Reactome | UniProt:P21359 NF1

chain	initiator methionine:1 chain:2-2839 chain:2-1305
checksum	C079475139DBD51E
comment	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.SUBUNIT Interacts with HTR6 (PubMed:23027611). Interacts with SPRED2 (PubMed:34626534).INTERACTION Experimental confirmation may be lacking for some isoforms.TISSUE SPECIFICITY Detected in brain, peripheral nerve, lung, colon and muscle.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.PTM Ubiquitinated by RNF7/RBX2, leading to its degradation.RNA EDITING 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 The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The gene represented in this entry may be involved in disease pathogenesis.CAUTION Was originally thought to be associated with LEOPARD (LS), an autosomal dominant syndrome.SEQUENCE CAUTION Truncated N-terminus.ONLINE INFORMATION Leiden Open Variation Database (LOVD)
crossReference	[DatabaseIdentifier:11521469] ENSEMBL:ENSG00000196712 [DatabaseIdentifier:12472529] RefSeq:NP_001035957.1 [DatabaseIdentifier:12472530] RefSeq:NP_001121619.1 [DatabaseIdentifier:12472531] RefSeq:NP_000258.1 [DatabaseIdentifier:12289989] Pharos - Targets:P21359 [DatabaseIdentifier:12272322] PRO:P21359 [DatabaseIdentifier:12211615] PDB:8EDM [DatabaseIdentifier:12211614] PDB:3PEG [DatabaseIdentifier:12160929] PDB:6V65 [DatabaseIdentifier:12211627] PDB:7PGQ [DatabaseIdentifier:12211619] PDB:8E20 [DatabaseIdentifier:12211629] PDB:7PGU [DatabaseIdentifier:12211613] PDB:7MP6 [DatabaseIdentifier:12211612] PDB:8EDO [DatabaseIdentifier:12211632] PDB:7PGS [DatabaseIdentifier:12211623] PDB:7R04 [DatabaseIdentifier:12211622] PDB:7R03 [DatabaseIdentifier:12211616] PDB:8EDN [DatabaseIdentifier:12211611] PDB:7MP5 [DatabaseIdentifier:12211631] PDB:1NF1 [DatabaseIdentifier:12211624] PDB:2E2X [DatabaseIdentifier:12160877] PDB:6OB3 [DatabaseIdentifier:12211628] PDB:7PGT [DatabaseIdentifier:12211620] PDB:3PG7 [DatabaseIdentifier:12160875] PDB:6OB2 [DatabaseIdentifier:12211630] PDB:7PGR [DatabaseIdentifier:12211618] PDB:7MOC [DatabaseIdentifier:12211617] PDB:8EDL [DatabaseIdentifier:12211626] PDB:7PGP [DatabaseIdentifier:12211625] PDB:2D4Q [DatabaseIdentifier:12211621] PDB:3P7Z [DatabaseIdentifier:12160957] PDB:6V6F [DatabaseIdentifier:12137951] Orphanet:NF1 [DatabaseIdentifier:12129778] OpenTargets:ENSG00000196712 [DatabaseIdentifier:11845138] HPA:ENSG00000196712-NF1 [DatabaseIdentifier:11808151] GlyGen:P21359 [DatabaseIdentifier:11792143] GeneCards:NF1 [DatabaseIdentifier:11763680] ENSEMBL:ENST00000356175 [DatabaseIdentifier:11763681] ENSEMBL:ENST00000358273 [DatabaseIdentifier:11763679] ENSEMBL:ENST00000487476 [DatabaseIdentifier:11763682] ENSEMBL:ENST00000431387 [DatabaseIdentifier:11640983] ENSEMBL:ENSP00000491589 [DatabaseIdentifier:11640982] ENSEMBL:ENSP00000412921 [DatabaseIdentifier:11640981] ENSEMBL:ENSP00000348498 [DatabaseIdentifier:11640980] ENSEMBL:ENSP00000351015
databaseName	UniProt
dbId	60115
description	recommendedName: Neurofibromin alternativeName: Neurofibromatosis-related protein NF-1 component recommendedName: Neurofibromin truncated /component
displayName	UniProt:P21359 NF1
geneName	NF1
identifier	P21359
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative splicing Cell membrane Disease variant GTPase activation Lipid-binding Membrane Nucleus Phosphoprotein Proteomics identification Reference proteome RNA editing Tumor suppressor Ubl conjugation
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	NF1
otherIdentifier	11731351_at 11739222_a_at 11739223_s_at 11739224_x_at 11739225_a_at 11739226_s_at 11741947_x_at 11741948_a_at 11741949_a_at 11745398_a_at 11751469_a_at 11752444_a_at 11752445_x_at 11758642_s_at 11759980_x_at 11763466_at 11763503_a_at 11763504_at 11763505_x_at 11763560_a_at 1236_s_at 16832920 204323_PM_x_at 204323_x_at 204325_PM_s_at 204325_s_at 210631_PM_at 210631_at 211094_PM_s_at 211094_s_at 211095_PM_at 211095_at 211914_PM_x_at 211914_x_at 212676_PM_at 212676_at 212678_PM_at 212678_at 216115_PM_at 216115_at 2340338 243476_PM_at 243476_at 2576364 2576372 2576378 2576384 2576388 3450594 3527040 3527063 3527067 35328_at 3612840 3612844 3612849 3612852 3612859 3716797 3716798 3716799 3717053 3717054 3717055 3717059 3717060 3717061 3717062 3717063 3717064 3717065 3717066 3717067 3717068 3717069 3717070 3717071 3717072 3717073 3717074 3717075 3717076 3717078 3717079 3717080 3717081 3717082 3717083 3717084 3717085 3717086 3717087 3717088 3717089 3717090 3717092 3717093 3717094 3717095 3717096 3717097 3717098 3717099 3717100 3717101 3717102 3717105 3717106 3717107 3717108 3717109 3717110 3717111 3717112 3717113 3717114 3717115 3717116 3717117 3717118 3717119 3717120 3717121 3717122 3717123 3717124 3717125 3717126 3717127 3717128 3717129 3717130 3717131 3717132 3717133 3717134 3717135 3717136 3717137 3717138 3717139 3717140 3717141 3717142 3717143 3717144 3717145 3717146 3717178 3717184 3717194 3717196 3717197 3717238 3717249 3717251 3717253 3717275 3717283 3717284 3717285 3717287 3800214 3800215 3800217 38289_r_at 3914708 3914709 3914725 3935682 3935683 3935685 3935686 3935689 3935692 3935693 3935696 4763 62316_at 739_at 75575_at 8006239 8006296 940_g_at 961_at A_14_P117287 A_14_P121459 A_14_P127545 A_14_P129024 A_14_P134602 A_23_P207596 A_24_P1919 A_24_P917026 D12625_at D42072_at GE54517 GE58128 GE845405 GE84602 GO:0000165 GO:0000902 GO:0001525 GO:0001649 GO:0001656 GO:0001666 GO:0001889 GO:0001935 GO:0001937 GO:0001938 GO:0001952 GO:0001953 GO:0002376 GO:0002686 GO:0005096 GO:0005515 GO:0005634 GO:0005654 GO:0005730 GO:0005737 GO:0005829 GO:0005886 GO:0006606 GO:0006886 GO:0006913 GO:0006915 GO:0007154 GO:0007265 GO:0007269 GO:0007405 GO:0007406 GO:0007420 GO:0007422 GO:0007507 GO:0007519 GO:0008283 GO:0008285 GO:0008289 GO:0008429 GO:0008542 GO:0008625 GO:0010468 GO:0010626 GO:0014009 GO:0014010 GO:0014044 GO:0016020 GO:0016477 GO:0016525 GO:0016601 GO:0021510 GO:0021764 GO:0021897 GO:0021915 GO:0021987 GO:0022011 GO:0030036 GO:0030154 GO:0030198 GO:0030199 GO:0030316 GO:0030325 GO:0030336 GO:0030424 GO:0030425 GO:0031210 GO:0032228 GO:0033024 GO:0033027 GO:0033028 GO:0033034 GO:0034605 GO:0035021 GO:0036135 GO:0042060 GO:0042127 GO:0042308 GO:0043065 GO:0043087 GO:0043408 GO:0043409 GO:0043473 GO:0043491 GO:0043525 GO:0043535 GO:0043547 GO:0045124 GO:0045671 GO:0045685 GO:0045765 GO:0046580 GO:0046929 GO:0048144 GO:0048147 GO:0048169 GO:0048485 GO:0048593 GO:0048708 GO:0048709 GO:0048712 GO:0048715 GO:0048745 GO:0048820 GO:0048844 GO:0048853 GO:0048856 GO:0048870 GO:0050793 GO:0050877 GO:0050890 GO:0051402 GO:0060253 GO:0060291 GO:0061534 GO:0061535 GO:0070372 GO:0070662 GO:0070667 GO:0071887 GO:0072089 GO:0097192 GO:0097529 GO:0098597 GO:0098772 GO:0098793 GO:0098978 GO:0099175 GO:1900148 GO:1900271 GO:1902531 GO:1904707 GO:1904738 GO:1904753 GO:1990874 GO:2000108 GO:2000647 GO:2001241 HMNXSV003013055 HMNXSV003024277 Hs.113577.0.A1_3p_at Hs.306713.0.S1_3p_x_at Hs.58220.0.S1_3p_at Hs.58220.0.S2_3p_at ILMN_1726387 M89914_s_at PH_hs_0005132 TC17000362.hg g1060900_3p_at g189159_3p_s_at g189162_3p_a_at g219939_3p_a_at g219939_3p_x_at g4557792_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-6802424] NF1 R816* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6802410] NF1 F1464L [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6802414] NF1 K1444E [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6802417] NF1 L1187I [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6802420] NF1 R1276P [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6802421] NF1 R1412S [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647532] NF1 R2517* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647468] NF1 Q616Gfs4 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647535] NF1 R2450 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647529] NF1 R2637* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647525] NF1 R2637Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647522] NF1 R304* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647550] NF1 R1276* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647486] NF1 C845Vfs33 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-947770] NF1(2-2839) [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5658418] ub-NF1(2-2839) [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647505] NF1 R69Nfs7 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647511] NF1 R440* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647508] NF1 R440Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9656596] NF1 G849E fs29 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647513] NF1 R416Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647519] NF1 R304Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647516] NF1 R416 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647489] NF1 G1133Dfs61 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647494] NF1 Y489C [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647492] NF1 I1009Ffs3 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647499] NF1 S980* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9656584] NF1 E163D fs2 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647502] NF1 S1053 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647539] NF1 R1534Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647473] NF1 R1241* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647542] NF1 R1534* [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647476] NF1 A131Vfs19 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647483] NF1 C324 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647547] NF1 R1276L [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647545] NF1 R1276Q [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-9647480] NF1 E133Nfs*32 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000196712] ENSEMBL:ENSG00000196712 NF1 [ReferenceDNASequence:12768507] UCSC:P21359 NF1 [ReferenceDNASequence:12114397] OMIM:613113 NF1 [ReferenceDNASequence:12099233] NCBI Gene:4763 NF1 [ReferenceDNASequence:12015140] Monarch:4763 NF1 [ReferenceDNASequence:11921905] KEGG:hsa:4763 NF1 [ReferenceDNASequence:11823822] HGNC:7765 NF1 [ReferenceDNASequence:11441478] dbSNP Gene:4763 NF1 [ReferenceDNASequence:11420170] CTD Gene:4763 NF1 [ReferenceDNASequence:11403832] COSMIC - genes:NF1 NF1 [ReferenceDNASequence:11385351] BioGPS Gene:4763 NF1
referenceTranscript	[ReferenceRNASequence:12654000] RefSeq:NM_001128147.3 NF1 [ReferenceRNASequence:12654002] RefSeq:NM_001042492.3 NF1 [ReferenceRNASequence:12654001] RefSeq:NM_000267.4 NF1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	NF1_HUMAN O00662 Q14284 Q14930 Q14931 Q9UMK3
sequenceLength	2839
species	[Species:48887] Homo sapiens
stId	uniprot:P21359
url	http://purl.uniprot.org/uniprot/P21359

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-6802424] NF1 R816* [cytosol] [EntityWithAccessionedSequence:R-HSA-6802410] NF1 F1464L [cytosol] [EntityWithAccessionedSequence:R-HSA-6802414] NF1 K1444E [cytosol] [EntityWithAccessionedSequence:R-HSA-6802417] NF1 L1187I [cytosol] [EntityWithAccessionedSequence:R-HSA-6802420] NF1 R1276P [cytosol] [EntityWithAccessionedSequence:R-HSA-6802421] NF1 R1412S [cytosol] [EntityWithAccessionedSequence:R-HSA-9647532] NF1 R2517* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647468] NF1 Q616Gfs4 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647535] NF1 R2450 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647529] NF1 R2637* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647525] NF1 R2637Q [cytosol] [EntityWithAccessionedSequence:R-HSA-9647522] NF1 R304* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647550] NF1 R1276* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647486] NF1 C845Vfs33 [cytosol] [EntityWithAccessionedSequence:R-HSA-947770] NF1(2-2839) [cytosol] [EntityWithAccessionedSequence:R-HSA-5658418] ub-NF1(2-2839) [cytosol] [EntityWithAccessionedSequence:R-HSA-9647505] NF1 R69Nfs7 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647511] NF1 R440* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647508] NF1 R440Q [cytosol] [EntityWithAccessionedSequence:R-HSA-9656596] NF1 G849E fs29 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647513] NF1 R416Q [cytosol] [EntityWithAccessionedSequence:R-HSA-9647519] NF1 R304Q [cytosol] [EntityWithAccessionedSequence:R-HSA-9647516] NF1 R416 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647489] NF1 G1133Dfs61 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647494] NF1 Y489C [cytosol] [EntityWithAccessionedSequence:R-HSA-9647492] NF1 I1009Ffs3 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647499] NF1 S980* [cytosol] [EntityWithAccessionedSequence:R-HSA-9656584] NF1 E163D fs2 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647502] NF1 S1053 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647539] NF1 R1534Q [cytosol] [EntityWithAccessionedSequence:R-HSA-9647473] NF1 R1241* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647542] NF1 R1534* [cytosol] [EntityWithAccessionedSequence:R-HSA-9647476] NF1 A131Vfs19 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647483] NF1 C324 [cytosol] [EntityWithAccessionedSequence:R-HSA-9647547] NF1 R1276L [cytosol] [EntityWithAccessionedSequence:R-HSA-9647545] NF1 R1276Q [cytosol] [EntityWithAccessionedSequence:R-HSA-9647480] NF1 E133Nfs*32 [cytosol]
(referenceSequence)	[NonsenseMutation:6802425] Nonsense mutation at L-arginine 816 [ReplacedResidue:6802408] L-phenylalanine 1464 replaced with L-leucine [ReplacedResidue:6802413] L-lysine 1444 replaced with L-glutamic acid [ReplacedResidue:6802415] L-leucine 1187 replaced with L-isoleucine [ReplacedResidue:6802419] L-arginine 1276 replaced with L-proline [ReplacedResidue:6802422] L-arginine 1412 replaced with L-serine [NonsenseMutation:9827815] Nonsense mutation at L-arginine 2517 [FragmentReplacedModification:9832056] Replacement of residues 616 to 618 by GRM [NonsenseMutation:9647425] Nonsense mutation at L-arginine 2450 [NonsenseMutation:9647429] Nonsense mutation at L-arginine 2637 [ReplacedResidue:9647426] L-arginine 2637 replaced with L-glutamine [NonsenseMutation:9647430] Nonsense mutation at L-arginine 304 [NonsenseMutation:9647419] Nonsense mutation at L-arginine 1276 [ModifiedResidue:5658422] ubiquitinylated lysine at unknown position [FragmentReplacedModification:9832062] Replacement of residues 69 to 74 by NIWRSC [NonsenseMutation:9647438] Nonsense mutation at L-arginine 440 [ReplacedResidue:9647436] L-arginine 440 replaced with L-glutamine [FragmentReplacedModification:9767519] Replacement of residues 849 to 849 by ECASSREAILAWQPIAHPWVQSVNVRVL [ReplacedResidue:9647433] L-arginine 416 replaced with L-glutamine [ReplacedResidue:9829019] L-arginine 304 replaced with L-glutamine [NonsenseMutation:9647434] Nonsense mutation at L-arginine 416 [FragmentReplacedModification:9831614] Replacement of residues 1133 to 1192 by DVSEAGITEALYGPCNVKLTQCQRRQWSHALHRLRLPQGSPDKSYIYGSSDKNPSTRHRI [ReplacedResidue:9647446] L-tyrosine 489 replaced with L-cysteine [FragmentReplacedModification:9827800] Replacement of residues 1009 to 1010 by FK [NonsenseMutation:9647445] Nonsense mutation at L-serine 980 [FragmentReplacedModification:9767516] Replacement of residues 163 to 163 by E [NonsenseMutation:9647443] Nonsense mutation at L-serine 1053 [ReplacedResidue:9647421] L-arginine 1534 replaced with L-glutamine [NonsenseMutation:9647413] Nonsense mutation at L-arginine 1241 [NonsenseMutation:9647423] Nonsense mutation at L-arginine 1534 [FragmentReplacedModification:9831610] Replacement of residues 131 to 148 by VCLWGFIFSQLQQLQCSL [NonsenseMutation:9647440] Nonsense mutation at L-cysteine 324 [ReplacedResidue:9647416] L-arginine 1276 replaced with L-leucine [ReplacedResidue:9647414] L-arginine 1276 replaced with L-glutamine [FragmentReplacedModification:9831663] Replacement of residues 133 to 163 by NFGILPLGFYFLSAATTSMQSLVAFLPGYRN [FragmentReplacedModification:9831730] Replacement of residues 845 to 876 by VPLGECASSREAILAWQPIAHPWVQSVNVRVL
(interactor)	[UndirectedInteraction:11159745] UniProt:P21359 <-> UniProt:P05067 (IntAct) [UndirectedInteraction:11159743] UniProt:P21359 <-> UniProt:P21709 (IntAct) [UndirectedInteraction:11159741] UniProt:P21359 <-> UniProt:Q9NY72 (IntAct) [UndirectedInteraction:11159739] UniProt:P21359 <-> UniProt:Q15762 (IntAct) [UndirectedInteraction:11159737] UniProt:P21359 <-> UniProt:Q7Z4N8 (IntAct) [UndirectedInteraction:11159735] UniProt:P21359 <-> UniProt:Q7Z699 (IntAct) [UndirectedInteraction:11159733] UniProt:P21359 <-> UniProt:P01112 (IntAct) [UndirectedInteraction:11159731] UniProt:P21359 <-> UniProt:Q04917 (IntAct) [UndirectedInteraction:11139261] UniProt:P31946 <-> UniProt:P21359 (IntAct)

UniProt:P21359 NF1 Show undefined attributes

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