UniProt functional annotation for P21359



	UniProt functional annotation for P21359

UniProt code: P21359.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:0000269|PubMed:2121371, ECO:0000269|PubMed:8417346}.

Subunit: Interacts with HTR6 (PubMed:23027611). {ECO:0000269|PubMed:23027611}.

Subcellular location: Nucleus {ECO:0000269|PubMed:14988005}. Nucleus, nucleolus {ECO:0000269|PubMed:14988005}.

Tissue specificity: Detected in brain, peripheral nerve, lung, colon and muscle. {ECO:0000269|PubMed:8417346}.

Domain: Binds phospholipids via its C-terminal CRAL-TRIO domain. Binds primarily glycerophospholipids with monounsaturated C18:1 and/or C16:1 fatty acid moieties and a phosphatidylethanolamine or phosphatidylcholine headgroup. Has lesser affinity for lipids containing phosphatidylserine and phosphatidylinositol. {ECO:0000269|PubMed:16397625, ECO:0000269|PubMed:17187824, ECO:0000269|PubMed:21089070}.

Rna editing: Modified_positions=1306 {ECO:0000269|PubMed:11727199, ECO:0000269|PubMed:8602361}; Note=The stop codon (UGA) at position 1306 is created by RNA editing. Various levels of RNA editing occurs in peripheral nerve-sheath tumor samples (PNSTs) from patients with NF1. Preferentially observed in transcripts containing exon 23A.;

Disease: 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:0000269|PubMed:10220149, ECO:0000269|PubMed:10336779, ECO:0000269|PubMed:10607834, ECO:0000269|PubMed:10712197, ECO:0000269|PubMed:10980545, ECO:0000269|PubMed:11258625, ECO:0000269|PubMed:11735023, ECO:0000269|PubMed:11857752, ECO:0000269|PubMed:12522551, ECO:0000269|PubMed:12552569, ECO:0000269|PubMed:12746402, ECO:0000269|PubMed:1302608, ECO:0000269|PubMed:15060124, ECO:0000269|PubMed:15146469, ECO:0000269|PubMed:15520408, ECO:0000269|PubMed:15523642, ECO:0000269|PubMed:15948193, ECO:0000269|PubMed:17160901, ECO:0000269|PubMed:21089070, ECO:0000269|PubMed:2114220, ECO:0000269|PubMed:21838856, ECO:0000269|PubMed:23758643, ECO:0000269|PubMed:24413922, ECO:0000269|PubMed:7981679, ECO:0000269|PubMed:8081387, ECO:0000269|PubMed:8544190, ECO:0000269|PubMed:8807336, ECO:0000269|PubMed:8834249, ECO:0000269|PubMed:9003501, ECO:0000269|PubMed:9101300, ECO:0000269|PubMed:9150739, ECO:0000269|PubMed:9298829, ECO:0000269|PubMed:9668168}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: 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 variants affecting the gene represented in this entry.

Disease: Watson syndrome (WTSN) [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 variants affecting the gene represented in this entry.

Disease: Familial spinal neurofibromatosis (FSNF) [MIM:162210]: Considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors. {ECO:0000269|PubMed:11704931}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: 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:0000269|PubMed:12707950, ECO:0000269|PubMed:16380919, ECO:0000269|PubMed:19845691}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: 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.

Sequence caution: Sequence=AAA59923.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:0000269\|PubMed:2121371, ECO:0000269\|PubMed:8417346}.


Subunit:		Interacts with HTR6 (PubMed:23027611). {ECO:0000269\|PubMed:23027611}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:14988005}. Nucleus, nucleolus {ECO:0000269\|PubMed:14988005}.
Tissue specificity:		Detected in brain, peripheral nerve, lung, colon and muscle. {ECO:0000269\|PubMed:8417346}.
Domain:		Binds phospholipids via its C-terminal CRAL-TRIO domain. Binds primarily glycerophospholipids with monounsaturated C18:1 and/or C16:1 fatty acid moieties and a phosphatidylethanolamine or phosphatidylcholine headgroup. Has lesser affinity for lipids containing phosphatidylserine and phosphatidylinositol. {ECO:0000269\|PubMed:16397625, ECO:0000269\|PubMed:17187824, ECO:0000269\|PubMed:21089070}.
Rna editing:		Modified_positions=1306 {ECO:0000269\|PubMed:11727199, ECO:0000269\|PubMed:8602361}; Note=The stop codon (UGA) at position 1306 is created by RNA editing. Various levels of RNA editing occurs in peripheral nerve-sheath tumor samples (PNSTs) from patients with NF1. Preferentially observed in transcripts containing exon 23A.;
Disease:		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:0000269\|PubMed:10220149, ECO:0000269\|PubMed:10336779, ECO:0000269\|PubMed:10607834, ECO:0000269\|PubMed:10712197, ECO:0000269\|PubMed:10980545, ECO:0000269\|PubMed:11258625, ECO:0000269\|PubMed:11735023, ECO:0000269\|PubMed:11857752, ECO:0000269\|PubMed:12522551, ECO:0000269\|PubMed:12552569, ECO:0000269\|PubMed:12746402, ECO:0000269\|PubMed:1302608, ECO:0000269\|PubMed:15060124, ECO:0000269\|PubMed:15146469, ECO:0000269\|PubMed:15520408, ECO:0000269\|PubMed:15523642, ECO:0000269\|PubMed:15948193, ECO:0000269\|PubMed:17160901, ECO:0000269\|PubMed:21089070, ECO:0000269\|PubMed:2114220, ECO:0000269\|PubMed:21838856, ECO:0000269\|PubMed:23758643, ECO:0000269\|PubMed:24413922, ECO:0000269\|PubMed:7981679, ECO:0000269\|PubMed:8081387, ECO:0000269\|PubMed:8544190, ECO:0000269\|PubMed:8807336, ECO:0000269\|PubMed:8834249, ECO:0000269\|PubMed:9003501, ECO:0000269\|PubMed:9101300, ECO:0000269\|PubMed:9150739, ECO:0000269\|PubMed:9298829, ECO:0000269\|PubMed:9668168}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		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 variants affecting the gene represented in this entry.
Disease:		Watson syndrome (WTSN) [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 variants affecting the gene represented in this entry.
Disease:		Familial spinal neurofibromatosis (FSNF) [MIM:162210]: Considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors. {ECO:0000269\|PubMed:11704931}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		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:0000269\|PubMed:12707950, ECO:0000269\|PubMed:16380919, ECO:0000269\|PubMed:19845691}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		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.
Sequence caution:		Sequence=AAA59923.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};