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antigen peptide transporter-2 (APT2), peptide transporter TAP2, peptide transporter PSF2, peptide supply factor 2 (PSF-2), RING11, Y1, PSF2, MTP-2 or HAM-2
Function:
- pump which delivers peptides to class 1 MHC molecules within the endoplasmic reticulum of antigen presenting cells
- role in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class 1 molecules
- acts as a molecular scaffold for final stage of MHC class 1 folding, binding of peptide
- nascent MHC class 1 molecules associate with TAP via tapasin
- inhibited by covalent attachment of herpes simplex virus ICP47 protein, which blocks peptide-binding site of TAP
- inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex & inhibits peptide translocation by specifically blocking ATP-binding to TAP1 & prevents the conformational rearrangement of TAP induced by peptide binding
- inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex & acts as a tapasin inhibitor, preventing MHC class 1/TAP association
- heterodimer of TAP1 & TAP2
Structure:
- peptide-binding site is shared between the cytoplasmic loops of TAP1 & TAP2
- belongs to the ABC transporter family, MHC peptide exporter (TC 3.A.1.209) subfamily
- contains 1 ABC transmembrane type-1 domain
- contains 1 ABC transporter domain
Compartment:
- endoplasmic reticulum membrane
- transmembrane segments seem to form a pore in the membrane
Expression:
- induced by interferon gamma
Polymorphism:
- 4 common alleles are officially recognized:
a) TAP2*0101 (TAP2A or PSF2A or RING11A)
b) TAP2*0102 (TAP2E),
c) TAP2*0103 (TAP2F)
d) TAP2*0201 (TAP2B or PSF2B or RING11B)
- other relatively common alleles have been identified: TAP2*01D, TAP2*01E, TAP2*01F, TAP2*01G, TAP2*01H, TAP2*02B, TAP2*02C (TAP2*0202), TAP2*02D, TAP2*02E, TAP2*02F, TAP2*03A & TAP2*04A
- allele TAP2*Bky2 is commonly found only in the Japanese population
Pathology:
- defects in TAP2 are a cause of bare lymphocyte syndrome
- allele TAP2*Bky2, commonly found only in the Japanese may be associated with susceptibility to Sjoegren syndrome
General
antigen peptide transporter (Transporter Associated with Antigen Processing, TAP)
transmembrane 9 protein
Properties
SIZE: entity length = 686 aa
MW = 76 kD
COMPARTMENT: endoplasmic reticulum
MOTIF: exoplasmic domain {1-6}
transmembrane domain {7-27}
cytoplasmic loop {28-56}
transmembrane domain {57-77}
exoplasmic loop {78-98}
transmembrane domain {99-119}
cytoplasmic loop {120-148}
transmembrane domain {149-169}
exoplasmic loop {170-187}
transmembrane domain {188-208}
cytoplasmic loop {209-266}
transmembrane domain {267-287}
exoplasmic loop {288-293}
transmembrane domain {294-314}
cytoplasmic loop {315-374}
MOTIF: binding site
SITE: 301-389
FOR-BINDING-OF: peptide
transmembrane domain {375-395}
exoplasmic loop {396-408}
transmembrane domain {409-429}
cytoplasmic domain {430-686}
MOTIF: binding site
SITE: 414-433
FOR-BINDING-OF: peptide
ABC transporter {468-686}
ATP-binding site
NAME: ATP-binding site
SITE: 503-510
Database Correlations
OMIM correlations
UniProt Q03519
PFAM correlations
References
- Parham Nature 357:193 1992
- TAP2base; note=TAP2 mutation db
http://bioinf.uta.fi/TAP2base/
- UniProt :accession Q03519
Component-of
TAP complex (MHC class 1 peptide loading complex)