. PMC 150410. PMID 12189246.
- Serwold T, Gonzalez F, Kim J, Jacob R, Shastri N (2002). "ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum". Nature. 419 (6906): 480–3. doi:10.1038/nature01074. PMID 12368856. S2CID 4379291.
- Saric T, Chang SC, Hattori A, York IA, Markant S, Rock KL, Tsujimoto M, Goldberg AL (2002). "An IFN-γ–induced aminopeptidase in the ER, ERAP1, trims precursors to MHC class I–presented peptides". Nature Immunology. 3 (12): 1169–76. doi:10.1038/ni859. PMID 12436109. S2CID 21648629.
- York IA, Chang SC, Saric T, Keys JA, Favreau JM, Goldberg AL, Rock KL (2002). "The ER aminopeptidase ERAP1 enhances or limits antigen presentation by trimming epitopes to 8–9 residues". Nature Immunology. 3 (12): 1177–84. doi:10.1038/ni860. PMID 12436110. S2CID 21337369.
- Cui X, Rouhani FN, Hawari F, Levine SJ (2003). "An Aminopeptidase, ARTS-1, Is Required for Interleukin-6 Receptor Shedding". Journal of Biological Chemistry. 278 (31): 28677–85. doi:10.1074/jbc.M300456200. PMID 12748171.
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- Cui X, Rouhani FN, Hawari F, Levine SJ (2003). "Shedding of the Type II IL-1 Decoy Receptor Requires a Multifunctional Aminopeptidase, Aminopeptidase Regulator of TNF Receptor Type 1 Shedding". The Journal of Immunology. 171 (12): 6814–9. doi:10.4049/jimmunol.171.12.6814. PMID 14662887.
- Shibata D, Ando H, Iwase A, Nagasaka T, Hattori A, Tsujimoto M, Mizutani S (2004). "Distribution of Adipocyte-derived Leucine Aminopeptidase (A-LAP)/ER-aminopeptidase (ERAP)-1 in Human Uterine Endometrium". Journal of Histochemistry and Cytochemistry. 52 (9): 1169–75. doi:10.1369/jhc.3A6216.2004. PMID 15314084.
