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Identification
HMDB Protein ID HMDBP09219
Secondary Accession Numbers
  • 15002
Name Endoplasmic reticulum aminopeptidase 1
Synonyms
  1. A-LAP
  2. ARTS-1
  3. Adipocyte-derived leucine aminopeptidase
  4. Aminopeptidase PILS
  5. PILS-AP
  6. Puromycin-insensitive leucyl-specific aminopeptidase
  7. Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator
Gene Name ERAP1
Protein Type Enzyme
Biological Properties
General Function Involved in proteolysis
Specific Function Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I- binding peptides. Peptide trimming is essential to customize longer precursor peptides to fit them to the correct length required for presentation on MHC class I molecules. Strongly prefers substrates 9-16 residues long. Rapidly degrades 13-mer to a 9-mer and then stops. Preferentially hydrolyzes the residue Leu and peptides with a hydrophobic C-terminus, while it has weak activity toward peptides with charged C-terminus. May play a role in the inactivation of peptide hormones. May be involved in the regulation of blood pressure through the inactivation of angiotensin II and/or the generation of bradykinin in the kidney
Pathways Not Available
Reactions Not Available
GO Classification
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
hydrolase activity
transition metal ion binding
zinc ion binding
peptidase activity
peptidase activity, acting on l-amino acid peptides
metallopeptidase activity
Process
metabolic process
macromolecule metabolic process
protein metabolic process
proteolysis
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Single-pass type II membrane protein (Probable)
Gene Properties
Chromosome Location Chromosome:5
Locus 5q15
SNPs ERAP1
Gene Sequence
>2826 bp
ATGGTGTTTCTGCCCCTCAAATGGTCCCTTGCAACCATGTCATTTCTACTTTCCTCACTG
TTGGCTCTCTTAACTGTGTCCACTCCTTCATGGTGTCAGAGCACTGAAGCATCTCCAAAA
CGTAGTGATGGGACACCATTTCCTTGGAATAAAATACGACTTCCTGAGTACGTCATCCCA
GTTCATTATGATCTCTTGATCCATGCAAACCTTACCACGCTGACCTTCTGGGGAACCACG
AAAGTAGAAATCACAGCCAGTCAGCCCACCAGCACCATCATCCTGCATAGTCACCACCTG
CAGATATCTAGGGCCACCCTCAGGAAGGGAGCTGGAGAGAGGCTATCGGAAGAACCCCTG
CAGGTCCTGGAACACCCCCGTCAGGAGCAAATTGCACTGCTGGCTCCCGAGCCCCTCCTT
GTCGGGCTCCCGTACACAGTTGTCATTCACTATGCTGGCAATCTTTCGGAGACTTTCCAC
GGATTTTACAAAAGCACCTACAGAACCAAGGAAGGGGAACTGAGGATACTAGCATCAACA
CAATTTGAACCCACTGCAGCTAGAATGGCCTTTCCCTGCTTTGATGAACCTGCCTTCAAA
GCAAGTTTCTCAATCAAAATTAGAAGAGAGCCAAGGCACCTAGCCATCTCCAATATGCCA
TTGGTGAAATCTGTGACTGTTGCTGAAGGACTCATAGAAGACCATTTTGATGTCACTGTG
AAGATGAGCACCTATCTGGTGGCCTTCATCATTTCAGATTTTGAGTCTGTCAGCAAGATA
ACCAAGAGTGGAGTCAAGGTTTCTGTTTATGCTGTGCCAGACAAGATAAATCAAGCAGAT
TATGCACTGGATGCTGCGGTGACTCTTCTAGAATTTTATGAGGATTATTTCAGCATACCG
TATCCCCTACCCAAACAAGATCTTGCTGCTATTCCCGACTTTCAGTCTGGTGCTATGGAA
AACTGGGGACTGACAACATATAGAGAATCTGCTCTGTTGTTTGATGCAGAAAAGTCTTCT
GCATCAAGTAAGCTTGGCATCACAATGACTGTGGCCCATGAACTGGCTCACCAGTGGTTT
GGGAACCTGGTCACTATGGAATGGTGGAATGATCTTTGGCTAAATGAAGGATTTGCCAAA
TTTATGGAGTTTGTGTCTGTCAGTGTGACCCATCCTGAACTGAAAGTTGGAGATTATTTC
TTTGGCAAATGTTTTGACGCAATGGAGGTAGATGCTTTAAATTCCTCACACCCTGTGTCT
ACACCTGTGGAAAATCCTGCTCAGATCCGGGAGATGTTTGATGATGTTTCTTATGATAAG
GGAGCTTGTATTCTGAATATGCTAAGGGAGTATCTTAGTGCTGACGCATTTAAAAGTGGT
ATTGTACAGTATCTCCAGAAGCATAGCTATAAAAATACAAAAAACGAGGACCTGTGGGAT
AGTATGGCAAGTATTTGCCCTACAGATGGTGTAAAAGGGATGGATGGCTTTTGCTCTAGA
AGTCAACATTCATCTTCATCCTCACATTGGCATCAGGAAGGGGTGGATGTGAAAACCATG
ATGAACACTTGGACACTGCAGAAGGGTTTTCCCCTAATAACCATCACAGTGAGGGGGAGG
AATGTACACATGAAGCAAGAGCACTACATGAAGGGCTCTGACGGCGCCCCGGACACTGGG
TACCTGTGGCATGTTCCATTGACATTCATCACCAGCAAATCCGACATGGTCCATCGATTT
TTGCTAAAAACAAAAACAGATGTGCTCATCCTCCCAGAAGAGGTGGAATGGATCAAATTT
AATGTGGGCATGAATGGCTATTACATTGTGCATTACGAGGATGATGGATGGGACTCTTTG
ACTGGCCTTTTAAAAGGAACACACACAGCAGTCAGCAGTAATGATCGGGCGAGTCTCATT
AACAATGCATTTCAGCTCGTCAGCATTGGGAAGCTGTCCATTGAAAAGGCCTTGGATTTA
TCCCTGTACTTGAAACATGAAACTGAAATTATGCCCGTGTTTCAAGGTTTGAATGAGCTG
ATTCCTATGTATAAGTTAATGGAGAAAAGAGATATGAATGAAGTGGAAACTCAATTCAAG
GCCTTCCTCATCAGGCTGCTAAGGGACCTCATTGATAAGCAGACATGGACAGACGAGGGC
TCAGTCTCAGAGCGAATGCTGCGGAGTCAACTACTACTCCTCGCCTGTGTGCACAACTAT
CAGCCGTGCGTACAGAGGGCAGAAGGCTATTTCAGAAAGTGGAAGGAATCCAATGGAAAC
TTGAGCCTGCCTGTCGACGTGACCTTGGCAGTGTTTGCTGTGGGGGCCCAGAGCACAGAA
GGCTGGGATTTTCTTTATAGTAAATATCAGTTTTCTTTGTCCAGTACTGAGAAAAGCCAA
ATTGAATTTGCCCTCTGCAGAACCCAAAATAAGGAAAAGCTTCAATGGCTACTAGATGAA
AGCTTTAAGGGAGATAAAATAAAAACTCAGGAGTTTCCACAAATTCTTACACTCATTGGC
AGGAACCCAGTAGGATACCCACTGGCCTGGCAATTTCTGAGGAAAAACTGGAACAAACTT
GTACAAAAGTTTGAACTTGGCTCATCTTCCATAGCCCACATGGTAATGGGTACAACAAAT
CAATTCTCCACAAGAACACGGCTTGAAGAGGTAAAAGGATTCTTCAGCTCTTTGAAAGAA
AATGGTTCTCAGCTCCGTTGTGTCCAACAGACAATTGAAACCATTGAAGAAAACATCGGT
TGGATGGATAAGAATTTTGATAAAATCAGAGTGTGGCTGCAAAGTGAAAAGCTTGAACGT
ATGTAA
Protein Properties
Number of Residues 941
Molecular Weight 107233.9
Theoretical pI 6.43
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • 2-21
Protein Sequence
>Endoplasmic reticulum aminopeptidase 1
MVFLPLKWSLATMSFLLSSLLALLTVSTPSWCQSTEASPKRSDGTPFPWNKIRLPEYVIP
VHYDLLIHANLTTLTFWGTTKVEITASQPTSTIILHSHHLQISRATLRKGAGERLSEEPL
QVLEHPRQEQIALLAPEPLLVGLPYTVVIHYAGNLSETFHGFYKSTYRTKEGELRILAST
QFEPTAARMAFPCFDEPAFKASFSIKIRREPRHLAISNMPLVKSVTVAEGLIEDHFDVTV
KMSTYLVAFIISDFESVSKITKSGVKVSVYAVPDKINQADYALDAAVTLLEFYEDYFSIP
YPLPKQDLAAIPDFQSGAMENWGLTTYRESALLFDAEKSSASSKLGITMTVAHELAHQWF
GNLVTMEWWNDLWLNEGFAKFMEFVSVSVTHPELKVGDYFFGKCFDAMEVDALNSSHPVS
TPVENPAQIREMFDDVSYDKGACILNMLREYLSADAFKSGIVQYLQKHSYKNTKNEDLWD
SMASICPTDGVKGMDGFCSRSQHSSSSSHWHQEGVDVKTMMNTWTLQKGFPLITITVRGR
NVHMKQEHYMKGSDGAPDTGYLWHVPLTFITSKSDMVHRFLLKTKTDVLILPEEVEWIKF
NVGMNGYYIVHYEDDGWDSLTGLLKGTHTAVSSNDRASLINNAFQLVSIGKLSIEKALDL
SLYLKHETEIMPVFQGLNELIPMYKLMEKRDMNEVETQFKAFLIRLLRDLIDKQTWTDEG
SVSERMLRSQLLLLACVHNYQPCVQRAEGYFRKWKESNGNLSLPVDVTLAVFAVGAQSTE
GWDFLYSKYQFSLSSTEKSQIEFALCRTQNKEKLQWLLDESFKGDKIKTQEFPQILTLIG
RNPVGYPLAWQFLRKNWNKLVQKFELGSSSIAHMVMGTTNQFSTRTRLEEVKGFFSSLKE
NGSQLRCVQQTIETIEENIGWMDKNFDKIRVWLQSEKLERM
GenBank ID Protein 94818891
UniProtKB/Swiss-Prot ID Q9NZ08
UniProtKB/Swiss-Prot Entry Name ERAP1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001040458.1
GeneCard ID ERAP1
GenAtlas ID ERAP1
HGNC ID HGNC:18173
References
General References
  1. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218 ]
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  3. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. 2002 Jun 30;9(3):99-106. [PubMed:12168954 ]
  4. 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: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309 ]
  5. Nagase T, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: 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 Res. 1998 Feb 28;5(1):31-9. [PubMed:9628581 ]
  6. Hattori A, Matsumoto H, Mizutani S, Tsujimoto M: Molecular cloning of adipocyte-derived leucine aminopeptidase highly related to placental leucine aminopeptidase/oxytocinase. J Biochem. 1999 May;125(5):931-8. [PubMed:10220586 ]
  7. Hattori A, Matsumoto K, Mizutani S, Tsujimoto M: Genomic organization of the human adipocyte-derived leucine aminopeptidase gene and its relationship to the placental leucine aminopeptidase/oxytocinase gene. J Biochem. 2001 Aug;130(2):235-41. [PubMed:11481040 ]
  8. Hattori A, Kitatani K, Matsumoto H, Miyazawa S, Rogi T, Tsuruoka N, Mizutani S, Natori Y, Tsujimoto M: Characterization of recombinant human adipocyte-derived leucine aminopeptidase expressed in Chinese hamster ovary cells. J Biochem. 2000 Nov;128(5):755-62. [PubMed:11056387 ]
  9. Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, Greer F, Schomburg L, Fruci D, Niedermann G, van Endert PM: Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol. 2005 Jul;6(7):689-97. Epub 2005 May 22. [PubMed:15908954 ]
  10. Chang SC, Momburg F, Bhutani N, Goldberg AL: The ER aminopeptidase, ERAP1, trims precursors to lengths of MHC class I peptides by a "molecular ruler" mechanism. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17107-12. Epub 2005 Nov 14. [PubMed:16286653 ]