FGFR2_HUMAN - dbPTM
FGFR2_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID FGFR2_HUMAN
UniProt AC P21802
Protein Name Fibroblast growth factor receptor 2
Gene Name FGFR2
Organism Homo sapiens (Human).
Sequence Length 821
Subcellular Localization Cell membrane
Single-pass type I membrane protein. Golgi apparatus. Cytoplasmic vesicle. Detected on osteoblast plasma membrane lipid rafts. After ligand binding, the activated receptor is rapidly internalized and degraded.
Isoform 1: Cell membrane
Protein Description Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1..
Protein Sequence MVSWGRFICLVVVTMATLSLARPSFSLVEDTTLEPEEPPTKYQISQPEVYVAAPGESLEVRCLLKDAAVISWTKDGVHLGPNNRTVLIGEYLQIKGATPRDSGLYACTASRTVDSETWYFMVNVTDAISSGDDEDDTDGAEDFVSENSNNKRAPYWTNTEKMEKRLHAVPAANTVKFRCPAGGNPMPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDVVERSPHRPILQAGLPANASTVVGGDVEFVCKVYSDAQPHIQWIKHVEKNGSKYGPDGLPYLKVLKAAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFHSAWLTVLPAPGREKEITASPDYLEIAIYCIGVFLIACMVVTVILCRMKNTTKKPDFSSQPAVHKLTKRIPLRRQVTVSAESSSSMNSNTPLVRITTRLSSTADTPMLAGVSEYELPEDPKWEFPRDKLTLGKPLGEGCFGQVVMAEAVGIDKDKPKEAVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRARRPPGMEYSYDINRVPEEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIDYYKKTTNGRLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRILTLTTNEEYLDLSQPLEQYSPSYPDTRSSCSSGDDSVFSPDPMPYEPCLPQYPHINGSVKT
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
40O-linked_GlycosylationLEPEEPPTKYQISQP
CCCCCCCCCCCCCCC		53.77OGP
83N-linked_GlycosylationGVHLGPNNRTVLIGE
CEEECCCCCEEEEEE		44.10UniProtKB CARBOHYD
123N-linked_GlycosylationETWYFMVNVTDAISS
CCEEEEEEHHHHHHC		21.13UniProtKB CARBOHYD
174PhosphorylationHAVPAANTVKFRCPA
HCCCCCCEEEEECCC		21.9827461979
215 (in isoform 23)Phosphorylation-13.0927251275
220 (in isoform 23)Phosphorylation-15.8427251275
228N-linked_GlycosylationVVPSDKGNYTCVVEN
ECCCCCCCEEEEEEE		34.38UniProtKB CARBOHYD
229 (in isoform 23)Phosphorylation-15.3627251275
230 (in isoform 23)Phosphorylation-11.6527251275
237 (in isoform 23)Phosphorylation-27.9627251275
239 (in isoform 23)Phosphorylation-21.2227251275
241N-linked_GlycosylationENEYGSINHTYHLDV
EECCCCEEEEEEEEE		24.12UniProtKB CARBOHYD
243 (in isoform 23)Phosphorylation-14.2427251275
244 (in isoform 23)Phosphorylation-7.8827251275
265N-linked_GlycosylationLQAGLPANASTVVGG
CCCCCCCCCCCEECC		32.27UniProtKB CARBOHYD
297N-linked_GlycosylationWIKHVEKNGSKYGPD
EEEEHHHCCCCCCCC		46.60UniProtKB CARBOHYD
314 (in isoform 20)Phosphorylation-12.8028348404
318N-linked_GlycosylationVLKAAGVNTTDKEIE
HHHHCCCCCCCCEEE		36.02UniProtKB CARBOHYD
331N-linked_GlycosylationIEVLYIRNVTFEDAG
EEEEEEECCCCCCCC		27.85UniProtKB CARBOHYD
341 (in isoform 4)Phosphorylation-9.2028348404
347PhosphorylationYTCLAGNSIGISFHS
EEECCCCEEEEEEEE		22.6719410646
429 (in isoform 8)Phosphorylation-10.6228348404
429 (in isoform 6)Phosphorylation-10.6228348404
429 (in isoform 5)Phosphorylation-10.6228348404
429PhosphorylationIPLRRQVTVSAESSS
CCCCCEEEEEEECCC		10.6228348404
430 (in isoform 18)Phosphorylation-5.5428348404
431PhosphorylationLRRQVTVSAESSSSM
CCCEEEEEEECCCCC		19.5628348404
432 (in isoform 16)Phosphorylation-19.1628348404
434PhosphorylationQVTVSAESSSSMNSN
EEEEEEECCCCCCCC		34.9327251275
435PhosphorylationVTVSAESSSSMNSNT
EEEEEECCCCCCCCC		20.2427251275
436PhosphorylationTVSAESSSSMNSNTP
EEEEECCCCCCCCCC		42.7727251275
437PhosphorylationVSAESSSSMNSNTPL
EEEECCCCCCCCCCE		24.7522210691
438PhosphorylationSAESSSSMNSNTPLV
EEECCCCCCCCCCEE		7.4327251275
440PhosphorylationESSSSMNSNTPLVRI
ECCCCCCCCCCEEEE		33.1822210691
442PhosphorylationSSSMNSNTPLVRITT
CCCCCCCCCEEEEEE		20.16-
448PhosphorylationNTPLVRITTRLSSTA
CCCEEEEEECCCCCC		8.6922496350
449PhosphorylationTPLVRITTRLSSTAD
CCEEEEEECCCCCCC		27.5222496350
450PhosphorylationPLVRITTRLSSTADT
CEEEEEECCCCCCCC		24.7527251275
452PhosphorylationVRITTRLSSTADTPM
EEEEECCCCCCCCCC		23.5020639409
453PhosphorylationRITTRLSSTADTPML
EEEECCCCCCCCCCC		32.0122496350
454PhosphorylationITTRLSSTADTPMLA
EEECCCCCCCCCCCC		25.7722496350
455PhosphorylationTTRLSSTADTPMLAG
EECCCCCCCCCCCCC		22.1927251275
457PhosphorylationRLSSTADTPMLAGVS
CCCCCCCCCCCCCCC		14.2422496350
464PhosphorylationTPMLAGVSEYELPED
CCCCCCCCCCCCCCC		33.2830206219
466PhosphorylationMLAGVSEYELPEDPK
CCCCCCCCCCCCCCC		18.4319060208
533PhosphorylationKDLSDLVSEMEMMKM
CCHHHHHHHHHHHHH		38.22-
539AcetylationVSEMEMMKMIGKHKN
HHHHHHHHHHHCCCC		26.5112437653
586PhosphorylationRRPPGMEYSYDINRV
HCCCCCCCCCCCCCC		12.0219060208
587PhosphorylationRPPGMEYSYDINRVP
CCCCCCCCCCCCCCC		11.7429978859
588PhosphorylationPPGMEYSYDINRVPE
CCCCCCCCCCCCCCH		21.6819060208
608PhosphorylationKDLVSCTYQLARGME
HHHHHHHHHHHHHHH		13.07-
616PhosphorylationQLARGMEYLASQKCI
HHHHHHHHHHHCCCH		9.93-
656PhosphorylationRDINNIDYYKKTTNG
CCCCCCCCEECCCCC		17.2522322096
657PhosphorylationDINNIDYYKKTTNGR
CCCCCCCEECCCCCC		11.4022322096
658PhosphorylationINNIDYYKKTTNGRL
CCCCCCEECCCCCCC		37.1027251275
673 (in isoform 21)Phosphorylation-48.7627794612
675 (in isoform 21)Phosphorylation-4.3527794612
676 (in isoform 21)Phosphorylation-7.9027794612
733PhosphorylationANCTNELYMMMRDCW
CCCCHHHHHHHHHHH		4.10-
751UbiquitinationPSQRPTFKQLVEDLD
CCCCCCHHHHHHHHH		45.24-
762PhosphorylationEDLDRILTLTTNEEY
HHHHHHHHCCCCHHH		21.4924043423
764PhosphorylationLDRILTLTTNEEYLD
HHHHHHCCCCHHHCC		23.4924043423
765PhosphorylationDRILTLTTNEEYLDL
HHHHHCCCCHHHCCC		43.6924043423
769PhosphorylationTLTTNEEYLDLSQPL
HCCCCHHHCCCCCCH		10.1919060208
772 (in isoform 9)Phosphorylation-4.7722210691
773PhosphorylationNEEYLDLSQPLEQYS
CHHHCCCCCCHHHCC		29.4424043423
779PhosphorylationLSQPLEQYSPSYPDT
CCCCHHHCCCCCCCC		17.1124043423
780PhosphorylationSQPLEQYSPSYPDTR
CCCHHHCCCCCCCCC		13.689150725
782PhosphorylationPLEQYSPSYPDTRSS
CHHHCCCCCCCCCCC		43.2718332103
783PhosphorylationLEQYSPSYPDTRSSC
HHHCCCCCCCCCCCC		14.4424043423
786PhosphorylationYSPSYPDTRSSCSSG
CCCCCCCCCCCCCCC		28.1324043423
788PhosphorylationPSYPDTRSSCSSGDD
CCCCCCCCCCCCCCC		37.48-
789PhosphorylationSYPDTRSSCSSGDDS
CCCCCCCCCCCCCCC		18.09-
791PhosphorylationPDTRSSCSSGDDSVF
CCCCCCCCCCCCCCC		39.03-
792PhosphorylationDTRSSCSSGDDSVFS
CCCCCCCCCCCCCCC		51.04-
805PhosphorylationFSPDPMPYEPCLPQY
CCCCCCCCCCCCCCC		26.67-
812PhosphorylationYEPCLPQYPHINGSV
CCCCCCCCCCCCCCC		8.549266968
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
769YPhosphorylationKinaseFGFR2P21802
PSP
780SPhosphorylationKinaseERK2P28482
PSP
780SPhosphorylationKinaseERK1P27361
PSP
-KUbiquitinationE3 ubiquitin ligaseCBLP22681
PMID:15190072
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference

Oops, there are no descriptions of PTM sites of FGFR2_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 FGFR2_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
FGFR2_HUMANFGFR2physical
11069186
FGF1_HUMANFGF1physical
8576175
FGF7_HUMANFGF7physical
9582367
FGF10_HUMANFGF10physical
9582367
ITA5_HUMANITGA5physical
15728256
STAT3_HUMANSTAT3physical
20388777
PRGR_HUMANPGRphysical
21464042
STA5A_HUMANSTAT5Aphysical
21464042
STA5B_HUMANSTAT5Bphysical
21464042
FRS2_HUMANFRS2physical
21596750
CBL_HUMANCBLphysical
15190072
HGS_HUMANHGSphysical
19362549
A4_HUMANAPPphysical
21832049
PPM1A_HUMANPPM1Aphysical
21988832
BEX1_HUMANBEX1physical
25640309
BEX2_HUMANBEX2physical
25640309
ERRFI_HUMANERRFI1physical
25640309
GLCE_HUMANGLCEphysical
25640309
HXC6_HUMANHOXC6physical
25640309
MTA3_HUMANMTA3physical
25640309
PDLI2_HUMANPDLIM2physical
25640309
RSLAB_HUMANRASL10Bphysical
25640309
RHBT2_HUMANRHOBTB2physical
25640309
S10AE_HUMANS100A14physical
25640309
TFF1_HUMANTFF1physical
25640309
FGF1_HUMANFGF1physical
25241761
FGF10_HUMANFGF10physical
25241761
FGF5_HUMANFGF5physical
25241761
FGF23_HUMANFGF23physical
25241761
FGF8_HUMANFGF8physical
25241761
PLCG1_HUMANPLCG1physical
25241761
FGF1_HUMANFGF1physical
18199118
FGF2_HUMANFGF2physical
18199118
FGF3_HUMANFGF3physical
18199118
FGF5_HUMANFGF5physical
18199118
FGF6_HUMANFGF6physical
18199118
FGF8_HUMANFGF8physical
18199118
FGF9_HUMANFGF9physical
18199118
FGF10_HUMANFGF10physical
18199118
FGF17_HUMANFGF17physical
18199118
M3K1_HUMANMAP3K1genetic
28319113
PTN6_HUMANPTPN6physical
28065597
PTN11_HUMANPTPN11physical
28065597
PTN12_HUMANPTPN12physical
28065597
PTPRR_HUMANPTPRRphysical
28065597
FGFR3_HUMANFGFR3physical
28514442
FGFR1_HUMANFGFR1physical
28514442
FGF2_HUMANFGF2physical
28514442
SNX24_HUMANSNX24physical
28514442
GAPD1_HUMANGAPVD1physical
28514442
SNX22_HUMANSNX22physical
28514442
UBE4A_HUMANUBE4Aphysical
28514442
IP6K1_HUMANIP6K1physical
28514442
KS6A3_HUMANRPS6KA3physical
28514442
IFFO2_HUMANIFFO2physical
28514442
DJC30_HUMANDNAJC30physical
28514442
XPR1_HUMANXPR1physical
28514442
GOGA3_HUMANGOLGA3physical
28514442
KDIS_HUMANKIDINS220physical
28514442
BC11A_HUMANBCL11Aphysical
28514442
CE295_HUMANCEP295physical
28514442
KS6A2_HUMANRPS6KA2physical
28514442
KS6A1_HUMANRPS6KA1physical
28514442
CHERP_HUMANCHERPphysical
28514442
SR140_HUMANU2SURPphysical
28514442
TIMP1_HUMANTIMP1physical
28514442
PKP4_HUMANPKP4physical
28514442
UBXN4_HUMANUBXN4physical
28514442
CTDS1_HUMANCTDSP1physical
28065597
CTDSL_HUMANCTDSPLphysical
28065597
DUS14_HUMANDUSP14physical
28065597
MTMR3_HUMANMTMR3physical
28065597
PLCG1_HUMANPLCG1physical
15629145
EPHA4_HUMANEPHA4physical
16365308
KALM_HUMANKAL1physical
19696444
Drug and Disease Associations
Kegg Disease
H00018 Gastric cancer
H00458 Craniosynostosis, including: Pfeiffer syndrome; Apert syndrome; Crouzon syndrome; Jackson-Weiss synd
H00642 Lacrimo-auriculo-dento-digital syndrome (LADD); Levy-Hollister syndrome
OMIM Disease
123500Crouzon syndrome (CS)
123150Jackson-Weiss syndrome (JWS)
101200Apert syndrome (APRS)
101600Pfeiffer syndrome (PS)
123790Beare-Stevenson cutis gyrata syndrome (BSTVS)
609579Familial scaphocephaly syndrome (FSPC)
149730Lacrimo-auriculo-dento-digital syndrome (LADDS)
207410Antley-Bixler syndrome, without genital anomalies or disordered steroidogenesis (ABS2)
614592Bent bone dysplasia syndrome (BBDS)
Kegg Drug
D08878 Brivanib alaninate (JAN/USAN/INN)
D08907 Dovitinib lactate (USAN)
D09589 Brivanib (USAN)
D09919 Lenvatinib (USAN/INN)
D09920 Lenvatinib mesilate (JAN); Lenvatinib mesylate (USAN)
D10396 Nintedanib esylate (USAN)
DrugBank
There are no disease associations of PTM sites.
Regulatory Network of FGFR2_HUMAN

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Related Literatures of Post-Translational Modification
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 THR-448 AND THR-449, ANDMASS SPECTROMETRY.
"A crystallographic snapshot of tyrosine trans-phosphorylation inaction.";
Chen H., Xu C.F., Ma J., Eliseenkova A.V., Li W., Pollock P.M.,Pitteloud N., Miller W.T., Neubert T.A., Mohammadi M.;
Proc. Natl. Acad. Sci. U.S.A. 105:19660-19665(2008).
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 458-778 IN COMPLEX WITH ATP,ACTIVE SITE, MASS SPECTROMETRY, AUTOPHOSPHORYLATION, ANDPHOSPHORYLATION AT TYR-466; TYR-586; TYR-588; TYR-656; TYR-657 ANDTYR-769.
"A molecular brake in the kinase hinge region regulates the activityof receptor tyrosine kinases.";
Chen H., Ma J., Li W., Eliseenkova A.V., Xu C., Neubert T.A.,Miller W.T., Mohammadi M.;
Mol. Cell 27:717-730(2007).
Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 458-778 IN COMPLEX WITH ATPANALOG; PEPTIDE SUBSTRATE AND MAGNESIUM, ENZYME REGULATION,PHOSPHORYLATION AT TYR-586; TYR-656 AND TYR-657, MUTAGENESIS OFASN-549 AND GLU-565, CHARACTERIZATION OF VARIANT FSPC GLU-526,CHARACTERIZATION OF VARIANT CS HIS-549, CHARACTERIZATION OF VARIANTSPS GLY-565 AND ARG-641, AND CHARACTERIZATION OF VARIANTCRANIOSYNOSTOSIS ASN-659.
"Novel phosphotyrosine targets of FGFR2IIIb signaling.";
Luo Y., Yang C., Jin C., Xie R., Wang F., McKeehan W.L.;
Cell. Signal. 21:1370-1378(2009).
Cited for: FUNCTION AS FGF7 RECEPTOR AND IN PHOSPHORYLATION OF PLCG1 AND FRS2,CATALYTIC ACTIVITY, PHOSPHORYLATION AT TYR-466; TYR-586; TYR-588;TYR-656 AND TYR-657, AND MASS SPECTROMETRY.
"Tyrosine 769 of the keratinocyte growth factor receptor is requiredfor receptor signaling but not endocytosis.";
Ceridono M., Belleudi F., Ceccarelli S., Torrisi M.R.;
Biochem. Biophys. Res. Commun. 327:523-532(2005).
Cited for: FUNCTION IN CELL PROLIFERATION AND ACTIVATION OF SIGNALING PATHWAYS,MUTAGENESIS OF TYR-769, PHOSPHORYLATION AT TYR-769, AND INTERACTIONWITH PLCG1.

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