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Protein

Macrophage colony-stimulating factor 1 receptor

Gene

CSF1R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.14 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation6 Publications

Enzyme regulationi

Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580.7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei616 – 6161ATPCurated
Active sitei778 – 7781Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi588 – 5969ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cytokine binding Source: UniProtKB
  • macrophage colony-stimulating factor receptor activity Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • axon guidance Source: Ensembl
  • cell-cell junction maintenance Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • cellular response to cytokine stimulus Source: UniProtKB
  • cellular response to macrophage colony-stimulating factor stimulus Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • forebrain neuron differentiation Source: Ensembl
  • hemopoiesis Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • macrophage colony-stimulating factor signaling pathway Source: BHF-UCL
  • macrophage differentiation Source: UniProtKB
  • mammary gland duct morphogenesis Source: UniProtKB
  • monocyte differentiation Source: UniProtKB
  • multicellular organism development Source: ProtInc
  • negative regulation of apoptotic process Source: Ensembl
  • negative regulation of cell proliferation Source: Ensembl
  • olfactory bulb development Source: Ensembl
  • osteoclast differentiation Source: UniProtKB
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • phosphatidylinositol-mediated signaling Source: UniProtKB
  • phosphatidylinositol metabolic process Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell motility Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of chemokine secretion Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of osteoclast differentiation Source: Ensembl
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of protein tyrosine kinase activity Source: UniProtKB
  • positive regulation of tyrosine phosphorylation of Stat3 protein Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of actin cytoskeleton reorganization Source: UniProtKB
  • regulation of bone resorption Source: UniProtKB
  • regulation of cell shape Source: UniProtKB
  • ruffle organization Source: UniProtKB
  • signal transduction Source: ProtInc
  • skeletal muscle tissue development Source: Ensembl
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-449147. Signaling by Interleukins.
SignaLinkiP07333.
SIGNORiP07333.

Names & Taxonomyi

Protein namesi
Recommended name:
Macrophage colony-stimulating factor 1 receptor
Alternative name(s):
CSF-1 receptor (EC:2.7.10.1)
Short name:
CSF-1-R
Short name:
CSF-1R
Short name:
M-CSF-R
Proto-oncogene c-Fms
CD_antigen: CD115
Gene namesi
Name:CSF1R
Synonyms:FMS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:2433. CSF1R.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 517498ExtracellularSequence analysisAdd
BLAST
Transmembranei518 – 53821HelicalSequence analysisAdd
BLAST
Topological domaini539 – 972434CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • CSF1-CSF1R complex Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • intracellular Source: Ensembl
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

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.

Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.

Leukoencephalopathy, diffuse hereditary, with spheroids (HDLS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes.
See also OMIM:221820
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti585 – 61935GKTLG…VKMLK → A in HDLS. 1 Publication
VAR_067396Add
BLAST
Natural varianti589 – 5891G → E in HDLS. 1 Publication
Corresponds to variant rs281860268 [ dbSNP | Ensembl ].
VAR_067397
Natural varianti633 – 6331E → K in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 Publication
Corresponds to variant rs281860269 [ dbSNP | Ensembl ].
VAR_067398
Natural varianti653 – 6531C → R in HDLS. 1 Publication
Corresponds to variant rs690016559 [ dbSNP | Ensembl ].
VAR_072081
Natural varianti766 – 7661M → T in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 Publication
Corresponds to variant rs281860270 [ dbSNP | Ensembl ].
VAR_067401
Natural varianti770 – 7701A → P in HDLS. 1 Publication
Corresponds to variant rs281860271 [ dbSNP | Ensembl ].
VAR_067402
Natural varianti774 – 81441Missing in HDLS. 1 Publication
VAR_067403Add
BLAST
Natural varianti775 – 7751I → N in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 Publication
Corresponds to variant rs281860273 [ dbSNP | Ensembl ].
VAR_067404
Natural varianti794 – 7941I → T in HDLS. 1 Publication
Corresponds to variant rs281860274 [ dbSNP | Ensembl ].
VAR_067405
Natural varianti837 – 8371D → Y in HDLS. 1 Publication
Corresponds to variant rs387906662 [ dbSNP | Ensembl ].
VAR_067406
Natural varianti843 – 8431I → F in HDLS. 1 Publication
Corresponds to variant rs690016558 [ dbSNP | Ensembl ].
VAR_072082
Natural varianti849 – 8491F → S in HDLS. 1 Publication
Corresponds to variant rs281860277 [ dbSNP | Ensembl ].
VAR_067407
Natural varianti849 – 8491Missing in HDLS. 1 Publication
VAR_067408
Natural varianti868 – 8681L → P in HDLS. 1 Publication
Corresponds to variant rs281860278 [ dbSNP | Ensembl ].
VAR_067409
Natural varianti875 – 8751M → T in HDLS. 1 Publication
Corresponds to variant rs281860279 [ dbSNP | Ensembl ].
VAR_067410
Natural varianti878 – 8781P → T in HDLS. 1 Publication
Corresponds to variant rs281860280 [ dbSNP | Ensembl ].
VAR_067411
Natural varianti906 – 9061I → T in HDLS. 1 Publication
Corresponds to variant rs690016560 [ dbSNP | Ensembl ].
VAR_072083

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi301 – 3011L → S: Constitutive kinase activity. 1 Publication
Mutagenesisi708 – 7081Y → F: Impairs degradation of activated CSF1R. 1 Publication
Mutagenesisi802 – 8021D → V: Constitutive kinase activity. Loss of inhibition by imatinib. 2 Publications
Mutagenesisi809 – 8091Y → F: Reduced kinase activity. Reduced interaction with SRC, FYN and YES1. 1 Publication
Mutagenesisi969 – 9691Y → F: Abolishes down-regulation of activated CSF1R. 1 Publication

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

MalaCardsiCSF1R.
MIMi221820. phenotype.
Orphaneti313808. Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.
PharmGKBiPA26936.

Chemistry

ChEMBLiCHEMBL1844.
DrugBankiDB00619. Imatinib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1806.

Polymorphism and mutation databases

BioMutaiCSF1R.
DMDMi547770.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 972953Macrophage colony-stimulating factor 1 receptorPRO_0000016765Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi42 ↔ 84PROSITE-ProRule annotation
Glycosylationi45 – 451N-linked (GlcNAc...)Sequence analysis
Glycosylationi73 – 731N-linked (GlcNAc...)Sequence analysis
Disulfide bondi127 ↔ 177PROSITE-ProRule annotation
Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence analysis
Disulfide bondi224 ↔ 278PROSITE-ProRule annotation
Glycosylationi240 – 2401N-linked (GlcNAc...)Sequence analysis
Glycosylationi275 – 2751N-linked (GlcNAc...)Sequence analysis
Glycosylationi302 – 3021N-linked (GlcNAc...)1 Publication
Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence analysis
Glycosylationi353 – 3531N-linked (GlcNAc...)1 Publication
Glycosylationi412 – 4121N-linked (GlcNAc...)Sequence analysis
Disulfide bondi419 ↔ 485PROSITE-ProRule annotation
Glycosylationi428 – 4281N-linked (GlcNAc...)Sequence analysis
Glycosylationi480 – 4801N-linked (GlcNAc...)Sequence analysis
Modified residuei546 – 5461Phosphotyrosine; by autocatalysis1 Publication
Modified residuei561 – 5611Phosphotyrosine; by autocatalysisBy similarity
Modified residuei699 – 6991Phosphotyrosine; by autocatalysisCombined sources1 Publication
Modified residuei708 – 7081Phosphotyrosine; by autocatalysis1 Publication
Modified residuei713 – 7131PhosphoserineCombined sources
Modified residuei723 – 7231Phosphotyrosine; by autocatalysis1 Publication
Modified residuei809 – 8091Phosphotyrosine; by autocatalysis1 Publication
Modified residuei923 – 9231Phosphotyrosine; by autocatalysisBy similarity
Modified residuei969 – 9691Phosphotyrosine; by autocatalysisBy similarity

Post-translational modificationi

Autophosphorylated in response to CSF1 or IL34 binding. Phosphorylation at Tyr-561 is important for normal down-regulation of signaling by ubiquitination, internalization and degradation. Phosphorylation at Tyr-561 and Tyr-809 is important for interaction with SRC family members, including FYN, YES1 and SRC, and for subsequent activation of these protein kinases. Phosphorylation at Tyr-699 and Tyr-923 is important for interaction with GRB2. Phosphorylation at Tyr-723 is important for interaction with PIK3R1. Phosphorylation at Tyr-708 is important for normal receptor degradation. Phosphorylation at Tyr-723 and Tyr-809 is important for interaction with PLCG2. Phosphorylation at Tyr-969 is important for interaction with CBL. Dephosphorylation by PTPN2 negatively regulates downstream signaling and macrophage differentiation.2 Publications
Ubiquitinated. Becomes rapidly polyubiquitinated after autophosphorylation, leading to its degradation.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP07333.
PeptideAtlasiP07333.
PRIDEiP07333.

PTM databases

iPTMnetiP07333.
PhosphoSiteiP07333.

Expressioni

Tissue specificityi

Expressed in bone marrow and in differentiated blood mononuclear cells.

Inductioni

Up-regulated by glucocorticoids.1 Publication

Gene expression databases

BgeeiENSG00000182578.
CleanExiHS_CSF1R.
ExpressionAtlasiP07333. baseline and differential.
GenevisibleiP07333. HS.

Organism-specific databases

HPAiCAB008970.
HPA012323.

Interactioni

Subunit structurei

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.By similarity4 Publications

GO - Molecular functioni

  • cytokine binding Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi107823. 18 interactions.
DIPiDIP-59421N.
IntActiP07333. 12 interactions.
MINTiMINT-8019993.
STRINGi9606.ENSP00000286301.

Chemistry

BindingDBiP07333.

Structurei

Secondary structure

1
972
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi22 – 254Combined sources
Beta strandi27 – 326Combined sources
Beta strandi38 – 436Combined sources
Beta strandi49 – 513Combined sources
Turni55 – 573Combined sources
Beta strandi58 – 625Combined sources
Beta strandi64 – 7310Combined sources
Helixi76 – 783Combined sources
Beta strandi80 – 856Combined sources
Beta strandi95 – 1017Combined sources
Beta strandi108 – 1114Combined sources
Beta strandi113 – 1186Combined sources
Beta strandi123 – 1253Combined sources
Beta strandi127 – 1304Combined sources
Helixi132 – 1376Combined sources
Beta strandi139 – 1424Combined sources
Helixi143 – 1453Combined sources
Beta strandi154 – 1574Combined sources
Turni158 – 1603Combined sources
Beta strandi161 – 1666Combined sources
Helixi169 – 1713Combined sources
Beta strandi173 – 1819Combined sources
Beta strandi184 – 1874Combined sources
Beta strandi191 – 1966Combined sources
Beta strandi204 – 2085Combined sources
Beta strandi210 – 2156Combined sources
Beta strandi216 – 2183Combined sources
Beta strandi220 – 23112Combined sources
Beta strandi234 – 2396Combined sources
Beta strandi248 – 2525Combined sources
Beta strandi257 – 26711Combined sources
Turni270 – 2723Combined sources
Beta strandi274 – 2829Combined sources
Beta strandi285 – 29814Combined sources
Beta strandi300 – 3045Combined sources
Beta strandi309 – 3146Combined sources
Beta strandi319 – 32911Combined sources
Beta strandi332 – 3387Combined sources
Beta strandi340 – 3423Combined sources
Beta strandi351 – 3544Combined sources
Beta strandi361 – 3688Combined sources
Helixi373 – 3753Combined sources
Beta strandi377 – 3859Combined sources
Beta strandi388 – 41124Combined sources
Beta strandi414 – 42512Combined sources
Beta strandi428 – 43710Combined sources
Turni443 – 4453Combined sources
Beta strandi446 – 4549Combined sources
Beta strandi456 – 4594Combined sources
Beta strandi466 – 4738Combined sources
Beta strandi479 – 48810Combined sources
Beta strandi493 – 4986Combined sources
Beta strandi551 – 5533Combined sources
Beta strandi556 – 5605Combined sources
Helixi566 – 5683Combined sources
Helixi573 – 5753Combined sources
Beta strandi581 – 59010Combined sources
Beta strandi592 – 60110Combined sources
Beta strandi605 – 6073Combined sources
Beta strandi612 – 6187Combined sources
Helixi624 – 64017Combined sources
Beta strandi649 – 6535Combined sources
Beta strandi655 – 6584Combined sources
Beta strandi660 – 6645Combined sources
Helixi671 – 6788Combined sources
Turni684 – 6863Combined sources
Turni742 – 7443Combined sources
Helixi753 – 77119Combined sources
Helixi781 – 7833Combined sources
Beta strandi785 – 7873Combined sources
Helixi788 – 7903Combined sources
Beta strandi791 – 7944Combined sources
Helixi798 – 8003Combined sources
Helixi803 – 8053Combined sources
Turni806 – 8083Combined sources
Beta strandi809 – 8113Combined sources
Beta strandi815 – 8173Combined sources
Helixi819 – 8213Combined sources
Helixi824 – 8296Combined sources
Helixi834 – 84815Combined sources
Turni849 – 8513Combined sources
Helixi863 – 8719Combined sources
Helixi883 – 89210Combined sources
Helixi897 – 8993Combined sources
Helixi903 – 92018Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I0VX-ray2.80A538-678[»]
A753-922[»]
2I0YX-ray1.90A538-678[»]
A753-922[»]
2I1MX-ray1.80A538-678[»]
A753-922[»]
2OGVX-ray2.70A543-918[»]
3BEAX-ray2.02A538-678[»]
A753-922[»]
3DPKX-ray1.95A538-678[»]
A771-922[»]
3KRJX-ray2.10A538-678[»]
A753-922[»]
3KRLX-ray2.40A538-678[»]
A753-922[»]
3LCDX-ray2.50A538-919[»]
3LCOX-ray3.40A550-919[»]
4DKDX-ray3.00C20-299[»]
4HW7X-ray2.90A542-919[»]
4LIQX-ray2.60E2-512[»]
4R7HX-ray2.80A542-919[»]
4R7IX-ray2.75A542-919[»]
4WRLX-ray2.80A/C20-296[»]
4WRMX-ray6.85A20-504[»]
ProteinModelPortaliP07333.
SMRiP07333. Positions 20-500, 544-945.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini21 – 10484Ig-like C2-type 1Add
BLAST
Domaini107 – 19791Ig-like C2-type 2Add
BLAST
Domaini203 – 29088Ig-like C2-type 3Add
BLAST
Domaini299 – 399101Ig-like C2-type 4Add
BLAST
Domaini402 – 502101Ig-like C2-type 5Add
BLAST
Domaini582 – 910329Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni542 – 57433Regulatory juxtamembrane domainAdd
BLAST
Regioni796 – 81823Activation loopAdd
BLAST

Domaini

The juxtamembrane domain functions as autoinhibitory region. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase.
The activation loop plays an important role in the regulation of kinase activity. Phosphorylation of tyrosine residues in this region leads to a conformation change and activation of the kinase.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000112008.
HOVERGENiHBG004335.
InParanoidiP07333.
KOiK05090.
OMAiWKIIESY.
OrthoDBiEOG091G01TL.
PhylomeDBiP07333.
TreeFamiTF325768.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR030658. CSF-1_receptor.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF47. PTHR24416:SF47. 3 hits.
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500947. CSF-1_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 5 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P07333-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGPGVLLLLL VATAWHGQGI PVIEPSVPEL VVKPGATVTL RCVGNGSVEW
60 70 80 90 100
DGPPSPHWTL YSDGSSSILS TNNATFQNTG TYRCTEPGDP LGGSAAIHLY
110 120 130 140 150
VKDPARPWNV LAQEVVVFED QDALLPCLLT DPVLEAGVSL VRVRGRPLMR
160 170 180 190 200
HTNYSFSPWH GFTIHRAKFI QSQDYQCSAL MGGRKVMSIS IRLKVQKVIP
210 220 230 240 250
GPPALTLVPA ELVRIRGEAA QIVCSASSVD VNFDVFLQHN NTKLAIPQQS
260 270 280 290 300
DFHNNRYQKV LTLNLDQVDF QHAGNYSCVA SNVQGKHSTS MFFRVVESAY
310 320 330 340 350
LNLSSEQNLI QEVTVGEGLN LKVMVEAYPG LQGFNWTYLG PFSDHQPEPK
360 370 380 390 400
LANATTKDTY RHTFTLSLPR LKPSEAGRYS FLARNPGGWR ALTFELTLRY
410 420 430 440 450
PPEVSVIWTF INGSGTLLCA ASGYPQPNVT WLQCSGHTDR CDEAQVLQVW
460 470 480 490 500
DDPYPEVLSQ EPFHKVTVQS LLTVETLEHN QTYECRAHNS VGSGSWAFIP
510 520 530 540 550
ISAGAHTHPP DEFLFTPVVV ACMSIMALLL LLLLLLLYKY KQKPKYQVRW
560 570 580 590 600
KIIESYEGNS YTFIDPTQLP YNEKWEFPRN NLQFGKTLGA GAFGKVVEAT
610 620 630 640 650
AFGLGKEDAV LKVAVKMLKS TAHADEKEAL MSELKIMSHL GQHENIVNLL
660 670 680 690 700
GACTHGGPVL VITEYCCYGD LLNFLRRKAE AMLGPSLSPG QDPEGGVDYK
710 720 730 740 750
NIHLEKKYVR RDSGFSSQGV DTYVEMRPVS TSSNDSFSEQ DLDKEDGRPL
760 770 780 790 800
ELRDLLHFSS QVAQGMAFLA SKNCIHRDVA ARNVLLTNGH VAKIGDFGLA
810 820 830 840 850
RDIMNDSNYI VKGNARLPVK WMAPESIFDC VYTVQSDVWS YGILLWEIFS
860 870 880 890 900
LGLNPYPGIL VNSKFYKLVK DGYQMAQPAF APKNIYSIMQ ACWALEPTHR
910 920 930 940 950
PTFQQICSFL QEQAQEDRRE RDYTNLPSSS RSGGSGSSSS ELEEESSSEH
960 970
LTCCEQGDIA QPLLQPNNYQ FC
Length:972
Mass (Da):107,984
Last modified:June 1, 1994 - v2
Checksum:iA8D99BE237573FE8
GO
Isoform 2 (identifier: P07333-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     297-306: ESAYLNLSSE → GTPSPSLCPA
     307-972: Missing.

Show »
Length:306
Mass (Da):33,248
Checksum:iDDAEA1B05EAAF3C2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541P → A in CAA27300 (PubMed:2421165).Curated
Sequence conflicti247 – 2471P → H in AAH47521 (PubMed:15489334).Curated
Sequence conflicti354 – 3541A → V in AAH47521 (PubMed:15489334).Curated
Sequence conflicti629 – 6291A → S in AAH47521 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti32 – 321V → G.1 Publication
Corresponds to variant rs56048668 [ dbSNP | Ensembl ].
VAR_042038
Natural varianti245 – 2451A → S.
Corresponds to variant rs41338945 [ dbSNP | Ensembl ].
VAR_061290
Natural varianti279 – 2791V → M.
Corresponds to variant rs3829986 [ dbSNP | Ensembl ].
VAR_049718
Natural varianti362 – 3621H → R.1 Publication
Corresponds to variant rs10079250 [ dbSNP | Ensembl ].
VAR_042039
Natural varianti413 – 4131G → S.1 Publication
Corresponds to variant rs34951517 [ dbSNP | Ensembl ].
VAR_042040
Natural varianti536 – 5361L → V.1 Publication
Corresponds to variant rs55942044 [ dbSNP | Ensembl ].
VAR_042041
Natural varianti585 – 61935GKTLG…VKMLK → A in HDLS. 1 Publication
VAR_067396Add
BLAST
Natural varianti589 – 5891G → E in HDLS. 1 Publication
Corresponds to variant rs281860268 [ dbSNP | Ensembl ].
VAR_067397
Natural varianti633 – 6331E → K in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 Publication
Corresponds to variant rs281860269 [ dbSNP | Ensembl ].
VAR_067398
Natural varianti653 – 6531C → R in HDLS. 1 Publication
Corresponds to variant rs690016559 [ dbSNP | Ensembl ].
VAR_072081
Natural varianti693 – 6931P → H in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
VAR_042042
Natural varianti710 – 7101R → H.1 Publication
Corresponds to variant rs201569135 [ dbSNP | Ensembl ].
VAR_067399
Natural varianti747 – 7471G → R.1 Publication
Corresponds to variant rs41355444 [ dbSNP | Ensembl ].
VAR_067400
Natural varianti766 – 7661M → T in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 Publication
Corresponds to variant rs281860270 [ dbSNP | Ensembl ].
VAR_067401
Natural varianti770 – 7701A → P in HDLS. 1 Publication
Corresponds to variant rs281860271 [ dbSNP | Ensembl ].
VAR_067402
Natural varianti774 – 81441Missing in HDLS. 1 Publication
VAR_067403Add
BLAST
Natural varianti775 – 7751I → N in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 Publication
Corresponds to variant rs281860273 [ dbSNP | Ensembl ].
VAR_067404
Natural varianti794 – 7941I → T in HDLS. 1 Publication
Corresponds to variant rs281860274 [ dbSNP | Ensembl ].
VAR_067405
Natural varianti837 – 8371D → Y in HDLS. 1 Publication
Corresponds to variant rs387906662 [ dbSNP | Ensembl ].
VAR_067406
Natural varianti843 – 8431I → F in HDLS. 1 Publication
Corresponds to variant rs690016558 [ dbSNP | Ensembl ].
VAR_072082
Natural varianti849 – 8491F → S in HDLS. 1 Publication
Corresponds to variant rs281860277 [ dbSNP | Ensembl ].
VAR_067407
Natural varianti849 – 8491Missing in HDLS. 1 Publication
VAR_067408
Natural varianti868 – 8681L → P in HDLS. 1 Publication
Corresponds to variant rs281860278 [ dbSNP | Ensembl ].
VAR_067409
Natural varianti875 – 8751M → T in HDLS. 1 Publication
Corresponds to variant rs281860279 [ dbSNP | Ensembl ].
VAR_067410
Natural varianti878 – 8781P → T in HDLS. 1 Publication
Corresponds to variant rs281860280 [ dbSNP | Ensembl ].
VAR_067411
Natural varianti906 – 9061I → T in HDLS. 1 Publication
Corresponds to variant rs690016560 [ dbSNP | Ensembl ].
VAR_072083
Natural varianti920 – 9201E → D.2 Publications
Corresponds to variant rs34030164 [ dbSNP | Ensembl ].
VAR_042043
Natural varianti921 – 9211R → Q.1 Publication
Corresponds to variant rs56059682 [ dbSNP | Ensembl ].
VAR_042044
Natural varianti969 – 9691Y → C.
Corresponds to variant rs1801271 [ dbSNP | Ensembl ].
VAR_011953

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei297 – 30610ESAYLNLSSE → GTPSPSLCPA in isoform 2. 1 PublicationVSP_047757
Alternative sequencei307 – 972666Missing in isoform 2. 1 PublicationVSP_047758Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03663 mRNA. Translation: CAA27300.1.
U63963 Genomic DNA. Translation: AAB51696.1.
M25786 mRNA. Translation: AAA58421.1.
EU826593 mRNA. Translation: ACF47629.1.
AC011382 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61749.1.
CH471062 Genomic DNA. Translation: EAW61750.1.
BC047521 mRNA. Translation: AAH47521.1.
M14002 Genomic DNA. Translation: AAA35849.1.
U78096 Genomic DNA. Translation: AAB51235.1.
M11067 Genomic DNA. Translation: AAA35848.1.
M14193 mRNA. Translation: AAA35834.1.
CCDSiCCDS4302.1. [P07333-1]
PIRiS08123. TVHUMD.
RefSeqiNP_001275634.1. NM_001288705.1. [P07333-1]
NP_005202.2. NM_005211.3. [P07333-1]
UniGeneiHs.586219.

Genome annotation databases

EnsembliENST00000286301; ENSP00000286301; ENSG00000182578. [P07333-1]
ENST00000543093; ENSP00000445282; ENSG00000182578. [P07333-2]
GeneIDi1436.
KEGGihsa:1436.
UCSCiuc003lrm.3. human. [P07333-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03663 mRNA. Translation: CAA27300.1.
U63963 Genomic DNA. Translation: AAB51696.1.
M25786 mRNA. Translation: AAA58421.1.
EU826593 mRNA. Translation: ACF47629.1.
AC011382 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61749.1.
CH471062 Genomic DNA. Translation: EAW61750.1.
BC047521 mRNA. Translation: AAH47521.1.
M14002 Genomic DNA. Translation: AAA35849.1.
U78096 Genomic DNA. Translation: AAB51235.1.
M11067 Genomic DNA. Translation: AAA35848.1.
M14193 mRNA. Translation: AAA35834.1.
CCDSiCCDS4302.1. [P07333-1]
PIRiS08123. TVHUMD.
RefSeqiNP_001275634.1. NM_001288705.1. [P07333-1]
NP_005202.2. NM_005211.3. [P07333-1]
UniGeneiHs.586219.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2I0VX-ray2.80A538-678[»]
A753-922[»]
2I0YX-ray1.90A538-678[»]
A753-922[»]
2I1MX-ray1.80A538-678[»]
A753-922[»]
2OGVX-ray2.70A543-918[»]
3BEAX-ray2.02A538-678[»]
A753-922[»]
3DPKX-ray1.95A538-678[»]
A771-922[»]
3KRJX-ray2.10A538-678[»]
A753-922[»]
3KRLX-ray2.40A538-678[»]
A753-922[»]
3LCDX-ray2.50A538-919[»]
3LCOX-ray3.40A550-919[»]
4DKDX-ray3.00C20-299[»]
4HW7X-ray2.90A542-919[»]
4LIQX-ray2.60E2-512[»]
4R7HX-ray2.80A542-919[»]
4R7IX-ray2.75A542-919[»]
4WRLX-ray2.80A/C20-296[»]
4WRMX-ray6.85A20-504[»]
ProteinModelPortaliP07333.
SMRiP07333. Positions 20-500, 544-945.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107823. 18 interactions.
DIPiDIP-59421N.
IntActiP07333. 12 interactions.
MINTiMINT-8019993.
STRINGi9606.ENSP00000286301.

Chemistry

BindingDBiP07333.
ChEMBLiCHEMBL1844.
DrugBankiDB00619. Imatinib.
DB01268. Sunitinib.
GuidetoPHARMACOLOGYi1806.

PTM databases

iPTMnetiP07333.
PhosphoSiteiP07333.

Polymorphism and mutation databases

BioMutaiCSF1R.
DMDMi547770.

Proteomic databases

PaxDbiP07333.
PeptideAtlasiP07333.
PRIDEiP07333.

Protocols and materials databases

DNASUi1436.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286301; ENSP00000286301; ENSG00000182578. [P07333-1]
ENST00000543093; ENSP00000445282; ENSG00000182578. [P07333-2]
GeneIDi1436.
KEGGihsa:1436.
UCSCiuc003lrm.3. human. [P07333-1]

Organism-specific databases

CTDi1436.
GeneCardsiCSF1R.
GeneReviewsiCSF1R.
HGNCiHGNC:2433. CSF1R.
HPAiCAB008970.
HPA012323.
MalaCardsiCSF1R.
MIMi164770. gene.
221820. phenotype.
neXtProtiNX_P07333.
Orphaneti313808. Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.
PharmGKBiPA26936.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118923.
HOGENOMiHOG000112008.
HOVERGENiHBG004335.
InParanoidiP07333.
KOiK05090.
OMAiWKIIESY.
OrthoDBiEOG091G01TL.
PhylomeDBiP07333.
TreeFamiTF325768.

Enzyme and pathway databases

BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-449147. Signaling by Interleukins.
SignaLinkiP07333.
SIGNORiP07333.

Miscellaneous databases

ChiTaRSiCSF1R. human.
EvolutionaryTraceiP07333.
GeneWikiiColony_stimulating_factor_1_receptor.
GenomeRNAii1436.
PROiP07333.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182578.
CleanExiHS_CSF1R.
ExpressionAtlasiP07333. baseline and differential.
GenevisibleiP07333. HS.

Family and domain databases

Gene3Di2.60.40.10. 5 hits.
InterProiIPR030658. CSF-1_receptor.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR013151. Immunoglobulin.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016243. Tyr_kinase_CSF1/PDGF_rcpt.
IPR001824. Tyr_kinase_rcpt_3_CS.
[Graphical view]
PANTHERiPTHR24416:SF47. PTHR24416:SF47. 3 hits.
PfamiPF00047. ig. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF500947. CSF-1_receptor. 1 hit.
PIRSF000615. TyrPK_CSF1-R. 1 hit.
SMARTiSM00409. IG. 5 hits.
SM00408. IGc2. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS50835. IG_LIKE. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS00240. RECEPTOR_TYR_KIN_III. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCSF1R_HUMAN
AccessioniPrimary (citable) accession number: P07333
Secondary accession number(s): B5A955
, D3DQG2, Q6LDW5, Q6LDY4, Q86VW7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: June 1, 1994
Last modified: September 7, 2016
This is version 194 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  8. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.