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Protein

Neurofibromin

Gene

NF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.2 Publications

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • phosphatidylcholine binding Source: UniProtKB
  • phosphatidylethanolamine binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:G66-32238-MONOMER.
ReactomeiR-HSA-5658442. Regulation of RAS by GAPs.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802953. RAS signaling downstream of NF1 loss-of-function variants.
R-HSA-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
SignaLinkiP21359.
SIGNORiP21359.

Names & Taxonomyi

Protein namesi
Recommended name:
Neurofibromin
Alternative name(s):
Neurofibromatosis-related protein NF-1
Cleaved into the following chain:
Gene namesi
Name:NF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:7765. NF1.

Subcellular locationi

GO - Cellular componenti

  • axon Source: HGNC
  • cytoplasm Source: HGNC
  • cytosol Source: Reactome
  • dendrite Source: HGNC
  • intrinsic component of the cytoplasmic side of the plasma membrane Source: GO_Central
  • membrane Source: UniProtKB
  • nucleolus Source: UniProtKB-SubCell
  • nucleus Source: HGNC
  • presynapse Source: GOC
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Neurofibromatosis 1 (NF1)32 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:162200
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03245931H → R in NF1. 1 PublicationCorresponds to variant rs199474725dbSNPEnsembl.1
Natural variantiVAR_02173082S → F in NF1. 1 PublicationCorresponds to variant rs199474729dbSNPEnsembl.1
Natural variantiVAR_07166893C → W in NF1. 1 Publication1
Natural variantiVAR_01755193C → Y in NF1. 1 PublicationCorresponds to variant rs199474728dbSNPEnsembl.1
Natural variantiVAR_010989117I → S in NF1. 1 PublicationCorresponds to variant rs199474731dbSNPEnsembl.1
Natural variantiVAR_032460145L → P in NF1. 1 PublicationCorresponds to variant rs199474734dbSNPEnsembl.1
Natural variantiVAR_021731157I → N in NF1. 1 PublicationCorresponds to variant rs199474744dbSNPEnsembl.1
Natural variantiVAR_065888160R → T in NF1. 1 PublicationCorresponds to variant rs199474752dbSNPEnsembl.1
Natural variantiVAR_032461186D → V in NF1; reduced splicing enhancement. 1 Publication1
Natural variantiVAR_021732216L → P in NF1. 1 PublicationCorresponds to variant rs199474756dbSNPEnsembl.1
Natural variantiVAR_032463324C → R in NF1. 1 PublicationCorresponds to variant rs199474735dbSNPEnsembl.1
Natural variantiVAR_032464337E → V in NF1. 1 PublicationCorresponds to variant rs199474736dbSNPEnsembl.1
Natural variantiVAR_010990338D → G in NF1. 1 PublicationCorresponds to variant rs199474773dbSNPEnsembl.1
Natural variantiVAR_021733357L → P in NF1. 1 PublicationCorresponds to variant rs137854563dbSNPEnsembl.1
Natural variantiVAR_032465489Y → C in NF1. 1 PublicationCorresponds to variant rs137854557dbSNPEnsembl.1
Natural variantiVAR_021734491Y → C in NF1. 1 PublicationCorresponds to variant rs199474757dbSNPEnsembl.1
Natural variantiVAR_010991508L → P in NF1. 1 PublicationCorresponds to variant rs137854558dbSNPEnsembl.1
Natural variantiVAR_032466532L → P in NF1. 1 PublicationCorresponds to variant rs199474737dbSNPEnsembl.1
Natural variantiVAR_021735549L → P in NF1. 1 PublicationCorresponds to variant rs199474758dbSNPEnsembl.1
Natural variantiVAR_032467574S → R in NF1. 1 Publication1
Natural variantiVAR_021736578L → R in NF1. 1 PublicationCorresponds to variant rs199474774dbSNPEnsembl.1
Natural variantiVAR_021737581I → T in NF1. 1 PublicationCorresponds to variant rs199474759dbSNPEnsembl.1
Natural variantiVAR_021738583K → R in NF1. 1 PublicationCorresponds to variant rs199474760dbSNPEnsembl.1
Natural variantiVAR_017553604L → V in NF1. 1 PublicationCorresponds to variant rs142712751dbSNPEnsembl.1
Natural variantiVAR_002653629G → R in NF1; affects splicing by creating a novel splice acceptor site. 3 PublicationsCorresponds to variant rs199474738dbSNPEnsembl.1
Natural variantiVAR_021739665S → F in NF1; unknown pathological significance. 2 PublicationsCorresponds to variant rs145891889dbSNPEnsembl.1
Natural variantiVAR_021740695L → P in NF1. 1 PublicationCorresponds to variant rs199474761dbSNPEnsembl.1
Natural variantiVAR_021741763L → P in NF1. 1 PublicationCorresponds to variant rs199474762dbSNPEnsembl.1
Natural variantiVAR_021743777W → S in NF1. 2 PublicationsCorresponds to variant rs199474745dbSNPEnsembl.1
Natural variantiVAR_021744780T → K in NF1. 4 PublicationsCorresponds to variant rs199474746dbSNPEnsembl.1
Natural variantiVAR_021745781H → P in NF1. 1 PublicationCorresponds to variant rs199474763dbSNPEnsembl.1
Natural variantiVAR_021746784W → C in NF1. 1 PublicationCorresponds to variant rs199474778dbSNPEnsembl.1
Natural variantiVAR_021747784W → R in NF1. 2 PublicationsCorresponds to variant rs199474730dbSNPEnsembl.1
Natural variantiVAR_010992844L → F in NF1. 2 PublicationsCorresponds to variant rs199474785dbSNPEnsembl.1
Natural variantiVAR_032468844L → P in NF1. 1 PublicationCorresponds to variant rs137854566dbSNPEnsembl.1
Natural variantiVAR_002654844L → R in NF1; sporadic. 3 PublicationsCorresponds to variant rs137854566dbSNPEnsembl.1
Natural variantiVAR_021748847L → P in NF1. 3 PublicationsCorresponds to variant rs199474747dbSNPEnsembl.1
Natural variantiVAR_021749848G → E in NF1. 2 PublicationsCorresponds to variant rs199474748dbSNPEnsembl.1
Natural variantiVAR_002655898L → P in NF1; sporadic. 2 PublicationsCorresponds to variant rs199474786dbSNPEnsembl.1
Natural variantiVAR_021750920L → P in NF1; patient with cafe-au-lait spots; may be a distinct form of NF1. 1 PublicationCorresponds to variant rs199474775dbSNPEnsembl.1
Natural variantiVAR_021751968M → R in NF1. 2 PublicationsCorresponds to variant rs199474749dbSNPEnsembl.1
Natural variantiVAR_002656991Missing in NF1; most patients carrying the mutation do not manifest cutaneous neurofibromas. 3 Publications1
Natural variantiVAR_0026571035M → R in NF1. 1 PublicationCorresponds to variant rs137854553dbSNPEnsembl.1
Natural variantiVAR_0716691048W → R in NF1. 1 Publication1
Natural variantiVAR_0324701073M → V in NF1. 1 PublicationCorresponds to variant rs199474740dbSNPEnsembl.1
Natural variantiVAR_0217521147L → P in NF1. 1 PublicationCorresponds to variant rs199474779dbSNPEnsembl.1
Natural variantiVAR_0217531156N → S in NF1. 1 PublicationCorresponds to variant rs199474764dbSNPEnsembl.1
Natural variantiVAR_0109931166G → D in NF1. 1 PublicationCorresponds to variant rs199474787dbSNPEnsembl.1
Natural variantiVAR_0716701189Q → R in NF1. 1 PublicationCorresponds to variant rs752039618dbSNPEnsembl.1
Natural variantiVAR_0217541193F → C in NF1. 1 PublicationCorresponds to variant rs199474780dbSNPEnsembl.1
Natural variantiVAR_0324711196L → R in NF1. 1 PublicationCorresponds to variant rs199474741dbSNPEnsembl.1
Natural variantiVAR_0217551204R → G in NF1. 1 PublicationCorresponds to variant rs199474732dbSNPEnsembl.1
Natural variantiVAR_0109941204R → W in NF1. 1 PublicationCorresponds to variant rs199474732dbSNPEnsembl.1
Natural variantiVAR_0324721243L → P in NF1; with neurofibromatous neuropathy. 1 PublicationCorresponds to variant rs137854564dbSNPEnsembl.1
Natural variantiVAR_0217561250R → P in NF1. 1 PublicationCorresponds to variant rs199474765dbSNPEnsembl.1
Natural variantiVAR_0324731276R → G in NF1. 1 PublicationCorresponds to variant rs199474742dbSNPEnsembl.1
Natural variantiVAR_0109951276R → P in NF1; complete loss of GAP activity. 2 PublicationsCorresponds to variant rs137854556dbSNPEnsembl.1
Natural variantiVAR_0175551276R → Q in NF1 and mismatch repair deficient cancer cells. 3 PublicationsCorresponds to variant rs137854556dbSNPEnsembl.1
Natural variantiVAR_0109961412R → S in NF1; significant reduction of GAP activity. 1 PublicationCorresponds to variant rs137854554dbSNPEnsembl.1
Natural variantiVAR_0324741430K → E in NF1. 1 Publication1
Natural variantiVAR_0109971440K → Q in NF1. 1 PublicationCorresponds to variant rs199474790dbSNPEnsembl.1
Natural variantiVAR_0026581440K → R in NF1. 1 PublicationCorresponds to variant rs199474788dbSNPEnsembl.1
Natural variantiVAR_0026591444K → E in NF1 and NFNS; significant reduction of intrinsic GAP activity. 4 PublicationsCorresponds to variant rs137854550dbSNPEnsembl.1
Natural variantiVAR_0217571444K → N in NF1. 2 PublicationsCorresponds to variant rs199474750dbSNPEnsembl.1
Natural variantiVAR_0217581444K → R in NF1. 1 PublicationCorresponds to variant rs199474781dbSNPEnsembl.1
Natural variantiVAR_0081291446L → P in NF1. 3 PublicationsCorresponds to variant rs199474733dbSNPEnsembl.1
Natural variantiVAR_0109981489S → G in NF1. 2 PublicationsCorresponds to variant rs199474743dbSNPEnsembl.1
Natural variantiVAR_0217591605I → V in NF1; reduces protein stability. 2 PublicationsCorresponds to variant rs199474766dbSNPEnsembl.1
Natural variantiVAR_0026601611R → W in NF1. 1 Publication1
Natural variantiVAR_0026611733L → LGHEQQKLPAATLAL in NF1. 1 Publication1
Natural variantiVAR_0217601785A → S in NF1. 1 PublicationCorresponds to variant rs199474782dbSNPEnsembl.1
Natural variantiVAR_0026621952W → R in NF1. 1 PublicationCorresponds to variant rs199474791dbSNPEnsembl.1
Natural variantiVAR_0026631953L → P in NF1. 1 PublicationCorresponds to variant rs199474792dbSNPEnsembl.1
Natural variantiVAR_0217611953Missing in NF1. 2 Publications1
Natural variantiVAR_0217622001G → R in NF1. 2 PublicationsCorresponds to variant rs199474751dbSNPEnsembl.1
Natural variantiVAR_0217632012D → N in NF1. 1 PublicationCorresponds to variant rs199474783dbSNPEnsembl.1
Natural variantiVAR_0716712125L → P in NF1. 1 Publication1
Natural variantiVAR_0026642164L → M in NF1. 1 PublicationCorresponds to variant rs137854551dbSNPEnsembl.1
Natural variantiVAR_0026652192Y → N in NF1. 1 PublicationCorresponds to variant rs267606598dbSNPEnsembl.1
Natural variantiVAR_0217642221P → A in NF1. 1 PublicationCorresponds to variant rs199474776dbSNPEnsembl.1
Natural variantiVAR_0217652357E → K in NF1. 1 PublicationCorresponds to variant rs199474784dbSNPEnsembl.1
Natural variantiVAR_0026662387 – 2388Missing in NF1. 2 Publications2
Natural variantiVAR_0217662507T → I in NF1. 1 PublicationCorresponds to variant rs149055633dbSNPEnsembl.1
Natural variantiVAR_0026672631T → A in NF1. 1 PublicationCorresponds to variant rs199474793dbSNPEnsembl.1
Isoform 1 (identifier: P21359-2)
Natural varianti1661C → R in NF1. 1 Publication1
Natural varianti1918I → T in NF1. 1 Publication1
Leukemia, juvenile myelomonocytic (JMML)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:607785
Watson syndrome (WTSN)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA syndrome characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. It is considered as an atypical form of neurofibromatosis.
See also OMIM:193520
Familial spinal neurofibromatosis (FSNF)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionConsidered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.
See also OMIM:162210
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0176692088L → P in FSNF; no cafe-au-lait macules; null mutation; 50% reduction of protein level. 1 PublicationCorresponds to variant rs137854561dbSNPEnsembl.1
Neurofibromatosis-Noonan syndrome (NFNS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized 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.
See also OMIM:601321
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_032462194L → R in NFNS. 1 PublicationCorresponds to variant rs199474753dbSNPEnsembl.1
Natural variantiVAR_0652361411L → F in NFNS. 1 PublicationCorresponds to variant rs199474789dbSNPEnsembl.1
Natural variantiVAR_0026591444K → E in NF1 and NFNS; significant reduction of intrinsic GAP activity. 4 PublicationsCorresponds to variant rs137854550dbSNPEnsembl.1
Natural variantiVAR_0324751451N → T in NFNS. 1 PublicationCorresponds to variant rs199474754dbSNPEnsembl.1
Natural variantiVAR_0324761453V → L in NFNS. 1 PublicationCorresponds to variant rs199474755dbSNPEnsembl.1
Natural variantiVAR_0324771459Missing in NFNS. 3 Publications1
Colorectal cancer (CRC)
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA 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.
See also OMIM:114500

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1691K → A: Reduces phospholipid binding; when associated with A-1695; A-1769 and A-1771. 1 Publication1
Mutagenesisi1695R → A: Reduces phospholipid binding; when associated with A-1691; A-1769 and A-1771. 1 Publication1
Mutagenesisi1769R → A: Reduces phospholipid binding; when associated with A-1691; A-1695 and A-1771. 1 Publication1
Mutagenesisi1771K → A: Reduces phospholipid binding; when associated with A-1691; A-169 and A-1769. 2 Publications1
Mutagenesisi1771Missing : Reduces protein stability. 2 Publications1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi4763.
MalaCardsiNF1.
MIMi114500. phenotype.
162200. phenotype.
162210. phenotype.
193520. phenotype.
601321. phenotype.
607785. phenotype.
OpenTargetsiENSG00000196712.
Orphaneti97685. 17q11 microdeletion syndrome.
139474. 17q11.2 microduplication syndrome.
86834. Juvenile myelomonocytic leukemia.
363700. Neurofibromatosis type 1 due to NF1mutation or intragenic deletion.
638. Neurofibromatosis-Noonan syndrome.
PharmGKBiPA31572.

Polymorphism and mutation databases

BioMutaiNF1.
DMDMi548350.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000107732 – 2839NeurofibrominAdd BLAST2838
ChainiPRO_00000107742 – 1305Neurofibromin truncatedAdd BLAST1304

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei864PhosphoserineCombined sources1
Modified residuei876PhosphoserineCombined sources1
Modified residuei2188PhosphoserineCombined sources1
Modified residuei2467PhosphoserineBy similarity1
Modified residuei2514PhosphothreonineBy similarity1
Modified residuei2515PhosphoserineCombined sources1
Modified residuei2521PhosphoserineCombined sources1
Modified residuei2523PhosphoserineCombined sources1
Modified residuei2543PhosphoserineCombined sources1
Modified residuei2565PhosphothreonineCombined sources1
Modified residuei2597PhosphoserineCombined sources1
Modified residuei2802PhosphoserineCombined sources1
Modified residuei2817PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP21359.
MaxQBiP21359.
PaxDbiP21359.
PeptideAtlasiP21359.
PRIDEiP21359.

PTM databases

iPTMnetiP21359.
PhosphoSitePlusiP21359.

Expressioni

Tissue specificityi

Detected in brain, peripheral nerve, lung, colon and muscle.1 Publication

Gene expression databases

BgeeiENSG00000196712.
CleanExiHS_NF1.
ExpressionAtlasiP21359. baseline and differential.
GenevisibleiP21359. HS.

Organism-specific databases

HPAiCAB004786.
HPA045502.

Interactioni

Subunit structurei

Interacts with HTR6 (PubMed:23027611).1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050673EBI-1172917,EBI-77613
SDC2P347414EBI-1172917,EBI-1172957

Protein-protein interaction databases

BioGridi110836. 32 interactors.
IntActiP21359. 12 interactors.
MINTiMINT-1504522.
STRINGi9606.ENSP00000351015.

Structurei

Secondary structure

12839
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1208 – 1216Combined sources9
Helixi1224 – 1228Combined sources5
Helixi1233 – 1235Combined sources3
Helixi1236 – 1248Combined sources13
Turni1249 – 1251Combined sources3
Helixi1253 – 1263Combined sources11
Beta strandi1266 – 1270Combined sources5
Helixi1282 – 1293Combined sources12
Helixi1296 – 1299Combined sources4
Beta strandi1300 – 1302Combined sources3
Turni1335 – 1337Combined sources3
Turni1339 – 1342Combined sources4
Helixi1343 – 1352Combined sources10
Turni1353 – 1356Combined sources4
Helixi1361 – 1370Combined sources10
Turni1394 – 1396Combined sources3
Helixi1402 – 1412Combined sources11
Helixi1414 – 1419Combined sources6
Helixi1434 – 1440Combined sources7
Helixi1442 – 1451Combined sources10
Helixi1462 – 1464Combined sources3
Helixi1465 – 1470Combined sources6
Helixi1472 – 1481Combined sources10
Helixi1510 – 1514Combined sources5
Helixi1517 – 1520Combined sources4
Helixi1535 – 1544Combined sources10
Helixi1569 – 1578Combined sources10
Turni1582 – 1586Combined sources5
Helixi1587 – 1590Combined sources4
Beta strandi1592 – 1598Combined sources7
Beta strandi1604 – 1609Combined sources6
Helixi1610 – 1612Combined sources3
Turni1615 – 1617Combined sources3
Helixi1620 – 1631Combined sources12
Turni1632 – 1636Combined sources5
Beta strandi1639 – 1644Combined sources6
Helixi1650 – 1652Combined sources3
Helixi1656 – 1661Combined sources6
Turni1662 – 1664Combined sources3
Helixi1668 – 1672Combined sources5
Beta strandi1674 – 1681Combined sources8
Helixi1684 – 1692Combined sources9
Helixi1694 – 1697Combined sources4
Turni1698 – 1702Combined sources5
Beta strandi1706 – 1711Combined sources6
Helixi1714 – 1717Combined sources4
Helixi1721 – 1723Combined sources3
Helixi1728 – 1732Combined sources5
Beta strandi1738 – 1749Combined sources12
Beta strandi1751 – 1757Combined sources7
Beta strandi1759 – 1767Combined sources9
Beta strandi1770 – 1772Combined sources3
Beta strandi1775 – 1777Combined sources3
Beta strandi1780 – 1784Combined sources5
Helixi1785 – 1787Combined sources3
Beta strandi1788 – 1795Combined sources8
Beta strandi1798 – 1803Combined sources6
Beta strandi1810 – 1813Combined sources4
Helixi1817 – 1833Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NF1X-ray2.50A1198-1551[»]
2D4QX-ray2.30A/B1581-1837[»]
2E2XX-ray2.50A/B1566-1837[»]
3P7ZX-ray2.65A/B1566-1837[»]
3PEGX-ray2.52A1566-1837[»]
3PG7X-ray2.19A/B1581-1837[»]
ProteinModelPortaliP21359.
SMRiP21359.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP21359.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1235 – 1451Ras-GAPPROSITE-ProRule annotationAdd BLAST217
Domaini1580 – 1738CRAL-TRIOPROSITE-ProRule annotationAdd BLAST159

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1580 – 1837Lipid bindingAdd BLAST258

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi2555 – 2571Bipartite nuclear localization signalAdd BLAST17

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1352 – 1355Poly-Ser4

Domaini

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.3 Publications

Sequence similaritiesi

Contains 1 CRAL-TRIO domain.PROSITE-ProRule annotation
Contains 1 Ras-GAP domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1826. Eukaryota.
ENOG410XRPJ. LUCA.
GeneTreeiENSGT00550000074797.
HOGENOMiHOG000047020.
HOVERGENiHBG006486.
InParanoidiP21359.
KOiK08052.
OMAiNSSDRFP.
OrthoDBiEOG091G03FI.
PhylomeDBiP21359.
TreeFamiTF300302.

Family and domain databases

Gene3Di1.25.10.10. 6 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR001251. CRAL-TRIO_dom.
IPR028553. Neurofibromin.
IPR023152. RasGAP_CS.
IPR001936. RasGAP_dom.
IPR008936. Rho_GTPase_activation_prot.
[Graphical view]
PANTHERiPTHR10194:SF90. PTHR10194:SF90. 5 hits.
PfamiPF13716. CRAL_TRIO_2. 1 hit.
PF00616. RasGAP. 1 hit.
[Graphical view]
SMARTiSM00323. RasGAP. 1 hit.
SM00516. SEC14. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF48371. SSF48371. 4 hits.
PROSITEiPS50191. CRAL_TRIO. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 2 (identifier: P21359-1) [UniParc]FASTAAdd to basket
Also known as: Type II

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAHRPVEWV QAVVSRFDEQ LPIKTGQQNT HTKVSTEHNK ECLINISKYK
60 70 80 90 100
FSLVISGLTT ILKNVNNMRI FGEAAEKNLY LSQLIILDTL EKCLAGQPKD
110 120 130 140 150
TMRLDETMLV KQLLPEICHF LHTCREGNQH AAELRNSASG VLFSLSCNNF
160 170 180 190 200
NAVFSRISTR LQELTVCSED NVDVHDIELL QYINVDCAKL KRLLKETAFK
210 220 230 240 250
FKALKKVAQL AVINSLEKAF WNWVENYPDE FTKLYQIPQT DMAECAEKLF
260 270 280 290 300
DLVDGFAEST KRKAAVWPLQ IILLILCPEI IQDISKDVVD ENNMNKKLFL
310 320 330 340 350
DSLRKALAGH GGSRQLTESA AIACVKLCKA STYINWEDNS VIFLLVQSMV
360 370 380 390 400
VDLKNLLFNP SKPFSRGSQP ADVDLMIDCL VSCFRISPHN NQHFKICLAQ
410 420 430 440 450
NSPSTFHYVL VNSLHRIITN SALDWWPKID AVYCHSVELR NMFGETLHKA
460 470 480 490 500
VQGCGAHPAI RMAPSLTFKE KVTSLKFKEK PTDLETRSYK YLLLSMVKLI
510 520 530 540 550
HADPKLLLCN PRKQGPETQG STAELITGLV QLVPQSHMPE IAQEAMEALL
560 570 580 590 600
VLHQLDSIDL WNPDAPVETF WEISSQMLFY ICKKLTSHQM LSSTEILKWL
610 620 630 640 650
REILICRNKF LLKNKQADRS SCHFLLFYGV GCDIPSSGNT SQMSMDHEEL
660 670 680 690 700
LRTPGASLRK GKGNSSMDSA AGCSGTPPIC RQAQTKLEVA LYMFLWNPDT
710 720 730 740 750
EAVLVAMSCF RHLCEEADIR CGVDEVSVHN LLPNYNTFME FASVSNMMST
760 770 780 790 800
GRAALQKRVM ALLRRIEHPT AGNTEAWEDT HAKWEQATKL ILNYPKAKME
810 820 830 840 850
DGQAAESLHK TIVKRRMSHV SGGGSIDLSD TDSLQEWINM TGFLCALGGV
860 870 880 890 900
CLQQRSNSGL ATYSPPMGPV SERKGSMISV MSSEGNADTP VSKFMDRLLS
910 920 930 940 950
LMVCNHEKVG LQIRTNVKDL VGLELSPALY PMLFNKLKNT ISKFFDSQGQ
960 970 980 990 1000
VLLTDTNTQF VEQTIAIMKN LLDNHTEGSS EHLGQASIET MMLNLVRYVR
1010 1020 1030 1040 1050
VLGNMVHAIQ IKTKLCQLVE VMMARRDDLS FCQEMKFRNK MVEYLTDWVM
1060 1070 1080 1090 1100
GTSNQAADDD VKCLTRDLDQ ASMEAVVSLL AGLPLQPEEG DGVELMEAKS
1110 1120 1130 1140 1150
QLFLKYFTLF MNLLNDCSEV EDESAQTGGR KRGMSRRLAS LRHCTVLAMS
1160 1170 1180 1190 1200
NLLNANVDSG LMHSIGLGYH KDLQTRATFM EVLTKILQQG TEFDTLAETV
1210 1220 1230 1240 1250
LADRFERLVE LVTMMGDQGE LPIAMALANV VPCSQWDELA RVLVTLFDSR
1260 1270 1280 1290 1300
HLLYQLLWNM FSKEVELADS MQTLFRGNSL ASKIMTFCFK VYGATYLQKL
1310 1320 1330 1340 1350
LDPLLRIVIT SSDWQHVSFE VDPTRLEPSE SLEENQRNLL QMTEKFFHAI
1360 1370 1380 1390 1400
ISSSSEFPPQ LRSVCHCLYQ ATCHSLLNKA TVKEKKENKK SVVSQRFPQN
1410 1420 1430 1440 1450
SIGAVGSAMF LRFINPAIVS PYEAGILDKK PPPRIERGLK LMSKILQSIA
1460 1470 1480 1490 1500
NHVLFTKEEH MRPFNDFVKS NFDAARRFFL DIASDCPTSD AVNHSLSFIS
1510 1520 1530 1540 1550
DGNVLALHRL LWNNQEKIGQ YLSSNRDHKA VGRRPFDKMA TLLAYLGPPE
1560 1570 1580 1590 1600
HKPVADTHWS SLNLTSSKFE EFMTRHQVHE KEEFKALKTL SIFYQAGTSK
1610 1620 1630 1640 1650
AGNPIFYYVA RRFKTGQING DLLIYHVLLT LKPYYAKPYE IVVDLTHTGP
1660 1670 1680 1690 1700
SNRFKTDFLS KWFVVFPGFA YDNVSAVYIY NCNSWVREYT KYHERLLTGL
1710 1720 1730 1740 1750
KGSKRLVFID CPGKLAEHIE HEQQKLPAAT LALEEDLKVF HNALKLAHKD
1760 1770 1780 1790 1800
TKVSIKVGST AVQVTSAERT KVLGQSVFLN DIYYASEIEE ICLVDENQFT
1810 1820 1830 1840 1850
LTIANQGTPL TFMHQECEAI VQSIIHIRTR WELSQPDSIP QHTKIRPKDV
1860 1870 1880 1890 1900
PGTLLNIALL NLGSSDPSLR SAAYNLLCAL TCTFNLKIEG QLLETSGLCI
1910 1920 1930 1940 1950
PANNTLFIVS ISKTLAANEP HLTLEFLEEC ISGFSKSSIE LKHLCLEYMT
1960 1970 1980 1990 2000
PWLSNLVRFC KHNDDAKRQR VTAILDKLIT MTINEKQMYP SIQAKIWGSL
2010 2020 2030 2040 2050
GQITDLLDVV LDSFIKTSAT GGLGSIKAEV MADTAVALAS GNVKLVSSKV
2060 2070 2080 2090 2100
IGRMCKIIDK TCLSPTPTLE QHLMWDDIAI LARYMLMLSF NNSLDVAAHL
2110 2120 2130 2140 2150
PYLFHVVTFL VATGPLSLRA STHGLVINII HSLCTCSQLH FSEETKQVLR
2160 2170 2180 2190 2200
LSLTEFSLPK FYLLFGISKV KSAAVIAFRS SYRDRSFSPG SYERETFALT
2210 2220 2230 2240 2250
SLETVTEALL EIMEACMRDI PTCKWLDQWT ELAQRFAFQY NPSLQPRALV
2260 2270 2280 2290 2300
VFGCISKRVS HGQIKQIIRI LSKALESCLK GPDTYNSQVL IEATVIALTK
2310 2320 2330 2340 2350
LQPLLNKDSP LHKALFWVAV AVLQLDEVNL YSAGTALLEQ NLHTLDSLRI
2360 2370 2380 2390 2400
FNDKSPEEVF MAIRNPLEWH CKQMDHFVGL NFNSNFNFAL VGHLLKGYRH
2410 2420 2430 2440 2450
PSPAIVARTV RILHTLLTLV NKHRNCDKFE VNTQSVAYLA ALLTVSEEVR
2460 2470 2480 2490 2500
SRCSLKHRKS LLLTDISMEN VPMDTYPIHH GDPSYRTLKE TQPWSSPKGS
2510 2520 2530 2540 2550
EGYLAATYPT VGQTSPRARK SMSLDMGQPS QANTKKLLGT RKSFDHLISD
2560 2570 2580 2590 2600
TKAPKRQEME SGITTPPKMR RVAETDYEME TQRISSSQQH PHLRKVSVSE
2610 2620 2630 2640 2650
SNVLLDEEVL TDPKIQALLL TVLATLVKYT TDEFDQRILY EYLAEASVVF
2660 2670 2680 2690 2700
PKVFPVVHNL LDSKINTLLS LCQDPNLLNP IHGIVQSVVY HEESPPQYQT
2710 2720 2730 2740 2750
SYLQSFGFNG LWRFAGPFSK QTQIPDYAEL IVKFLDALID TYLPGIDEET
2760 2770 2780 2790 2800
SEESLLTPTS PYPPALQSQL SITANLNLSN SMTSLATSQH SPGIDKENVE
2810 2820 2830
LSPTTGHCNS GRTRHGSASQ VQKQRSAGSF KRNSIKKIV
Length:2,839
Mass (Da):319,372
Last modified:June 1, 1994 - v2
Checksum:iC079475139DBD51E
GO
Isoform 1 (identifier: P21359-2) [UniParc]FASTAAdd to basket
Also known as: Type I

The sequence of this isoform differs from the canonical sequence as follows:
     1371-1391: Missing.

Show »
Length:2,818
Mass (Da):317,033
Checksum:i7E5B89158317C56C
GO
Isoform 3 (identifier: P21359-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     548-551: ALLV → VRGK
     552-2839: Missing.

Show »
Length:551
Mass (Da):62,300
Checksum:iD783EC85BCE926D7
GO
Isoform 4 (identifier: P21359-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1591-1598: SIFYQAGT → TPPPEPET
     1599-2839: Missing.

Show »
Length:1,598
Mass (Da):180,213
Checksum:iF76BC6C54FC08C8C
GO
Isoform 5 (identifier: P21359-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     574-593: SSQMLFYICKKLTSHQMLSS → RYMYFYFLNSTFKFYFVFLS
     594-2839: Missing.

Show »
Length:593
Mass (Da):67,543
Checksum:i9ECE9DBD67A10A16
GO
Isoform 6 (identifier: P21359-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1371-1391: Missing.
     2792-2792: P → PASLPCSNSAVFMQLFPHQ

Show »
Length:2,836
Mass (Da):318,992
Checksum:i3D265EB28B8F8282
GO

Sequence cautioni

The sequence AAA59923 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti496M → I in AAA74897 (PubMed:2116237).Curated1
Sequence conflicti496M → I in AAB59558 (PubMed:2116237).Curated1
Sequence conflicti1094 – 1095EL → ST in AAA59923 (PubMed:2121370).Curated2
Sequence conflicti1576H → HH in AAA74897 (PubMed:2116237).Curated1
Sequence conflicti1576H → HH in AAB59558 (PubMed:2116237).Curated1

RNA editingi

Edited at position 1306.2 Publications
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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03245931H → R in NF1. 1 PublicationCorresponds to variant rs199474725dbSNPEnsembl.1
Natural variantiVAR_01755074A → D in mismatch repair deficient cancer cells. 1 PublicationCorresponds to variant rs199474726dbSNPEnsembl.1
Natural variantiVAR_02225480Y → C.1 PublicationCorresponds to variant rs4795581dbSNPEnsembl.1
Natural variantiVAR_04913580Y → S.Corresponds to variant rs4795581dbSNPEnsembl.1
Natural variantiVAR_02173082S → F in NF1. 1 PublicationCorresponds to variant rs199474729dbSNPEnsembl.1
Natural variantiVAR_07166893C → W in NF1. 1 Publication1
Natural variantiVAR_01755193C → Y in NF1. 1 PublicationCorresponds to variant rs199474728dbSNPEnsembl.1
Natural variantiVAR_010989117I → S in NF1. 1 PublicationCorresponds to variant rs199474731dbSNPEnsembl.1
Natural variantiVAR_032460145L → P in NF1. 1 PublicationCorresponds to variant rs199474734dbSNPEnsembl.1
Natural variantiVAR_021731157I → N in NF1. 1 PublicationCorresponds to variant rs199474744dbSNPEnsembl.1
Natural variantiVAR_065888160R → T in NF1. 1 PublicationCorresponds to variant rs199474752dbSNPEnsembl.1
Natural variantiVAR_017552176D → E Found in mismatch repair deficient cancer cells; also found in a cutaneous neurofibroma from a patient with neurofibromatosis; somatic mutation. 5 PublicationsCorresponds to variant rs112306990dbSNPEnsembl.1
Natural variantiVAR_032461186D → V in NF1; reduced splicing enhancement. 1 Publication1
Natural variantiVAR_032462194L → R in NFNS. 1 PublicationCorresponds to variant rs199474753dbSNPEnsembl.1
Natural variantiVAR_021732216L → P in NF1. 1 PublicationCorresponds to variant rs199474756dbSNPEnsembl.1
Natural variantiVAR_032463324C → R in NF1. 1 PublicationCorresponds to variant rs199474735dbSNPEnsembl.1
Natural variantiVAR_067201330A → T in a cutaneous neurofibroma from a patient with neurofibromatosis; somatic mutation. 1 PublicationCorresponds to variant rs199474767dbSNPEnsembl.1
Natural variantiVAR_032464337E → V in NF1. 1 PublicationCorresponds to variant rs199474736dbSNPEnsembl.1
Natural variantiVAR_010990338D → G in NF1. 1 PublicationCorresponds to variant rs199474773dbSNPEnsembl.1
Natural variantiVAR_021733357L → P in NF1. 1 PublicationCorresponds to variant rs137854563dbSNPEnsembl.1
Natural variantiVAR_067202393H → D in a cutaneous neurofibroma from a patient with neurofibromatosis; somatic mutation. 1 PublicationCorresponds to variant rs199474768dbSNPEnsembl.1
Natural variantiVAR_067203393H → L in a cutaneous neurofibroma from a patient with neurofibromatosis; somatic mutation. 1 PublicationCorresponds to variant rs199474769dbSNPEnsembl.1
Natural variantiVAR_032465489Y → C in NF1. 1 PublicationCorresponds to variant rs137854557dbSNPEnsembl.1
Natural variantiVAR_021734491Y → C in NF1. 1 PublicationCorresponds to variant rs199474757dbSNPEnsembl.1
Natural variantiVAR_010991508L → P in NF1. 1 PublicationCorresponds to variant rs137854558dbSNPEnsembl.1
Natural variantiVAR_067204519Q → P in a cutaneous neurofibroma from a patient with neurofibromatosis; somatic mutation. 1 PublicationCorresponds to variant rs199474770dbSNPEnsembl.1
Natural variantiVAR_032466532L → P in NF1. 1 PublicationCorresponds to variant rs199474737dbSNPEnsembl.1
Natural variantiVAR_021735549L → P in NF1. 1 PublicationCorresponds to variant rs199474758dbSNPEnsembl.1
Natural variantiVAR_032467574S → R in NF1. 1 Publication1
Natural variantiVAR_021736578L → R in NF1. 1 PublicationCorresponds to variant rs199474774dbSNPEnsembl.1
Natural variantiVAR_021737581I → T in NF1. 1 PublicationCorresponds to variant rs199474759dbSNPEnsembl.1
Natural variantiVAR_021738583K → R in NF1. 1 PublicationCorresponds to variant rs199474760dbSNPEnsembl.1
Natural variantiVAR_017553604L → V in NF1. 1 PublicationCorresponds to variant rs142712751dbSNPEnsembl.1
Natural variantiVAR_002653629G → R in NF1; affects splicing by creating a novel splice acceptor site. 3 PublicationsCorresponds to variant rs199474738dbSNPEnsembl.1
Natural variantiVAR_021739665S → F in NF1; unknown pathological significance. 2 PublicationsCorresponds to variant rs145891889dbSNPEnsembl.1
Natural variantiVAR_022255678P → L.1 PublicationCorresponds to variant rs17881753dbSNPEnsembl.1
Natural variantiVAR_021740695L → P in NF1. 1 PublicationCorresponds to variant rs199474761dbSNPEnsembl.1
Natural variantiVAR_017554712H → R in mismatch repair deficient cancer cells. 1 PublicationCorresponds to variant rs199474727dbSNPEnsembl.1
Natural variantiVAR_021741763L → P in NF1. 1 PublicationCorresponds to variant rs199474762dbSNPEnsembl.1
Natural variantiVAR_021742765R → H.1 PublicationCorresponds to variant rs199474777dbSNPEnsembl.1
Natural variantiVAR_067205776A → T in a cutaneous neurofibroma from a patient with neurofibromatosis; somatic mutation. 1 PublicationCorresponds to variant rs199474771dbSNPEnsembl.1
Natural variantiVAR_021743777W → S in NF1. 2 PublicationsCorresponds to variant rs199474745dbSNPEnsembl.1
Natural variantiVAR_021744780T → K in NF1. 4 PublicationsCorresponds to variant rs199474746dbSNPEnsembl.1
Natural variantiVAR_021745781H → P in NF1. 1 PublicationCorresponds to variant rs199474763dbSNPEnsembl.1
Natural variantiVAR_021746784W → C in NF1. 1 PublicationCorresponds to variant rs199474778dbSNPEnsembl.1
Natural variantiVAR_021747784W → R