Reactome | G466E BRAF [cytosol]

G466E BRAF

Stable Identifier

R-HSA-6802374

Type

Protein [EntityWithAccessionedSequence]

Species

Homo sapiens

Compartment

cytosol

Synonyms

B-RAF

Locations in the PathwayBrowser

Expand all

Disease (Homo sapiens)

- Diseases of signal transduction (Homo sapiens)
  - Oncogenic MAPK signaling (Homo sapiens)
    - Paradoxical activation of RAF signaling by kinase inactive BRAF (Homo sapiens)
      - Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants (Homo sapiens)
        
        RAS:GTP: inactive p-RAF:p-2S MAP2Ks:MAPKs:scaffold proteins [plasma membrane] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        RAS:GTP:inactive p-RAF:p-2S MAP2Ks:p-T,Y MAPKs:scaffold proteins [plasma membrane] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
      - Dissociation of paradoxically activated RAS:BRAF complexes (Homo sapiens)
        
        RAS:GTP:inactive p-RAF:p-2S MAP2Ks:p-T,Y MAPKs:scaffold proteins [plasma membrane] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
      - Inactive BRAF mutants bind mutant RAS:GTP (Homo sapiens)
        
        chemically or genetically inactive BRAF mutants:mutant RAS:GTP [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
      - Inactive BRAF mutants:mutant RAS:GTP bind RAF1 (Homo sapiens)
        
        chemically or genetically inactive BRAF mutants:mutant RAS:GTP [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        mutant RAS:inactive BRAF:RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
      - RAF is paradoxically phosphorylated downstream of kinase-inactive RAF (Homo sapiens)
        
        mutant RAS:inactive BRAF:RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
      - RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks (Homo sapiens)
        
        RAS:GTP: inactive p-RAF:p-2S MAP2Ks:MAPKs:scaffold proteins [plasma membrane] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        RAS:GTP:inactive p-RAF:MAP2Ks:MAPKs:scaffold proteins [plasma membrane] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
      - RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs (Homo sapiens)
        
        RAS:GTP:inactive p-RAF:MAP2Ks:MAPKs:scaffold proteins [plasma membrane] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)
        
        mutant RAS:inactive BRAF:p-S338,T491,S494,S729 RAF1 [plasma membrane] (Homo sapiens)
        
        genetically or chemically inactive BRAF [cytosol] (Homo sapiens)
        
        kinase dead BRAF mutants [cytosol] (Homo sapiens)
        
        G466E BRAF [cytosol] (Homo sapiens)

Literature References

PubMed ID	Title	Journal	Year
15035987	Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF Wan, PT, Garnett, MJ, Roe, SM, Lee, S, Niculescu-Duvaz, D, Good, VM, Jones, CM, Marshall, CJ, Springer, CJ, Barford, D, Marais, R	Cell	2004
12068308	Mutations of the BRAF gene in human cancer Davies, H, Bignell, GR, Cox, C, Stephens, P, Edkins, S, Clegg, S, Teague, J, Woffendin, H, Garnett, MJ, Bottomley, W, Davis, N, Dicks, E, Ewing, R, Floyd, Y, Gray, K, Hall, S, Hawes, R, Hughes, J, Kosmidou, V, Menzies, A, Mould, C, Parker, A, Stevens, C, Watt, S, Hooper, S, Wilson, R, Jayatilake, H, Gusterson, BA, Cooper, C, Shipley, J, Hargrave, D, Pritchard-Jones, K, Maitland, N, Chenevix-Trench, G, Riggins, GJ, Bigner, DD, Palmieri, G, Cossu, A, Flanagan, A, Nicholson, A, Ho, JW, Leung, SY, Yuen, ST, Weber, BL, Seigler, HF, Darrow, TL, Paterson, H, Marais, R, Marshall, CJ, Wooster, R, Stratton, MR, Futreal, PA	Nature	2002

External Reference Information

External Reference

UniProt:P15056 BRAF

Gene Names

BRAF, BRAF1, RAFB1

Chain

initiator methionine:1, chain:2-766

Reference Genes

BioGPS Gene:673 BRAF

COSMIC (genes):BRAF BRAF

CTD Gene:673 BRAF

dbSNP Gene:673 BRAF

ENSEMBL:ENSG00000157764 BRAF

HGNC:1097 BRAF

KEGG Gene (Homo sapiens):hsa:673 BRAF

Monarch:673 BRAF

NCBI Gene:673 BRAF

OMIM:164757 BRAF

UCSC:P15056 BRAF

Reference Transcript

RefSeq:NM_004333.4 BRAF

Other Identifiers

11732491_s_at

1328

1654_at

17063631

1UWH

1UWJ

206044_s_at

2FB8

2L05

3076367

3076368

3076370

3076372

3076374

3076375

3076380

3076381

3076382

3076383

3076384

3076385

3076386

3076388

3076392

3076393

3076396

3076399

3076414

3076416

3076439

3076440

3982166

3982173

3C4C

3D4Q

3IDP

3II5

3NY5

3OG7

3PPJ

3PPK

3PRF

3PRI

3PSB

3PSD

3Q4C

3Q96

3SKC

3TV4

3TV6

40306_at

4552

4CQE

4DBN

4E26

4E4X

4EHE

4EHG

4FC0

4FK3

4G9C

4G9R

4H58

4JVG

4KSP

4KSQ

4MBJ

4MNE

4MNF

4PP7

4R5Y

4RZV

4RZW

4WO5

4XV1

4XV2

4XV3

4XV9

4YHT

5C9C

5CSW

5CSX

5CT7

5FD2

5HI2

5HID

5HIE

5ITA

5J17

5J18

5J2R

5JRQ

5JSM

5JT2

5VAL

5VAM

5VYK

673

6B8U

6CAD

71048

8143417

A_23_P42935

AAA35609

AAA96495

AAD15551

AAD43193

AAI01758

AAI12080

AC006344

AC006347

ACD11489

AM989472

AM989473

AM989474

AM989475

AM989476

AM989477

BC101757

BC112079

BRAF

BRAF-201

CAA46301

CAB004552

CAQ43111

CAQ43112

CAQ43113

CAQ43114

CAQ43115

CAQ43116

CH236950

EAL24023

ENSG00000157764

ENSP00000288602

ENSP00000419060

ENSP00000493543

ENST00000288602

ENST00000496384

ENST00000644905

ENST00000646891

EntrezGene:673

EU600171

g4757867_3p_a_at

GE58163

GO:0000165

GO:0000166

GO:0000186

GO:0003674

GO:0004672

GO:0004674

GO:0004709

GO:0004871

GO:0005509

GO:0005515

GO:0005524

GO:0005575

GO:0005622

GO:0005623

GO:0005634

GO:0005737

GO:0005829

GO:0005886

GO:0005975

GO:0006464

GO:0006468

GO:0006810

GO:0006950

GO:0007165

GO:0008150

GO:0008219

GO:0009887

GO:0009968

GO:0010628

GO:0010828

GO:0016020

GO:0016301

GO:0016310

GO:0016740

GO:0019899

GO:0030154

GO:0031434

GO:0033138

GO:0035556

GO:0042802

GO:0043066

GO:0043167

GO:0043226

GO:0043231

GO:0046872

GO:0048856

GO:0055085

GO:0070374

GO:0070413

GO:0071277

GO:0090150

HGNC:1097

HPA001328

HPA071048

ILMN_1652472

IPR000719

IPR001245

IPR002219

IPR003116

IPR008271

IPR011009

IPR017441

IPR020454

IPR029071

LRG_299

LRG_299t1

M21001

M95712

M95712_at

MIM:115150

MIM:163950

MIM:164757

MIM:211980

MIM:613706

MIM:613707

PF00130

PF02196

PF07714

PH_hs_0027912

PR00008

SM00109

SM00220

SM00455

TC07001927.hg

uc003vwc.5

UPI000D18C53F

X65187

XR_001744857

Participant Of

hasMember

kinase dead BRAF mutants [cytosol]

Other forms of this molecule

p-S,T-BRAF [cytosol]

BRAF-MACF1fusion [cytosol]

p-BRAF-MACF1 fusion [cytosol]

D594N BRAF [cytosol]

G596R BRAF [cytosol]

D594V BRAF [cytosol]

D594G BRAF [cytosol]

F595L BRAF [cytosol]

L597V BRAF [cytosol]

G464E BRAF [cytosol]

E586K BRAF [cytosol]

V600K BRAF [cytosol]

p-L597V BRAF [plasma membrane]

p-G464E BRAF [plasma membrane]

p-F595L BRAF [plasma membrane]

p-E586K BRAF [plasma membrane]

p-V600K BRAF [plasma membrane]

BRAF 599dupT [cytosol]

G469A BRAF [cytosol]

V600E BRAF [cytosol]

V600E BRAF V169_M438del [cytosol]

V600E BRAF V47_D380del [cytosol]

V600E BRAF V47_M438del [cytosol]

V600E BRAF V169_D380del [cytosol]

p-S445,S729-BRAF [plasma membrane]

BRAF [cytosol]

p-S338-BRAF [plasma membrane]

BRAF [plasma membrane]

p-S365,S445,S729 BRAF [cytosol]

hyperphosphorylated BRAF [plasma membrane]

p-S445,T599,S602,S729 BRAF [plasma membrane]

p-S445,S729-BRAF [cytosol]

p-S445,T599,S602,S729 BRAF [cytosol]

Modified Residues

Name

glycine 466 replaced with L-glutamic acid

Coordinate

466

PsiMod HEY

L-glutamic acid residue [MOD:00015]

A protein modification that effectively converts a source amino acid residue to an L-glutamic acid.

glycine removal [MOD:01638]

A protein modification that effectively removes or replaces an glycine.

Disease

Name	Identifier	Synonyms
melanoma	1909	Naevocarcinoma, melanoma, melanoma, malignant melanoma, morphology (morphologic abnormality), malignant melanoma NOS (morphologic abnormality), malignant melanoma (disorder), malignant melanoma, malignant melanoma, malignant melanoma, malignant melanoma

Cross References

RefSeq

NP_004324.2

ZINC - World Drugs

BRAF_HUMAN

ZINC - FDA approved

BRAF_HUMAN

ZINC - Substances

BRAF_HUMAN

ZINC - Biogenic

BRAF_HUMAN

ZINC target

P15056

PRO

P15056

PDB

5FD2, 3PSB, 3PPJ, 4XV1, 3TV4, 4RZV, 5J18, 4H58, 4FC0, 3PSD, 4R5Y, 3NY5, 3SKC, 4EHG, 6CAD, 5ITA, 5J17, 4DBN, 4MNF, 4XV3, 4CQE, 4KSP, 4MBJ, 4PP7, 5JRQ, 3IDP, 4JVG, 1UWJ, 4KSQ, 5CSX, 3OG7, 3PPK, 4FK3, 4RZW, 3C4C, 6B8U, 3TV6, 5CSW, 3Q4C, 4XV2, 4MNE, 5HID, 4G9C, 5VAM, 5J2R, 5VAL, 4EHE, 4XV9, 3Q96, 3II5, 1UWH, 2FB8, 5VYK, 5CT7, 5HI2, 3PRI, 4E26, 5JT2, 4WO5, 3D4Q, 4YHT, 4E4X, 3PRF, 2L05, 5JSM, 5C9C, 4G9R, 5HIE

ZINC - Metabolites

BRAF_HUMAN

COSMIC

COSM453

GeneCards

P15056

BRENDA (Homo sapiens)

2.7.11.1

ZINC - Predictions - Purchasable

BRAF_HUMAN

Orphanet

15376

HMDB Protein

HMDBP02597

Interactors (16)

Accession	#Entities	Entities	Confidence Score	Evidence (IntAct)
UniProt:Q02750 MAP2K1	7	MAP2K1(2-8) [cytosol] (R-HSA-5211342) MAP2K1(9-393) [cytosol] (R-HSA-5211353) p-S,218, S222,T292 MAP2K1 [cytosol] (R-HSA-5674490) p-T286,T292-MAP2K1 [cytosol] (R-HSA-112374) p-S218,S222,T286,T292-MAP2K1 [cytosol] (R-HSA-112339) MAP2K1 [cytosol] (R-HSA-59502) p-S218,S222-MAP2K1 [cytosol] (R-HSA-109837)	0.976	58
UniProt:P04049 RAF1	11	p-S338,Y340,Y341-RAF1 [cytosol] (R-HSA-5624465) RAF1 [cytosol] (R-HSA-167205) p-S338-RAF1 [cytosol] (R-HSA-5624469) p-S338-RAF1 [plasma membrane] (R-HSA-444236) p-S259,S621-RAF1 [cytosol] (R-HSA-109786) hyperphosphorylated RAF1 [plasma membrane] (R-HSA-5675193) p-S621-RAF1 [plasma membrane] (R-HSA-206222) p-Y341,T491,S494,S621 RAF1 [plasma membrane] (R-HSA-5675420) p-S621-RAF1 [cytosol] (R-HSA-206028) p-S338,Y341,T491,S494,S621 RAF1 [plasma membrane] (R-HSA-5672665) p-S338,Y341,T491,S494,S621 RAF1 [cytosol] (R-HSA-5672664)	0.957	55
UniProt:P15056 BRAF	34	BRAF-MACF1fusion [cytosol] (R-HSA-6802402) p-S,T-BRAF [cytosol] (R-HSA-169856) p-BRAF-MACF1 fusion [cytosol] (R-HSA-6802536) D594N BRAF [cytosol] (R-HSA-6802299) G596R BRAF [cytosol] (R-HSA-6802385) D594V BRAF [cytosol] (R-HSA-6802305) G466E BRAF [cytosol] (R-HSA-6802374) D594G BRAF [cytosol] (R-HSA-6802295) F595L BRAF [cytosol] (R-HSA-6802316) L597V BRAF [cytosol] (R-HSA-6802397) G464E BRAF [cytosol] (R-HSA-6802369) E586K BRAF [cytosol] (R-HSA-6802308) V600K BRAF [cytosol] (R-HSA-6802502) p-L597V BRAF [plasma membrane] (R-HSA-8936647) p-G464E BRAF [plasma membrane] (R-HSA-8936645) p-F595L BRAF [plasma membrane] (R-HSA-8936641) p-E586K BRAF [plasma membrane] (R-HSA-8936639) p-V600K BRAF [plasma membrane] (R-HSA-8936651) BRAF 599dupT [cytosol] (R-HSA-6802281) G469A BRAF [cytosol] (R-HSA-6802381) V600E BRAF [cytosol] (R-HSA-6802498) V600E BRAF V169_M438del [cytosol] (R-HSA-6802489) V600E BRAF V47_D380del [cytosol] (R-HSA-6802491) V600E BRAF V47_M438del [cytosol] (R-HSA-6802495) V600E BRAF V169_D380del [cytosol] (R-HSA-6802486) p-S445,S729-BRAF [plasma membrane] (R-HSA-8933622) BRAF [cytosol] (R-HSA-167224) p-S338-BRAF [plasma membrane] (R-HSA-1063700) BRAF [plasma membrane] (R-HSA-934547) p-S365,S445,S729 BRAF [cytosol] (R-HSA-5672667) hyperphosphorylated BRAF [plasma membrane] (R-HSA-5675199) p-S445,T599,S602,S729 BRAF [plasma membrane] (R-HSA-5672679) p-S445,S729-BRAF [cytosol] (R-HSA-5672673) p-S445,T599,S602,S729 BRAF [cytosol] (R-HSA-5672676)	0.907	13
UniProt:P63104 YWHAZ	2	YWHAZ [cytosol] (R-HSA-206099) YWHAZ [nucleoplasm] (R-HSA-450469)	0.822	6
UniProt:P31946 YWHAB	1	YWHAB [cytosol] (R-HSA-48888)	0.763	5
UniProt:P01112 HRAS	8	Q61L HRAS [plasma membrane] (R-HSA-6802452) Q61R HRAS [plasma membrane] (R-HSA-6802458) Q61K HRAS [plasma membrane] (R-HSA-6802442) G12V HRAS [plasma membrane] (R-HSA-6802350) G13R HRAS [plasma membrane] (R-HSA-6802368) G12S HRAS [plasma membrane] (R-HSA-6802343) HRAS [cytosol] (R-HSA-205771) HRAS [plasma membrane] (R-HSA-62717)	0.719	4
UniProt:P61981 YWHAG	1	YWHAG [cytosol] (R-HSA-380312)	0.688	3
UniProt:P27348 YWHAQ	1	YWHAQ [cytosol] (R-HSA-1445116)	0.688	3
UniProt:P10398 ARAF	4	p-S299,S302,T452,T455,S576 ARAF [plasma membrane] (R-HSA-5672648) p-S299,S302,T452,T455,S576 ARAF [cytosol] (R-HSA-5672646) p-S576 ARAF [cytosol] (R-HSA-5672681) p-S214,S576 ARAF [cytosol] (R-HSA-5672639)	0.669	3
UniProt:P36507 MAP2K2	5	MAP2K2(11-400) [cytosol] (R-HSA-5211337) MAP2K2(1-10) [cytosol] (R-HSA-5211334) p-S,T-MAP2K2 [cytosol] (R-HSA-109848) MAP2K2 [cytosol] (R-HSA-59504) p-S222,S226-MAP2K2 [cytosol] (R-HSA-169292)	0.669	6
UniProt:Q13233 MAP3K1	2	p-Y1400,Y1412-MAP3K1 [cytosol] (R-HSA-2685607) MAP3K1 [cytosol] (R-HSA-166866)	0.609	2
UniProt:P01111 NRAS	8	G13D NRAS [plasma membrane] (R-HSA-6802363) NRAS [tertiary granule membrane] (R-HSA-6800190) Q61R NRAS [plasma membrane] (R-HSA-6802461) Q61L NRAS [plasma membrane] (R-HSA-6802455) G12S NRAS [plasma membrane] (R-HSA-6802347) Q61K NRAS [plasma membrane] (R-HSA-6802446) G12D NRAS [plasma membrane] (R-HSA-6802339) NRAS [plasma membrane] (R-HSA-62725)	0.591	3
UniProt:P08238 HSP90AB1	5	HSP90AB1 [secretory granule lumen] (R-HSA-6801477) HSP90AB1 [cytosol] (R-HSA-419617) HSP90AB1 [extracellular region] (R-HSA-6806463) HSP90AB1 [ficolin-1-rich granule lumen] (R-HSA-6801491) HSP90AB1 [nucleoplasm] (R-HSA-5082399)	0.564	2
UniProt:P46940 IQGAP1	3	IQGAP1 [secretory granule membrane] (R-HSA-6804803) IQGAP1 [cytosol] (R-HSA-5626371) IQGAP1 [plasma membrane] (R-HSA-381681)	0.544	4
UniProt:Q61097	5	KSR1 [cytosol] (R-MMU-5672587) phospho-p-S311,S406 KSR1 [cytosol] (R-MMU-5672654) phospho-p-S311 KSR1 [cytosol] (R-MMU-5672652) phospho-p-S311,Y552 KSR1 [plasma membrane] (R-MMU-5672659) phospho-p-S311,Y552 KSR1 [cytosol] (R-MMU-5672656)	0.499	3
UniProt:Q99N57	11	phospho-p-S338,Y340,Y341-RAF1 [cytosol] (R-MMU-5624465) RAF1 [cytosol] (R-MMU-167205) phospho-p-S338-RAF1 [cytosol] (R-MMU-5624469) phospho-p-S338-RAF1 [plasma membrane] (R-MMU-444236) phospho-p-S259,S621-RAF1 [cytosol] (R-MMU-109786) phospho-hyperphosphorylated RAF1 [plasma membrane] (R-MMU-5675193) phospho-p-S621-RAF1 [plasma membrane] (R-MMU-206222) phospho-p-Y341,T491,S494,S621 RAF1 [plasma membrane] (R-MMU-5675420) phospho-p-S621-RAF1 [cytosol] (R-MMU-206028) phospho-p-S338,Y341,T491,S494,S621 RAF1 [plasma membrane] (R-MMU-5672665) phospho-p-S338,Y341,T491,S494,S621 RAF1 [cytosol] (R-MMU-5672664)	0.499	3