ERAP1

ERAP1
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2YD0, 3MDJ, 3QNF, 3RJO
Identifikatori
Aliasi	ERAP1
Vanjski ID-jevi	OMIM: 606832 MGI: 1933403 HomoloGene: 140581 GeneCards: ERAP1
Lokacija gena (čovjek)
Hrom.	Hromosom 5 (čovjek)
Kraj	96,808,100 bp
Lokacija gena (miš)
Hrom.	Hromosom 13 (miš)
Kraj	74,841,320 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• interleukin-6 receptor binding; • peptide binding; • vezivanje iona cinka; • vezivanje iona metala; • interleukin-1, type II receptor binding; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • aminopeptidase activity; • metalloexopeptidase activity; • hydrolase activity; • metallopeptidase activity; • endopeptidase activity; • metalloaminopeptidase activity;
Ćelijska komponenta	• citoplazma; • integral component of membrane; • citosol; • endoplasmic reticulum membrane; • membrana; • extracellular region; • Endoplazmatski retikulum; • Egzosom; • Vanćelijsko; • endoplasmic reticulum lumen; • ćelijska membrana;
Biološki proces	• regulation of innate immune response; • adaptive immune response; • response to bacterium; • immune system process; • antigen processing and presentation of peptide antigen via MHC class I; • Proteoliza; • positive regulation of angiogenesis; • membrane protein ectodomain proteolysis; • Angiogeneza; • fat cell differentiation; • peptide catabolic process; • antigen processing and presentation of endogenous peptide antigen via MHC class I; • regulation of blood pressure; • GO:0072468 Transdukcija signala; • cell-cell signaling;
	Izvori:Amigo / QuickGO
Ortolozi
	51752
	80898
	ENSG00000164307
	ENSMUSG00000021583
	Q9NZ08
	Q9EQH2
	NM_001040458; NM_001198541; NM_016442; NM_001349244
	NM_030711
	NP_001035548; NP_001185470; NP_057526; NP_001336173
	NP_109636
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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]

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.

Nomenklatura

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)

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 941 aminokiselina, а molekulska težina 107.235 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

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

Funkcija

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:

Izbacivanje različitih receptora citokina i receptora mamaca
Skraćivanje antigenih peptida prije vezivanja za MHC klasa I, što utiče na prezentaciju antigena u citotoksičnim T-limfocitima
Stimulacija fagocitoza nakon oslobađanja od strane makrofaga^[10]

Klinički značaj

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]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000164307 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021583 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c ^d EntrezGene 51752
^ "HGNC". HGNC. Arhivirano s originala, 11. 4. 2015. Pristupljeno 27. 3. 2014.
^ 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.
^ "UniProt, Q9NZ08" (jezik: engleski). Pristupljeno 14. 10. 2021.
^ "ERAP1 - endoplasmic reticulum aminopeptidase 1 - Genetics Home Reference".
^ Goto Y, Ogawa K, Hattori A, Tsujimoto M (juni 2011). "Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma". The Journal of Biological Chemistry. 286 (24): 21906–14. doi:10.1074/jbc.M111.239111. PMC 3122245. PMID 21531727.
^ Brionez TF, Reveille JD (2008). "The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis". Current Opinion in Rheumatology. 20 (4): 384–91. doi:10.1097/BOR.0b013e32830460fe. PMID 18525349. S2CID 205485848.

Dopunska literatura

Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (2002). "Construction of Expression-ready cDNA Clones for KIAA Genes: Manual Curation of 330 KIAA cDNA Clones". DNA Research. 9 (3): 99–106. CiteSeerX 10.1.1.500.923. doi:10.1093/dnares/9.3.99. PMID 12168954.
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.
Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Research. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
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.

Vanjski linkovi

Lokacija ljudskog genoma ERAP1 i stranica sa detaljima o genu ERAP1 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000164307 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021583 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez1-5] EntrezGene 51752

[HGNC_ERAP1-6] "HGNC". HGNC. Arhivirano s originala, 11. 4. 2015. Pristupljeno 27. 3. 2014.

[7] 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.

[UniProt-8] "UniProt, Q9NZ08" (jezik: engleski). Pristupljeno 14. 10. 2021.

[urlERAP1_-_endoplasmic_reticulum_aminopeptidase_1_-_Genetics_Home_Reference-9] "ERAP1 - endoplasmic reticulum aminopeptidase 1 - Genetics Home Reference".

[10] Goto Y, Ogawa K, Hattori A, Tsujimoto M (juni 2011). "Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma". The Journal of Biological Chemistry. 286 (24): 21906–14. doi:10.1074/jbc.M111.239111. PMC 3122245. PMID 21531727.

[pmid18525349-11] Brionez TF, Reveille JD (2008). "The contribution of genes outside the major histocompatibility complex to susceptibility to ankylosing spondylitis". Current Opinion in Rheumatology. 20 (4): 384–91. doi:10.1097/BOR.0b013e32830460fe. PMID 18525349. S2CID 205485848.

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