PROSITE documentation PDOC51055
ITAM motif profiles


Signal transduction by T and B cell antigen receptors and certain receptors for Ig Fc regions involves a conserved sequence motif, termed an immunoreceptor tyrosine-based activation motif (ITAM). It is also found in the cytoplasmic domain of apoptosis receptor. Phosphorylation of the two ITAM tyrosines is a critical event in signal transduction. All (p)2ITAMs, but not their nonphosphorylated counterparts, induced extensive protein tyrosine phosphorylation in permeabilized cells. After binding of the ligand, via SH2 domain (see <PDOC50001>), phosphorylation of the two conserved tyrosines of ITAM creates binding sites for downstream signaling molecules and thus enables the initiation of signalling events. This phosphorylation was found to reflect activation of the src family kinase Lyn and Syk. Different ITAMs may preferentially activate distinct signaling pathways as a consequence of distinct SH2 effector binding preference [1,2]. Furthermore, in viruses, ITAMs may play key roles in viral pathogenesis by regulating viral clearance, immune cell activation, immune cell recruitment through binding of cellular kinases and thereby down regulate their function [3].

This motif can be found in one to three copies and in association with the Ig-like domain (see <PDOC50835>).

Proteins currently known to contain an ITAM motif are:

  • Mammalian α and β immunoglobulin proteins, TCR γ receptors, FCR γ receptors subunits, CD3 chains receptors and NFAT activation molecule.
  • Hantavirus cytoplasmic elements [3].

Two profiles were developed for this motif. The first one picks up mammalian ITAM while the second one is specific to hantavirus ITAM motif.


The ITAM motif is also found in some strains of simian immunodeficiency virus, the GP30 of bovine leukemia virus, the LMP2A of the Epstein-Barr virus, and the K1 protein of Kaposi's sarcoma-associated herpes virus but the low conservation of the motif in this viral species do not permit us to match them [3,4].


This motif has been variably referred in the literature as the TAM, ARH1, ARAM, YXXL and Reth motif, leading to great confusion [5].

Last update:

January 2005 / First entry.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

ITAM_1, PS51055; ITAM motif mammalian type profile  (MATRIX)

ITAM_2, PS51056; ITAM motif hantavirus type profile  (MATRIX)


1AuthorsJohnson S.A. Pleiman C.M. Pao L. Schneringer J. Hippen K. Cambier J.C.
TitlePhosphorylated immunoreceptor signaling motifs (ITAMs) exhibit unique abilities to bind and activate Lyn and Syk tyrosine kinases.
SourceJ. Immunol. 155:4596-4603(1995).
PubMed ID7594458

2AuthorsPitcher L.A. van Oers N.S.
TitleT-cell receptor signal transmission: who gives an ITAM?
SourceTrends Immunol. 24:554-560(2003).
PubMed ID14552840

3AuthorsGeimonen E. LaMonica R. Springer K. Farooqui Y. Gavrilovskaya I.N. Mackow E.R.
TitleHantavirus pulmonary syndrome-associated hantaviruses contain conserved and functional ITAM signaling elements.
SourceJ. Virol. 77:1638-1643(2003).
PubMed ID12502882

4AuthorsWillems L. Gatot J.S. Mammerickx M. Portetelle D. Burny A. Kerkhofs P. Kettmann R.
TitleThe YXXL signalling motifs of the bovine leukemia virus transmembrane protein are required for in vivo infection and maintenance of high viral loads.
SourceJ. Virol. 69:4137-4141(1995).
PubMed ID7769672

5AuthorsCambier J.C.
TitleNew nomenclature for the Reth motif (or ARH1/TAM/ARAM/YXXL).
SourceImmunol. Today. 16:110-110(1995).
PubMed ID7888063

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