DB code: M00330

RLCP classification 3.103.130000.1162 : Transfer
CATH domain -.-.-.- :
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
-.-.-.- :
-.-.-.- :
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
-.-.-.- :
E.C. 2.7.10.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
2.60.40.10 : Immunoglobulin-like M00131 T00257 T00005 M00113 M00127 M00132 M00323 M00325 M00327 M00329 M00331 M00332 T00307 D00166 D00500 M00112 M00193 T00063 T00065 T00067 T00245
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00130 M00132 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00331 M00332 M00333 M00335 M00339 M00344
3.30.200.20 : Phosphorylase Kinase; domain 1 M00125 M00124 M00131 T00224 M00127 M00129 M00130 M00132 M00136 M00196 M00197 M00198 M00304 M00323 M00325 M00326 M00327 M00328 M00329 M00331 M00332 M00333 M00335 M00339 M00344 D00298

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P09581 Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms)AltName: CD_antigen=CD115;
None NP_001032948.2 (Protein)
NM_001037859.2 (DNA/RNA sequence)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical View]
P07333 Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms)AltName: CD_antigen=CD115;
None NP_005202.2 (Protein)
NM_005211.3 (DNA/RNA sequence)
PF00047 (ig)
PF07714 (Pkinase_Tyr)
[Graphical View]

KEGG enzyme name
Receptor protein-tyrosine kinase
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
C-FMS
CD115
CKIT
CSF1R
KIT
Protein-tyrosine kinase (ambiguous)
Protein tyrosine kinase (ambiguous)
Receptor protein tyrosine kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P09581 CSF1R_MOUSE ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts with INPPL1/SHIP2 and THOC5. Interacts (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2. Cell membrane, Single-pass type I membrane protein. Note=The autophosphorylated receptor is ubiquitinated and internalized, leading to its degradation.
P07333 CSF1R_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Interacts with INPPL1/SHIP2 and THOC5 (By similarity). Monomer. Homodimer. Interacts with CSF1 and IL34. Interaction with dimeric CSF1 or IL34 leads to receptor homodimerization. Interacts (tyrosine phosphorylated) with PLCG2 (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1 (via SH2 domain). Interacts (tyrosine phosphorylated) with FYN, YES1 and SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with CBL, GRB2 and SLA2. Cell membrane, Single-pass type I membrane protein.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00585 C00008 C01167
E.C.
Compound Mg ATP [protein]-L-tyrosine ADP [protein]-L-tyrosine phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide aromatic ring (only carbon atom),peptide/protein amine group,nucleotide aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6022
 6022
3ejjX01 Unbound Unbound Unbound Unbound Unbound
4expX01 Unbound Unbound Unbound Unbound Unbound
4dkdC01 Unbound Unbound Unbound Unbound Unbound
3ejjX02 Unbound Unbound Unbound Unbound Unbound
4expX02 Unbound Unbound Unbound Unbound Unbound
4dkdC02 Unbound Unbound Unbound Unbound Unbound
3ejjX03 Unbound Unbound Unbound Unbound Unbound
4expX03 Unbound Unbound Unbound Unbound Unbound
4dkdC03 Unbound Unbound Unbound Unbound Unbound
2i0vA01 Unbound Unbound Unbound Unbound Unbound
2i0yA01 Unbound Unbound Unbound Unbound Unbound
2i1mA01 Unbound Unbound Unbound Unbound Unbound
2ogvA01 Unbound Unbound Unbound Unbound Unbound
3beaA01 Unbound Unbound Unbound Unbound Unbound
3dpkA01 Unbound Unbound Unbound Unbound Unbound
3krjA01 Unbound Unbound Unbound Unbound Unbound
3krlA01 Unbound Unbound Unbound Unbound Unbound
3lcdA01 Unbound Unbound Unbound Unbound Unbound
3lcoA01 Unbound Unbound Unbound Unbound Unbound
2i0vA02 Unbound Unbound Unbound Unbound Unbound
2i0yA02 Unbound Unbound Unbound Unbound Unbound
2i1mA02 Unbound Unbound Unbound Unbound Unbound
2ogvA02 Unbound Unbound Unbound Unbound Unbound
3beaA02 Unbound Unbound Unbound Unbound Unbound
3dpkA02 Unbound Unbound Unbound Unbound Unbound
3krjA02 Unbound Unbound Unbound Unbound Unbound
3krlA02 Unbound Unbound Unbound Unbound Unbound
3lcdA02 Unbound Unbound Unbound Unbound Unbound
3lcoA02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [6], [7] & Swiss-prot;P09581, P07333

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
3ejjX01
4expX01
4dkdC01
3ejjX02
4expX02
4dkdC02
3ejjX03
4expX03
4dkdC03
2i0vA01
2i0yA01
2i1mA01
2ogvA01
3beaA01
3dpkA01
3krjA01
3krlA01
3lcdA01
3lcoA01
2i0vA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
2i0yA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
2i1mA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
2ogvA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
3beaA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
3dpkA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
3krjA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
3krlA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
3lcdA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)
3lcoA02 ASP 778;ARG 782 ASN 783;ASP 796(Magnesium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments
Medline ID
PubMed ID 2140428
Journal Mol Cell Biol
Year 1990
Volume 10
Pages 2528-38
Authors Tapley P, Kazlauskas A, Cooper JA, Rohrschneider LR
Title Macrophage colony-stimulating factor-induced tyrosine phosphorylation of c-fms proteins expressed in FDC-P1 and BALB/c 3T3 cells.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2168557
Journal Proc Natl Acad Sci U S A
Year 1990
Volume 87
Pages 6738-42
Authors Roussel MF, Shurtleff SA, Downing JR, Sherr CJ
Title A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1652061
Journal Mol Cell Biol
Year 1991
Volume 11
Pages 4698-709
Authors van der Geer P, Hunter T
Title Tyrosine 706 and 807 phosphorylation site mutants in the murine colony-stimulating factor-1 receptor are unaffected in their ability to bind or phosphorylate phosphatidylinositol-3 kinase but show differential defects in their ability to induce early response gene transcription.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 10705574
Journal Growth Factors
Year 2000
Volume 17
Pages 155-66
Authors Bourette RP, Rohrschneider LR
Title Early events in M-CSF receptor signaling.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 15519852
Journal Trends Cell Biol
Year 2004
Volume 14
Pages 628-38
Authors Pixley FJ, Stanley ER
Title CSF-1 regulation of the wandering macrophage: complexity in action.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 17132624
Journal J Biol Chem
Year 2007
Volume 282
Pages 4094-101
Authors Schubert C, Schalk-Hihi C, Struble GT, Ma HC, Petrounia IP, Brandt B, Deckman IC, Patch RJ, Player MR, Spurlino JC, Springer BA
Title Crystal structure of the tyrosine kinase domain of colony-stimulating factor-1 receptor (cFMS) in complex with two inhibitors.
Related PDB 2i0v 2i0y 2i1m
Related UniProtKB P07333
[7]
Resource
Comments
Medline ID
PubMed ID 17292918
Journal J Mol Biol
Year 2007
Volume 367
Pages 839-47
Authors Walter M, Lucet IS, Patel O, Broughton SE, Bamert R, Williams NK, Fantino E, Wilks AF, Rossjohn J
Title The 2.7 A crystal structure of the autoinhibited human c-Fms kinase domain.
Related PDB 2ogv
Related UniProtKB P07333
[8]
Resource
Comments
Medline ID
PubMed ID 18342505
Journal Bioorg Med Chem Lett
Year 2008
Volume 18
Pages 2355-61
Authors Huang H, Hutta DA, Hu H, DesJarlais RL, Schubert C, Petrounia IP, Chaikin MA, Manthey CL, Player MR
Title Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors.
Related PDB 3bea
Related UniProtKB P07333
[9]
Resource
Comments
Medline ID
PubMed ID 19017797
Journal Proc Natl Acad Sci U S A
Year 2008
Volume 105
Pages 18267-72
Authors Chen X, Liu H, Focia PJ, Shim AH, He X
Title Structure of macrophage colony stimulating factor bound to FMS: diverse signaling assemblies of class III receptor tyrosine kinases.
Related PDB 3ejj
Related UniProtKB P09581
[10]
Resource
Comments
Medline ID
PubMed ID 19193011
Journal J Med Chem
Year 2009
Volume 52
Pages 1081-99
Authors Huang H, Hutta DA, Rinker JM, Hu H, Parsons WH, Schubert C, DesJarlais RL, Crysler CS, Chaikin MA, Donatelli RR, Chen Y, Cheng D, Zhou Z, Yurkow E, Manthey CL, Player MR
Title Pyrido[2,3-d]pyrimidin-5-ones: a novel class of antiinflammatory macrophage colony-stimulating factor-1 receptor inhibitors.
Related PDB 3dpk
Related UniProtKB P07333
[11]
Resource
Comments
Medline ID
PubMed ID 20137931
Journal Bioorg Med Chem Lett
Year 2010
Volume 20
Pages 1543-7
Authors Meyers MJ, Pelc M, Kamtekar S, Day J, Poda GI, Hall MK, Michener ML, Reitz BA, Mathis KJ, Pierce BS, Parikh MD, Mischke DA, Long SA, Parlow JJ, Anderson DR, Thorarensen A
Title Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode.
Related PDB 3lcd 3lco
Related UniProtKB P07333

Comments
This enzyme belongs to platelet-derived growth factor (PDGF) receptor family (see [6]), along with homologous enzymes, such as Receptor-type tyrosine-protein kinase FLT3 (M00331 in EzCatDB) and Tyrosine-protein kinase Kit (M00323 in EzCatDB). This enzyme seems to interact with different proteins from those proteins which are interacted with the homologous enzymes.
The catalytic domain of this enzyme is homologous to that of vascular endothelial growth factor receptor (M00131 in EzCatDB).

Created Updated
2011-11-17 2012-12-05