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neurofibromatosis type 1 [NF1] protein or neurofibromin

Function: - homologous to ras GAP [suggested to modulate ras GAP] activity - stimulates the GTPase activity of Ras - NF1 shows greater affinity for Ras GAP, but lower specific activity - may be a regulator of Ras activity Structure: - contains 1 CRAL-TRIO domain - contains 1 Ras-GAP domain - homologous to ras GAP - may be mammalian homolog of yeast Ira-protein Alternative splicing: named isoforms=4 RNA editing: - modified_positions=1306 - stop codon (UGA) at position 1306 is created by RNA editing - various levels of RNA editing occurs in peripheral nerve-sheath tumor samples - preferentially observed in transcripts containing exon 23A Pathology: - defects in NF1 are the cause of a) neurofibromatosis type-1 b) juvenile myelomonocytic leukemia c) Watson syndrome c) familial spinal neurofibromatosis d) neurofibromatosis-Noonan syndrome e) colorectal cancer Note: - originally thought to be associated with LEOPARD, an autosomal dominant syndrome

Interactions

molecular events

Related

merlin; moesin-ezrin-radixin-like protein; neurofibromin-2; schwannomin; schwannomerlin (NF2, SCH) neurofibromatosis type-1 gene or NF1 gene

General

phosphoprotein ras GTPase activator protein (Ras p21 protein activator, p120, rasGAP, RASA1)

Properties

SIZE: entity length = 2839 aa MW = 319 kD COMPARTMENT: cytoplasm MOTIF: Ser phosphorylation site {S864} ras-GAP domain NAME: ras-GAP domain SITE: 1235-1451 MOTIF: serine-rich region {1352-1355} MOTIF: serine residue (SEVERAL) CRAL-TRIO lipid binding domain {1580-1738} Ser phosphorylation site {S2188} Thr phosphorylation site {T2514} Ser phosphorylation site {S2515} Ser phosphorylation site {S2829}

Database Correlations

OMIM correlations UniProt P21359 Pfam PF00616 Entrez Gene 4763 Kegg hsa:4763

References

  1. Bourne HR et al, The GTPase superfamily: a conserved switch for diverse cell functions Nature 348:125 1990 PMID: 2122258
  2. Boguski MS & McCormick F Proteins regulating Ras and its relative. Nature 366:643 1993 PMID: 8259209
  3. Nordlund et al J Neuroscience 13(4):1588 1993
  4. NF1 genetic mutation analysis consortium http://www.upmc.edu/neurofibro/NNFFconsortium.htm
  5. Atlas of genetics & cytogenetics in oncology & Haematology http://atlasgeneticsoncology.org/genes/NF1ID134.html
  6. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=NF
  7. UniProt :accession P21359