CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004947
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Neurofibromin 
Protein Synonyms/Alias
 Neurofibromatosis-related protein NF-1; Neurofibromin truncated 
Gene Name
 NF1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
24FDEQLPIKTGQQNTHubiquitination[1]
261DGFAESTKRKAAVWPubiquitination[1, 2]
362NLLFNPSKPFSRGSQubiquitination[3, 4]
449MFGETLHKAVQGCGAubiquitination[1]
471PSLTFKEKVTSLKFKubiquitination[1]
478KVTSLKFKEKPTDLEubiquitination[1]
798ILNYPKAKMEDGQAAubiquitination[1]
874MGPVSERKGSMISVMubiquitination[1]
1036LSFCQEMKFRNKMVEubiquitination[1]
1517LLWNNQEKIGQYLSSubiquitination[5, 6]
1581TRHQVHEKEEFKALKacetylation[7]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 
Functional Description
 Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. 
Sequence Annotation
 DOMAIN 1235 1451 Ras-GAP.
 DOMAIN 1580 1738 CRAL-TRIO.
 MOD_RES 2 2 N-acetylalanine (By similarity).
 MOD_RES 864 864 Phosphoserine.
 MOD_RES 876 876 Phosphoserine.
 MOD_RES 2188 2188 Phosphoserine.
 MOD_RES 2514 2514 Phosphothreonine (By similarity).
 MOD_RES 2515 2515 Phosphoserine.
 MOD_RES 2521 2521 Phosphoserine.
 MOD_RES 2543 2543 Phosphoserine.
 MOD_RES 2817 2817 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; Complete proteome; Disease mutation; GTPase activation; Phosphoprotein; Polymorphism; Reference proteome; RNA editing; Tumor suppressor. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2839 AA 
Protein Sequence
MAAHRPVEWV QAVVSRFDEQ LPIKTGQQNT HTKVSTEHNK ECLINISKYK FSLVISGLTT 60
ILKNVNNMRI FGEAAEKNLY LSQLIILDTL EKCLAGQPKD TMRLDETMLV KQLLPEICHF 120
LHTCREGNQH AAELRNSASG VLFSLSCNNF NAVFSRISTR LQELTVCSED NVDVHDIELL 180
QYINVDCAKL KRLLKETAFK FKALKKVAQL AVINSLEKAF WNWVENYPDE FTKLYQIPQT 240
DMAECAEKLF DLVDGFAEST KRKAAVWPLQ IILLILCPEI IQDISKDVVD ENNMNKKLFL 300
DSLRKALAGH GGSRQLTESA AIACVKLCKA STYINWEDNS VIFLLVQSMV VDLKNLLFNP 360
SKPFSRGSQP ADVDLMIDCL VSCFRISPHN NQHFKICLAQ NSPSTFHYVL VNSLHRIITN 420
SALDWWPKID AVYCHSVELR NMFGETLHKA VQGCGAHPAI RMAPSLTFKE KVTSLKFKEK 480
PTDLETRSYK YLLLSMVKLI HADPKLLLCN PRKQGPETQG STAELITGLV QLVPQSHMPE 540
IAQEAMEALL VLHQLDSIDL WNPDAPVETF WEISSQMLFY ICKKLTSHQM LSSTEILKWL 600
REILICRNKF LLKNKQADRS SCHFLLFYGV GCDIPSSGNT SQMSMDHEEL LRTPGASLRK 660
GKGNSSMDSA AGCSGTPPIC RQAQTKLEVA LYMFLWNPDT EAVLVAMSCF RHLCEEADIR 720
CGVDEVSVHN LLPNYNTFME FASVSNMMST GRAALQKRVM ALLRRIEHPT AGNTEAWEDT 780
HAKWEQATKL ILNYPKAKME DGQAAESLHK TIVKRRMSHV SGGGSIDLSD TDSLQEWINM 840
TGFLCALGGV CLQQRSNSGL ATYSPPMGPV SERKGSMISV MSSEGNADTP VSKFMDRLLS 900
LMVCNHEKVG LQIRTNVKDL VGLELSPALY PMLFNKLKNT ISKFFDSQGQ VLLTDTNTQF 960
VEQTIAIMKN LLDNHTEGSS EHLGQASIET MMLNLVRYVR VLGNMVHAIQ IKTKLCQLVE 1020
VMMARRDDLS FCQEMKFRNK MVEYLTDWVM GTSNQAADDD VKCLTRDLDQ ASMEAVVSLL 1080
AGLPLQPEEG DGVELMEAKS QLFLKYFTLF MNLLNDCSEV EDESAQTGGR KRGMSRRLAS 1140
LRHCTVLAMS NLLNANVDSG LMHSIGLGYH KDLQTRATFM EVLTKILQQG TEFDTLAETV 1200
LADRFERLVE LVTMMGDQGE LPIAMALANV VPCSQWDELA RVLVTLFDSR HLLYQLLWNM 1260
FSKEVELADS MQTLFRGNSL ASKIMTFCFK VYGATYLQKL LDPLLRIVIT SSDWQHVSFE 1320
VDPTRLEPSE SLEENQRNLL QMTEKFFHAI ISSSSEFPPQ LRSVCHCLYQ ATCHSLLNKA 1380
TVKEKKENKK SVVSQRFPQN SIGAVGSAMF LRFINPAIVS PYEAGILDKK PPPRIERGLK 1440
LMSKILQSIA NHVLFTKEEH MRPFNDFVKS NFDAARRFFL DIASDCPTSD AVNHSLSFIS 1500
DGNVLALHRL LWNNQEKIGQ YLSSNRDHKA VGRRPFDKMA TLLAYLGPPE HKPVADTHWS 1560
SLNLTSSKFE EFMTRHQVHE KEEFKALKTL SIFYQAGTSK AGNPIFYYVA RRFKTGQING 1620
DLLIYHVLLT LKPYYAKPYE IVVDLTHTGP SNRFKTDFLS KWFVVFPGFA YDNVSAVYIY 1680
NCNSWVREYT KYHERLLTGL KGSKRLVFID CPGKLAEHIE HEQQKLPAAT LALEEDLKVF 1740
HNALKLAHKD TKVSIKVGST AVQVTSAERT KVLGQSVFLN DIYYASEIEE ICLVDENQFT 1800
LTIANQGTPL TFMHQECEAI VQSIIHIRTR WELSQPDSIP QHTKIRPKDV PGTLLNIALL 1860
NLGSSDPSLR SAAYNLLCAL TCTFNLKIEG QLLETSGLCI PANNTLFIVS ISKTLAANEP 1920
HLTLEFLEEC ISGFSKSSIE LKHLCLEYMT PWLSNLVRFC KHNDDAKRQR VTAILDKLIT 1980
MTINEKQMYP SIQAKIWGSL GQITDLLDVV LDSFIKTSAT GGLGSIKAEV MADTAVALAS 2040
GNVKLVSSKV IGRMCKIIDK TCLSPTPTLE QHLMWDDIAI LARYMLMLSF NNSLDVAAHL 2100
PYLFHVVTFL VATGPLSLRA STHGLVINII HSLCTCSQLH FSEETKQVLR LSLTEFSLPK 2160
FYLLFGISKV KSAAVIAFRS SYRDRSFSPG SYERETFALT SLETVTEALL EIMEACMRDI 2220
PTCKWLDQWT ELAQRFAFQY NPSLQPRALV VFGCISKRVS HGQIKQIIRI LSKALESCLK 2280
GPDTYNSQVL IEATVIALTK LQPLLNKDSP LHKALFWVAV AVLQLDEVNL YSAGTALLEQ 2340
NLHTLDSLRI FNDKSPEEVF MAIRNPLEWH CKQMDHFVGL NFNSNFNFAL VGHLLKGYRH 2400
PSPAIVARTV RILHTLLTLV NKHRNCDKFE VNTQSVAYLA ALLTVSEEVR SRCSLKHRKS 2460
LLLTDISMEN VPMDTYPIHH GDPSYRTLKE TQPWSSPKGS EGYLAATYPT VGQTSPRARK 2520
SMSLDMGQPS QANTKKLLGT RKSFDHLISD TKAPKRQEME SGITTPPKMR RVAETDYEME 2580
TQRISSSQQH PHLRKVSVSE SNVLLDEEVL TDPKIQALLL TVLATLVKYT TDEFDQRILY 2640
EYLAEASVVF PKVFPVVHNL LDSKINTLLS LCQDPNLLNP IHGIVQSVVY HEESPPQYQT 2700
SYLQSFGFNG LWRFAGPFSK QTQIPDYAEL IVKFLDALID TYLPGIDEET SEESLLTPTS 2760
PYPPALQSQL SITANLNLSN SMTSLATSQH SPGIDKENVE LSPTTGHCNS GRTRHGSASQ 2820
VQKQRSAGSF KRNSIKKIV 2839 
Gene Ontology
 GO:0030424; C:axon; IDA:HGNC.
 GO:0005737; C:cytoplasm; ISS:HGNC.
 GO:0030425; C:dendrite; IDA:HGNC.
 GO:0031235; C:intrinsic to internal side of plasma membrane; IBA:RefGenome.
 GO:0005634; C:nucleus; ISS:HGNC.
 GO:0005099; F:Ras GTPase activator activity; IDA:HGNC.
 GO:0030036; P:actin cytoskeleton organization; ISS:HGNC.
 GO:0030325; P:adrenal gland development; ISS:HGNC.
 GO:0048844; P:artery morphogenesis; ISS:HGNC.
 GO:0048593; P:camera-type eye morphogenesis; ISS:HGNC.
 GO:0021987; P:cerebral cortex development; ISS:HGNC.
 GO:0030199; P:collagen fibril organization; ISS:HGNC.
 GO:0021897; P:forebrain astrocyte development; ISS:HGNC.
 GO:0048853; P:forebrain morphogenesis; ISS:HGNC.
 GO:0007507; P:heart development; ISS:HGNC.
 GO:0001889; P:liver development; ISS:HGNC.
 GO:0000165; P:MAPK cascade; ISS:HGNC.
 GO:0001656; P:metanephros development; ISS:HGNC.
 GO:0022011; P:myelination in peripheral nervous system; ISS:HGNC.
 GO:0016525; P:negative regulation of angiogenesis; IEA:Compara.
 GO:0048712; P:negative regulation of astrocyte differentiation; IEA:Compara.
 GO:0030336; P:negative regulation of cell migration; IMP:MGI.
 GO:0001953; P:negative regulation of cell-matrix adhesion; IEA:Compara.
 GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:HGNC.
 GO:0048147; P:negative regulation of fibroblast proliferation; ISS:UniProtKB.
 GO:0043407; P:negative regulation of MAP kinase activity; ISS:HGNC.
 GO:0007406; P:negative regulation of neuroblast proliferation; ISS:HGNC.
 GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:Compara.
 GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISS:HGNC.
 GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Compara.
 GO:0035021; P:negative regulation of Rac protein signal transduction; IEA:Compara.
 GO:0046580; P:negative regulation of Ras protein signal transduction; IBA:RefGenome.
 GO:0042992; P:negative regulation of transcription factor import into nucleus; ISS:HGNC.
 GO:0021915; P:neural tube development; IEA:Compara.
 GO:0001649; P:osteoblast differentiation; ISS:HGNC.
 GO:0014065; P:phosphatidylinositol 3-kinase cascade; ISS:HGNC.
 GO:0043473; P:pigmentation; ISS:HGNC.
 GO:0045762; P:positive regulation of adenylate cyclase activity; ISS:HGNC.
 GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Compara.
 GO:0043525; P:positive regulation of neuron apoptotic process; ISS:HGNC.
 GO:0007265; P:Ras protein signal transduction; ISS:HGNC.
 GO:0045765; P:regulation of angiogenesis; IMP:HGNC.
 GO:0043535; P:regulation of blood vessel endothelial cell migration; IMP:HGNC.
 GO:0045124; P:regulation of bone resorption; ISS:HGNC.
 GO:0001952; P:regulation of cell-matrix adhesion; ISS:HGNC.
 GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Compara.
 GO:0032228; P:regulation of synaptic transmission, GABAergic; IEA:Compara.
 GO:0001666; P:response to hypoxia; ISS:HGNC.
 GO:0007519; P:skeletal muscle tissue development; IEA:Compara.
 GO:0048745; P:smooth muscle tissue development; ISS:HGNC.
 GO:0021510; P:spinal cord development; ISS:HGNC.
 GO:0048485; P:sympathetic nervous system development; ISS:HGNC.
 GO:0008542; P:visual learning; ISS:HGNC.
 GO:0042060; P:wound healing; ISS:HGNC. 
Interpro
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR001251; CRAL-TRIO_dom.
 IPR001936; RasGAP.
 IPR023152; RasGAP_CS.
 IPR008936; Rho_GTPase_activation_prot. 
Pfam
 PF00616; RasGAP 
SMART
 SM00323; RasGAP
 SM00516; SEC14 
PROSITE
 PS50191; CRAL_TRIO
 PS00509; RAS_GTPASE_ACTIV_1
 PS50018; RAS_GTPASE_ACTIV_2 
PRINTS