PMID- 26002027
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20191008
IS  - 1531-6963 (Electronic)
IS  - 1040-8711 (Print)
IS  - 1040-8711 (Linking)
VI  - 27
IP  - 4
DP  - 2015 Jul
TI  - Endoplasmic reticulum aminopeptidase 1 and rheumatic disease: functional 
      variation.
PG  - 357-63
LID - 10.1097/BOR.0000000000000188 [doi]
AB  - PURPOSE OF REVIEW: To review the recent developments in our understanding of 
      endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) function in relation to its 
      role in major histocompatibility complex (MHC) class I peptide presentation and 
      human leukocyte antigen (HLA) class I-associated diseases. RECENT FINDINGS: ERAP1 
      polymorphisms exhibiting loss-of-function have been associated with protection 
      from AS. The aminopeptidase function of ERAP1 optimizes peptides for binding and 
      presentation by MHC class I. Most of the studies have revealed reduced MHC class 
      I expression in situations of reduced ERAP1 function. Under these circumstances, 
      the presented peptides are often N-terminally extended, and cell surface 
      complexes are unstable and fall apart more readily. In contrast, peptides 
      presented by HLA-B*27 : 05 when ERAP1 is silenced are frequently extended on the 
      C-terminus. Recent work has emphasized on the importance of assessing the 
      function of allotypes encoded by ERAP1 haplotypes, rather than effects of single 
      amino acid substitutions. The allotypes found in a series of AS patients were 
      poorer at restoring HLA-B27 expression than allotypes found in unaffected 
      controls, which may seem contrary to the genetic data linking loss-of-function to 
      protection. SUMMARY: More work is needed to understand how ERAP1 variants 
      associated with risk and protection influence the quality and quantity of 
      peptides available for binding to HLA class I molecules in the ER. Moreover, we 
      need to determine allele-specific effects of ERAP1 variants in the context of 
      HLA-B*51 and HLA-Cw*6, which are associated with Behcet's disease and psoriasis, 
      respectively.
FAU - Tran, Tri M
AU  - Tran TM
AD  - Pediatric Translational Research Branch, National Institute of Arthritis and 
      Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, 
      Maryland, USA.
FAU - Colbert, Robert A
AU  - Colbert RA
LA  - eng
GR  - Z99 AR999999/Intramural NIH HHS/United States
GR  - Z01 AR041184/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Review
PL  - United States
TA  - Curr Opin Rheumatol
JT  - Current opinion in rheumatology
JID - 9000851
RN  - 0 (HLA-B27 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - EC 3.4.11.- (Aminopeptidases)
RN  - EC 3.4.11.- (ERAP1 protein, human)
SB  - IM
MH  - Aminopeptidases/*genetics/physiology
MH  - Genetic Predisposition to Disease
MH  - HLA-B27 Antigen/immunology
MH  - Haplotypes
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Minor Histocompatibility Antigens
MH  - Polymorphism, Single Nucleotide
MH  - Rheumatic Diseases/*genetics/immunology
PMC - PMC4495904
MID - NIHMS701012
EDAT- 2015/05/24 06:00
MHDA- 2016/02/18 06:00
PMCR- 2016/07/01
CRDT- 2015/05/24 06:00
PHST- 2015/05/24 06:00 [entrez]
PHST- 2015/05/24 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - 10.1097/BOR.0000000000000188 [doi]
PST - ppublish
SO  - Curr Opin Rheumatol. 2015 Jul;27(4):357-63. doi: 10.1097/BOR.0000000000000188.