FLT3_HUMAN - dbPTM
FLT3_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID FLT3_HUMAN
UniProt AC P36888
Protein Name Receptor-type tyrosine-protein kinase FLT3
Gene Name FLT3
Organism Homo sapiens (Human).
Sequence Length 993
Subcellular Localization Membrane
Single-pass type I membrane protein. Endoplasmic reticulum lumen. Constitutively activated mutant forms with internal tandem duplications are less efficiently transported to the cell surface and a significant proportion is retained in an im
Protein Description Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways..
Protein Sequence MPALARDGGQLPLLVVFSAMIFGTITNQDLPVIKCVLINHKNNDSSVGKSSSYPMVSESPEDLGCALRPQSSGTVYEAAAVEVDVSASITLQVLVDAPGNISCLWVFKHSSLNCQPHFDLQNRGVVSMVILKMTETQAGEYLLFIQSEATNYTILFTVSIRNTLLYTLRRPYFRKMENQDALVCISESVPEPIVEWVLCDSQGESCKEESPAVVKKEEKVLHELFGTDIRCCARNELGRECTRLFTIDLNQTPQTTLPQLFLKVGEPLWIRCKAVHVNHGFGLTWELENKALEEGNYFEMSTYSTNRTMIRILFAFVSSVARNDTGYYTCSSSKHPSQSALVTIVEKGFINATNSSEDYEIDQYEEFCFSVRFKAYPQIRCTWTFSRKSFPCEQKGLDNGYSISKFCNHKHQPGEYIFHAENDDAQFTKMFTLNIRRKPQVLAEASASQASCFSDGYPLPSWTWKKCSDKSPNCTEEITEGVWNRKANRKVFGQWVSSSTLNMSEAIKGFLVKCCAYNSLGTSCETILLNSPGPFPFIQDNISFYATIGVCLLFIVVLTLLICHKYKKQFRYESQLQMVQVTGSSDNEYFYVDFREYEYDLKWEFPRENLEFGKVLGSGAFGKVMNATAYGISKTGVSIQVAVKMLKEKADSSEREALMSELKMMTQLGSHENIVNLLGACTLSGPIYLIFEYCCYGDLLNYLRSKREKFHRTWTEIFKEHNFSFYPTFQSHPNSSMPGSREVQIHPDSDQISGLHGNSFHSEDEIEYENQKRLEEEEDLNVLTFEDLLCFAYQVAKGMEFLEFKSCVHRDLAARNVLVTHGKVVKICDFGLARDIMSDSNYVVRGNARLPVKWMAPESLFEGIYTIKSDVWSYGILLWEIFSLGVNPYPGIPVDANFYKLIQNGFKMDQPFYATEEIYIIMQSCWAFDSRKRPSFPNLTSFLGCQLADAEEAMYQNVDGRVSECPHTYQNRRPFSREMDLGLLSPQAQVEDS
Overview of Protein Modification Sites with Functional and Structural Information
Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations Modification Substrate Peptides
&
Secondary Structure		 ASA (%) Reference Orthologous
Protein Cluster
43N-linked_GlycosylationVLINHKNNDSSVGKS
EEEECCCCCCCCCCC		56.1821389326
100N-linked_GlycosylationVLVDAPGNISCLWVF
EEECCCCCEEEEEEE		23.1821389326
151N-linked_GlycosylationFIQSEATNYTILFTV
EEEECCCCEEEEEEE		38.7121389326
166PhosphorylationSIRNTLLYTLRRPYF
EECCHHHHHHCCHHH		13.5719369195
167PhosphorylationIRNTLLYTLRRPYFR
ECCHHHHHHCCHHHH		17.4824719451
306N-linked_GlycosylationEMSTYSTNRTMIRIL
EEEECCCCHHHHHHH		31.3321389326
315UbiquitinationTMIRILFAFVSSVAR
HHHHHHHHHHHHHHC		10.6521890473
318PhosphorylationRILFAFVSSVARNDT
HHHHHHHHHHHCCCC		16.7930631047
319PhosphorylationILFAFVSSVARNDTG
HHHHHHHHHHCCCCC		17.9430631047
321UbiquitinationFAFVSSVARNDTGYY
HHHHHHHHCCCCCEE		13.4021890473
323N-linked_GlycosylationFVSSVARNDTGYYTC
HHHHHHCCCCCEEEC		41.2721389326
324UbiquitinationVSSVARNDTGYYTCS
HHHHHCCCCCEEECC		35.6421890473
330UbiquitinationNDTGYYTCSSSKHPS
CCCCEEECCCCCCCC		1.8321890473
343PhosphorylationPSQSALVTIVEKGFI
CCCCEEEEEEHHCCC		21.83-
351N-linked_GlycosylationIVEKGFINATNSSED
EEHHCCCCCCCCCCC		38.1521389326
354N-linked_GlycosylationKGFINATNSSEDYEI
HCCCCCCCCCCCCCE		40.9221389326
401PhosphorylationQKGLDNGYSISKFCN
HCCCCCCCCHHHHCC		14.7519369195
416PhosphorylationHKHQPGEYIFHAEND
CCCCCCCEEEECCCC		18.1419369195
439UbiquitinationTLNIRRKPQVLAEAS
EEECCCCHHHHHCCC		27.9221890473
448UbiquitinationVLAEASASQASCFSD
HHHCCCCCHHHHCCC		24.6321890473
473N-linked_GlycosylationKCSDKSPNCTEEITE
ECCCCCCCCCHHHHH		53.05UniProtKB CARBOHYD
502N-linked_GlycosylationWVSSSTLNMSEAIKG
CCCCCCCCHHHHHHH		31.83UniProtKB CARBOHYD
541N-linked_GlycosylationPFPFIQDNISFYATI
CCCCCCCHHHHHHHH		18.54UniProtKB CARBOHYD
542UbiquitinationFPFIQDNISFYATIG
CCCCCCHHHHHHHHH		3.9721890473
551UbiquitinationFYATIGVCLLFIVVL
HHHHHHHHHHHHHHH		2.0021890473
572PhosphorylationKYKKQFRYESQLQMV
HHHHHCCCCCCEEEE		22.6316684964
574PhosphorylationKKQFRYESQLQMVQV
HHHCCCCCCEEEEEE		27.5316684964
589PhosphorylationTGSSDNEYFYVDFRE
ECCCCCEEEEEEEEE		13.3811971190
591PhosphorylationSSDNEYFYVDFREYE
CCCCEEEEEEEEEEE		9.759737679
595UbiquitinationEYFYVDFREYEYDLK
EEEEEEEEEEEEEEC		40.9221890473
597PhosphorylationFYVDFREYEYDLKWE
EEEEEEEEEEEECEE		18.6111971190
599PhosphorylationVDFREYEYDLKWEFP
EEEEEEEEEECEECC		26.1911971190
602UbiquitinationREYEYDLKWEFPREN
EEEEEEECEECCHHH		41.60-
604UbiquitinationYEYDLKWEFPRENLE
EEEEECEECCHHHCC		44.1621890473
614UbiquitinationRENLEFGKVLGSGAF
HHHCCCCCEECCCHH		39.3421890473
614UbiquitinationRENLEFGKVLGSGAF
HHHCCCCCEECCCHH		39.3421890473
623UbiquitinationLGSGAFGKVMNATAY
ECCCHHHHHHEEEEC		31.6821890473
623UbiquitinationLGSGAFGKVMNATAY
ECCCHHHHHHEEEEC		31.6821890473
630PhosphorylationKVMNATAYGISKTGV
HHHEEEECCCCCCCC		15.6121552520
633PhosphorylationNATAYGISKTGVSIQ
EEEECCCCCCCCCHH		21.5722210691
634UbiquitinationATAYGISKTGVSIQV
EEECCCCCCCCCHHH		47.58-
638PhosphorylationGISKTGVSIQVAVKM
CCCCCCCCHHHHHHH		14.5122210691
644UbiquitinationVSIQVAVKMLKEKAD
CCHHHHHHHHHHHCC		28.86-
719UbiquitinationRTWTEIFKEHNFSFY
HHHHHHHHHCCCCCC		64.82-
726PhosphorylationKEHNFSFYPTFQSHP
HHCCCCCCCCCCCCC		10.5221552520
728PhosphorylationHNFSFYPTFQSHPNS
CCCCCCCCCCCCCCC		23.9521552520
749PhosphorylationEVQIHPDSDQISGLH
EEEECCCCCCCCCCC		35.5528450419
753PhosphorylationHPDSDQISGLHGNSF
CCCCCCCCCCCCCCC		29.6628450419
759PhosphorylationISGLHGNSFHSEDEI
CCCCCCCCCCCHHHH		29.0028450419
762PhosphorylationLHGNSFHSEDEIEYE
CCCCCCCCHHHHHHH		44.7428450419
768PhosphorylationHSEDEIEYENQKRLE
CCHHHHHHHHHHHHC		26.3328450419
772UbiquitinationEIEYENQKRLEEEED
HHHHHHHHHHCCCCC		71.21-
793PhosphorylationEDLLCFAYQVAKGME
HHHHHHHHHHHCCCC		5.3519477218
820PhosphorylationAARNVLVTHGKVVKI
HHCCEEEECCCEEEE		22.2828674151
840PhosphorylationARDIMSDSNYVVRGN
CCHHHCCCCEEEECC		23.8223401153
842PhosphorylationDIMSDSNYVVRGNAR
HHHCCCCEEEECCCC		12.3228450419
915PhosphorylationMDQPFYATEEIYIIM
CCCCCEECCCEEEEE		23.8329083192
919PhosphorylationFYATEEIYIIMQSCW
CEECCCEEEEEHHHH		6.4129083192
924PhosphorylationEIYIIMQSCWAFDSR
CEEEEEHHHHCCCCC		8.3429083192
930PhosphorylationQSCWAFDSRKRPSFP
HHHHCCCCCCCCCCC		32.9929083192
932UbiquitinationCWAFDSRKRPSFPNL
HHCCCCCCCCCCCCH		73.03-
955PhosphorylationADAEEAMYQNVDGRV
CCHHHHHHHCCCCCH		12.1821552520
968PhosphorylationRVSECPHTYQNRRPF
CHHCCCCCCCCCCCC		16.3728176486
969PhosphorylationVSECPHTYQNRRPFS
HHCCCCCCCCCCCCC		10.7621552520
976PhosphorylationYQNRRPFSREMDLGL
CCCCCCCCHHCCCCC		29.9828450419
993PhosphorylationPQAQVEDS-------
CCCCCCCC-------		100.0011442493
Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)
Modified Location Modified Residue Modification Type of Upstream Proteins Gene Name of Upstream Proteins UniProt AC of Upstream Proteins Sources
572YPhosphorylationKinaseFLT3P36888
GPS
589YPhosphorylationKinaseFLT3P36888
PSP
591YPhosphorylationKinaseFLT3P36888
PSP
597YPhosphorylationKinaseFLT3P36888
PhosphoELM
599YPhosphorylationKinaseFLT3P36888
PSP
726YPhosphorylationKinaseFLT3P36888
PSP
842YPhosphorylationKinaseFLT3P36888
PSP
955YPhosphorylationKinaseFLT3P36888
PSP
969YPhosphorylationKinaseFLT3P36888
PSP
-KUbiquitinationE3 ubiquitin ligaseRNF126Q9BV68
PMID:22199232
-KUbiquitinationE3 ubiquitin ligaseRNF115Q9Y4L5
PMID:22199232
-KUbiquitinationE3 ubiquitin ligaseSIAH1Q8IUQ4
PMID:20508617
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference

Oops, there are no descriptions of PTM sites of FLT3_HUMAN !!
Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location Modification Variant Position
(Distance <= 10) 		Residue Change SAP Related Disease Reference

Oops, there are no SNP-PTM records of FLT3_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
HS90A_HUMANHSP90AA1physical
18394702
P85A_HUMANPIK3R1physical
16982329
SLAP1_HUMANSLAphysical
23300935
SOCS2_HUMANSOCS2physical
23548639
CBL_HUMANCBLphysical
17446348
FLT3_HUMANFLT3physical
21389326
VHL_HUMANVHLgenetic
28319113
Drug and Disease Associations
Kegg Disease
H00003 Acute myeloid leukemia (AML)
OMIM Disease
601626Leukemia, acute myelogenous (AML)
Kegg Drug
D04696 Lestaurtinib (USAN/INN)
D05029 Midostaurin (USAN/INN)
D05819 Semaxanib (USAN/INN)
D06005 Tandutinib (USAN/INN)
D06272 Sorafenib tosilate (JAN); Sorafenib tosylate (USAN); Nexavar (TN)
D06402 Sunitinib malate (JAN/USAN); Sutent (TN)
D08279 Tozasertib (USAN)
D08344 Tozasertib lactate (USAN); MK-0457
D08503 Toceranib (USAN)
D08524 Sorafenib (USAN/INN)
D08544 Toceranib phosphate (USAN)
D08552 Sunitinib (INN)
D09955 Quizartinib (USAN/INN)
D09956 Quizartinib dihydrochloride (USAN)
D10396 Nintedanib esylate (USAN)
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of FLT3_HUMAN

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Related Literatures of Post-Translational Modification
N-linked Glycosylation
ReferencePubMed
"Structural insights into the extracellular assembly of thehematopoietic Flt3 signaling complex.";
Verstraete K., Vandriessche G., Januar M., Elegheert J.,Shkumatov A.V., Desfosses A., Van Craenenbroeck K., Svergun D.I.,Gutsche I., Vergauwen B., Savvides S.N.;
Blood 118:60-68(2011).
Cited for: X-RAY CRYSTALLOGRAPHY (4.3 ANGSTROMS) OF 27-436 IN COMPLEX WITHFLT3LG, SUBUNIT, INTERACTION WITH FLT3LG, GLYCOSYLATION AT ASN-43;ASN-100; ASN-151; ASN-306; ASN-323; ASN-351 AND ASN-354, MASSSPECTROMETRY, AND DISULFIDE BONDS.
Phosphorylation
ReferencePubMed
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-166; TYR-401; TYR-416;TYR-726; THR-728; SER-759; TYR-842; TYR-969 AND SER-993, AND MASSSPECTROMETRY.
"Identification of Y589 and Y599 in the juxtamembrane domain of Flt3as ligand-induced autophosphorylation sites involved in binding of Srcfamily kinases and the protein tyrosine phosphatase SHP2.";
Heiss E., Masson K., Sundberg C., Pedersen M., Sun J., Bengtsson S.,Ronnstrand L.;
Blood 108:1542-1550(2006).
Cited for: INTERACTION WITH PTPN11/SHP2; LYN; FGR; HCK AND SRC,AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-589 AND TYR-599, ANDPHOSPHORYLATION AT TYR-572; SER-574; TYR-589; TYR-591 AND TYR-599.
"Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinaseFLT3 signaling.";
Arora D., Stopp S., Bohmer S.A., Schons J., Godfrey R., Masson K.,Razumovskaya E., Ronnstrand L., Tanzer S., Bauer R., Bohmer F.D.,Muller J.P.;
J. Biol. Chem. 286:10918-10929(2011).
Cited for: INTERACTION WITH PTPRJ/DEP1, FUNCTION IN ACTIVATION OF MAPK1/ERK2;MAPK3/ERK1; PLCG1; STAT5A AND/OR STAT5B, GLYCOSYLATION,UBIQUITINATION, AND PHOSPHORYLATION AT TYR-572; TYR-589; TYR-591;TYR-599; TYR-768; TYR-793; TYR-842 AND TYR-955.
"Oncogenic Flt3 receptors display different specificity and kineticsof autophosphorylation.";
Razumovskaya E., Masson K., Khan R., Bengtsson S., Ronnstrand L.;
Exp. Hematol. 37:979-989(2009).
Cited for: PHOSPHORYLATION AT TYR-589; TYR-591; TYR-599; TYR-726; TYR-768;TYR-793; TYR-842 AND TYR-955.
"Tyrosine phosphorylation regulates maturation of receptor tyrosinekinases.";
Schmidt-Arras D.E., Bohmer A., Markova B., Choudhary C., Serve H.,Bohmer F.D.;
Mol. Cell. Biol. 25:3690-3703(2005).
Cited for: SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-591,DEPHOSPHORYLATION BY PTPN1; PTPN6/SHP-1 AND PTPN12, PROTEASOMALDEGRADATION, GLYCOSYLATION, AND MUTAGENESIS OF LYS-644.

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