FGR_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: FGR_HUMAN
• UniProt AC: P09769
• Protein Name: Tyrosine-protein kinase Fgr
• Gene Name: FGR
• Organism: Homo sapiens (Human).
• Sequence Length: 529
• Subcellular Localization: Cell membrane ; Lipid-anchor ; Cytoplasmic side . Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, ruffle membrane. Cytoplasm, cytosol. Cytoplasm, cytoskeleton. Mitochondrion inner membrane. Mitochondrion intermembrane space.
• Protein Description: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1..
• Protein Sequence: MGCVFCKKLEPVATAKEDAGLEGDFRSYGAADHYGPDPTKARPASSFAHIPNYSNFSSQAINPGFLDSGTIRGVSGIGVTLFIALYDYEARTEDDLTFTKGEKFHILNNTEGDWWEARSLSSGKTGCIPSNYVAPVDSIQAEEWYFGKIGRKDAERQLLSPGNPQGAFLIRESETTKGAYSLSIRDWDQTRGDHVKHYKIRKLDMGGYYITTRVQFNSVQELVQHYMEVNDGLCNLLIAPCTIMKPQTLGLAKDAWEISRSSITLERRLGTGCFGDVWLGTWNGSTKVAVKTLKPGTMSPKAFLEEAQVMKLLRHDKLVQLYAVVSEEPIYIVTEFMCHGSLLDFLKNPEGQDLRLPQLVDMAAQVAEGMAYMERMNYIHRDLRAANILVGERLACKIADFGLARLIKDDEYNPCQGSKFPIKWTAPEAALFGRFTIKSDVWSFGILLTELITKGRIPYPGMNKREVLEQVEQGYHMPCPPGCPASLYEAMEQTWRLDPEERPTFEYLQSFLEDYFTSAEPQYQPGDQT

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
2	Myristoylation	------MGCVFCKKL ------CCCEECCCC	19.12	-
3	S-palmitoylation	-----MGCVFCKKLE -----CCCEECCCCE	1.73	-
6	S-palmitoylation	--MGCVFCKKLEPVA --CCCEECCCCEECE	1.57	-
16	Ubiquitination	LEPVATAKEDAGLEG CEECEECCCCCCCCC	52.34	-
27	Phosphorylation	GLEGDFRSYGAADHY CCCCCHHHCCCCCCC	28.10	26356563
28	Phosphorylation	LEGDFRSYGAADHYG CCCCHHHCCCCCCCC	13.41	26356563
34	Phosphorylation	SYGAADHYGPDPTKA HCCCCCCCCCCCCCC	30.79	27155012
39	Phosphorylation	DHYGPDPTKARPASS CCCCCCCCCCCCCHH	44.72	26356563
45	Phosphorylation	PTKARPASSFAHIPN CCCCCCCHHHCCCCC	28.77	28348404
46	Phosphorylation	TKARPASSFAHIPNY CCCCCCHHHCCCCCC	28.67	28857561
53	Phosphorylation	SFAHIPNYSNFSSQA HHCCCCCCCCCCCCC	10.31	28348404
54	Phosphorylation	FAHIPNYSNFSSQAI HCCCCCCCCCCCCCC	37.73	28857561
57	Phosphorylation	IPNYSNFSSQAINPG CCCCCCCCCCCCCCC	26.28	28348404
58	Phosphorylation	PNYSNFSSQAINPGF CCCCCCCCCCCCCCC	21.35	28348404
86	Phosphorylation	VTLFIALYDYEARTE EEEEEEEEECCCCCC	13.88	25884760
97	Phosphorylation	ARTEDDLTFTKGEKF CCCCCCCEECCCCEE	35.93	29759185
99	Phosphorylation	TEDDLTFTKGEKFHI CCCCCEECCCCEEEE	32.67	29759185
173	Phosphorylation	GAFLIRESETTKGAY CCEEEEECCCCCCEE	30.32	28152594
175	Phosphorylation	FLIRESETTKGAYSL EEEEECCCCCCEEEE	42.99	28152594
176	Phosphorylation	LIRESETTKGAYSLS EEEECCCCCCEEEEE	24.35	28152594
177	Ubiquitination	IRESETTKGAYSLSI EEECCCCCCEEEEEE	49.30	21890473
180	Phosphorylation	SETTKGAYSLSIRDW CCCCCCEEEEEEEEC	20.86	30266825
181	Phosphorylation	ETTKGAYSLSIRDWD CCCCCEEEEEEEECC	18.33	30266825
183	Phosphorylation	TKGAYSLSIRDWDQT CCCEEEEEEEECCCC	15.05	28152594
208	Phosphorylation	RKLDMGGYYITTRVQ EEECCCCEEEEEEEE	5.98	27155012
209	Phosphorylation	KLDMGGYYITTRVQF EECCCCEEEEEEEEC	8.61	30108239
211	Phosphorylation	DMGGYYITTRVQFNS CCCCEEEEEEEECCC	7.76	26356563
212	Phosphorylation	MGGYYITTRVQFNSV CCCEEEEEEEECCCH	21.20	26356563
218	Phosphorylation	TTRVQFNSVQELVQH EEEEECCCHHHHHHH	26.85	-
259	Phosphorylation	AKDAWEISRSSITLE CCCHHHHCCCCCCCH	18.00	27251275
261	Phosphorylation	DAWEISRSSITLERR CHHHHCCCCCCCHHH	21.21	30108239
262	Phosphorylation	AWEISRSSITLERRL HHHHCCCCCCCHHHC	20.62	23911959
292	Phosphorylation	STKVAVKTLKPGTMS CEEEEEEECCCCCCC	33.15	-
301	Ubiquitination	KPGTMSPKAFLEEAQ CCCCCCHHHHHHHHH	44.45	-
341	Phosphorylation	TEFMCHGSLLDFLKN EEEEECHHHHHHHHC	11.33	27251275
412	Phosphorylation	RLIKDDEYNPCQGSK HHCCCCCCCCCCCCC	31.25	27155012
418	Phosphorylation	EYNPCQGSKFPIKWT CCCCCCCCCCCCEEC	12.78	30108239
453	Phosphorylation	ILLTELITKGRIPYP HHHHHHHHCCCCCCC	39.82	-
459	Phosphorylation	ITKGRIPYPGMNKRE HHCCCCCCCCCCHHH	15.28	20860994
523	Phosphorylation	FTSAEPQYQPGDQT- HHCCCCCCCCCCCC-	27.65	7515063
529	Phosphorylation	QYQPGDQT------- CCCCCCCC-------	45.37	23532336

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
412	Y	Phosphorylation	Kinase	FGR	P09769	PhosphoELM
523	Y	Phosphorylation	Kinase	CSK	P41240	PhosphoELM
523	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	SMURF1	Q9HCE7	PMID:20804422
-	K	Ubiquitination	E3 ubiquitin ligase	CBL	P22681	PMID:12435267

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of FGR_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of FGR_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
WASP_HUMAN	WAS	physical	8805332
CBL_HUMAN	CBL	physical	12435267
WASP_HUMAN	WAS	physical	8824280
TNFL6_HUMAN	FASLG	physical	17164290
SH3K1_HUMAN	SH3KBP1	physical	15707590
KHDR1_HUMAN	KHDRBS1	physical	15190072
HS90A_HUMAN	HSP90AA1	physical	22939624
STAT3_HUMAN	STAT3	physical	21988832
NR1I2_HUMAN	NR1I2	physical	21988832
NEMO_HUMAN	IKBKG	physical	23131831

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"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 SER-27; TYR-34; TYR-412;TYR-523 AND THR-529, AND MASS SPECTROMETRY.
PubMed: 19369195

"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28; TYR-34; TYR-208 ANDTYR-412, AND MASS SPECTROMETRY.
PubMed: 18083107