EKS-HOS-00411

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00411

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/PDGFR	576.0	1.6E-172	582	910	329

Status

Reviewed

Ensembl Protein

ENSP00000286301

UniProt Accession

P07333; D3DQG2; Q6LDW5; Q6LDY4; Q86VW7;

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; FMS;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000182578	ENSP00000427545	ENST00000515068
ENSG00000182578	ENSP00000422212	ENST00000504875
ENSG00000182578	ENSP00000421174	ENST00000511344
ENSG00000182578	ENSP00000286301	ENST00000286301
ENSG00000182578	ENSP00000445282	ENST00000543093

Organism

Homo sapiens

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

972

Protein Sequence
(FASTA)

MGPGVLLLLL VATAWHGQGI PVIEPSVPEL VVKPGATVTL RCVGNGSVEW DGPPSPHWTL 60

YSDGSSSILS TNNATFQNTG TYRCTEPGDP LGGSAAIHLY VKDPARPWNV LAQEVVVFED 120

QDALLPCLLT DPVLEAGVSL VRVRGRPLMR HTNYSFSPWH GFTIHRAKFI QSQDYQCSAL 180

MGGRKVMSIS IRLKVQKVIP GPPALTLVPA ELVRIRGEAA QIVCSASSVD VNFDVFLQHN 240

NTKLAIPQQS DFHNNRYQKV LTLNLDQVDF QHAGNYSCVA SNVQGKHSTS MFFRVVESAY 300

LNLSSEQNLI QEVTVGEGLN LKVMVEAYPG LQGFNWTYLG PFSDHQPEPK LANATTKDTY 360

RHTFTLSLPR LKPSEAGRYS FLARNPGGWR ALTFELTLRY PPEVSVIWTF INGSGTLLCA 420

ASGYPQPNVT WLQCSGHTDR CDEAQVLQVW DDPYPEVLSQ EPFHKVTVQS LLTVETLEHN 480

QTYECRAHNS VGSGSWAFIP ISAGAHTHPP DEFLFTPVVV ACMSIMALLL LLLLLLLYKY 540

KQKPKYQVRW KIIESYEGNS YTFIDPTQLP YNEKWEFPRN NLQFGKTLGA GAFGKVVEAT 600

AFGLGKEDAV LKVAVKMLKS TAHADEKEAL MSELKIMSHL GQHENIVNLL GACTHGGPVL 660

VITEYCCYGD LLNFLRRKAE AMLGPSLSPG QDPEGGVDYK NIHLEKKYVR RDSGFSSQGV 720

DTYVEMRPVS TSSNDSFSEQ DLDKEDGRPL ELRDLLHFSS QVAQGMAFLA SKNCIHRDVA 780

ARNVLLTNGH VAKIGDFGLA RDIMNDSNYI VKGNARLPVK WMAPESIFDC VYTVQSDVWS 840

YGILLWEIFS LGLNPYPGIL VNSKFYKLVK DGYQMAQPAF APKNIYSIMQ ACWALEPTHR 900

PTFQQICSFL QEQAQEDRRE RDYTNLPSSS RSGGSGSSSS ELEEESSSEH LTCCEQGDIA 960

QPLLQPNNYQ FC 972

Nucleotide Sequence
(FASTA)

ATGGGCCCAG GAGTTCTGCT GCTCCTGCTG GTGGCCACAG CTTGGCATGG TCAGGGAATC 60

CCAGTGATAG AGCCCAGTGT CCCTGAGCTG GTCGTGAAGC CAGGAGCAAC GGTGACCTTG 120

CGATGTGTGG GCAATGGCAG CGTGGAATGG GATGGCCCCC CATCACCTCA CTGGACCCTG 180

TACTCTGATG GCTCCAGCAG CATCCTCAGC ACCAACAACG CTACCTTCCA AAACACGGGG 240

ACCTATCGCT GCACTGAGCC TGGAGACCCC CTGGGAGGCA GCGCCGCCAT CCACCTCTAT 300

GTCAAAGACC CTGCCCGGCC CTGGAACGTG CTAGCACAGG AGGTGGTCGT GTTCGAGGAC 360

CAGGACGCAC TACTGCCCTG TCTGCTCACA GACCCGGTGC TGGAAGCAGG CGTCTCGCTG 420

GTGCGTGTGC GTGGCCGGCC CCTCATGCGC CACACCAACT ACTCCTTCTC GCCCTGGCAT 480

GGCTTCACCA TCCACAGGGC CAAGTTCATT CAGAGCCAGG ACTATCAATG CAGTGCCCTG 540

ATGGGTGGCA GGAAGGTGAT GTCCATCAGC ATCCGGCTGA AAGTGCAGAA AGTCATCCCA 600

GGGCCCCCAG CCTTGACACT GGTGCCTGCA GAGCTGGTGC GGATTCGAGG GGAGGCTGCC 660

CAGATCGTGT GCTCAGCCAG CAGCGTTGAT GTTAACTTTG ATGTCTTCCT CCAACACAAC 720

AACACCAAGC TCGCAATCCC TCAACAATCT GACTTTCATA ATAACCGTTA CCAAAAAGTC 780

CTGACCCTCA ACCTCGATCA AGTAGATTTC CAACATGCCG GCAACTACTC CTGCGTGGCC 840

AGCAACGTGC AGGGCAAGCA CTCCACCTCC ATGTTCTTCC GGGTGGTAGA GAGTGCCTAC 900

TTGAACTTGA GCTCTGAGCA GAACCTCATC CAGGAGGTGA CCGTGGGGGA GGGGCTCAAC 960

CTCAAAGTCA TGGTGGAGGC CTACCCAGGC CTGCAAGGTT TTAACTGGAC CTACCTGGGA 1020

CCCTTTTCTG ACCACCAGCC TGAGCCCAAG CTTGCTAATG CTACCACCAA GGACACATAC 1080

AGGCACACCT TCACCCTCTC TCTGCCCCGC CTGAAGCCCT CTGAGGCTGG CCGCTACTCC 1140

TTCCTGGCCA GAAACCCAGG AGGCTGGAGA GCTCTGACGT TTGAGCTCAC CCTTCGATAC 1200

CCCCCAGAGG TAAGCGTCAT ATGGACATTC ATCAACGGCT CTGGCACCCT TTTGTGTGCT 1260

GCCTCTGGGT ACCCCCAGCC CAACGTGACA TGGCTGCAGT GCAGTGGCCA CACTGATAGG 1320

TGTGATGAGG CCCAAGTGCT GCAGGTCTGG GATGACCCAT ACCCTGAGGT CCTGAGCCAG 1380

GAGCCCTTCC ACAAGGTGAC GGTGCAGAGC CTGCTGACTG TTGAGACCTT AGAGCACAAC 1440

CAAACCTACG AGTGCAGGGC CCACAACAGC GTGGGGAGTG GCTCCTGGGC CTTCATACCC 1500

ATCTCTGCAG GAGCCCACAC GCATCCCCCG GATGAGTTCC TCTTCACACC AGTGGTGGTC 1560

GCCTGCATGT CCATCATGGC CTTGCTGCTG CTGCTGCTCC TGCTGCTATT GTACAAGTAT 1620

AAGCAGAAGC CCAAGTACCA GGTCCGCTGG AAGATCATCG AGAGCTATGA GGGCAACAGT 1680

TATACTTTCA TCGACCCCAC GCAGCTGCCT TACAACGAGA AGTGGGAGTT CCCCCGGAAC 1740

AACCTGCAGT TTGGTAAGAC CCTCGGAGCT GGAGCCTTTG GGAAGGTGGT GGAGGCCACG 1800

GCCTTTGGTC TGGGCAAGGA GGATGCTGTC CTGAAGGTGG CTGTGAAGAT GCTGAAGTCC 1860

ACGGCCCATG CTGATGAGAA GGAGGCCCTC ATGTCCGAGC TGAAGATCAT GAGCCACCTG 1920

GGCCAGCACG AGAACATCGT CAACCTTCTG GGAGCCTGTA CCCATGGAGG CCCTGTACTG 1980

GTCATCACGG AGTACTGTTG CTATGGCGAC CTGCTCAACT TTCTGCGAAG GAAGGCTGAG 2040

GCCATGCTGG GACCCAGCCT GAGCCCCGGC CAGGACCCCG AGGGAGGCGT CGACTATAAG 2100

AACATCCACC TCGAGAAGAA ATATGTCCGC AGGGACAGTG GCTTCTCCAG CCAGGGTGTG 2160

GACACCTATG TGGAGATGAG GCCTGTCTCC ACTTCTTCAA ATGACTCCTT CTCTGAGCAA 2220

GACCTGGACA AGGAGGATGG ACGGCCCCTG GAGCTCCGGG ACCTGCTTCA CTTCTCCAGC 2280

CAAGTAGCCC AGGGCATGGC CTTCCTCGCT TCCAAGAATT GCATCCACCG GGACGTGGCA 2340

GCGCGTAACG TGCTGTTGAC CAATGGTCAT GTGGCCAAGA TTGGGGACTT CGGGCTGGCT 2400

AGGGACATCA TGAATGACTC CAACTACATT GTCAAGGGCA ATGCCCGCCT GCCTGTGAAG 2460

TGGATGGCCC CAGAGAGCAT CTTTGACTGT GTCTACACGG TTCAGAGCGA CGTCTGGTCC 2520

TATGGCATCC TCCTCTGGGA GATCTTCTCA CTTGGGCTGA ATCCCTACCC TGGCATCCTG 2580

GTGAACAGCA AGTTCTATAA ACTGGTGAAG GATGGATACC AAATGGCCCA GCCTGCATTT 2640

GCCCCAAAGA ATATATACAG CATCATGCAG GCCTGCTGGG CCTTGGAGCC CACCCACAGA 2700

CCCACCTTCC AGCAGATCTG CTCCTTCCTT CAGGAGCAGG CCCAAGAGGA CAGGAGAGAG 2760

CGGGACTATA CCAATCTGCC GAGCAGCAGC AGAAGCGGTG GCAGCGGCAG CAGCAGCAGT 2820

GAGCTGGAGG AGGAGAGCTC TAGTGAGCAC CTGACCTGCT GCGAGCAAGG GGATATCGCC 2880

CAGCCCTTGC TGCAGCCCAA CAACTATCAG TTCTGCTGA 2919

Domain Profile

S: 1     lelGkvlGsGafGkvveatayGlsksdavlkvavkmlkstarssekealmselkilshlG  60

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

Q: 582   LQFGKTLGAGAFGKVVEATAFGLGKEDAVLKVAVKMLKSTAHADEKEALMSELKIMSHLG  641

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

S: 61    ehenivnllGactkgGpiyviteyccyGdllnylrrkresflkkslekkkekeeeldska  120

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

Q: 642   QHENIVNLLGACTHGGPVLVITEYCCYGDLLNFLRRKAEAMLGPSLSPGQDPEGGVDYKN  701

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

S: 121   l.ladkslrsksslssesseeyvdlkkdvsdvssskadklasekkksalerevkaaleee  179

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

Q: 702   IhLEKKYVRRDSGFSSQGVDTYVEMRP----VSTSSNDSFSEQD------------LDKE  745

         *999***********************....9999999999988............8899

S: 180   dsevleledllsfsyqvakGmeflaskncvhrdlaarnvllteGkvvkicdfGlardimk  239

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

Q: 746   DGRPLELRDLLHFSSQVAQGMAFLASKNCIHRDVAARNVLLTNGHVAKIGDFGLARDIMN  805

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

S: 240   dsnyvvkGnarlpvkwmapesifdslytvksdvwsyGillweifslGstpypgllvdskf  299

         dsny+vkGnarlpvkwmapesifd++ytv+sdvwsyGillweifslG +pypg+lv+skf

Q: 806   DSNYIVKGNARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGLNPYPGILVNSKF  865

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

S: 300   yklikeGyrmaqpayateeiyeimqkcweaepekrpsfkqlvell  344

         ykl+k+Gy+maqpa+a+++iy+imq+cw+ ep++rp+f+q++++l

Q: 866   YKLVKDGYQMAQPAFAPKNIYSIMQACWALEPTHRPTFQQICSFL  910

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

Domain Sequence
(FASTA)

LQFGKTLGAG AFGKVVEATA FGLGKEDAVL KVAVKMLKST AHADEKEALM SELKIMSHLG 60

QHENIVNLLG ACTHGGPVLV ITEYCCYGDL LNFLRRKAEA MLGPSLSPGQ DPEGGVDYKN 120

IHLEKKYVRR DSGFSSQGVD TYVEMRPVST SSNDSFSEQD LDKEDGRPLE LRDLLHFSSQ 180

VAQGMAFLAS KNCIHRDVAA RNVLLTNGHV AKIGDFGLAR DIMNDSNYIV KGNARLPVKW 240

MAPESIFDCV YTVQSDVWSY GILLWEIFSL GLNPYPGILV NSKFYKLVKD GYQMAQPAFA 300

PKNIYSIMQA CWALEPTHRP TFQQICSFL 329

Keyword

3D-structure; ATP-binding; Cell membrane; Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Inflammatory response; Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; 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"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>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:0005887	; C:integral to 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:0042803	; F:protein homodimerization 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:0030225	; P:macrophage differentiation
GO:0060603	; P:mammary gland duct morphogenesis
GO:0030224	; P:monocyte differentiation
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

hsa:1436

;

InterPros

IPR007110	; Ig-like.
IPR013783	; Ig-like_fold.
IPR003599	; Ig_sub.
IPR003598	; Ig_sub2.
IPR013151	; Immunoglobulin.
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

PF00047	; ig; 1.
PF07714	; Pkinase_Tyr; 1.

SMARTs

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

Prosites

PS50835	; IG_LIKE; 3.
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