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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)DescriptionActionsGraphical viewLength
Binding sitei616ATPCurated1
Active sitei778Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi588 – 596ATPPROSITE-ProRule annotation9

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 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
  • 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)DescriptionActionsGraphical viewLength
Topological domaini20 – 517ExtracellularSequence analysisAdd BLAST498
Transmembranei518 – 538HelicalSequence analysisAdd BLAST21
Topological domaini539 – 972CytoplasmicSequence analysisAdd BLAST434

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • CSF1-CSF1R complex Source: BHF-UCL
  • integral component of plasma membrane Source: ProtInc
  • intracellular Source: GOC
  • 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_067396585 – 619GKTLG…VKMLK → A in HDLS. 1 PublicationAdd BLAST35
Natural variantiVAR_067397589G → E in HDLS. 1 PublicationCorresponds to variant rs281860268dbSNPEnsembl.1
Natural variantiVAR_067398633E → K in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 PublicationCorresponds to variant rs281860269dbSNPEnsembl.1
Natural variantiVAR_072081653C → R in HDLS. 1 PublicationCorresponds to variant rs690016559dbSNPEnsembl.1
Natural variantiVAR_067401766M → T in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 PublicationCorresponds to variant rs281860270dbSNPEnsembl.1
Natural variantiVAR_067402770A → P in HDLS. 1 PublicationCorresponds to variant rs281860271dbSNPEnsembl.1
Natural variantiVAR_067403774 – 814Missing in HDLS. 1 PublicationAdd BLAST41
Natural variantiVAR_067404775I → N in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 PublicationCorresponds to variant rs281860273dbSNPEnsembl.1
Natural variantiVAR_067405794I → T in HDLS. 1 PublicationCorresponds to variant rs281860274dbSNPEnsembl.1
Natural variantiVAR_067406837D → Y in HDLS. 1 PublicationCorresponds to variant rs387906662dbSNPEnsembl.1
Natural variantiVAR_072082843I → F in HDLS. 1 PublicationCorresponds to variant rs690016558dbSNPEnsembl.1
Natural variantiVAR_067407849F → S in HDLS. 1 PublicationCorresponds to variant rs281860277dbSNPEnsembl.1
Natural variantiVAR_067408849Missing in HDLS. 1 Publication1
Natural variantiVAR_067409868L → P in HDLS. 1 PublicationCorresponds to variant rs281860278dbSNPEnsembl.1
Natural variantiVAR_067410875M → T in HDLS. 1 PublicationCorresponds to variant rs281860279dbSNPEnsembl.1
Natural variantiVAR_067411878P → T in HDLS. 1 PublicationCorresponds to variant rs281860280dbSNPEnsembl.1
Natural variantiVAR_072083906I → T in HDLS. 1 PublicationCorresponds to variant rs690016560dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi301L → S: Constitutive kinase activity. 1 Publication1
Mutagenesisi708Y → F: Impairs degradation of activated CSF1R. 1 Publication1
Mutagenesisi802D → V: Constitutive kinase activity. Loss of inhibition by imatinib. 2 Publications1
Mutagenesisi809Y → F: Reduced kinase activity. Reduced interaction with SRC, FYN and YES1. 1 Publication1
Mutagenesisi969Y → F: Abolishes down-regulation of activated CSF1R. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi1436.
MalaCardsiCSF1R.
MIMi221820. phenotype.
OpenTargetsiENSG00000182578.
Orphaneti313808. Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia.
PharmGKBiPA26936.

Chemistry databases

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

Polymorphism and mutation databases

BioMutaiCSF1R.
DMDMi547770.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001676520 – 972Macrophage colony-stimulating factor 1 receptorAdd BLAST953

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 84PROSITE-ProRule annotation
Glycosylationi45N-linked (GlcNAc...)Sequence analysis1
Glycosylationi73N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi127 ↔ 177PROSITE-ProRule annotation
Glycosylationi153N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi224 ↔ 278PROSITE-ProRule annotation
Glycosylationi240N-linked (GlcNAc...)Sequence analysis1
Glycosylationi275N-linked (GlcNAc...)Sequence analysis1
Glycosylationi302N-linked (GlcNAc...)1 Publication1
Glycosylationi335N-linked (GlcNAc...)Sequence analysis1
Glycosylationi353N-linked (GlcNAc...)1 Publication1
Glycosylationi412N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi419 ↔ 485PROSITE-ProRule annotation
Glycosylationi428N-linked (GlcNAc...)Sequence analysis1
Glycosylationi480N-linked (GlcNAc...)Sequence analysis1
Modified residuei546Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei561Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei699Phosphotyrosine; by autocatalysisCombined sources1 Publication1
Modified residuei708Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei713PhosphoserineCombined sources1
Modified residuei723Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei809Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei923Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei969Phosphotyrosine; by autocatalysisBy similarity1

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.
PhosphoSitePlusiP07333.

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 interactors.
DIPiDIP-59421N.
IntActiP07333. 12 interactors.
MINTiMINT-8019993.
STRINGi9606.ENSP00000286301.

Chemistry databases

BindingDBiP07333.

Structurei

Secondary structure

1972
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 25Combined sources4
Beta strandi27 – 32Combined sources6
Beta strandi38 – 43Combined sources6
Beta strandi49 – 51Combined sources3
Turni55 – 57Combined sources3
Beta strandi58 – 62Combined sources5
Beta strandi64 – 73Combined sources10
Helixi76 – 78Combined sources3
Beta strandi80 – 85Combined sources6
Beta strandi95 – 101Combined sources7
Beta strandi108 – 111Combined sources4
Beta strandi113 – 118Combined sources6
Beta strandi123 – 125Combined sources3
Beta strandi127 – 130Combined sources4
Helixi132 – 137Combined sources6
Beta strandi139 – 142Combined sources4
Helixi143 – 145Combined sources3
Beta strandi154 – 157Combined sources4
Turni158 – 160Combined sources3
Beta strandi161 – 166Combined sources6
Helixi169 – 171Combined sources3
Beta strandi173 – 181Combined sources9
Beta strandi184 – 187Combined sources4
Beta strandi191 – 196Combined sources6
Beta strandi204 – 208Combined sources5
Beta strandi210 – 215Combined sources6
Beta strandi216 – 218Combined sources3
Beta strandi220 – 231Combined sources12
Beta strandi234 – 239Combined sources6
Beta strandi248 – 252Combined sources5
Beta strandi257 – 267Combined sources11
Turni270 – 272Combined sources3
Beta strandi274 – 282Combined sources9
Beta strandi285 – 298Combined sources14
Beta strandi300 – 304Combined sources5
Beta strandi309 – 314Combined sources6
Beta strandi319 – 329Combined sources11
Beta strandi332 – 338Combined sources7
Beta strandi340 – 342Combined sources3
Beta strandi351 – 354Combined sources4
Beta strandi361 – 368Combined sources8
Helixi373 – 375Combined sources3
Beta strandi377 – 385Combined sources9
Beta strandi388 – 411Combined sources24
Beta strandi414 – 425Combined sources12
Beta strandi428 – 437Combined sources10
Turni443 – 445Combined sources3
Beta strandi446 – 454Combined sources9
Beta strandi456 – 459Combined sources4
Beta strandi466 – 473Combined sources8
Beta strandi479 – 488Combined sources10
Beta strandi493 – 498Combined sources6
Beta strandi551 – 553Combined sources3
Beta strandi556 – 560Combined sources5
Helixi566 – 568Combined sources3
Helixi573 – 575Combined sources3
Beta strandi581 – 590Combined sources10
Beta strandi592 – 601Combined sources10
Beta strandi605 – 607Combined sources3
Beta strandi612 – 618Combined sources7
Helixi624 – 640Combined sources17
Beta strandi649 – 653Combined sources5
Beta strandi655 – 658Combined sources4
Beta strandi660 – 664Combined sources5
Helixi671 – 678Combined sources8
Turni684 – 686Combined sources3
Turni742 – 744Combined sources3
Helixi753 – 771Combined sources19
Helixi781 – 783Combined sources3
Beta strandi785 – 787Combined sources3
Helixi788 – 790Combined sources3
Beta strandi791 – 794Combined sources4
Helixi798 – 800Combined sources3
Helixi803 – 805Combined sources3
Turni806 – 808Combined sources3
Beta strandi809 – 811Combined sources3
Beta strandi815 – 817Combined sources3
Helixi819 – 821Combined sources3
Helixi824 – 829Combined sources6
Helixi834 – 848Combined sources15
Turni849 – 851Combined sources3
Helixi863 – 871Combined sources9
Helixi883 – 892Combined sources10
Helixi897 – 899Combined sources3
Helixi903 – 920Combined sources18

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP07333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini21 – 104Ig-like C2-type 1Add BLAST84
Domaini107 – 197Ig-like C2-type 2Add BLAST91
Domaini203 – 290Ig-like C2-type 3Add BLAST88
Domaini299 – 399Ig-like C2-type 4Add BLAST101
Domaini402 – 502Ig-like C2-type 5Add BLAST101
Domaini582 – 910Protein kinasePROSITE-ProRule annotationAdd BLAST329

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni542 – 574Regulatory juxtamembrane domainAdd BLAST33
Regioni796 – 818Activation loopAdd BLAST23

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.

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54P → A in CAA27300 (PubMed:2421165).Curated1
Sequence conflicti247P → H in AAH47521 (PubMed:15489334).Curated1
Sequence conflicti354A → V in AAH47521 (PubMed:15489334).Curated1
Sequence conflicti629A → S in AAH47521 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04203832V → G.1 PublicationCorresponds to variant rs56048668dbSNPEnsembl.1
Natural variantiVAR_061290245A → S.Corresponds to variant rs41338945dbSNPEnsembl.1
Natural variantiVAR_049718279V → M.Corresponds to variant rs3829986dbSNPEnsembl.1
Natural variantiVAR_042039362H → R.1 PublicationCorresponds to variant rs10079250dbSNPEnsembl.1
Natural variantiVAR_042040413G → S.1 PublicationCorresponds to variant rs34951517dbSNPEnsembl.1
Natural variantiVAR_042041536L → V.1 PublicationCorresponds to variant rs55942044dbSNPEnsembl.1
Natural variantiVAR_067396585 – 619GKTLG…VKMLK → A in HDLS. 1 PublicationAdd BLAST35
Natural variantiVAR_067397589G → E in HDLS. 1 PublicationCorresponds to variant rs281860268dbSNPEnsembl.1
Natural variantiVAR_067398633E → K in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 PublicationCorresponds to variant rs281860269dbSNPEnsembl.1
Natural variantiVAR_072081653C → R in HDLS. 1 PublicationCorresponds to variant rs690016559dbSNPEnsembl.1
Natural variantiVAR_042042693P → H in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_067399710R → H.1 PublicationCorresponds to variant rs201569135dbSNPEnsembl.1
Natural variantiVAR_067400747G → R.1 PublicationCorresponds to variant rs41355444dbSNPEnsembl.1
Natural variantiVAR_067401766M → T in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 PublicationCorresponds to variant rs281860270dbSNPEnsembl.1
Natural variantiVAR_067402770A → P in HDLS. 1 PublicationCorresponds to variant rs281860271dbSNPEnsembl.1
Natural variantiVAR_067403774 – 814Missing in HDLS. 1 PublicationAdd BLAST41
Natural variantiVAR_067404775I → N in HDLS; impairs autophosphorylation upon stimulation with CSF1. 1 PublicationCorresponds to variant rs281860273dbSNPEnsembl.1
Natural variantiVAR_067405794I → T in HDLS. 1 PublicationCorresponds to variant rs281860274dbSNPEnsembl.1
Natural variantiVAR_067406837D → Y in HDLS. 1 PublicationCorresponds to variant rs387906662dbSNPEnsembl.1
Natural variantiVAR_072082843I → F in HDLS. 1 PublicationCorresponds to variant rs690016558dbSNPEnsembl.1
Natural variantiVAR_067407849F → S in HDLS. 1 PublicationCorresponds to variant rs281860277dbSNPEnsembl.1
Natural variantiVAR_067408849Missing in HDLS. 1 Publication1
Natural variantiVAR_067409868L → P in HDLS. 1 PublicationCorresponds to variant rs281860278dbSNPEnsembl.1
Natural variantiVAR_067410875M → T in HDLS. 1 PublicationCorresponds to variant rs281860279dbSNPEnsembl.1
Natural variantiVAR_067411878P → T in HDLS. 1 PublicationCorresponds to variant rs281860280dbSNPEnsembl.1
Natural variantiVAR_072083906I → T in HDLS. 1 PublicationCorresponds to variant rs690016560dbSNPEnsembl.1
Natural variantiVAR_042043920E → D.2 PublicationsCorresponds to variant rs34030164dbSNPEnsembl.1
Natural variantiVAR_042044921R → Q.1 PublicationCorresponds to variant rs56059682dbSNPEnsembl.1
Natural variantiVAR_011953969Y → C.Corresponds to variant rs1801271dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047757297 – 306ESAYLNLSSE → GTPSPSLCPA in isoform 2. 1 Publication10
Alternative sequenceiVSP_047758307 – 972Missing in isoform 2. 1 PublicationAdd BLAST666

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

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

PTM databases

iPTMnetiP07333.
PhosphoSitePlusiP07333.

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.
DisGeNETi1436.
GeneCardsiCSF1R.
GeneReviewsiCSF1R.
HGNCiHGNC:2433. CSF1R.
HPAiCAB008970.
HPA012323.
MalaCardsiCSF1R.
MIMi164770. gene.
221820. phenotype.
neXtProtiNX_P07333.
OpenTargetsiENSG00000182578.
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: November 2, 2016
This is version 196 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.