EKS-MUM-00437

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00437

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/PDGFR	574.4	2.4E-172	580	908	329

Status

Reviewed

Ensembl Protein

ENSMUSP00000025523

UniProt Accession

P09581; Q3U3P1; Q9DBH9;

Protein Name

Macrophage colony-stimulating factor 1 receptor

Protein Synonyms/Alias

CSF-1 receptor; CSF-1-R; CSF-1R; M-CSF-R; Proto-oncogene c-Fms;

Gene Name

Csf1r

Gene Synonyms/Alias

Csf1r; Csfmr, Fms;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000024621	ENSMUSP00000025523	ENSMUST00000025523
ENSMUSG00000024621	ENSMUSP00000110923	ENSMUST00000115268

Organism

Mus musculus

Functional Description

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

Protein Length

977

Protein Sequence
(FASTA)

MELGPPLVLL LATVWHGQGA PVIEPSGPEL VVEPGETVTL RCVSNGSVEW DGPISPYWTL 60

DPESPGSTLT TRNATFKNTG TYRCTELEDP MAGSTTIHLY VKDPAHSWNL LAQEVTVVEG 120

QEAVLPCLIT DPALKDSVSL MREGGRQVLR KTVYFFSPWR GFIIRKAKVL DSNTYVCKTM 180

VNGRESTSTG IWLKVNRVHP EPPQIKLEPS KLVRIRGEAA QIVCSATNAE VGFNVILKRG 240

DTKLEIPLNS DFQDNYYKKV RALSLNAVDF QDAGIYSCVA SNDVGTRTAT MNFQVVESAY 300

LNLTSEQSLL QEVSVGDSLI LTVHADAYPS IQHYNWTYLG PFFEDQRKLE FITQRAIYRY 360

TFKLFLNRVK ASEAGQYFLM AQNKAGWNNL TFELTLRYPP EVSVTWMPVN GSDVLFCDVS 420

GYPQPSVTWM ECRGHTDRCD EAQALQVWND THPEVLSQKP FDKVIIQSQL PIGTLKHNMT 480

YFCKTHNSVG NSSQYFRAVS LGQSKQLPDE SLFTPVVVAC MSVMSLLVLL LLLLLYKYKQ 540

KPKYQVRWKI IERYEGNSYT FIDPTQLPYN EKWEFPRNNL QFGKTLGAGA FGKVVEATAF 600

GLGKEDAVLK VAVKMLKSTA HADEKEALMS ELKIMSHLGQ HENIVNLLGA CTHGGPVLVI 660

TEYCCYGDLL NFLRRKAEAM LGPSLSPGQD SEGDSSYKNI HLEKKYVRRD SGFSSQGVDT 720

YVEMRPVSTS SSDSFFKQDL DKEASRPLEL WDLLHFSSQV AQGMAFLASK NCIHRDVAAR 780

NVLLTSGHVA KIGDFGLARD IMNDSNYVVK GNARLPVKWM APESIFDCVY TVQSDVWSYG 840

ILLWEIFSLG LNPYPGILVN NKFYKLVKDG YQMAQPVFAP KNIYSIMQSC WDLEPTRRPT 900

FQQICFLLQE QARLERRDQD YANLPSSGGS SGSDSGGGSS GGSSSEPEEE SSSEHLACCE 960

PGDIAQPLLQ PNNYQFC 977

Nucleotide Sequence
(FASTA)

ATGGAGTTGG GGCCTCCTCT GGTCCTGCTG CTGGCCACAG TTTGGCATGG TCAGGGGGCC 60

CCTGTCATCG AGCCTAGTGG CCCAGAACTG GTTGTAGAGC CGGGTGAAAC GGTGACCCTG 120

CGATGTGTGA GCAATGGCAG TGTGGAATGG GATGGCCCCA TCTCTCCCTA CTGGACCTTG 180

GACCCTGAAT CTCCCGGAAG CACCCTGACC ACAAGAAACG CGACCTTCAA AAACACTGGG 240

ACCTACCGTT GTACCGAGCT TGAAGACCCC ATGGCAGGCA GTACCACCAT CCACTTGTAT 300

GTCAAAGATC CGGCCCACTC TTGGAATTTG CTGGCACAGG AGGTGACAGT GGTTGAGGGC 360

CAGGAAGCTG TGCTGCCCTG TCTGATCACT GACCCTGCAC TGAAGGACAG TGTCTCACTG 420

ATGCGTGAGG GGGGCAGGCA GGTCTTACGC AAAACGGTCT ACTTCTTCTC GCCATGGCGA 480

GGGTTCATTA TCCGCAAGGC TAAAGTCCTT GACAGCAATA CCTACGTGTG CAAGACCATG 540

GTGAATGGTA GGGAATCCAC CTCCACTGGC ATCTGGCTTA AGGTGAATCG AGTCCACCCA 600

GAGCCCCCAC AGATAAAATT GGAGCCTAGC AAGCTGGTGC GGATTCGAGG GGAGGCTGCG 660

CAGATCGTGT GCTCGGCCAC TAACGCCGAA GTGGGATTCA ACGTTATCCT CAAACGTGGA 720

GACACCAAGC TGGAAATCCC CCTAAACAGT GACTTCCAAG ATAACTATTA TAAAAAAGTC 780

CGGGCTCTCA GTCTCAACGC TGTGGACTTC CAAGACGCTG GCATATATTC TTGTGTGGCC 840

AGCAATGATG TTGGCACACG CACGGCCACC ATGAACTTCC AGGTGGTGGA GAGTGCCTAC 900

TTAAACTTGA CCTCTGAGCA GAGCCTCTTG CAGGAGGTGT CTGTGGGTGA CAGCCTCATC 960

CTCACGGTCC ATGCAGATGC CTACCCTAGC ATACAGCATT ACAACTGGAC CTACCTAGGT 1020

CCATTCTTTG AAGACCAGCG CAAGCTTGAG TTTATCACCC AAAGGGCCAT ATACAGGTAC 1080

ACATTCAAGC TCTTTCTGAA CCGTGTAAAG GCCTCAGAGG CGGGCCAGTA CTTCTTAATG 1140

GCACAAAACA AGGCAGGCTG GAATAATCTG ACCTTTGAGC TCACCCTGCG ATATCCCCCA 1200

GAGGTCAGTG TTACATGGAT GCCTGTGAAT GGCTCTGATG TCCTGTTCTG TGACGTCTCT 1260

GGGTACCCTC AGCCCAGCGT GACATGGATG GAGTGCAGGG GCCACACCGA TAGGTGTGAT 1320

GAAGCCCAGG CTTTGCAGGT TTGGAATGAC ACCCACCCTG AAGTCCTGAG TCAGAAGCCC 1380

TTCGACAAAG TGATCATTCA GAGCCAGCTG CCCATTGGGA CCTTAAAACA CAACATGACT 1440

TATTTTTGCA AAACCCACAA CAGTGTGGGT AACAGCTCTC AGTACTTCAG GGCCGTCTCC 1500

CTAGGACAAA GCAAGCAGCT CCCCGATGAG TCCCTCTTCA CTCCGGTGGT GGTGGCCTGT 1560

ATGTCTGTCA TGTCTCTGCT GGTGCTACTG CTGTTGCTGC TCTTGTACAA GTACAAGCAG 1620

AAGCCGAAGT ACCAGGTGCG CTGGAAGATC ATCGAGAGAT ACGAAGGCAA TAGCTACACC 1680

TTCATTGACC CTACTCAGTT GCCCTACAAT GAGAAGTGGG AGTTCCCTCG GAACAACCTG 1740

CAGTTTGGTA AGACTCTAGG AGCCGGTGCC TTTGGGAAGG TGGTGGAGGC TACAGCCTTT 1800

GGTCTGGGCA AAGAAGATGC AGTGCTGAAG GTGGCTGTGA AGATGCTAAA GTCCACGGCT 1860

CATGCTGATG AGAAGGAGGC CCTGATGTCA GAGCTGAAGA TCATGAGTCA CCTGGGACAG 1920

CACGAGAATA TAGTCAACCT CTTGGGAGCC TGTACTCACG GAGGACCTGT CCTGGTCATC 1980

ACTGAATACT GCTGCTATGG AGACCTACTC AACTTTCTCC GAAGGAAGGC CGAGGCTATG 2040

CTAGGACCCA GCCTGAGTCC TGGTCAGGAC TCCGAGGGAG ACTCCAGCTA CAAGAACATC 2100

CACCTGGAGA AGAAATATGT GCGCAGGGAC AGTGGCTTCT CCAGTCAGGG TGTAGACACC 2160

TACGTGGAGA TGAGGCCTGT CTCGACTTCT TCAAGTGACT CCTTCTTTAA GCAAGATCTG 2220

GACAAAGAGG CCAGCCGGCC CCTGGAGCTC TGGGACCTGC TCCACTTCTC CAGCCAAGTG 2280

GCTCAGGGCA TGGCCTTCCT TGCTTCTAAA AACTGCATCC ACCGGGACGT AGCAGCTCGA 2340

AACGTGCTGT TGACCAGCGG ACATGTGGCC AAGATTGGGG ACTTTGGACT GGCTAGGGAC 2400

ATCATGAATG ACTCCAACTA TGTTGTCAAG GGCAATGCCC GCCTGCCTGT AAAGTGGATG 2460

GCCCCAGAGA GCATCTTTGA CTGCGTCTAC ACAGTTCAGA GTGATGTGTG GTCCTACGGC 2520

ATCCTCCTCT GGGAGATCTT CTCGCTTGGT CTGAACCCCT ACCCCGGCAT CCTAGTGAAC 2580

AACAAGTTCT ACAAACTGGT GAAGGATGGA TACCAAATGG CCCAGCCTGT ATTTGCACCG 2640

AAGAACATAT ACAGCATCAT GCAGTCCTGC TGGGACCTGG AGCCTACCAG AAGACCCACC 2700

TTCCAACAGA TCTGCTTCCT CCTCCAGGAG CAGGCCCGAC TGGAGAGGAG AGACCAGGAC 2760

TATGCTAACC TGCCAAGCAG CGGTGGCAGC AGCGGCAGTG ACAGTGGTGG TGGCAGCAGC 2820

GGTGGCAGCA GCAGTGAGCC AGAAGAGGAG AGCTCCAGTG AACACCTGGC CTGCTGTGAG 2880

CCAGGGGACA TCGCCCAGCC CCTGCTGCAG CCTAACAACT ACCAGTTCTG CTGA 2934

Domain Profile

S: 1     lelGkvlGsGafGkvveatayGlsksdavlkvavkmlkstarssekealmselkilshlG  60

         l++Gk+lG+GafGkvveata+Gl+k+davlkvavkmlksta+++ekealmselki+shlG

Q: 580   LQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLG  639

         79**********************************************************

S: 61    ehenivnllGactkgGpiyviteyccyGdllnylrrkresflkkslekkkekeeeldska  120

         +henivnllGact+gGp++viteyccyGdlln+lrrk+e++l  sl+  +++e + ++k+

Q: 640   QHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDSEGDSSYKN  699

         ************************************************************

S: 121   l.ladkslrsksslssesseeyvdlkkdvsdvssskadklasekkksalerevkaaleee  179

         + l++k++r++s +ss++ ++yv++++    vs+s++d++ +++            l++e

Q: 700   IhLEKKYVRRDSGFSSQGVDTYVEMRP----VSTSSSDSFFKQD------------LDKE  743

         *999***********************....9999*99999998............7899

S: 180   dsevleledllsfsyqvakGmeflaskncvhrdlaarnvllteGkvvkicdfGlardimk  239

          s++lel+dll+fs+qva+Gm+flasknc+hrd+aarnvllt+G+v+ki+dfGlardim+

Q: 744   ASRPLELWDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTSGHVAKIGDFGLARDIMN  803

         9***********************************************************

S: 240   dsnyvvkGnarlpvkwmapesifdslytvksdvwsyGillweifslGstpypgllvdskf  299

         dsnyvvkGnarlpvkwmapesifd++ytv+sdvwsyGillweifslG +pypg+lv++kf

Q: 804   DSNYVVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNNKF  863

         ************************************************************

S: 300   yklikeGyrmaqpayateeiyeimqkcweaepekrpsfkqlvell  344

         ykl+k+Gy+maqp +a+++iy+imq+cw+ ep++rp+f+q++ ll

Q: 864   YKLVKDGYQMAQPVFAPKNIYSIMQSCWDLEPTRRPTFQQICFLL  908

         ******************************************986

Domain Sequence
(FASTA)

LQFGKTLGAG AFGKVVEATA FGLGKEDAVL KVAVKMLKST AHADEKEALM SELKIMSHLG 60

QHENIVNLLG ACTHGGPVLV ITEYCCYGDL LNFLRRKAEA MLGPSLSPGQ DSEGDSSYKN 120

IHLEKKYVRR DSGFSSQGVD TYVEMRPVST SSSDSFFKQD LDKEASRPLE LWDLLHFSSQ 180

VAQGMAFLAS KNCIHRDVAA RNVLLTSGHV AKIGDFGLAR DIMNDSNYVV KGNARLPVKW 240

MAPESIFDCV YTVQSDVWSY GILLWEIFSL GLNPYPGILV NNKFYKLVKD GYQMAQPVFA 300

PKNIYSIMQS CWDLEPTRRP TFQQICFLL 329

Keyword

3D-structure; ATP-binding; Cell membrane; Complete proteome; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0009986	; C:cell surface
GO:0016021	; C:integral to membrane
GO:0005886	; C:plasma membrane
GO:0043235	; C:receptor complex
GO:0005524	; F:ATP binding
GO:0019955	; F:cytokine binding
GO:0005011	; F:macrophage colony-stimulating factor receptor activity
GO:0008283	; P:cell proliferation
GO:0045217	; P:cell-cell junction maintenance
GO:0006954	; P:inflammatory response
GO:0045087	; P:innate immune response
GO:0030316	; P:osteoclast differentiation
GO:0018108	; P:peptidyl-tyrosine phosphorylation
GO:0046488	; P:phosphatidylinositol metabolic process
GO:0048015	; P:phosphatidylinositol-mediated signaling
GO:0030335	; P:positive regulation of cell migration
GO:0008284	; P:positive regulation of cell proliferation
GO:0090197	; P:positive regulation of chemokine secretion
GO:0070374	; P:positive regulation of ERK1 and ERK2 cascade
GO:0071902	; P:positive regulation of protein serine/threonine kinase activity
GO:0061098	; P:positive regulation of protein tyrosine kinase activity
GO:0042517	; P:positive regulation of tyrosine phosphorylation of Stat3 protein
GO:0046777	; P:protein autophosphorylation
GO:2000249	; P:regulation of actin cytoskeleton reorganization
GO:0045124	; P:regulation of bone resorption
GO:0008360	; P:regulation of cell shape
GO:0031529	; P:ruffle organization
GO:0007169	; P:transmembrane receptor protein tyrosine kinase signaling pathway

KEGG

mmu:12978

;

InterPros

IPR007110	; Ig-like.
IPR013783	; Ig-like_fold.
IPR013098	; Ig_I-set.
IPR003599	; Ig_sub.
IPR003598	; Ig_sub2.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_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.

Pfam

PF07679	; I-set; 1.
PF07714	; Pkinase_Tyr; 1.

SMARTs

SM00409	; IG; 3.
SM00408	; IGc2; 1.
SM00219	; TyrKc; 1.

Prosites

PS50835	; IG_LIKE; 4.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS00240	; RECEPTOR_TYR_KIN_III; 1.

Prints

Created Date

20-Feb-2013