Homo sapiens Protein: NF1
InnateDB Protein IDBP-39466.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol NF1
Protein Name neurofibromin 1
Synonyms NFNS; VRNF; WSS;
Species Homo sapiens
Ensembl Protein ENSP00000351015
InnateDB Gene IDBG-39462 (NF1)
Protein Structure
UniProt Annotation
Function Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. {ECO:0000269PubMed:2121371, ECO:0000269PubMed:8417346}.
Subcellular Localization Nucleus {ECO:0000269PubMed:14988005}. Nucleus, nucleolus {ECO:0000269PubMed:14988005}.
Disease Associations Neurofibromatosis 1 (NF1) [MIM:162200]: A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors. {ECO:0000269PubMed:10220149, ECO:0000269PubMed:10336779, ECO:0000269PubMed:10607834, ECO:0000269PubMed:10712197, ECO:0000269PubMed:10980545, ECO:0000269PubMed:11258625, ECO:0000269PubMed:11735023, ECO:0000269PubMed:11857752, ECO:0000269PubMed:12522551, ECO:0000269PubMed:12552569, ECO:0000269PubMed:12746402, ECO:0000269PubMed:1302608, ECO:0000269PubMed:15060124, ECO:0000269PubMed:15146469, ECO:0000269PubMed:15520408, ECO:0000269PubMed:15523642, ECO:0000269PubMed:15948193, ECO:0000269PubMed:2114220, ECO:0000269PubMed:21838856, ECO:0000269PubMed:7981679, ECO:0000269PubMed:8081387, ECO:0000269PubMed:8544190, ECO:0000269PubMed:8807336, ECO:0000269PubMed:8834249, ECO:0000269PubMed:9003501, ECO:0000269PubMed:9101300, ECO:0000269PubMed:9150739, ECO:0000269PubMed:9298829, ECO:0000269PubMed:9668168}. Note=The disease is caused by mutations affecting the gene represented in this entry.Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An aggressive pediatric myelodysplastic syndrome/myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Patients have splenomegaly, enlarged lymph nodes, rashes, and hemorrhages. Note=The disease is caused by mutations affecting the gene represented in this entry.Watson syndrome (WS) [MIM:193520]: A syndrome characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. It is considered as an atypical form of neurofibromatosis. Note=The disease is caused by mutations affecting the gene represented in this entry.Familial spinal neurofibromatosis (FSNF) [MIM:162210]: Considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors. {ECO:0000269PubMed:11704931}. Note=The disease is caused by mutations affecting the gene represented in this entry.Neurofibromatosis-Noonan syndrome (NFNS) [MIM:601321]: Characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. {ECO:0000269PubMed:12707950, ECO:0000269PubMed:16380919, ECO:0000269PubMed:19845691}. Note=The disease is caused by mutations affecting the gene represented in this entry.Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis.
Tissue Specificity Detected in brain, peripheral nerve, lung, colon and muscle. {ECO:0000269PubMed:8417346}.
Number of Interactions This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 6 interaction(s) predicted by orthology.
Experimentally validated
Total 26 [view]
Protein-Protein 23 [view]
Protein-DNA 3 [view]
Protein-RNA 0
Predicted by orthology
Total 6 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005096 GTPase activator activity
GO:0005099 Ras GTPase activator activity
GO:0005488 binding
GO:0005515 protein binding
GO:0008429 phosphatidylethanolamine binding
GO:0031210 phosphatidylcholine binding
Biological Process
GO:0000165 MAPK cascade
GO:0001649 osteoblast differentiation
GO:0001656 metanephros development
GO:0001666 response to hypoxia
GO:0001889 liver development
GO:0001937 negative regulation of endothelial cell proliferation
GO:0001938 positive regulation of endothelial cell proliferation
GO:0001952 regulation of cell-matrix adhesion
GO:0001953 negative regulation of cell-matrix adhesion
GO:0006469 negative regulation of protein kinase activity
GO:0007154 cell communication
GO:0007165 signal transduction
GO:0007265 Ras protein signal transduction
GO:0007406 negative regulation of neuroblast proliferation
GO:0007420 brain development
GO:0007422 peripheral nervous system development
GO:0007507 heart development
GO:0007519 skeletal muscle tissue development
GO:0008285 negative regulation of cell proliferation
GO:0008542 visual learning
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0014044 Schwann cell development
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0016525 negative regulation of angiogenesis
GO:0021510 spinal cord development
GO:0021897 forebrain astrocyte development
GO:0021915 neural tube development
GO:0021987 cerebral cortex development
GO:0022011 myelination in peripheral nervous system
GO:0030036 actin cytoskeleton organization
GO:0030198 extracellular matrix organization
GO:0030199 collagen fibril organization
GO:0030325 adrenal gland development
GO:0030336 negative regulation of cell migration
GO:0032228 regulation of synaptic transmission, GABAergic
GO:0032318 regulation of Ras GTPase activity
GO:0032320 positive regulation of Ras GTPase activity
GO:0035021 negative regulation of Rac protein signal transduction
GO:0042060 wound healing
GO:0042127 regulation of cell proliferation
GO:0042992 negative regulation of transcription factor import into nucleus
GO:0043065 positive regulation of apoptotic process
GO:0043407 negative regulation of MAP kinase activity
GO:0043409 negative regulation of MAPK cascade
GO:0043473 pigmentation
GO:0043525 positive regulation of neuron apoptotic process
GO:0043535 regulation of blood vessel endothelial cell migration
GO:0045124 regulation of bone resorption
GO:0045671 negative regulation of osteoclast differentiation
GO:0045685 regulation of glial cell differentiation
GO:0045762 positive regulation of adenylate cyclase activity
GO:0045765 regulation of angiogenesis
GO:0046580 negative regulation of Ras protein signal transduction
GO:0046929 negative regulation of neurotransmitter secretion
GO:0048147 negative regulation of fibroblast proliferation
GO:0048169 regulation of long-term neuronal synaptic plasticity
GO:0048485 sympathetic nervous system development
GO:0048593 camera-type eye morphogenesis
GO:0048712 negative regulation of astrocyte differentiation
GO:0048715 negative regulation of oligodendrocyte differentiation
GO:0048745 smooth muscle tissue development
GO:0048844 artery morphogenesis
GO:0048853 forebrain morphogenesis
GO:0050890 cognition
GO:0051056 regulation of small GTPase mediated signal transduction
GO:1902043 positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
Cellular Component
GO:0005622 intracellular
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0016020 membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0031235 intrinsic component of the cytoplasmic side of the plasma membrane
Protein Structure and Domains
InterPro IPR001251 CRAL-TRIO domain
IPR001936 Ras GTPase-activating protein
IPR008936 Rho GTPase activation protein
IPR016024 Armadillo-type fold
PFAM PF00650
Post-translational Modifications
SwissProt P21359
PhosphoSite PhosphoSite-P21359
UniProt Splice Variant
Entrez Gene 4763
UniGene Hs.721732
RefSeq NP_001035957
OMIM 613113
HPRD 01203
EMBL AB195812 AB195813 AC004222 AC079915 AC134669 AC135724 AC138207 AC139072 AH000834 AY796305 CH471147 D10490 D12625 D42072 M38106 M38107 M60496 M60915 M61213 M82814 M89914 S51751 U17084 U17656 U17659 U17662 U17667 U17668 U17673 U17676 U17677 U17680 U17681 U17682 U17683 U17684 U17685 U17686 U17687 U17688 U17689 U17690 Y07853
GenPept AAA18483 AAA56765 AAA59921 AAA59922 AAA59923 AAA59924 AAA59925 AAA59928 AAA74897 AAB24636 AAB48373 AAB48374 AAB48375 AAB48376 AAB48377 AAB48378 AAB48379 AAB48380 AAB59558 AAV50004 BAA01371 BAA02150 BAA07669 BAD98998 BAD98999 CAA69179 EAW80272 EAW80275