CSF1R_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CSF1R_HUMAN
• UniProt AC: P07333
• Protein Name: Macrophage colony-stimulating factor 1 receptor
• Gene Name: CSF1R
• Organism: Homo sapiens (Human).
• Sequence Length: 972
• Subcellular Localization: Cell membrane; Single-pass type I membrane protein.
• Protein Description: Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor..
• Protein Sequence: MGPGVLLLLLVATAWHGQGIPVIEPSVPELVVKPGATVTLRCVGNGSVEWDGPPSPHWTLYSDGSSSILSTNNATFQNTGTYRCTEPGDPLGGSAAIHLYVKDPARPWNVLAQEVVVFEDQDALLPCLLTDPVLEAGVSLVRVRGRPLMRHTNYSFSPWHGFTIHRAKFIQSQDYQCSALMGGRKVMSISIRLKVQKVIPGPPALTLVPAELVRIRGEAAQIVCSASSVDVNFDVFLQHNNTKLAIPQQSDFHNNRYQKVLTLNLDQVDFQHAGNYSCVASNVQGKHSTSMFFRVVESAYLNLSSEQNLIQEVTVGEGLNLKVMVEAYPGLQGFNWTYLGPFSDHQPEPKLANATTKDTYRHTFTLSLPRLKPSEAGRYSFLARNPGGWRALTFELTLRYPPEVSVIWTFINGSGTLLCAASGYPQPNVTWLQCSGHTDRCDEAQVLQVWDDPYPEVLSQEPFHKVTVQSLLTVETLEHNQTYECRAHNSVGSGSWAFIPISAGAHTHPPDEFLFTPVVVACMSIMALLLLLLLLLLYKYKQKPKYQVRWKIIESYEGNSYTFIDPTQLPYNEKWEFPRNNLQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLGQHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDPEGGVDYKNIHLEKKYVRRDSGFSSQGVDTYVEMRPVSTSSNDSFSEQDLDKEDGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTNGHVAKIGDFGLARDIMNDSNYIVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNSKFYKLVKDGYQMAQPAFAPKNIYSIMQACWALEPTHRPTFQQICSFLQEQAQEDRRERDYTNLPSSSRSGGSGSSSSELEEESSSEHLTCCEQGDIAQPLLQPNNYQFC

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
45	N-linked_Glycosylation	VTLRCVGNGSVEWDG EEEEEECCCCEECCC	21.11	UniProtKB CARBOHYD
73	N-linked_Glycosylation	SSILSTNNATFQNTG CCEEECCCCEECCCC	40.21	UniProtKB CARBOHYD
153	N-linked_Glycosylation	RPLMRHTNYSFSPWH EECCCCCCCCCCCCC	25.07	UniProtKB CARBOHYD
178	Phosphorylation	QSQDYQCSALMGGRK CCCCCCEEHHHCCEE	14.65	24114839
240	N-linked_Glycosylation	FDVFLQHNNTKLAIP EEEEECCCCEEEECC	44.92	UniProtKB CARBOHYD
275	N-linked_Glycosylation	VDFQHAGNYSCVASN CCCEECCCEEEEEEE	26.74	UniProtKB CARBOHYD
302	N-linked_Glycosylation	VVESAYLNLSSEQNL HHHHHHHCCCCCCCE	25.79	16335952
335	N-linked_Glycosylation	YPGLQGFNWTYLGPF CCCCCCCCEEEECCC	36.68	UniProtKB CARBOHYD
353	N-linked_Glycosylation	QPEPKLANATTKDTY CCCCCCCCCCCCCCC	48.53	16335952
363	Phosphorylation	TKDTYRHTFTLSLPR CCCCCCCEEEEECCC	14.87	-
365	Phosphorylation	DTYRHTFTLSLPRLK CCCCCEEEEECCCCC	19.32	-
367	Phosphorylation	YRHTFTLSLPRLKPS CCCEEEEECCCCCHH	33.02	24719451
374	Phosphorylation	SLPRLKPSEAGRYSF ECCCCCHHHCCCEEE	38.19	22210691
380	Phosphorylation	PSEAGRYSFLARNPG HHHCCCEEEEEECCC	16.66	24719451
397	Phosphorylation	RALTFELTLRYPPEV EEEEEEEEECCCCCE	11.29	24719451
412	N-linked_Glycosylation	SVIWTFINGSGTLLC EEEEEEECCCCCEEE	34.09	UniProtKB CARBOHYD
428	N-linked_Glycosylation	ASGYPQPNVTWLQCS ECCCCCCCEEEEEEC	38.31	UniProtKB CARBOHYD
480	N-linked_Glycosylation	TVETLEHNQTYECRA EEEECCCCCEEEEEC	26.89	UniProtKB CARBOHYD
546	Phosphorylation	KYKQKPKYQVRWKII HHCCCCCCEEEEEEE	22.29	22817900
555	Phosphorylation	VRWKIIESYEGNSYT EEEEEEEECCCCEEE	20.34	22817900
556	Phosphorylation	RWKIIESYEGNSYTF EEEEEEECCCCEEEE	18.31	22817900
560	Phosphorylation	IESYEGNSYTFIDPT EEECCCCEEEEECCC	36.08	-
561	Phosphorylation	ESYEGNSYTFIDPTQ EECCCCEEEEECCCC	15.07	7730365
562	Phosphorylation	SYEGNSYTFIDPTQL ECCCCEEEEECCCCC	17.59	22817900
567	Phosphorylation	SYTFIDPTQLPYNEK EEEEECCCCCCCCCC	38.70	22817900
571	Phosphorylation	IDPTQLPYNEKWEFP ECCCCCCCCCCCCCC	44.54	-
586	Ubiquitination	RNNLQFGKTLGAGAF CCCCCCCCEECCCCC	41.69	21890473
586	Ubiquitination	RNNLQFGKTLGAGAF CCCCCCCCEECCCCC	41.69	21890473
586	Ubiquitination	RNNLQFGKTLGAGAF CCCCCCCCEECCCCC	41.69	21890473
686	Phosphorylation	AEAMLGPSLSPGQDP HHHHHCCCCCCCCCC	39.41	-
688	Phosphorylation	AMLGPSLSPGQDPEG HHHCCCCCCCCCCCC	31.18	-
699	Phosphorylation	DPEGGVDYKNIHLEK CCCCCCCCCCEEEEE	11.97	17360941
708	Phosphorylation	NIHLEKKYVRRDSGF CEEEEEEEEECCCCC	15.40	N.N.
713	Phosphorylation	KKYVRRDSGFSSQGV EEEEECCCCCCCCCC	39.67	26657352
716	Phosphorylation	VRRDSGFSSQGVDTY EECCCCCCCCCCCCE	25.85	22817900
717	Phosphorylation	RRDSGFSSQGVDTYV ECCCCCCCCCCCCEE	28.79	26657352
722	Phosphorylation	FSSQGVDTYVEMRPV CCCCCCCCEEEEEEC	27.36	30576142
723	Phosphorylation	SSQGVDTYVEMRPVS CCCCCCCEEEEEECC	7.02	10648820
733	Phosphorylation	MRPVSTSSNDSFSEQ EEECCCCCCCCCCHH	44.75	30576142
759	Phosphorylation	LRDLLHFSSQVAQGM HHHHHHHHHHHHHHH	14.76	27251275
809	Phosphorylation	DIMNDSNYIVKGNAR HHHCCCCEEEECCCC	15.84	N.N.
812	Ubiquitination	NDSNYIVKGNARLPV CCCCEEEECCCCCCC	36.57	21890473
812	Ubiquitination	NDSNYIVKGNARLPV CCCCEEEECCCCCCC	36.57	21890473
812	Ubiquitination	NDSNYIVKGNARLPV CCCCEEEECCCCCCC	36.57	21890473
864	Ubiquitination	PGILVNSKFYKLVKD CCEEECHHHHHHHCC	47.73	22817900
867	Ubiquitination	LVNSKFYKLVKDGYQ EECHHHHHHHCCCHH	50.35	21890473
867	Ubiquitination	LVNSKFYKLVKDGYQ EECHHHHHHHCCCHH	50.35	21890473
867	Ubiquitination	LVNSKFYKLVKDGYQ EECHHHHHHHCCCHH	50.35	21890473
870	Ubiquitination	SKFYKLVKDGYQMAQ HHHHHHHCCCHHHCC	56.74	22817900
870	Ubiquitination	SKFYKLVKDGYQMAQ HHHHHHHCCCHHHCC	56.74	21890473
870	Ubiquitination	SKFYKLVKDGYQMAQ HHHHHHHCCCHHHCC	56.74	21890473
873	Phosphorylation	YKLVKDGYQMAQPAF HHHHCCCHHHCCCCC	12.78	22817900
923	Phosphorylation	EDRRERDYTNLPSSS HHHHHHCCCCCCCCC	12.07	22817900
969	Phosphorylation	PLLQPNNYQFC---- CCCCCCCCCCC----	15.03	-

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
546	Y	Phosphorylation	Kinase	CSF1R	P07333	GPS
561	Y	Phosphorylation	Kinase	CSF1R	P07333	PhosphoELM
699	Y	Phosphorylation	Kinase	CSF1R	P07333	GPS
708	Y	Phosphorylation	Kinase	CSF1R	P07333	GPS
723	Y	Phosphorylation	Kinase	CSF1R	P07333	GPS
809	Y	Phosphorylation	Kinase	CSF1R	P07333	PhosphoELM
923	Y	Phosphorylation	Kinase	CSF1R	P07333	GPS
969	Y	Phosphorylation	Kinase	CSF1R	P07333	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	CBL	P22681	PMID:11847211

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of CSF1R_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 CSF1R_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
GRB2_HUMAN	GRB2	physical	9380408
SOCS1_HUMAN	SOCS1	physical	11297560
CSF1_HUMAN	CSF1	physical	8355686
CBL_HUMAN	CBL	physical	11847211
FYN_HUMAN	FYN	physical	7681396
SRC_HUMAN	SRC	physical	7681396
YES_HUMAN	YES1	physical	7681396
CBL_HUMAN	CBL	physical	10025673
SOS1_HUMAN	SOS1	physical	10025673
P85A_HUMAN	PIK3R1	physical	10025673
SHC1_HUMAN	SHC1	physical	10025673
GRB2_HUMAN	GRB2	physical	10025673
STAP2_HUMAN	STAP2	physical	17512498
CBL_HUMAN	CBL	physical	7782294
CBL_HUMAN	CBL	physical	10648820
P85B_HUMAN	PIK3R2	physical	1334406
CTDS1_HUMAN	CTDSP1	physical	28065597
CTDS2_HUMAN	CTDSP2	physical	28065597
KIT_HUMAN	KIT	physical	9949175
CSF1R_HUMAN	CSF1R	physical	9380408
PK3CA_HUMAN	PIK3CA	physical	9380408

Drug and Disease Associations

• Kegg Disease
• H00028: Choriocarcinoma
• OMIM Disease
• : Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.
• 221820:
• 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

N-linked Glycosylation

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction,hydrazide chemistry, and mass spectrometry.";
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,Moore R.J., Smith R.D.;
J. Proteome Res. 4:2070-2080(2005).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-302 AND ASN-353, AND MASSSPECTROMETRY.
PubMed: 16335952

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 TYR-699; SER-713 ANDSER-716, AND MASS SPECTROMETRY.
PubMed: 19369195

"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column.";
Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.;
Anal. Sci. 24:161-166(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-555; TYR-556; THR-562AND THR-567, AND MASS SPECTROMETRY.
PubMed: 18187866

"Functional overlap but differential expression of CSF-1 and IL-34 intheir CSF-1 receptor-mediated regulation of myeloid cells.";
Wei S., Nandi S., Chitu V., Yeung Y.G., Yu W., Huang M.,Williams L.T., Lin H., Stanley E.R.;
J. Leukoc. Biol. 88:495-505(2010).
Cited for: FUNCTION AS IL34 AND CSF1 RECEPTOR; ACTIVATION OF MAPK1/ERK2;MAPK3/ERK1; PHOSPHORYLATION AT TYR-723, AND AUTOPHOSPHORYLATION.
PubMed: 20504948

"IL-34 and M-CSF share the receptor Fms but are not identical inbiological activity and signal activation.";
Chihara T., Suzu S., Hassan R., Chutiwitoonchai N., Hiyoshi M.,Motoyoshi K., Kimura F., Okada S.;
Cell Death Differ. 17:1917-1927(2010).
Cited for: FUNCTION AS RECEPTOR FOR IL34 AND CSF1, PHOSPHORYLATION AT TYR-546;TYR-699; TYR-708; TYR-723 AND TYR-809, AUTOPHOSPHORYLATION, ENZYMEREGULATION, AND INTERACTION WITH IL34 AND CSF1.
PubMed: 20489731