Human immune associated nucleotide 1: a member of a new guanosine triphosphatase family expressed in resting T and B cells.
TAL-1 is a basic helix-loop-helix oncoprotein that is expressed in up to 30% of T-cell acute lymphoblastic leukemias but not in the T lineage. We have cloned a complementary DNA, called Human Immune Associated Nucleotide 1 (hIAN1), whose messenger RNA (mRNA) level expression is inversely correlated to the TAL-1 mRNA level in human leukemic T-cell lines. The hIAN1 encodes a 38-kd protein that belongs to a novel family of proteins conserved from plants to humans and characterized by motifs related to, but highly divergent from, the consensus motifs found in guanosine triphosphate (GTP)-binding proteins. Despite these divergent amino acids at positions involved in GTP/guanosine diphosphate (GDP) binding and guanosine triphosphatase (GTPase) activities, we found that hIAN1 specifically binds GDP (K(d) = 0.47 microM) and GTP (K(d) = 6 microM) and exhibits intrinsic GTPase activity. Among mature hematopoietic cells, hIAN1 is specifically expressed in resting T and B lymphocytes, and its expression level tremendously decreased at the protein but not the mRNA level during B- or T-lymphocyte activation, suggesting a specific role for this new type of GTPase during the immune response.
Cambot
Marie
M
Institut National de la Santé et de la Recherche Médicale U474, ICGM, Maternité Port-Royal, Paris, France.
Aresta
Sandra
S
Kahn-Perlès
Brigitte
B
de Gunzburg
Jean
J
Roméo
Paul-Henri
PH
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D002897:Chromosomes, Human, Pair 7; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000737:chemistry; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D016415:Sequence Alignment; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C485688:GIMAP4 protein, human; C489366:Tal1 protein, mouse; C067143:TAL1 protein, human