Reactome | FLT3 N676K [plasma membrane]

FLT3 N676K [plasma membrane]

Stable Identifier

R-HSA-9695721

Type

Protein [EntityWithAccessionedSequence]

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

STK-1

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Locations in the PathwayBrowser

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Disease (Homo sapiens)

- Diseases of signal transduction by growth factor receptors and second messengers (Homo sapiens)
  - FLT3 signaling in disease (Homo sapiens)
    - Drug resistance of FLT3 mutants (Homo sapiens)
      - midostaurin-resistant FLT3 mutants (Homo sapiens)
        
        midostaurin-resistant FLT3 mutants don't bind midostaurin (Homo sapiens)
        
        midostaurin-resistant FLT3 mutants [plasma membrane] (Homo sapiens)
        
        FLT3 N676K dimer [plasma membrane] (Homo sapiens)
        
        FLT3 N676K [plasma membrane] (Homo sapiens)
    - FLT3 mutants bind TKIs (Homo sapiens)
      - FLT mutants bind type I TKIs (Homo sapiens)
        
        type I TKI sensitive FLT3 mutants [plasma membrane] (Homo sapiens)
        
        gilteritinib-sensitive FLT3 mutants [plasma membrane] (Homo sapiens)
        
        FLT3 N676K dimer [plasma membrane] (Homo sapiens)
        
        FLT3 N676K [plasma membrane] (Homo sapiens)
        
        type I TKI-sensitive FLT3 mutants:type I TKIs [plasma membrane] (Homo sapiens)
        
        type I TKI sensitive FLT3 mutants [plasma membrane] (Homo sapiens)
        
        gilteritinib-sensitive FLT3 mutants [plasma membrane] (Homo sapiens)
        
        FLT3 N676K dimer [plasma membrane] (Homo sapiens)
        
        FLT3 N676K [plasma membrane] (Homo sapiens)
    - Signaling by FLT3 ITD and TKD mutants (Homo sapiens)
      - Constitutive phosphorylation of FLT3 mutants (Homo sapiens)
        
        FLT3 extracellular domain, kinase domain and juxtamembrane domain mutant dimers [plasma membrane] (Homo sapiens)
        
        kinase domain mutant dimers of FLT3 [plasma membrane] (Homo sapiens)
        
        FLT3 N676K dimer [plasma membrane] (Homo sapiens)
        
        FLT3 N676K [plasma membrane] (Homo sapiens)
      - Ligand-independent dimerization of FLT3 mutants (Homo sapiens)
        
        FLT3 extracellular domain, kinase domain and juxtamembrane domain mutant dimers [plasma membrane] (Homo sapiens)
        
        kinase domain mutant dimers of FLT3 [plasma membrane] (Homo sapiens)
        
        FLT3 N676K dimer [plasma membrane] (Homo sapiens)
        
        FLT3 N676K [plasma membrane] (Homo sapiens)
        
        FLT3 extracellular domain, kinase domain and juxtamembrane domain mutants [plasma membrane] (Homo sapiens)
        
        kinase domain mutants of FLT3 [plasma membrane] (Homo sapiens)
        
        FLT3 N676K [plasma membrane] (Homo sapiens)

Literature References

PubMed ID	Title	Journal	Year
26891877	Leukemogenic potency of the novel FLT3-N676K mutant Huang, K, Scherr, M, Yang, M, Welte, K, Pan, Z, von Neuhoff, N, Büsche, G, Eder, M, Li, Z, Ganser, A, Heidel, FH, Fischer, T	Ann. Hematol.	2016

External Reference Information

External Reference

UniProt:P36888 FLT3

Gene Names

FLT3, CD135, FLK2, STK1

Chain

signal peptide:1-26, chain:27-993

Reference Genes

BioGPS Gene:2322 FLT3

COSMIC (genes):FLT3 FLT3

CTD Gene:2322 FLT3

dbSNP Gene:2322 FLT3

ENSEMBL:ENSG00000122025.15 FLT3

HGNC:3765 FLT3

KEGG Gene (Homo sapiens):2322 FLT3

Monarch:2322 FLT3

NCBI Gene:2322 FLT3

OMIM:136351 FLT3

UCSC:P36888 FLT3

Reference Transcript

RefSeq:NM_004119.2 FLT3

Other Identifiers

0006290286

1065_at

11737027_a_at

16777685

206674_PM_at

206674_at

2322

34583_at

3507201

3507202

3507205

3507206

3507207

3507210

3507211

3507212

3507213

3507216

3507217

3507218

3507219

3507221

3507222

3507223

3507224

3507225

3507226

3507228

3507229

3507230

3507231

3507233

3507234

3507237

3507239

3507242

3507243

3507244

7970737

GE58857

GO:0000166

GO:0001776

GO:0002318

GO:0002328

GO:0002376

GO:0004672

GO:0004713

GO:0004714

GO:0004896

GO:0005021

GO:0005515

GO:0005524

GO:0005622

GO:0005634

GO:0005737

GO:0005768

GO:0005783

GO:0005788

GO:0005829

GO:0005886

GO:0005887

GO:0006468

GO:0006629

GO:0007169

GO:0008284

GO:0010008

GO:0010243

GO:0012501

GO:0014068

GO:0016020

GO:0016021

GO:0016301

GO:0016310

GO:0016740

GO:0018108

GO:0019221

GO:0019838

GO:0023052

GO:0030097

GO:0030154

GO:0030183

GO:0031100

GO:0031401

GO:0031410

GO:0032991

GO:0033674

GO:0035259

GO:0035726

GO:0036211

GO:0038084

GO:0042127

GO:0042531

GO:0042981

GO:0043226

GO:0043235

GO:0043406

GO:0043410

GO:0043552

GO:0043621

GO:0044877

GO:0046651

GO:0046777

GO:0048584

GO:0048856

GO:0060089

GO:0071345

GO:0071385

GO:0097028

GO:0140096

HMNXSV003001807

ILMN_1766363

PH_hs_0000046

TC13000515.hg

TC13001385.hg

U02687_at

g4758395_3p_at

Participates

as a member of

kinase domain mutants of FLT3 [plasma membrane] (Homo sapiens)

as a component of

FLT3 N676K dimer [plasma membrane] (Homo sapiens)

Other forms of this molecule

FLT3 F691I [plasma membrane]

FLT3 N676D [plasma membrane]

FLT3 R834Q [plasma membrane]

FLT3 Y572C [plasma membrane]

FLT3 A848P [plasma membrane]

FLT3 A627P [plasma membrane]

FLT3 F621L [plasma membrane]

p-Y768,Y969 FLT3 [plasma membrane]

Ub-pY FLT3 [endosome membrane]

Ub-pY FLT3 [plasma membrane]

FLT3 V592G [plasma membrane]

FLT3 Y589_F590insFYVDFREYEYDLKWEF [plasma membrane]

FLT3 F590G Y591D [plasma membrane]

FLT3 F594L [plasma membrane]

FLT3 E611_F612insGDNEYFYVDFREYEYDLKWEFPRENLE [plasma membrane]

FLT3 V579A [plasma membrane]

FLT3 Y599_D600insGLYVDFREYEY [plasma membrane]

FLT3 Y591_V592insVDFREDREHH [plasma membrane]

FLT3 D600_L601insMGMGGECNPGRQ [plasma membrane]

FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE [plasma membrane]

FLT3 Y591_V592insVDFREYEYDH [plasma membrane]

FLT3 F612_G613insGYVDFREYEYDLKWEFRPRENLF [plasma membrane]

FLT3 Y599_F600insFYVDFREYEYDLKWEF [plasma membrane]

FLT3 E598_Y599insYDLKWEFRRENLEFG [plasma membrane]

FLT3 N609_L610insSSDNEYFYVDFREYEYDLKW [plasma membrane]

FLT3 F594_R595insREYEYDL [plasma membrane]

FLT3 L601_K602insREYEYDL [plasma membrane]

FLT3 N609_L610insSSDNEYFYVDFREYEYDLKWEFPREN [plasma membrane]

FLT3 E596_Y597insRTDFRE [plasma membrane]

FLT3 D586_E587insEYFYVDFREY [plasma membrane]

FLT3 E598_Y599insFYVDFREY [plasma membrane]

FLT3 V592A [plasma membrane]

FLT3 L610_E611insCSSDNEYFYVDFREYEYDLKWEFPRENL [plasma membrane]

FLT3 E598_Y599insVDFREYE [plasma membrane]

FLT3 E598_Y599insFDFREYE [plasma membrane]

FLT3 K602_W603insYEYDLK [plasma membrane]

FLT3 L610_E611insLKWEFPRENL [plasma membrane]

FLT3 V579L [plasma membrane]

FLT3 F594V [plasma membrane]

FLT3 F594I [plasma membrane]

FLT3 V579E [plasma membrane]

FLT3 V592D [plasma membrane]

FLT3 V579I [plasma membrane]

FLT3 F594S [plasma membrane]

FLT3 D835del [plasma membrane]

FLT3 K663Q [plasma membrane]

FLT3 I836del [plasma membrane]

FLT3 D835N [plasma membrane]

FLT3 D835V [plasma membrane]

FLT3 Y842C [plasma membrane]

FLT3 D835H [plasma membrane]

FLT3 A627E_T628insYEYDLKWEFPRENLEFGKVLGSGAFGKVMNA [plasma membrane]

FLT3 I836LInsD [plasma membrane]

FLT3 D835E [plasma membrane]

FLT3 D835A [plasma membrane]

FLT3 D835Y [plasma membrane]

FLT3 N841I [plasma membrane]

FLT3 F691L [plasma membrane]

FLT3 D839G [plasma membrane]

FLT3 K633N [plasma membrane]

FLT3 D839N [plasma membrane]

FLT3 N841Y [plasma membrane]

FLT3 D835G [plasma membrane]

FLT3 K633R [plasma membrane]

FLT3 N841T [plasma membrane]

FLT3 D835F [plasma membrane]

FLT3 N676T [plasma membrane]

FLT3 N676S [plasma membrane]

FLT3 N841K [plasma membrane]

FLT3 D839H [plasma membrane]

FLT3 F691V [plasma membrane]

FLT3 N841H [plasma membrane]

FLT3 D839E [plasma membrane]

FLT3 Y842H [plasma membrane]

FLT3 S451F [plasma membrane]

p-6Y FLT3 N676K [plasma membrane]

p-6Y FLT3 D839G [plasma membrane]

p-6Y FLT3 D835A [plasma membrane]

p-6Y FLT3 I836del [plasma membrane]

p-6Y FLT3 D835H [plasma membrane]

p-6Y FLT3 D835del [plasma membrane]

p-6Y FLT3 D835Y [plasma membrane]

p-6Y FLT3 D835V [plasma membrane]

p-6Y FLT3 D835N [plasma membrane]

p-6Y FLT3 N841I [plasma membrane]

p-6Y FLT3 K663Q [plasma membrane]

p-6Y FLT3 F691L [plasma membrane]

p-6Y FLT3 Y842C [plasma membrane]

p-6Y FLT3 D835E [plasma membrane]

p-6Y FLT3 D839H [plasma membrane]

p-6Y FLT3 N841T [plasma membrane]

p-6Y FLT3 D839N [plasma membrane]

p-6Y FLT3 N676T [plasma membrane]

p-6Y FLT3 K633N [plasma membrane]

p-6Y FLT3 Y842H [plasma membrane]

p-6Y FLT3 N841K [plasma membrane]

p-6Y FLT3 D835F [plasma membrane]

p-6Y FLT3 N841H [plasma membrane]

p-6Y FLT3 K633R [plasma membrane]

p-6Y FLT3 D835G [plasma membrane]

p-6Y FLT3 F691V [plasma membrane]

p-6Y FLT3 N676S [plasma membrane]

p-6Y FLT3 N841Y [plasma membrane]

p-6Y FLT3 D839E [plasma membrane]

p-6Y FLT3 S451F [plasma membrane]

p-6Y FLT3 F590G Y591D [plasma membrane]

p-6Y FLT3 E596_Y597insRTDFRE [plasma membrane]

p-6Y FLT3 F594L [plasma membrane]

p-6Y FLT3 V592A [plasma membrane]

p-6Y FLT3 V579A [plasma membrane]

p-6Y FLT3 E611_F612insGDNEYFYVDFREYEYDLKWEFPRENLE [plasma membrane]

p-6Y FLT3 V592G [plasma membrane]

p-6Y FLT3 F594S [plasma membrane]

p-6Y FLT3 V579L [plasma membrane]

p-6Y FLT3 F594I [plasma membrane]

p-6Y FLT3 V579I [plasma membrane]

p-6Y FLT3 V592D [plasma membrane]

p-6Y FLT3 F594V [plasma membrane]

p-6Y FLT3 V579E [plasma membrane]

p-6Y FLT3 E598_Y599insVDFREYE [plasma membrane]

p-6Y FLT3 F594_R595insREYEYDL [plasma membrane]

p-6Y FLT3 E598_Y599insFYVDFREY [plasma membrane]

p-6Y FLT3 L601_K602insREYEYDL [plasma membrane]

p-6Y FLT3 L610_E611insLKWEFPRENL [plasma membrane]

p-6Y FLT3 A627E_T628insYEYDLKWEFPRENLEFGKVLGSGAFGKVMNA [plasma membrane]

p-6Y FLT3 N609_L610insSSDNEYFYVDFREYEYDLKW [plasma membrane]

p-6Y FLT3 N609_L610insSSDNEYFYVDFREYEYDLKWEFPREN [plasma membrane]

p-6Y FLT3 K602_W603insYEYDLK [plasma membrane]

p-6Y FLT3 E598_Y599insGLVQVTGSSDNEYFYVDFREYE [plasma membrane]

p-6Y FLT3 Y589_F590insFYVDFREYEYDLKWEF [plasma membrane]

p-6Y FLT3 E598_Y599insFDFREYE [plasma membrane]

p-6Y FLT3 E598_Y599insYDLKWEFRRENLEFG [plasma membrane]

p-6Y FLT3 D600_L601insMGMGGECNPGRQ [plasma membrane]

p-6Y FLT3 Y600_D601insGLYVDFREYEY [plasma membrane]

p-6Y FLT3 Y599_F600insFYVDFREYEYDLKWEF [plasma membrane]

p-6Y FLT3 L610_E611insCSSDNEYFYVDFREYEYDLKWEFPRENL [plasma membrane]

p-6Y FLT3 Y591_V592insVDFREDREHH [plasma membrane]

p-6Y FLT3 F612_G613insGYVDFREYEYDLKWEFRPRENLF [plasma membrane]

p-6Y FLT3 D586_E587insEYFYVDFREY [plasma membrane]

p-6Y FLT3 Y591_V592insVDFREYEYDH [plasma membrane]

p-6Y FLT3 I836LInsD [plasma membrane]

FLT3 [plasma membrane]

Autophosphorylated FLT3 [plasma membrane]

Modified Residues

Name

L-asparagine 676 replaced with L-lysine

Coordinate

676

PsiMod

L-lysine residue [MOD:00021]

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

L-asparagine removal [MOD:01633]

A protein modification that effectively removes or replaces an L-asparagine.

Disease

Name	Identifier	Synonyms
cancer	DOID:162	malignant tumor, malignant neoplasm, primary cancer
acute myeloid leukemia	DOID:9119	Leukemia, Myelocytic, acute, acute myeloblastic leukemia, acute myelogenous leukemia, AML - acute Myeloid Leukemia

Cross References

RefSeq

NP_004110.2

ZINC - World Drugs

FLT3_HUMAN

Guide to Pharmacology - Targets

1807

OpenTargets

ENSG00000122025

ZINC - FDA approved

FLT3_HUMAN

ZINC - Substances

FLT3_HUMAN

ZINC target

P36888

ZINC - Biogenic

FLT3_HUMAN

PRO

P36888

PDB

5X02, 4XUF, 6JQR, 4RT7, 3QS7, 6IL3, 3QS9, 1RJB

ZINC - Investigational

FLT3_HUMAN

ZINC - Metabolites

FLT3_HUMAN

COSMIC

COSM7335709, COSV54051954, COSV54042688

HPA

ENSG00000122025-FLT3

GeneCards

P36888

Ensembl

ENSP00000241453, ENST00000241453, ENSG00000122025

Pharos - Targets

P36888

Orphanet

16784

ZINC - Predictions - Purchasable

FLT3_HUMAN

HMDB Protein

HMDBP01189

Interactors (5)

Accession	#Entities	Entities	Confidence Score	Evidence (IntAct)
UniProt:P43405 SYK	6	p-Y-SYK [cytosol] (R-HSA-9705732) p-Y-SYK [plasma membrane] (R-HSA-429432) SYK [plasma membrane] (R-HSA-139844) p-6Y-SYK [cytosol] (R-HSA-1861712) p-Y348-SYK [cytosol] (R-HSA-437953) SYK [cytosol] (R-HSA-58268)	0.737	22
UniProt:Q13322 GRB10	2	p-Y GRB10 [cytosol] (R-HSA-9706168) GRB10 [cytosol] (R-HSA-110009)	0.591	6
UniProt:P42684 ABL2	1	ABL2 [cytosol] (R-HSA-375998)	0.544	3
UniProt:Q8R4L0	1	Sla2 [cytosol] (R-MMU-9706161)	0.524	14
UniProt:Q06124 PTPN11	4	p-Y546-PTPN11 [cytosol] (R-HSA-1369081) PTPN11 [nucleoplasm] (R-HSA-8937745) PTPN11 [cytosol] (R-HSA-162563) p-Y546,Y584-PTPN11 [cytosol] (R-HSA-162573)	0.462	2

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