P14238 (FES_FELCA) 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

Felis catus (Cat) (Felis silvestris catus) [Complete proteome]

Taxonomic identifier

9685 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Carnivora › Feliformia › Felidae › Felinae › Felis

Protein attributes

Sequence length	820 AA.
Sequence status	Complete.
Protein existence	Inferred from homology

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 By similarity.
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-711. Present in an inactive form in the absence of activating stimuli By similarity.
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.
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-711 in response to FGF2. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK By similarity.
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 SH2 domain
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete 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 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 cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB cytoplasmic membrane-bounded vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 820	820	Tyrosine-protein kinase Fes/Fps		PRO_0000088085
Regions
	Domain	1 – 94	94	FCH
	Domain	458 – 547	90	SH2
	Domain	559 – 820	262	Protein kinase
	Nucleotide binding	565 – 573	9	ATP By similarity
	Region	1 – 298	298	Important for interaction with membranes containing phosphoinositides By similarity
	Coiled coil	123 – 163	41	Potential
	Coiled coil	318 – 389	72	Potential
Sites
	Active site	681	1	Proton acceptor By similarity
	Binding site	588	1	ATP By similarity
Amino acid modifications
	Modified residue	65	1	Phosphoserine By similarity
	Modified residue	259	1	Phosphotyrosine By similarity
	Modified residue	419	1	Phosphothreonine By similarity
	Modified residue	711	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	714	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P14238 [UniParc]. Last modified February 1, 1996. Version 2. Checksum: F3A52B750236834E	FASTA	820	92,975
	10 20 30 40 50 60 MGFSSELCSP QGHGAVQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDGGGRG 70 80 90 100 110 120 TGPYSPISQS WAEITSQTEG LSRLLRQHAE DLNSGPLSKL GLLIRERQQL RKTYSEQWQQ 130 140 150 160 170 180 LQQELTKTHN QDIEKLKSQY RALARDSAQA RRKYQEASKD KDRDKAKDKY VRSLWKLFAH 190 200 210 220 230 240 HNRYVLGVRA AQLHHHHHHQ LMLPGLLQSL QDLHQEMACI LKEILQEYLE ISSLVQDEVV 250 260 270 280 290 300 AIHLEMAAAV ARIQPEAEYQ GFLRQYGSTP DVPPCVTFDE SLLEEGEPLE PGELQLNELT 310 320 330 340 350 360 VESVQHTLTS VTDELTVATQ TVLSRQEAVA QLQRELQNEE QNTHPRERVQ LLAKKQVLQE 370 380 390 400 410 420 ALQALQVALC SQAKLQAQRE LLQAKLEQLG PGEPPPVLLL QDDRHSTSSS EQEREGGRTP 430 440 450 460 470 480 TLEILKSHIS GIFRPKFSLP PPLQLVPEVQ KPLHEQLWYH GALPRAEVAE LLTHSGDFLV 490 500 510 520 530 540 RESQGKQEYV LSVLWDGQPR HFIIESADNL YRLEGDGFAS IPLLVDHLLR SQQPLTKKSG 550 560 570 580 590 600 IVLNRAVPKD KWVLNHEDLV LGEQIGRGNF GEVFSGRLRA DNTLVAVKSC RETLPPDIKA 610 620 630 640 650 660 KFLQEAKILK QYSHPNIVRL IGVCTQKQPI YIVMELVQGG DFLTFLRTEG ARLRMKTLLQ 670 680 690 700 710 720 MVGDAAAGME YLESKCCIHR DLAARNCLVT EKNVLKISDF GMSREEADGI YAASGGLRQV 730 740 750 760 770 780 PVKWTAPEAL NYGRYSSESD VWSFGILLWE TFSLGASPYP NLSNQQTREF VEKGGRLPCP 790 800 810 820 ELCPDAVFRL MEQCWAYEPG QRPSFSAIYQ ELQSIRKRHR

References

[1]	"Structure of the feline c-fes/fps proto-oncogene: genesis of a retroviral oncogene." Roebroek A.J.M., Schalken J.A., Onnekink C., Bloemers H.P.J., van de Ven W.J.M. J. Virol. 61:2009-2016(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	M16705 , M16666, M16667, M16668, M16669, M16670, M16671, M16706, M16672, M16673, M16674, M16698, M16700, M16701, M16702, M16704 Genomic DNA. Translation: AAA30808.1.
PIR	TVCTFF. A27824.
3D structure databases
ProteinModelPortal	P14238.
SMR	P14238. Positions 447-819.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG005655.
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...

Entry information

Entry name

FES_FELCA

Accession

Primary (citable) accession number: P14238

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	February 1, 1996
Last modified:	May 1, 2013
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program