1. Home
  2. Targets
  3. defense/immunity protein
  4. immunoglobulin receptor superfamily
  5. Tapasin

Tbio Tapasin

Involved in the association of MHC class I with transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading).

This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

 Comments

Property Summary

NCBI Gene PubMed Count 83
PubMed Score 373.58
PubTator Score 66.83

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (6)

Disease Target Count
Bare Lymphocyte Syndrome, Type I 4
Disease Target Count Z-score Confidence
Rheumatoid Arthritis 1170 0.0 1.0
Disease Target Count
Bare lymphocyte syndrome type 1 4
Disease Target Count
Bare lymphocyte syndrome 1 3

Expression

  Differential Expression (14)

Disease log2 FC p
ependymoma 1.200 5.7e-03
oligodendroglioma 1.300 1.7e-03
esophageal adenocarcinoma 1.200 1.8e-02
psoriasis -1.600 2.1e-04
osteosarcoma -2.319 1.9e-05
astrocytoma 1.900 2.0e-03
glioblastoma 1.300 3.4e-03
juvenile dermatomyositis 1.486 9.9e-11
Atopic dermatitis 1.400 1.6e-05
intraductal papillary-mucinous carcinoma... 1.100 2.4e-02
lung cancer -2.300 5.8e-06
COPD -1.200 4.7e-03
acute myeloid leukemia 1.600 3.4e-02
ovarian cancer 2.800 4.0e-07

Synonym

Accession O15533 A2AB91 A2ABC0 B0V003 B0V0A6 B2ZUA4 E9PGM2 O15210 O15272 Q5STJ8 Q5STK6 Q5STQ5 Q5STQ6 Q66K65 Q96KK7 Q9HAN8 Q9UEE0 Q9UEE4 Q9UIZ6 Q9Y6K2 TPN
Symbols TPN
TAPA
TPSN
NGS17

Gene

TAPBP

PANTHER Protein Class (2)

PDB

3F8U  

  Ortholog (1)

Species Source Disease
Macaque OMA Inparanoid

 UniProt Keyword (14)

See all...

 GO Function (6)

 GO Component (6)

 GO Process (8)

 Compartment GO Term (39)

See all...

 MGI Phenotype (2)

 HCA RNA Cell Line (55)

See all...

Pathway (8)

Protein-protein Interaction (12)

SEC22B   HLA-B   HLA-B   HLA-C   HLA-B   HLA-C   HLA-C   HLA-B   HLA-B   HLA-B   HLA-C   HLA-C  

Gene RIF (51)

PMID Text
26519531 TAP/TPN complex formation is driven by hydrophobic interactions via leucine zipper-like motifs.
26416272 Data suggest that tapasin (Tsn) binds to MHC I with suboptimal cargo and thereby adjusts the energy landscape in favor of MHC I complexes with immunodominant epitopes.
26310568 reduction in tapasin expression is associated with tumor progression in colorectal cancer
25874709 TAP2, HLA-DOA, HLA-DOB, and tapasin loci are novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population
25175688 Analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for glioblastoma multiforme patients, especially when considering immunotherapy.
24163410 the data indicate that TAPBPR and tapasin bind in a similar orientation to the same face of MHC class I.
23940558 Targeted re-sequencing identified rs3106189 at the 5' UTR of TAPBP and rs1052918 at the 3' UTR of TCF3 to be associated with the overall survival of colorectal cancer patients.
23736108 TAPBP polymorphisms may play a role in the development of aspirin-exacerbated respiratory disease.
23640800 Modified TAPBP gene function may contribute to the development of refractory chronic rhinosinusitis via reduction of circulating CD8 lymphocytes.
23519916 isoform lacking exon 3 affects MHC class I-peptide binding
22923333 Data indicate that the peptide-loading complex (PLC) consists maximally of 2x tapasin-ERp57/MHC I per TAP complex, but one tapasin-ERp57/MHC I in the PLC is essential and sufficient for antigen processing.
21518758 Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes formed with natural ligands.
21248040 On infection with human cytomegalovirus tapasin mRNA levels were continuously downregulated during infection, while tapasin transcripts remained stable and long-lived.
20532727 Downregulation of tapasin is associated with a poor clinical outcome for oral squamous cell carcinoma patients and may serve as a prognostic biomarker
20070606 The interactions of tapasin with both TAP and ERp57 are correlated with strong MHC class I recruitment and assembly enhancement.
20017190 find that in a competitive situation between high- and low-affinity peptides, tapasin mediates the binding of the high-affinity peptide to class I by accelerating the dissociation of the peptide from an unstable intermediate of the binding reaction.
19851445 Observational study of gene-disease association. (HuGE Navigator)
19776380 Observational study of gene-disease association. (HuGE Navigator)
19728311 The N-terminal region of Tapasin (Tpn) can be recombinantly expressed and adopt a structure, which at least partially resembles that of wild-type Tpn. This region of Tpn features chaperone activity facilitating peptide binding of MHC-I.
19701894 tapasin conjugation with ERp57 is as critical as its integration into the membrane for efficient MHC class I assembly, surface expression, and Ag presentation to CD8+ T cells.
19217216 Observational study of gene-disease association. (HuGE Navigator)
19167761 HLA-B27 polymorphism drives the tapasin dependency, rates of intracellular maturation and expressions of homodimers.
19119025 the 2.6 A resolution structure of the tapasin-ERp57 core of the peptide-loading complex
18694960 These data reveal a novel "feed-forward" mechanism induced by NF-kappaB which ensures that acutely synthesized IRF-1 operates in concert with NF-kappaB to amplify the immunoproteasome and antigen-processing functions of CD40.
18261958 In this review, interaction of accessory protein tapasin with HLA-DM crucially influences the selection of peptides that bind to major histocompatibility complex (MHC) molecules during antigen presentation.
18248301 Observational study of gene-disease association. (HuGE Navigator)
18196518 Transgenic tapasin establishes hierarchical responses in vivo according to peptide-major histocompatibility complex class I stability.
18039656 A ternary complex between heavy chain, ERp57, and tapasin was observed and shown to be stabilized by a disulfide between both tapasinheavy chain and tapasin-ERp57.
17498802 Besides beta(2)m and tapasin, an extra unidentified component is also critical for the expression of certain human class I alleles.
17389020 Observational study of gene-disease association. (HuGE Navigator)
16322289 Down-regulation of tapasin expression was associated with glioblastoma multiforme
16193070 Tapasin association specifically inhibits the escape pathway required for disulfide-bond isomerization within conventional protein substrates, suggesting a specific structural role for ERp57 within the MHC class I peptide-loading complex.
15743475 Observational study of gene-disease association. (HuGE Navigator)
15634919 Substitutions at position lysine-408 in tapasin are shown to affect the expression of major histocompatibility complex class I molecules at the cell surface, by down-regulating tapasin stabilization of TAP.
15455354 Defective tapasin transcription and thus absence of HLA-B44 expression is associateed with colorectal tumors.
15163903 Transfection of tapasin into the Panc02 cells did not quantitatively increase MHC class I surface expression or detectably affect MHC class I association with tumor-specific peptides and beta(2)-microglubulin (beta(2)m).
14978101 Mutational analysis of tapasin provides insight into aspects of tapasin structure that are crucial to its ability to assist major histocompatibility complex class I assembly.
14607930 In its role as peptide facilitator, tapasin stabilizes the peptide-free conformation of class I major histocompatibility (MHC) complex molecules in the endoplasmic reticulum and thus increases the number and variety of peptides bound to class I MHC.
14519625 Defects in tapasin and HLA class I antigen expression in primary maxillary sinus SCC lesions may play a role in the clinical course of the maxillary sinus cancer, because these defects were associated with poor prognosis.
13678524 The ERp57-tapasin conjugate can also be modified with the oxidizing agent diamide, indicating that within the pool of ERp57-tapasin complexes the free, non-tapasin-linked CXXC motif exists in both oxidized and reduced states
12682852 Downregulation of tapasin in advanced stages of human melanoma may reflect accumulation of alterations in antigen-presenting/processing machinery associated with neoplastic progression. May contribute to immune escape phenotype of human melanoma cells.
12594855 A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression.
12582157 tapasin has a essential function of tapasin in quality control of HLA-G molecules
12463753 The domain organization of tapasin is an assembly of two core regions of different sizes loosely connected by a linker or loop comprising residues ~85-93.
12213826 Tapasin enhances the structural stability of TAP1.TAP2 complexes.
12149238 results suggest that tapasin deficiency is another cause of type I bare lymphocyte syndrome
11972874 tapasin is not required for calreticulin to bind to the alpha1 domain of MHC class I molecules
11970875 MHC class I molecules can optimize their peptide repertoire over time and that this process is dependent on tapasin.
11862402 tapasin is a modified Mhc class I molecule
11823531 recruits MHC class I molecules to TAP complex during antigen processing
11132161 Observational study of genotype prevalence. (HuGE Navigator)

AA Sequence 

MKSLSLLLAVALGLATAVSAGPAVIECWFVEDASGKGLAKRPGALLLRQGPGEPPPRPDLDPELYLSVHD      1 - 70
PAGALQAAFRRYPRGAPAPHCEMSRFVPLPASAKWASGLTPAQNCPRALDGAWLMVSISSPVLSLSSLLR     71 - 140
PQPEPQQEPVLITMATVVLTVLTHTPAPRVRLGQDALLDLSFAYMPPTSEAASSLAPGPPPFGLEWRRQH    141 - 210
LGKGHLLLAATPGLNGQMPAAQEGAVAFAAWDDDEPWGPWTGNGTFWLPRVQPFQEGTYLATIHLPYLQG    211 - 280
QVTLELAVYKPPKVSLMPATLARAAPGEAPPELLCLVSHFYPSGGLEVEWELRGGPGGRSQKAEGQRWLS    281 - 350
ALRHHSDGSVSLSGHLQPPPVTTEQHGARYACRIHHPSLPASGRSAEVTLEVAGLSGPSLEDSVGLFLSA    351 - 420
FLLLGLFKALGWAAVYLSTCKDSKKKAE                                              421 - 448
//

Text Mined References (86)

PMID Year Title
26519531 2015 Hydrophobic Interactions Are Key To Drive the Association of Tapasin with Peptide Transporter Subunit TAP2.
26416272 2015 Mechanistic Basis for Epitope Proofreading in the Peptide-Loading Complex.
26310568 2015 Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer.
25944712 2015 N-terminome analysis of the human mitochondrial proteome.
25874709 2015 Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection.
25175688 2014 Tapasin and human leukocyte antigen class I dysregulation correlates with survival in glioblastoma multiforme.
24163410 2013 The binding of TAPBPR and Tapasin to MHC class I is mutually exclusive.
23940558 2013 Targeted re-sequencing identified rs3106189 at the 5' UTR of TAPBP and rs1052918 at the 3' UTR of TCF3 to be associated with the overall survival of colorectal cancer patients.
23736108 2013 Association analysis of tapasin polymorphisms with aspirin-exacerbated respiratory disease in asthmatics.
23640800 2013 CD8A gene polymorphisms predict severity factors in chronic rhinosinusitis.
23519916 2013 A natural tapasin isoform lacking exon 3 modifies peptide loading complex function.
22923333 2012 Molecular architecture of the MHC I peptide-loading complex: one tapasin molecule is essential and sufficient for antigen processing.
22810586 2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins.
21518758 2011 Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes formed with natural ligands.
21269460 2011 Initial characterization of the human central proteome.
21248040 2011 Human cytomegalovirus disrupts the major histocompatibility complex class I peptide-loading complex and inhibits tapasin gene transcription.
20600451 2010 Identification of an alternate splice form of tapasin in human melanoma.
20532727 2010 Downregulation of tapasin expression in primary human oral squamous cell carcinoma: association with clinical outcome.
20070606 2010 Mechanisms of function of tapasin, a critical major histocompatibility complex class I assembly factor.
20017190 2010 Tapasin edits peptides on MHC class I molecules by accelerating peptide exchange.
19851445 2009 High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions.
19776380 2009 Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP.
19728311 2009 The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I.
19701894 2009 Functional significance of tapasin membrane association and disulfide linkage to ERp57 in MHC class I presentation.
19217216 2009 Transporter associated with antigen processing and the chaperone tapasin: are non-classical HLA genes keys to the pathogenesis of schizophrenia?
19201886 2009 Specific targeting of the EBV lytic phase protein BNLF2a to the transporter associated with antigen processing results in impairment of HLA class I-restricted antigen presentation.
19167761 2009 HLA-B27 polymorphism at position 116 critically influences the association with TAP/tapasin, intracellular trafficking and conformational homodimers formation.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19119025 2009 Insights into MHC class I peptide loading from the structure of the tapasin-ERp57 thiol oxidoreductase heterodimer.
18802093 2008 The varicellovirus UL49.5 protein blocks the transporter associated with antigen processing (TAP) by inhibiting essential conformational transitions in the 6+6 transmembrane TAP core complex.
18694960 2008 CD40 induces antigen transporter and immunoproteasome gene expression in carcinomas via the coordinated action of NF-kappaB and of NF-kappaB-mediated de novo synthesis of IRF-1.
18261958 2008 The convergent roles of tapasin and HLA-DM in antigen presentation.
18248301 2008 Variation in HLA class I antigen-processing genes and susceptibility to human papillomavirus type 16-associated cervical cancer.
18196518 2008 Tapasin shapes immunodominance hierarchies according to the kinetic stability of peptide-MHC class I complexes.
18039656 2008 Formation of a major histocompatibility complex class I tapasin disulfide indicates a change in spatial organization of the peptide-loading complex during assembly.
17947644 2007 Molecular architecture of the TAP-associated MHC class I peptide-loading complex.
17498802 2007 An extra molecule in addition to human tapasin is required for surface expression of beta2m linked HLA-B4402 on murine cell.
17389020 2007 Sequence variation within the major histocompatibility complex subregion centromeric of HLA class II in type 1 diabetes.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
17055437 2006 Redox regulation facilitates optimal peptide selection by MHC class I during antigen processing.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16322289 2005 Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors.
16193070 2005 Tapasin and ERp57 form a stable disulfide-linked dimer within the MHC class I peptide-loading complex.
15793001 2005 Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing.
15743475 2005 Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case-control study.
15634919 2005 A charged amino acid residue in the transmembrane/cytoplasmic region of tapasin influences MHC class I assembly and maturation.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15455354 2005 Involvement of the chaperone tapasin in HLA-B44 allelic losses in colorectal tumors.
15163903 2004 Tapasin decreases immune responsiveness to a model tumor antigen.
14978101 2004 The Ig-like domain of tapasin influences intermolecular interactions.
14668790 2004 Generation of a functional, soluble tapasin protein from an alternatively spliced mRNA.
14607930 2003 Tapasin is a facilitator, not an editor, of class I MHC peptide binding.
14574404 2003 The DNA sequence and analysis of human chromosome 6.
14519625 2003 Association of tapasin and HLA class I antigen down-regulation in primary maxillary sinus squamous cell carcinoma lesions with reduced survival of patients.
13678524 2003 Characterization of the ERp57-Tapasin complex by rapid cellular acidification and thiol modification.
12788224 2003 Chaperones and folding of MHC class I molecules in the endoplasmic reticulum.
12682852 2003 Downregulation of tapasin expression in progressive human malignant melanoma.
12594855 2003 A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression.
12582157 2003 An essential function of tapasin in quality control of HLA-G molecules.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12463753 2002 A characterization of the lumenal region of human tapasin reveals the presence of two structural domains.
12213826 2002 Tapasin interacts with the membrane-spanning domains of both TAP subunits and enhances the structural stability of TAP1 x TAP2 Complexes.
12200052 2002 Tapasin-the keystone of the loading complex optimizing peptide binding by MHC class I molecules in the endoplasmic reticulum.
12149238 2002 A subject with a novel type I bare lymphocyte syndrome has tapasin deficiency due to deletion of 4 exons by Alu-mediated recombination.
12047747 2002 Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits.
12018464 2002 The interface between tapasin and MHC class I: identification of amino acid residues in both proteins that influence their interaction.
11972874 2002 Calreticulin binds to the alpha1 domain of MHC class I independently of tapasin.
11970875 2002 Optimization of the MHC class I peptide cargo is dependent on tapasin.
11884415 2002 Association of tapasin and COPI provides a mechanism for the retrograde transport of major histocompatibility complex (MHC) class I molecules from the Golgi complex to the endoplasmic reticulum.
11862402 2001 Is tapasin a modified Mhc class I molecule?
11823531 2002 Recruitment of MHC class I molecules by tapasin into the transporter associated with antigen processing-associated complex is essential for optimal peptide loading.
11132161 2000 Identification of novel Tapasin polymorphisms and linkage disequilibrium to MHC class I alleles.
10636848 2000 Tapasin is required for efficient peptide binding to transporter associated with antigen processing.
10508608 1999 Nucleotide binding by TAP mediates association with peptide and release of assembled MHC class I molecules.
10382748 1999 The N-terminal region of tapasin is required to stabilize the MHC class I loading complex.
10088603 1999 Granulocyte-macrophage colony-stimulating factor modulates tapasin expression in human neutrophils.
9802609 1998 Polymorphism of TAPASIN and its linkage disequilibria with HLA class II genes in the Japanese population.
9545376 1998 TAPASIN, DAXX, RGL2, HKE2 and four new genes (BING 1, 3 to 5) form a dense cluster at the centromeric end of the MHC.
9545232 1998 ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly.
9521053 1998 Genomic analysis of the Tapasin gene, located close to the TAP loci in the MHC.
9271576 1997 A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes.
9238042 1997 Cloning and functional characterization of a subunit of the transporter associated with antigen processing.
9110174 1997 Large-scale concatenation cDNA sequencing.
8805302 1996 Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP.
8769474 1996 Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP.
8619474 1996 A "double adaptor" method for improved shotgun library construction.