Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0013573
UniProt IDP07333
Primary gene name(s)CSF1R
Synonym gene name(s)FMS
Protein nameMacrophage colony-stimulating factor 1 receptor
Protein functionTyrosine-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. {ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, ECO:0000269|PubMed:7683918}.
Subcellular locationCell membrane;
Single-pass type I membrane protein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P07333
Gene Ontology
(Biological Process)
Complete annatation
axon guidance [GO:0007411];
cell-cell junction maintenance [GO:0045217];
cell proliferation [GO:0008283];
cellular response to cytokine stimulus [GO:0071345];
cellular response to macrophage colony-stimulating factor stimulus [GO:0036006];
cytokine-mediated signaling pathway [GO:0019221];
forebrain neuron differentiation [GO:0021879];
hemopoiesis [GO:0030097];
inflammatory response [GO:0006954];
innate immune response [GO:0045087];
macrophage colony-stimulating factor signaling pathway [GO:0038145];
macrophage differentiation [GO:0030225];
mammary gland duct morphogenesis [GO:0060603];
monocyte differentiation [GO:0030224];
multicellular organism development [GO:0007275];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cell proliferation [GO:0008285];
olfactory bulb development [GO:0021772];
osteoclast differentiation [GO:0030316];
peptidyl-tyrosine phosphorylation [GO:0018108];
phosphatidylinositol-mediated signaling [GO:0048015];
phosphatidylinositol metabolic process [GO:0046488];
positive regulation of cell migration [GO:0030335];
positive regulation of cell motility [GO:2000147];
positive regulation of cell proliferation [GO:0008284];
positive regulation of chemokine secretion [GO:0090197];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of protein serine/threonine kinase activity [GO:0071902];
positive regulation of protein tyrosine kinase activity [GO:0061098];
positive regulation of tyrosine phosphorylation of Stat3 protein [GO:0042517];
protein autophosphorylation [GO:0046777];
regulation of actin cytoskeleton reorganization [GO:2000249];
regulation of bone resorption [GO:0045124];
regulation of cell shape [GO:0008360];
ruffle organization [GO:0031529];
signal transduction [GO:0007165];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]
Gene Ontology
(Molecular Function)
Complete annatation
unknown
Gene Ontology
(Cellular Component)
Complete annatation
unknown
Protein-protein interaction107823
Phylogenetic treeP07333
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 1.73729 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB01268 Sunitinib approved, investigational yes Inhibitor
DB00619 Imatinib approved unknown antagonist
DB06080 ABT-869 investigational unknown unknown
DB07167 5-CYANO-FURAN-2-CARBOXYLIC ACID [5-HYDROXYMETHYL-2-(4-METHYL-PIPERIDIN-1-YL)-PHENYL]-AMIDE experimental unknown unknown
DB07202 6-CHLORO-3-(3-METHYLISOXAZOL-5-YL)-4-PHENYLQUINOLIN-2(1H)-ONE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2I0V X-ray 2.8Å A=538-678# A=753-922.
2I0Y X-ray 1.9Å A=538-678# A=753-922.
2I1M X-ray 1.8Å A=538-678# A=753-922.
2OGV X-ray 2.7Å A=543-918.
3BEA X-ray 2.0Å A=538-678# A=753-922.
3DPK X-ray 1.9Å A=538-678# A=771-922.
3KRJ X-ray 2.1Å A=538-678# A=753-922.
3KRL X-ray 2.4Å A=538-678# A=753-922.
3LCD X-ray 2.5Å A=538-919.
3LCO X-ray 3.4Å A=550-919.
4DKD X-ray 3.0Å C=20-299.
4HW7 X-ray 2.9Å A=542-919.
4LIQ X-ray 2.6Å E=2-512.
4R7H X-ray 2.8Å A=542-919.
4R7I X-ray 2.7Å A=542-919.
4WRL X-ray 2.8Å A/C=20-296.
4WRM X-ray 6.8Å A=20-504.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef disrupts 19585521
21567396
Nef inhibits 15626739
17893228
Nef downregulates 22407921
Nef deglycosylates 21567396

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04060 Cytokine-cytokine receptor interaction - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04640 Hematopoietic cell lineage - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
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