P16879 (FES_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Fes/Fps
EC=2.7.10.2

Alternative name(s):
Proto-oncogene c-Fes

Gene names

Name:	Fes
Synonyms:	Fps

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	822 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down-stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28. Ref.7 Ref.8 Ref.10
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Kinase activity is tightly regulated. Activated in response to signaling from a cell surface receptor. Activation probably requires binding of a substrate via the SH2 domain, plus autophosphorylation at Tyr-713. Present in an inactive form in the absence of activating stimuli. Ref.7
Subunit structure	Homooligomer. Interacts with BCR. Interacts (when activated, via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with phosphorylated KIT. Interacts with FLT3. Interacts (via FCH domain) with soluble tubulin. Interacts (via SH2 domain) with microtubules By similarity. Ref.8
Subcellular location	Cytoplasm › cytosol By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmic vesicle By similarity. Golgi apparatus By similarity. Cell junction › focal adhesion By similarity. Note: Distributed throughout the cytosol when the kinase is not activated. Association with microtubules requires activation of the kinase activity. Shuttles between focal adhesions and cell-cell contacts in epithelial cells. Recruited to the lateral cell membrane in polarized epithelial cells by interaction with phosphorylated EZR. Detected at tubular membrane structures in the cytoplasm and at the cell periphery By similarity.
Domain	The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins By similarity. The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes By similarity.
Post-translational modification	Autophosphorylated on Tyr-713 in response to FGF2. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK By similarity. Ref.7 Ref.8
Disruption phenotype	No visible phenotype. Mice are fertile and healthy, display slightly reduced numbers of myeloid cells and are more sensitive to lipopolysaccharide (LPS). Mice lacking both Fps/Fes and Fer activity are viable and fertile, but produce fewer offspring than normal. They display elevated levels of circulating neutrophils, erythrocytes and platelets, while other cell counts are normal. Ref.2 Ref.6
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily. Contains 1 FCH domain. Contains 1 protein kinase domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Cytoplasmic vesicle Cytoskeleton Golgi apparatus Membrane
Disease	Proto-oncogene Tumor suppressor
Domain	Coiled coil
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of microtubule polymerization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of myeloid cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell motility Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB regulation of mast cell degranulation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB focal adhesion Inferred from sequence or structural similarity. Source: UniProtKB microtubule cytoskeleton Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW immunoglobulin receptor binding Inferred from sequence or structural similarity. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
H2-K1	P01901	3	EBI-771815,EBI-1265227
Ptpn11	P35235	2	EBI-771815,EBI-397236

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 822	822	Tyrosine-protein kinase Fes/Fps		PRO_0000088089
Regions
	Domain	1 – 96	96	FCH
	Domain	460 – 549	90	SH2
	Domain	561 – 818	258	Protein kinase
	Nucleotide binding	567 – 575	9	ATP By similarity
	Region	1 – 300	300	Important for interaction with membranes containing phosphoinositides By similarity
	Coiled coil	133 – 165	33	Potential
	Coiled coil	320 – 369	50	Potential
Sites
	Active site	683	1	Proton acceptor By similarity
	Binding site	590	1	ATP By similarity
Amino acid modifications
	Modified residue	67	1	Phosphoserine By similarity
	Modified residue	261	1	Phosphotyrosine By similarity
	Modified residue	421	1	Phosphothreonine By similarity
	Modified residue	713	1	Phosphotyrosine; by autocatalysis Ref.9
	Modified residue	716	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	110 – 111	2	QH → HS in CAA31138. Ref.1
	Sequence conflict	413 – 414	2	Missing in CAA31138. Ref.1
	Sequence conflict	413 – 414	2	Missing in AAN33122. Ref.2
	Sequence conflict	467	1	R → W in CAA31138. Ref.1
	Sequence conflict	477	1	S → T in CAA31138. Ref.1
	Sequence conflict	477	1	S → T in AAN33122. Ref.2
	Sequence conflict	500	1	Q → H in CAA31138. Ref.1
	Sequence conflict	500	1	Q → H in AAN33122. Ref.2
	Sequence conflict	509	1	S → L in CAA31138. Ref.1
	Sequence conflict	509	1	S → L in AAN33122. Ref.2
	Sequence conflict	664	1	V → M in CAA31138. Ref.1
	Sequence conflict	716 – 717	2	SA → CS in CAA31138. Ref.1
	Sequence conflict	716 – 717	2	SA → CS in AAA40012. Ref.5
	Sequence conflict	749	1	L → P in AAA40012. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	P16879 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: 939280C56ACF25EE	FASTA	822	93,779
	10 20 30 40 50 60 MGFSSELCSP QGHGAVQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 70 80 90 100 110 120 WSSGPDSPVS QSWAEITSQT ENLSRVLRQH AEDLNSGPLS KLSVLIRERQ HLRKTYNEQW 130 140 150 160 170 180 QQLQQELTKT HSQDIEKLKT QYRTLVRDST QARRKYQEAS KDKDRDKAKD KYVRSLWKLF 190 200 210 220 230 240 AHHNRYVLGV RAAQLHHHHH HRFMLPGLLQ SLQDLHEEMA GILKDILQEY LEISSLVQDD 250 260 270 280 290 300 VASIHRELAA AAARIQPEFE YLGFLRQYGS TPDVPPCVTF DESLLEDGEQ LEPGELQLNE 310 320 330 340 350 360 LTLESVQHTL TSVTDELAVA TKEVLSRQEM VSQLQRELQS EEQNTHPRER VQLLSKRQML 370 380 390 400 410 420 QEAIQGLQIA LCSQDKLQAQ QELLQSKMEQ LGTGEPPAVP LLQDDRHSTS STEQEREGGR 430 440 450 460 470 480 TPTLEILKSH FSGIFRPKFS IPPPLQLVPE VQKPLYEQLW YHGAIPRAEV AELLTHSGDF 490 500 510 520 530 540 LVRESQGKQE YVLSVMWDGQ PRHFIIQSSD NLYRLEGDGF PSIPLLITHL LSSQQPLTKK 550 560 570 580 590 600 SGVVLFRAVP KDKWVLKHED LVLGEQIGRG NFGEVFSGRL RADNTPVAVK SCRETLPPDL 610 620 630 640 650 660 KAKFLQEARI LKQYNHPNIV RLIGVCTQKQ PIYIVMELVQ GGDFLTFLRT EGARLRVKTL 670 680 690 700 710 720 LQMVGDAAAG MEYLESKCCI HRDLAARNCL VTEKNVLKIS DFGMSREEAD GIYAASAGLR 730 740 750 760 770 780 QVPVKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGASP YPNLTNQQTR EFVEKGHRLP 790 800 810 820 CPELCPDAVF RLMEQCWAYE PGQRPSFSII CQELHSIRKR HR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and structural analysis of murine c-fes cDNA clones." Wilks A.F., Kurban R.R. Oncogene 3:289-294(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis." Zirngibl R.A., Senis Y., Greer P.A. Mol. Cell. Biol. 22:2472-2486(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], DISRUPTION PHENOTYPE. Strain: 129/SvJ.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J and NOD. Tissue: Spleen.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The application of the polymerase chain reaction to cloning members of the protein tyrosine kinase family." Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J. Gene 85:67-74(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 680-749.
[6]	"Fps/Fes and Fer protein-tyrosine kinases play redundant roles in regulating hematopoiesis." Senis Y.A., Craig A.W., Greer P.A. Exp. Hematol. 31:673-681(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[7]	"Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation." Udell C.M., Samayawardhena L.A., Kawakami Y., Kawakami T., Craig A.W. J. Biol. Chem. 281:20949-20957(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MAST CELL ACTIVATION AND PHOSPHORYLATION OF PECAM1, PHOSPHORYLATION, ENZYME REGULATION.
[8]	"The tyrosine kinase FES is an essential effector of KITD816V proliferation signal." Voisset E., Lopez S., Dubreuil P., De Sepulveda P. Blood 110:2593-2599(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH KIT, PHOSPHORYLATION, MASS SPECTROMETRY.
[9]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-713, MASS SPECTROMETRY. Tissue: Mast cell.
[10]	"Fps/Fes protein-tyrosine kinase regulates mast cell adhesion and migration downstream of Kit and beta1 integrin receptors." Smith J.A., Samayawardhena L.A., Craig A.W. Cell. Signal. 22:427-436(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X12616 mRNA. Translation: CAA31138.1. AF542394 Genomic DNA. Translation: AAN33122.1. M33421 mRNA. Translation: AAA40012.1. AK143639 mRNA. Translation: BAE25475.1. AK170418 mRNA. Translation: BAE41784.1. BC129919 mRNA. Translation: AAI29920.1.
IPI	IPI00109075.
PIR	I48347.
RefSeq	NP_034324.2. NM_010194.2.
UniGene	Mm.48757.
3D structure databases
ProteinModelPortal	P16879.
SMR	P16879. Positions 1-402, 449-821.
ModBase	Search...
Protein-protein interaction databases
IntAct	P16879. 3 interactions.
PTM databases
PhosphoSite	P16879.
Proteomic databases
PRIDE	P16879.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000080932; ENSMUSP00000079733; ENSMUSG00000053158.
GeneID	14159.
KEGG	mmu:14159.
UCSC	uc009ias.1. mouse.
Organism-specific databases
CTD	2242.
MGI	MGI:95514. Fes.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00600000084126.
HOGENOM	HOG000059550.
HOVERGEN	HBG005655.
InParanoid	P16879.
KO	K07527.
OMA	GAIPRAE.
OrthoDB	EOG4VDPXW.
Enzyme and pathway databases
BRENDA	2.7.10.2. 3474.
Reactome	REACT_127416. Developmental Biology.
Gene expression databases
Bgee	P16879.
CleanEx	MM_FES.
Genevestigator	P16879.
GermOnline	ENSMUSG00000053158. Mus musculus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR001060. FCH_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016250. Tyr_kinase_non-rcpt_Fes_subgr. [Graphical view]
Pfam	PF00611. FCH. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PIRSF	PIRSF000632. TyrPK_fps. 1 hit.
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
SMART	SM00055. FCH. 1 hit. SM00252. SH2. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50133. FCH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	285286.
SOURCE	Search...

Entry information

Entry name

FES_MOUSE

Accession

Primary (citable) accession number: P16879
Secondary accession number(s): Q3TD20, Q62122, Q8CG02

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 15, 2008
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program