Molecule Information

General Information of the Molecule (ID: Mol00661)

• Name: Antigen peptide transporter 1 (TAP1) ,Homo sapiens
• Synonyms: APT1; ATP-binding cassette sub-family B member 2; Peptide supply factor 1; Peptide transporter PSF1; PSF-1; Peptide transporter TAP1; Peptide transporter involved in antigen processing 1; Really interesting new gene 4 protein; RING4; ABCB2; PSF1; RING4; Y3
• Molecule Type: Protein
• Gene Name: TAP1
• Gene ID: 6890
• Location: chr6:32845209-32853816[-]
• Sequence:
  MASSRCPAPRGCRCLPGASLAWLGTVLLLLADWVLLRTALPRIFSLLVPTALPLLRVWAV
  GLSRWAVLWLGACGVLRATVGSKSENAGAQGWLAALKPLAAALGLALPGLALFRELISWG
  APGSADSTRLLHWGSHPTAFVVSYAAALPAAALWHKLGSLWVPGGQGGSGNPVRRLLGCL
  GSETRRLSLFLVLVVLSSLGEMAIPFFTGRLTDWILQDGSADTFTRNLTLMSILTIASAV
  LEFVGDGIYNNTMGHVHSHLQGEVFGAVLRQETEFFQQNQTGNIMSRVTEDTSTLSDSLS
  ENLSLFLWYLVRGLCLLGIMLWGSVSLTMVTLITLPLLFLLPKKVGKWYQLLEVQVRESL
  AKSSQVAIEALSAMPTVRSFANEEGEAQKFREKLQEIKTLNQKEAVAYAVNSWTTSISGM
  LLKVGILYIGGQLVTSGAVSSGNLVTFVLYQMQFTQAVEVLLSIYPRVQKAVGSSEKIFE
  YLDRTPRCPPSGLLTPLHLEGLVQFQDVSFAYPNRPDVLVLQGLTFTLRPGEVTALVGPN
  GSGKSTVAALLQNLYQPTGGQLLLDGKPLPQYEHRYLHRQVAAVGQEPQVFGRSLQENIA
  YGLTQKPTMEEITAAAVKSGAHSFISGLPQGYDTEVDEAGSQLSGGQRQAVALARALIRK
  PCVLILDDATSALDANSQLQVEQLLYESPERYSRSVLLITQHLSLVEQADHILFLEGGAI
  REGGTHQQLMEKKGCYWAMVQAPADAPE
• Function: ABC transporter associated with antigen processing. In complex with TAP2 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. During the transport cycle alternates between 'inward-facing' state with peptide binding site facing the cytosol to 'outward-facing' state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent 'outward-facing' conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the 'inward facing' state for a new cycle. Typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome. Binds peptides with free N- and C-termini, the first three and the C-terminal residues being critical. Preferentially selects peptides having a highly hydrophobic residue at position 3 and hydrophobic or charged residues at the C-terminal anchor. Proline at position 2 has the most destabilizing effect. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.
• Uniprot ID: TAP1_HUMAN
• Ensembl ID: ENSG00000168394
• HGNC ID: HGNC:43

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cefadroxil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Bacterial infection [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cefadroxil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: Ussing chamber system assay
• Mechanism Description: Cefadroxil and methotrexate (each 10 uM) were selected as substrates to evaluate the functions of the uptake transport mediated by PEPT1 and PCFT, respectively. Gly-Sar (20 mM) and folate (200 uM), typical substrates of PEPT1 and PCFT, respectively, were used to saturate the functions of PEPT1 and PCFT. The mucosal-to-serosal transport and mucosal uptake of cefadroxil and methotrexate were significantly decreased in the presence of PEPT1/PCFT inhibitor cocktail in all batches of tissue sections.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 01

Bacterial infection [ICD-11: 1A00-1C4Z]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gingival tissue
• The Specified Disease: Bacterial infection of gingival
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.54E-01; Fold-change: 1.39E-01; Z-score: 2.53E-01

References

• Ref 1: Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum. Drug Metab Dispos. 2021 Jan;49(1):84-93. doi: 10.1124/dmd.120.000138. Epub 2020 Oct 21.