Affinage

TAPBP

Tapasin · UniProt O15533

Length
448 aa
Mass
47.6 kDa
Annotated
2026-06-10
100 papers in source corpus 4 papers cited in narrative 4 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAPBP (tapasin) is a V-C1 immunoglobulin superfamily molecule of the endoplasmic reticulum that links MHC class I molecules to the transporter associated with antigen processing (TAP) within the peptide-loading complex (PMID:11920573). Consistent with this bridging role, TALEN-mediated disruption of TAPBP in human embryonic stem cells abolishes normal MHC class I surface expression and reduces immunogenicity without perturbing pluripotency, karyotype, or differentiation, establishing TAPBP as required for MHC class I display (PMID:27068360). Beyond its function in antigen presentation, no further direct mechanistic detail on the tapasin protein has been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 4 steps
  1. 2002 Medium

    Established the molecular role of tapasin by placing it as the bridge linking MHC class I to the TAP transporter in the ER, defining its position in the peptide-loading machinery.

    Evidence Genomic/sequence analysis with subcellular localization by fractionation and biotinylation

    PMID:11920573

    Open questions at the time
    • Bridging activity inferred from sequence/localization context, not from direct reconstitution of the TAP-MHC I interaction
    • Localization data shown directly for the related TAPASIN-R, not exhaustively for tapasin itself
  2. 2002 Low

    Provided structural context for how peptide-MHC assembly occurs within the tapasin-associated loading complex, clarifying the chemistry that tapasin-assisted loading must satisfy.

    Evidence X-ray crystallography of rat MHC class Ia molecules and peptide-MHC assembly analysis

    PMID:12470953

    Open questions at the time
    • Tapasin was not directly studied structurally; only its MHC partners were crystallized
    • No structure of tapasin bound to MHC class I or TAP
  3. 2016 Medium

    Demonstrated causally that TAPBP is required for MHC class I surface expression by loss-of-function, moving its role from inferred to experimentally established in human cells.

    Evidence TALEN-mediated knockout in human embryonic stem cells with flow cytometry and pluripotency/differentiation assays

    PMID:27068360

    Open questions at the time
    • Phenotype defined at the level of surface MHC class I, without dissection of which loading-complex step fails
    • Single cell type; no rescue with point mutants to map functional residues
  4. 2024 Low

    Linked TAPBP expression regulation to m6A modification and explored a downstream signaling role in cancer, expanding context beyond antigen loading.

    Evidence MeRIP-seq, RNA-seq, case-control and database analysis, siRNA knockdown and overexpression in cervical cancer cells

    PMID:38992170

    Open questions at the time
    • Pathway placement in JAK/STAT/MICB inferred from knockdown readouts without direct biochemical reconstitution
    • m6A mechanism supported by correlation rather than direct enzymatic reconstitution
    • Causal contribution of the 3' UTR SNP to tumor phenotype not established by editing

Open questions

Synthesis pass · forward-looking unresolved questions
  • How tapasin mechanistically catalyzes or stabilizes peptide editing within the loading complex, and the structural basis of its MHC class I and TAP contacts, remain unresolved in the available corpus.
  • No direct structure of tapasin with its binding partners in the timeline
  • No reconstitution defining tapasin's peptide-editing activity
  • Functional residues required for MHC class I support not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 1
Localization
GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-168256 Immune System 1
Partners
Complex memberships
MHC class I peptide-loading complex

Evidence

Reading pass · 4 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 TAPBP (tapasin) was identified as a V-C1 immunoglobulin superfamily molecule that links MHC class I molecules to the transporter associated with antigen processing (TAP) in the endoplasmic reticulum (ER), and is encoded near the MHC at 6p21.3. A related gene TAPBP-R was identified at 12p13.3; its product TAPASIN-R shares structural motifs with tapasin but differs in V domain, transmembrane, and cytoplasmic regions. Subcellular localization experiments showed the bulk of TAPASIN-R resides in the ER, with some cell-surface expression detected by biotinylation. Genomic/sequence analysis, subcellular localization by fractionation and biotinylation experiments European journal of immunology Medium 11920573
2002 Crystal structures of rat MHC class Ia molecules (RT1-Aa and RT1-A1c) revealed the molecular basis of peptide-MHC assembly and how tapasin participates in the MHC class I peptide-loading complex in the ER, with the structures showing how peptide C-termini match the F-pocket chemistry and providing structural context for tapasin-associated loading. X-ray crystallography of MHC class Ia molecules, biochemical analysis of peptide-MHC assembly rates Journal of molecular biology Low 12470953
2016 Disruption of TAPBP (tapasin) in human embryonic stem cells (hESCs) using TALEN-mediated genome editing resulted in deficient MHC class I expression on the cell surface and reduced immunogenicity, while pluripotency, karyotype, and differentiation ability were maintained. This experimentally established that TAPBP is required for normal MHC class I surface expression. TALEN-mediated gene knockout in hESCs, flow cytometry for MHC class I surface expression, pluripotency and differentiation assays Bioscience, biotechnology, and biochemistry Medium 27068360
2024 A risk SNP rs1059288 (A>G) in the 3' UTR of TAPBP increases m6A modification of TAPBP mRNA, facilitated by the m6A methyltransferase METTL14 and reader protein YTHDF2. Upregulation of TAPBP promoted cervical cancer cell growth, migration, tumor-forming ability, and chemotherapy resistance, and knockdown of TAPBP inhibited the JAK/STAT/MICB signaling pathway while upregulating immune genes including HLA-A. MeRIP-seq, RNA-seq, TCGA/JENGER database analysis, case-control study, immunohistochemistry, siRNA knockdown, overexpression assays, pathway analysis Archives of toxicology Low 38992170

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 TEN versus TPN following major abdominal trauma--reduced septic morbidity. The Journal of trauma 609 2501509
1998 CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annual review of immunology 419 9597125
1995 The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annual review of immunology 396 7542009
1990 TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Molecular and cellular biology 357 1695320
1998 Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions. The Journal of cell biology 227 9566977
1996 Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). Journal of immunology (Baltimore, Md. : 1950) 200 8757325
1993 Functional dissection of the CD21/CD19/TAPA-1/Leu-13 complex of B lymphocytes. The Journal of experimental medicine 196 7690834
1994 Association of four antigens of the tetraspans family (CD37, CD53, TAPA-1, and R2/C33) with MHC class II glycoproteins. Immunogenetics 166 8119731
2003 GLP-2-mediated up-regulation of intestinal blood flow and glucose uptake is nitric oxide-dependent in TPN-fed piglets 1. Gastroenterology 163 12851879
2000 GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis. American journal of physiology. Gastrointestinal and liver physiology 156 11093948
1990 TAPA-1, the target of an antiproliferative antibody, is associated on the cell surface with the Leu-13 antigen. Journal of immunology (Baltimore, Md. : 1950) 141 2398277
1992 The effect of glutamine-enriched TPN on gut immune cellularity. The Journal of surgical research 103 1548865
1993 The CD19 signal transduction complex of B lymphocytes. Deletion of the CD19 cytoplasmic domain alters signal transduction but not complex formation with TAPA-1 and Leu 13. Journal of immunology (Baltimore, Md. : 1950) 101 7690791
2004 Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. The Journal of nutrition 98 15173413
1997 A temporal study of TPN-induced changes in gut-associated lymphoid tissue and mucosal immunity. Archives of surgery (Chicago, Ill. : 1960) 88 9403534
1987 Failure of TPN supplementation to improve liver function, immunity, and mortality in thermally injured patients. The Journal of trauma 81 3102754
2001 TPN decreases IL-4 and IL-10 mRNA expression in lipopolysaccharide stimulated intestinal lamina propria cells but glutamine supplementation preserves the expression. Shock (Augusta, Ga.) 75 11303733
1993 The CD19-CR2-TAPA-1 complex, CD45 and signaling by the antigen receptor of B lymphocytes. Current opinion in immunology 75 7688513
1993 The TAPA-1 molecule is associated on the surface of B cells with HLA-DR molecules. Journal of immunology (Baltimore, Md. : 1950) 73 8409388
1991 Structure and membrane topology of TAPA-1. The Journal of biological chemistry 71 1860863
1993 Anti-TAPA-1 antibodies induce protein tyrosine phosphorylation that is prevented by increasing intracellular thiol levels. Journal of immunology (Baltimore, Md. : 1950) 65 7688390
2014 Functional analysis of the accessory protein TapA in Bacillus subtilis amyloid fiber assembly. Journal of bacteriology 64 24488317
1996 Astrocyte growth, reactivity, and the target of the antiproliferative antibody, TAPA. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 8757260
1984 Protein metabolism during total parenteral nutrition (TPN) in injured rats using medium-chain triglycerides. Metabolism: clinical and experimental 59 6434897
1991 Genomic organization and chromosomal localization of the TAPA-1 gene. Journal of immunology (Baltimore, Md. : 1950) 56 1650385
1993 Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN). Digestive diseases and sciences 51 8359071
1981 Protein and fat metabolism in rats during repletion with total parenteral nutrition (TPN). The Journal of nutrition 51 6778978
2002 A human TAPBP (TAPASIN)-related gene, TAPBP-R. European journal of immunology 49 11920573
2002 Alterations in enterocyte proliferation and apoptosis accompany TPN-induced mucosal hypoplasia and IGF-I-induced hyperplasia in rats. The Journal of nutrition 47 12097684
1983 Effect of postoperative total parenteral nutrition (TPN) as an adjunct to gastrectomy for advanced gastric carcinoma. The British journal of surgery 44 6405838
2004 Increased expression of specific intestinal amino acid and peptide transporter mRNA in rats fed by TPN is reversed by GLP-2. The Journal of nutrition 42 15514259
1982 Protein sparing and protein replacement in acutely injured patients during TPN with and without amino acid supply. Intensive care medicine 39 6799558
2003 Combined growth hormone/insulin-like growth factor I in addition to glutamine-supplemented TPN results in net protein anabolism in critical illness. American journal of physiology. Endocrinology and metabolism 33 12759221
2001 Modulation of organ ICAM-1 expression during IV-TPN with glutamine and bombesin. Shock (Augusta, Ga.) 33 11198353
1977 Identification of D-threo-alpha-methylisocitrate as stereochemically specific substrate for bovine heart aconitase and inhibitor of TPN-linked isocitrate dehydrogenase. The Journal of biological chemistry 33 856801
1983 Modification of TPN-dependent isocitrate dehydrogenase by the 2', 3'-dialdehyde derivatives of TPNH and TPN. The Journal of biological chemistry 32 6874692
2000 Up-regulation of CD81 (target of the antiproliferative antibody; TAPA) by reactive microglia and astrocytes after spinal cord injury in the rat. The Journal of comparative neurology 31 11064366
1998 Delivery of total parenteral nutrition (TPN) via umbilical catheterization: development of a piglet model to investigate therapies to improve gastrointestinal structure and enzyme activity during TPN. Biology of the neonate 30 9573459
1998 Expression of rat target of the antiproliferative antibody (TAPA) in the developing brain. The Journal of comparative neurology 28 9624590
1975 Events Surrounding the Early Development of Euglena Chloroplasts: VI. Action Spectra for the Formation of Chlorophyll, Lag Elimination in Chlorophyll Synthesis, and Appearance of TPN-dependent Triose Phosphate Dehydrogenase and Alkaline DNase Activities. Plant physiology 28 16659294
2004 Effects of lipid administration on liver apoptotic signals in a mouse model of total parenteral nutrition (TPN). Pediatric surgery international 27 15034728
2015 TPN-associated intestinal epithelial cell atrophy is modulated by TLR4/EGF signaling pathways. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 25782989
2003 Blood-brain barrier transport of a novel micro 1-specific opioid peptide, H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA). Journal of neurochemistry 24 12603838
2009 Comparison of two types of TPN prescription methods in preterm neonates. Pharmacy world & science : PWS 23 19169838
2003 Changes in epithelial cell turnover and extracellular matrix in human small intestine after TPN. The Journal of surgical research 23 12643847
2002 Photoprotection prevents TPN-induced lung procollagen mRNA in newborn guinea pigs. Free radical biology & medicine 23 12160933
2020 The majority of the matrix protein TapA is dispensable for Bacillus subtilis colony biofilm architecture. Molecular microbiology 21 32491277
1988 Inhibition of TPN-associated intestinal mucosal atrophy with monoacetoacetin. The Journal of surgical research 21 3129616
1984 Serum lipids and fatty acids composition of tissues in rats on total parenteral nutrition (TPN). Lipids 21 6438428
1984 Protein dynamics during refeeding of protein-depleted rats: effects of increasing amino acid intake by TPN or enteral continuous feeding. The Journal of nutrition 20 6420525
2013 Treatment of diabetes mellitus with microencapsulated fetal human liver (FH-B-TPN) engineered cells. Biomaterials 19 23453199
1996 Ligation of TAPA-1 (CD81) or major histocompatibility complex class II in co-cultures of human B and T lymphocytes enhances interleukin-4 synthesis by antigen-specific CD4+ T cells. European journal of immunology 19 8766544
2009 Up-regulation of intestinal Toll-Like receptors and cytokines expressions change after TPN administration and a lack of enteral feeding. The Journal of surgical research 18 19524259
2016 Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs administered new generation lipid emulsions. Journal of lipid research 17 27474222
1991 Zinc and copper status of severely burned children during TPN. Journal of the American College of Nutrition 17 1901324
1988 Inhibition of post-traumatic septic proteolysis and ureagenesis and stimulation of hepatic acute-phase protein production by branched-chain amino acid TPN. The Journal of trauma 16 2457711
2023 TapA acts as specific chaperone in TasA filament formation by strand complementation. Proceedings of the National Academy of Sciences of the United States of America 15 37068239
2016 Generating hESCs with reduced immunogenicity by disrupting TAP1 or TAPBP. Bioscience, biotechnology, and biochemistry 15 27068360
1997 Pyrogen testing of lipid-based TPN using Mono Mac 6 monocyte cell line and DELFIA. Journal of clinical pharmacy and therapeutics 14 19160716
1996 Triggering of target of an antiproliferative antibody-1 (TAPA-1/CD81) up-regulates the release of tumour necrosis factor-alpha by the EBV-B lymphoblastoid cell line JY. Scandinavian journal of immunology 14 8668914
1984 Trace metal requirements in total parenteral nutrition (TPN). 5. Formation constants for the copper(II)--histidine ternary complexes with threonine, lysine, glycine, phenylalanine, valine, and cystine, and discussion of their implications regarding the copper distribution in blood plasma during TPN and the evaluation of the daily dose of copper. Journal of inorganic biochemistry 14 6425456
2018 The Bacterial Extracellular Matrix Protein TapA Is a Two-Domain Partially Disordered Protein. Chembiochem : a European journal of chemical biology 13 30371005
1999 The expression of TAPA (CD81) correlates with the reactive response of astrocytes in the developing rat CNS. Experimental neurology 13 10619563
1998 The target of the antiproliferative antibody (TAPA) in the normal and injured rat retina. Molecular vision 13 9485486
1983 Cellular localization of liver vitamin A in rats given total parenteral nutrition (TPN) solutions intravenously or orally. The Journal of nutrition 13 6406651
2010 Lack of a rewarding effect and a locomotor-enhancing effect of the selective μ-opioid receptor agonist amidino-TAPA. Psychopharmacology 12 20683583
2007 Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA. European journal of pharmacology 12 17307162
1992 Expression of TAPA-1 in preimplantation mouse embryos. Biochemical and biophysical research communications 12 1380797
1975 Alpha-methylisocitrate. A selective inhibitor of TPN-linked isocitrate dehydrogenase from bovine heart and rat liver. The Journal of biological chemistry 12 239945
2002 Retinal pigment epithelium of the rat express CD81, the target of the anti-proliferative antibody (TAPA). Investigative ophthalmology & visual science 11 11773042
2002 Crystal structures of two rat MHC class Ia (RT1-A) molecules that are associated differentially with peptide transporter alleles TAP-A and TAP-B. Journal of molecular biology 11 12470953
1985 Post-operative substrate utilisation and gas exchange using two different TPN-systems: glucose versus fat. Clinical nutrition (Edinburgh, Scotland) 11 16831738
2020 Computational investigation for modeling the protein-protein interaction of TasA(28-261)-TapA(33-253): a decisive process in biofilm formation by Bacillus subtilis. Journal of molecular modeling 10 32779018
2007 Variations in metabolic response to TPN are influenced more by sex than by light exposure. Journal of pediatric gastroenterology and nutrition 10 18030236
2001 TPN-evoked dysfunction of islet lysosomal activity mediates impairment of glucose-stimulated insulin release. American journal of physiology. Endocrinology and metabolism 10 11404235
2016 Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial. Physiological reports 9 27273879
2005 Postoperative nutritional management after esophagectomy: is TPN the standard of nutritional care? International surgery 9 15912897
1977 Structure-function relationships in TPN-dependent isocitrate dehydrogenase. I. Electron paramagnetic resonance studies of the interaction of enzyme-bound Mn(II) with substrates, cofactors, and substrate analogues. Biochemistry 9 19044
2004 Candida parapsilosis detected in TPN using the BacT/Alert system and characterized by randomly amplified polymorphic DNA. The Journal of hospital infection 8 15066740
1987 The effect of total parenteral nutrition (TPN) on gastrin release in the rat. Regulatory peptides 8 3125565
1984 Does total parenteral nutrition (TPN) really promote tumor growth? A morphometric study. Cancer 8 6434177
2016 A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll-like receptor 2 signal-promoted activation of the MCP1 gene. Immunology 7 26694804
1985 The effect of total parenteral nutrition (TPN) on the enteroinsular axis in the rat. Regulatory peptides 7 3922014
2005 The role of polyamines in glucagon-like peptide-2 prevention of TPN-induced gut hypoplasia. Peptides 6 16274854
1995 Induction of heat-shock proteins and accumulation of trehalose by TPN in Saccharomyces cerevisiae. Biochemical and biophysical research communications 6 7488177
1991 Nitrogen and energy balance in depleted patients undergoing major gastrointestinal surgery: response to TPN. Clinical nutrition (Edinburgh, Scotland) 6 16839892
2022 Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) for Shoulder Mobility Improvement in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Multicenter Controlled Clinical Trial. Journal of clinical medicine 5 35456327
2021 Inadvertent Acute Lipid Injectable Emulsion Overdose Resulting in Fat Overload Syndrome and Pancreatitis in a Patient with TPN Dependence. JPGN reports 5 37168746
2010 Dose variation of hepatocyte growth factor and its effects on an animal model of TPN-induced liver injury. The Journal of surgical research 5 20691983
2010 Involvement of mouse μ-opioid receptor splice variants in the spinal antinociception induced by the dermorphin tetrapeptide analog amidino-TAPA. European journal of pharmacology 5 21047509
2003 Homocysteine prevents total parenteral nutrition (TPN)-induced cholestasis without changes in hepatic oxidative stress in the rat. Journal of pediatric gastroenterology and nutrition 5 12548054
1990 Glucose-based versus fat-based total parenteral nutrition (TPN): effects on hepatic function in septic patients complicated with cholestatic jaundice. Clinical nutrition (Edinburgh, Scotland) 5 16837362
2024 A genetic variant in the TAPBP gene enhances cervical cancer susceptibility by increasing m6A modification. Archives of toxicology 4 38992170
2013 Involvement of spinal release of α-neo-endorphin on the antinociceptive effect of TAPA. Peptides 4 24126280
1986 Effect of DL-3-hydroxybutyrate infusions on leucine and glucose kinetics in burned rats receiving TPN. The Journal of nutrition 4 3080557
2016 In-vitro detection of mannan and galactomannan in components of total parenteral nutrition (TPN). Die Pharmazie 3 27348965
1988 Effect of TPN on bone marrow kinetics--therapeutic implications. The Journal of surgical research 3 3138500
2013 Distinct physiological role of amidino-TAPA-sensitive and DAMGO-insensitive μ-opioid receptor splice variants in the mouse spinal cord. European journal of pharmacology 2 23623932
1998 Effects of total parental nutrition (TPN) during high-dose interleukin-2 treatment for metastatic cancer. Journal of immunotherapy (Hagerstown, Md. : 1997) 2 9456439
1985 Glucose balance and muscle glycogen during TPN in the early post-operative phase. Clinical nutrition (Edinburgh, Scotland) 2 16831739

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