Heteromeric amino acid transporters: biochemistry, genetics, and physiology

Am J Physiol Renal Physiol. 2001 Dec;281(6):F995-1018. doi: 10.1152/ajprenal.2001.281.6.F995.


The heteromeric amino acid transporters (HATs) are composed of two polypeptides: a heavy subunit (HSHAT) and a light subunit (LSHAT) linked by a disulfide bridge. HSHATs are N-glycosylated type II membrane glycoproteins, whereas LSHATs are nonglycosylated polytopic membrane proteins. The HSHATs have been known since 1992, and the LSHATs have been described in the last three years. HATs represent several of the classic mammalian amino acid transport systems (e.g., L isoforms, y(+)L isoforms, asc, x(c)(-), and b(0,+)). Members of the HAT family are the molecular bases of inherited primary aminoacidurias cystinuria and lysinuric protein intolerance. In addition to the role in amino acid transport, one HSHAT [the heavy subunit of the cell-surface antigen 4F2 (also named CD98)] is involved in other cell functions that might be related to integrin activation. This review covers the biochemistry, human genetics, and cell physiology of HATs, including the multifunctional character of CD98.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Transport Systems* / chemistry
  • Amino Acid Transport Systems* / genetics
  • Amino Acid Transport Systems* / physiology
  • Animals
  • Biological Transport
  • Fusion Regulatory Protein-1 / physiology
  • Humans
  • Integrins / metabolism
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Neoplasms / etiology
  • Renal Aminoacidurias / etiology
  • Sequence Homology, Amino Acid
  • Structure-Activity Relationship


  • Amino Acid Transport Systems
  • Fusion Regulatory Protein-1
  • Integrins