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Transporter Associated with Antigen Processing; antigen peptide transporter-1; peptide transporter TAP1, peptide transporter PSF1, peptide supply factor 1; PSF-1 (TAP1, APT1, RING4, Y3, MTP-1, HAM-1)
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, namely the 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 the 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
- expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting transport of peptides into the endoplasmic reticulum & subsequent peptide loading by MHC class 1 molecules
- 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 membran
- transmembrane segments seem to form a pore in the membrane
Expression:
- induced by interferon gamma polymorphism
- five common alleles; TAP1*0101 (PSF1A), TAP1*0201 (PSF1B), TAP1*0301 (PSF1C), TAP1*0104 & TAP1*x
Pathology:
- defects in TAP1 are a cause of bare lymphocyte syndrome type 1
General
antigen peptide transporter (Transporter Associated with Antigen Processing, TAP)
transmembrane 10 protein
Properties
SIZE: entity length = 748 aa
MW = 81 kD
COMPARTMENT: endoplasmic reticulum
MOTIF: cytoplasmic domain {1-15}
transmembrane domain {16-36}
exoplasmic loop {37-53}
transmembrane domain {54-76}
cytoplasmic loop {77-92}
transmembrane domain {93-113}
exoplasmic loop {114-133}
transmembrane domain {134-154}
cytoplasmic loop {155-186}
transmembrane domain {187-207}
exoplasmic loop {208-227}
transmembrane domain {228-248}
cytoplasmic loop {249-298}
transmembrane domain {299-319}
exoplasmic loop {320-328}
transmembrane domain {329-349}
cytoplasmic loop {350-418}
MOTIF: binding site
SITE: 375-420
FOR-BINDING-OF: peptide
transmembrane domain {419-439}
exoplasmic loop {440-443}
transmembrane domain {444-464}
MOTIF: binding site
SITE: 453-464
FOR-BINDING-OF: peptide
cytoplasmic domain {465-748}
MOTIF: binding site
SITE: 465-487
FOR-BINDING-OF: peptide
ABC transporter {503-742}
ATP-binding site
NAME: ATP-binding site
SITE: 538-545
Database Correlations
OMIM 170260
UniProt Q03518
References
- Parham Nature 357:193 1992
- TAP1base; note=TAP1 mutation db
http://bioinf.uta.fi/TAP1base/
- UniProt :accession Q03518
Component-of
TAP complex (MHC class 1 peptide loading complex)