P07332 (FES_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Feline sarcoma/Fujinami avian sarcoma oncogene homolog
Proto-oncogene c-Fes
Proto-oncogene c-Fps
p93c-fes

Gene names

Name:	FES
Synonyms:	FPS

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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.8 Ref.10 Ref.12 Ref.14 Ref.15 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27 Ref.29
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.8 Ref.9 Ref.12 Ref.15 Ref.16 Ref.31
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.10 Ref.31
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. Ref.12 Ref.14 Ref.15 Ref.18 Ref.21 Ref.22 Ref.25 Ref.27
Subcellular location	Cytoplasm › cytosol. Cytoplasm › cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicle. Golgi apparatus. Cell junction › focal adhesion. 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. Ref.11 Ref.15 Ref.19 Ref.21 Ref.22 Ref.25
Tissue specificity	Widely expressed. Detected in adult colon epithelium. Ref.19 Ref.23
Domain	The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins. Ref.12 Ref.22 The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes. Ref.12 Ref.22
Post-translational modification	Autophosphorylated on Tyr-713. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK. Ref.9 Ref.10 Ref.12 Ref.15 Ref.16 Ref.21 Ref.22 Ref.25 Ref.27 Ref.31
Involvement in disease	Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (Ref.27). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (Ref.8). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (Ref.19). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (Ref.19). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (Ref.29). May promote growth of renal carcinoma cells (Ref.24).
Miscellaneous	Cellular homolog of retroviral oncogenes. In contrast to the viral oncoproteins, the kinase activity of cellular FSP/FES is tightly regulated, and the kinase is inactive in normal cells in the absence of activating stimuli (Ref.15).
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
Coding sequence diversity	Alternative splicing Polymorphism
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Traceable author statement. Source: Reactome cell proliferation Traceable author statement PubMed 6264598. Source: ProtInc peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.12Ref.15. Source: UniProtKB positive regulation of actin cytoskeleton reorganization Inferred from mutant phenotype Ref.14. Source: UniProtKB positive regulation of microtubule polymerization Inferred from mutant phenotype Ref.15. Source: UniProtKB positive regulation of myeloid cell differentiation Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of neuron projection development Inferred from mutant phenotype Ref.14. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.9. Source: UniProtKB regulation of cell adhesion Inferred from mutant phenotype Ref.12. Source: UniProtKB regulation of cell motility Inferred from mutant phenotype Ref.21. Source: UniProtKB regulation of cell proliferation Inferred from mutant phenotype Ref.12. Source: UniProtKB regulation of cell shape Inferred from mutant phenotype Ref.12Ref.21. Source: UniProtKB regulation of mast cell degranulation Inferred from mutant phenotype Ref.25. 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 direct assay Ref.21Ref.25. Source: UniProtKB focal adhesion Inferred from direct assay Ref.21. Source: UniProtKB microtubule cytoskeleton Inferred from direct assay Ref.15. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW immunoglobulin receptor binding Inferred from direct assay Ref.25. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.15. Source: UniProtKB phosphatidylinositol binding Inferred from direct assay Ref.25. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P07332-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P07332-2)

Also known as: Variant 1;

The sequence of this isoform differs from the canonical sequence as follows:
     72-129: Missing.
     441-510: Missing.

Isoform 3 (identifier: P07332-3)

Also known as: Variant 3;

The sequence of this isoform differs from the canonical sequence as follows:
     72-129: Missing.

Isoform 4 (identifier: P07332-4)

Also known as: Variant 4;

The sequence of this isoform differs from the canonical sequence as follows:
     441-510: Missing.

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_0000088088

Regions

Domain

1 – 69

69

FCH

Domain

460 – 549

90

SH2

Domain

561 – 822

262

Protein kinase

Nucleotide binding

567 – 575

9

ATP By similarity

Region

1 – 300

300

Important for interaction with membranes containing phosphoinositides

Coiled coil

125 – 169

45

Potential

Coiled coil

324 – 368

45

Potential

Sites

Active site

683

1

Proton acceptor By similarity

Binding site

590

1

ATP By similarity

Amino acid modifications

Modified residue

64

1

Phosphoserine Ref.26

Modified residue

67

1

Phosphoserine Ref.26

Modified residue

261

1

Phosphotyrosine Ref.26

Modified residue

421

1

Phosphothreonine Ref.27

Modified residue

713

1

Phosphotyrosine; by autocatalysis Ref.9 Ref.15 Ref.21 Ref.22 Ref.26 Ref.31

Modified residue

716

1

Phosphoserine Ref.26

Natural variations

Alternative sequence

72 – 129

58

Missing in isoform 2 and isoform 3.

VSP_041748

Alternative sequence

441 – 510

70

Missing in isoform 2 and isoform 4.

VSP_041749

Natural variant

85

1

R → C. Ref.32
Corresponds to variant rs56041861 [ dbSNP | Ensembl ].

VAR_041697

Natural variant

246

1

R → Q. Ref.32
Corresponds to variant rs34573430 [ dbSNP | Ensembl ].

VAR_041698

Natural variant

323

1

M → V. Ref.32
Corresponds to variant rs56296062 [ dbSNP | Ensembl ].

VAR_041699

Experimental info

Mutagenesis

113 – 114

2

RK → EE: Reduced binding to membranes containing phosphoinositides. Ref.25

Mutagenesis

113 – 114

2

RK → QQ: Reduced binding to membranes containing phosphoinositides. Ref.25

Mutagenesis

145

1

L → P: Constitutively activated kinase that can act as oncogene. Promotes myeloid cell survival and proliferation. Ref.12 Ref.15 Ref.25

Mutagenesis

334

1

L → P: Abolishes autophosphorylation. Ref.12 Ref.25

Mutagenesis

463

1

G → V: Abolishes kinase activity. Ref.25 Ref.31

Mutagenesis

483

1

R → M: Abolishes pTyr binding. Abolishes association with microtubules. Abolishes autophosphorylation. Reduced kinase activity. Ref.15 Ref.25 Ref.31

Mutagenesis

590

1

K → E: Abolishes kinase activity. Ref.15 Ref.25

Mutagenesis

704

1

M → V: Reduced autophosphorylation and strongly reduced kinase activity. Ref.16 Ref.19 Ref.25

Mutagenesis

706

1

R → Q: Negligible effect on autophosphorylation and kinase activity. Ref.16 Ref.19 Ref.25

Mutagenesis

713

1

Y → F: Reduces kinase activity by over 90%. Ref.9 Ref.25

Mutagenesis

743

1

V → M: Strongly reduced autophosphorylation and kinase activity. Ref.16 Ref.19 Ref.25

Mutagenesis

759

1

S → F: Reduced autophosphorylation and strongly reduced kinase activity. Ref.16 Ref.19 Ref.25

Sequence conflict

719

1

L → S in CAA36438. Ref.1

Sequence conflict

719

1

L → S in AAS82866. Ref.3

Sequence conflict

719

1

L → S in AAS82869. Ref.3

Sequence conflict

719

1

L → S in AAS82868. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

822

Helix Strand Turn

Details...

Helix

3 – 6

4

Helix

10 – 51

42

Helix

68 – 96

29

Helix

98 – 131

34

Helix

133 – 154

22

Helix

167 – 202

36

Helix

204 – 234

31

Beta strand

236 – 238

3

Helix

239 – 254

16

Helix

257 – 259

3

Helix

262 – 268

7

Turn

300 – 302

3

Helix

303 – 344

42

Helix

350 – 353

4

Helix

354 – 389

36

Turn

390 – 393

4

Helix

450 – 452

3

Helix

455 – 457

3

Beta strand

461 – 464

4

Helix

467 – 473

7

Beta strand

479 – 484

6

Turn

486 – 489

4

Beta strand

491 – 494

4

Beta strand

503 – 506

4

Beta strand

507 – 509

3

Beta strand

512 – 517

6

Beta strand

520 – 522

3

Helix

523 – 533

11

Turn

539 – 541

3

Helix

558 – 560

3

Beta strand

561 – 570

10

Beta strand

573 – 580

8

Turn

581 – 583

3

Beta strand

586 – 591

6

Helix

598 – 601

4

Helix

602 – 605

4

Helix

606 – 611

6

Beta strand

622 – 626

5

Beta strand

628 – 631

4

Beta strand

633 – 637

5

Helix

644 – 651

8

Helix

652 – 654

3

Helix

657 – 676

20

Helix

686 – 688

3

Beta strand

689 – 691

3

Beta strand

697 – 699

3

Helix

702 – 704

3

Beta strand

711 – 714

4

Beta strand

720 – 723

4

Helix

724 – 726

3

Helix

729 – 734

6

Beta strand

736 – 738

3

Helix

739 – 754

16

Turn

755 – 757

3

Helix

766 – 774

9

Helix

787 – 796

10

Helix

801 – 803

3

Helix

807 – 820

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 3, 2006. Version 3. Checksum: 4C2A90555857F045	FASTA	822	93,497
	10 20 30 40 50 60 MGFSSELCSP QGHGVLQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 70 80 90 100 110 120 RAISPDSPIS QSWAEITSQT EGLSRLLRQH AEDLNSGPLS KLSLLIRERQ QLRKTYSEQW 130 140 150 160 170 180 QQLQQELTKT HSQDIEKLKS QYRALARDSA QAKRKYQEAS KDKDRDKAKD KYVRSLWKLF 190 200 210 220 230 240 AHHNRYVLGV RAAQLHHQHH HQLLLPGLLR SLQDLHEEMA CILKEILQEY LEISSLVQDE 250 260 270 280 290 300 VVAIHREMAA AAARIQPEAE YQGFLRQYGS APDVPPCVTF DESLLEEGEP LEPGELQLNE 310 320 330 340 350 360 LTVESVQHTL TSVTDELAVA TEMVFRRQEM VTQLQQELRN EEENTHPRER VQLLGKRQVL 370 380 390 400 410 420 QEALQGLQVA LCSQAKLQAQ QELLQTKLEH LGPGEPPPVL LLQDDRHSTS SSEQEREGGR 430 440 450 460 470 480 TPTLEILKSH ISGIFRPKFS LPPPLQLIPE VQKPLHEQLW YHGAIPRAEV AELLVHSGDF 490 500 510 520 530 540 LVRESQGKQE YVLSVLWDGL PRHFIIQSLD NLYRLEGEGF PSIPLLIDHL LSTQQPLTKK 550 560 570 580 590 600 SGVVLHRAVP KDKWVLNHED LVLGEQIGRG NFGEVFSGRL RADNTLVAVK SCRETLPPDL 610 620 630 640 650 660 KAKFLQEARI LKQYSHPNIV RLIGVCTQKQ PIYIVMELVQ GGDFLTFLRT EGARLRVKTL 670 680 690 700 710 720 LQMVGDAAAG MEYLESKCCI HRDLAARNCL VTEKNVLKIS DFGMSREEAD GVYAASGGLR 730 740 750 760 770 780 QVPVKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGASP YPNLSNQQTR EFVEKGGRLP 790 800 810 820 CPELCPDAVF RLMEQCWAYE PGQRPSFSTI YQELQSIRKR HR
	Isoform 2 (Variant 1) [UniParc]. Checksum: 9BFFA652C8C3B8EB	FASTA	694	78,633
	10 20 30 40 50 60 MGFSSELCSP QGHGVLQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 70 80 90 100 110 120 RAISPDSPIS QTHSQDIEKL KSQYRALARD SAQAKRKYQE ASKDKDRDKA KDKYVRSLWK 130 140 150 160 170 180 LFAHHNRYVL GVRAAQLHHQ HHHQLLLPGL LRSLQDLHEE MACILKEILQ EYLEISSLVQ 190 200 210 220 230 240 DEVVAIHREM AAAAARIQPE AEYQGFLRQY GSAPDVPPCV TFDESLLEEG EPLEPGELQL 250 260 270 280 290 300 NELTVESVQH TLTSVTDELA VATEMVFRRQ EMVTQLQQEL RNEEENTHPR ERVQLLGKRQ 310 320 330 340 350 360 VLQEALQGLQ VALCSQAKLQ AQQELLQTKL EHLGPGEPPP VLLLQDDRHS TSSSEQEREG 370 380 390 400 410 420 GRTPTLEILK SHISGIFRPK FSNLYRLEGE GFPSIPLLID HLLSTQQPLT KKSGVVLHRA 430 440 450 460 470 480 VPKDKWVLNH EDLVLGEQIG RGNFGEVFSG RLRADNTLVA VKSCRETLPP DLKAKFLQEA 490 500 510 520 530 540 RILKQYSHPN IVRLIGVCTQ KQPIYIVMEL VQGGDFLTFL RTEGARLRVK TLLQMVGDAA 550 560 570 580 590 600 AGMEYLESKC CIHRDLAARN CLVTEKNVLK ISDFGMSREE ADGVYAASGG LRQVPVKWTA 610 620 630 640 650 660 PEALNYGRYS SESDVWSFGI LLWETFSLGA SPYPNLSNQQ TREFVEKGGR LPCPELCPDA 670 680 690 VFRLMEQCWA YEPGQRPSFS TIYQELQSIR KRHR
	Isoform 3 (Variant 3) [UniParc]. Checksum: 3F3713631F1D08A2	FASTA	764	86,663
	10 20 30 40 50 60 MGFSSELCSP QGHGVLQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 70 80 90 100 110 120 RAISPDSPIS QTHSQDIEKL KSQYRALARD SAQAKRKYQE ASKDKDRDKA KDKYVRSLWK 130 140 150 160 170 180 LFAHHNRYVL GVRAAQLHHQ HHHQLLLPGL LRSLQDLHEE MACILKEILQ EYLEISSLVQ 190 200 210 220 230 240 DEVVAIHREM AAAAARIQPE AEYQGFLRQY GSAPDVPPCV TFDESLLEEG EPLEPGELQL 250 260 270 280 290 300 NELTVESVQH TLTSVTDELA VATEMVFRRQ EMVTQLQQEL RNEEENTHPR ERVQLLGKRQ 310 320 330 340 350 360 VLQEALQGLQ VALCSQAKLQ AQQELLQTKL EHLGPGEPPP VLLLQDDRHS TSSSEQEREG 370 380 390 400 410 420 GRTPTLEILK SHISGIFRPK FSLPPPLQLI PEVQKPLHEQ LWYHGAIPRA EVAELLVHSG 430 440 450 460 470 480 DFLVRESQGK QEYVLSVLWD GLPRHFIIQS LDNLYRLEGE GFPSIPLLID HLLSTQQPLT 490 500 510 520 530 540 KKSGVVLHRA VPKDKWVLNH EDLVLGEQIG RGNFGEVFSG RLRADNTLVA VKSCRETLPP 550 560 570 580 590 600 DLKAKFLQEA RILKQYSHPN IVRLIGVCTQ KQPIYIVMEL VQGGDFLTFL RTEGARLRVK 610 620 630 640 650 660 TLLQMVGDAA AGMEYLESKC CIHRDLAARN CLVTEKNVLK ISDFGMSREE ADGVYAASGG 670 680 690 700 710 720 LRQVPVKWTA PEALNYGRYS SESDVWSFGI LLWETFSLGA SPYPNLSNQQ TREFVEKGGR 730 740 750 760 LPCPELCPDA VFRLMEQCWA YEPGQRPSFS TIYQELQSIR KRHR
	Isoform 4 (Variant 4) [UniParc]. Checksum: 0580B667FEF3FDD1	FASTA	752	85,466
	10 20 30 40 50 60 MGFSSELCSP QGHGVLQQMQ EAELRLLEGM RKWMAQRVKS DREYAGLLHH MSLQDSGGQS 70 80 90 100 110 120 RAISPDSPIS QSWAEITSQT EGLSRLLRQH AEDLNSGPLS KLSLLIRERQ QLRKTYSEQW 130 140 150 160 170 180 QQLQQELTKT HSQDIEKLKS QYRALARDSA QAKRKYQEAS KDKDRDKAKD KYVRSLWKLF 190 200 210 220 230 240 AHHNRYVLGV RAAQLHHQHH HQLLLPGLLR SLQDLHEEMA CILKEILQEY LEISSLVQDE 250 260 270 280 290 300 VVAIHREMAA AAARIQPEAE YQGFLRQYGS APDVPPCVTF DESLLEEGEP LEPGELQLNE 310 320 330 340 350 360 LTVESVQHTL TSVTDELAVA TEMVFRRQEM VTQLQQELRN EEENTHPRER VQLLGKRQVL 370 380 390 400 410 420 QEALQGLQVA LCSQAKLQAQ QELLQTKLEH LGPGEPPPVL LLQDDRHSTS SSEQEREGGR 430 440 450 460 470 480 TPTLEILKSH ISGIFRPKFS NLYRLEGEGF PSIPLLIDHL LSTQQPLTKK SGVVLHRAVP 490 500 510 520 530 540 KDKWVLNHED LVLGEQIGRG NFGEVFSGRL RADNTLVAVK SCRETLPPDL KAKFLQEARI 550 560 570 580 590 600 LKQYSHPNIV RLIGVCTQKQ PIYIVMELVQ GGDFLTFLRT EGARLRVKTL LQMVGDAAAG 610 620 630 640 650 660 MEYLESKCCI HRDLAARNCL VTEKNVLKIS DFGMSREEAD GVYAASGGLR QVPVKWTAPE 670 680 690 700 710 720 ALNYGRYSSE SDVWSFGILL WETFSLGASP YPNLSNQQTR EFVEKGGRLP CPELCPDAVF 730 740 750 RLMEQCWAYE PGQRPSFSTI YQELQSIRKR HR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human and mouse c-fes cDNA clones and identification of the 5' end of the gene." Alcalay M., Antolini F., van de Ven W.J.M., Lanfrancone L., Grignani F., Pelicci P.G. Oncogene 5:267-275(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The structure of the human c-fes/fps proto-oncogene." Roebroek A.J.M., Schalken J.A., Verbeek J.S., van den Ouweland A.M.W., Onnekink C., Bloemers H.P.J., van de Ven W.J.M. EMBO J. 4:2897-2903(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]	Lefebvre J.-C. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Tongue.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 1). Tissue: Brain.
[8]	"K562 leukemia cells transfected with the human c-fes gene acquire the ability to undergo myeloid differentiation." Yu G., Smithgall T.E., Glazer R.I. J. Biol. Chem. 264:10276-10281(1989) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL DIFFERENTIATION AND AS TUMOR SUPPRESSOR, CATALYTIC ACTIVITY.
[9]	"Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713)." Hjermstad S.J., Peters K.L., Briggs S.D., Glazer R.I., Smithgall T.E. Oncogene 8:2283-2292(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-713, CATALYTIC ACTIVITY, MUTAGENESIS OF TYR-713.
[10]	"Co-expression with BCR induces activation of the FES tyrosine kinase and phosphorylation of specific N-terminal BCR tyrosine residues." Li J., Smithgall T.E. J. Biol. Chem. 271:32930-32936(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN BCR PHOSPHORYLATION, AUTOPHOSPHORYLATION, ENZYME REGULATION.
[11]	"Subcellular localization analysis of the closely related Fps/Fes and Fer protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking." Zirngibl R., Schulze D., Mirski S.E., Cole S.P., Greer P.A. Exp. Cell Res. 266:87-94(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"A point mutation in the N-terminal coiled-coil domain releases c-Fes tyrosine kinase activity and survival signaling in myeloid leukemia cells." Cheng H.Y., Schiavone A.P., Smithgall T.E. Mol. Cell. Biol. 21:6170-6180(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION AND CELL SPREADING, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBUNIT, DOMAIN, MUTAGENESIS OF LEU-145 AND LEU-334.
[13]	"Closing in on the biological functions of Fps/Fes and Fer." Greer P. Nat. Rev. Mol. Cell Biol. 3:278-289(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[14]	"The c-Fes tyrosine kinase cooperates with the breakpoint cluster region protein (Bcr) to induce neurite extension in a Rac- and Cdc42-dependent manner." Laurent C.E., Smithgall T.E. Exp. Cell Res. 299:188-198(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN REORGANIZATION OF THE ACTIN CYTOSKELETON AND CELL DIFFERENTIATION, INTERACTION WITH BCR.
[15]	"The human c-Fes tyrosine kinase binds tubulin and microtubules through separate domains and promotes microtubule assembly." Laurent C.E., Delfino F.J., Cheng H.Y., Smithgall T.E. Mol. Cell. Biol. 24:9351-9358(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TUBULIN AND MICROTUBULES, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION BY HCK, MUTAGENESIS OF LEU-145; ARG-483 AND LYS-590.
[16]	"An identity crisis for fps/fes: oncogene or tumor suppressor?" Sangrar W., Zirgnibl R.A., Gao Y., Muller W.J., Jia Z., Greer P.A. Cancer Res. 65:3518-3522(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF MET-704; ARG-706; VAL-743 AND SER-759.
[17]	"Expression of c-Fes protein isoforms correlates with differentiation in myeloid leukemias." Carlson A., Berkowitz J.M., Browning D., Slamon D.J., Gasson J.C., Yates K.E. DNA Cell Biol. 24:311-316(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING.
[18]	"The KRAB-associated co-repressor KAP-1 is a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase." Delfino F.J., Shaffer J.M., Smithgall T.E. Biochem. J. 399:141-150(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRIM28.
[19]	"A growth-suppressive function for the c-fes protein-tyrosine kinase in colorectal cancer." Delfino F.J., Stevenson H., Smithgall T.E. J. Biol. Chem. 281:8829-8835(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN STAT3 PHOSPHORYLATION, ROLE AS PUTATIVE TUMOR SUPPRESSOR IN COLON CANCER, MUTAGENESIS OF MET-704; ARG-706; VAL-743 AND SER-759, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[20]	"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 IN KIT SIGNALING, POSSIBLE ROLE IN CANCER CELL PROLIFERATION.
[21]	"Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering." Naba A., Reverdy C., Louvard D., Arpin M. EMBO J. 27:38-50(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CYTOSKELETON REORGANIZATION, INTERACTION WITH EZR, PHOSPHORYLATION AT TYR-713, SUBCELLULAR LOCATION.
[22]	"Bimolecular fluorescence complementation demonstrates that the c-Fes protein-tyrosine kinase forms constitutive oligomers in living cells." Shaffer J.M., Hellwig S., Smithgall T.E. Biochemistry 48:4780-4788(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-713, PHOSPHORYLATION BY HCK, DOMAIN.
[23]	"Promoter methylation blocks FES protein-tyrosine kinase gene expression in colorectal cancer." Shaffer J.M., Smithgall T.E. Genes Chromosomes Cancer 48:272-284(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, ROLE AS PUTATIVE TUMOR SUPPRESSOR IN COLON CANCER.
[24]	"Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of human renal carcinoma cells." Kanda S., Miyata Y., Kanetake H., Smithgall T.E. Int. J. Oncol. 34:89-96(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PUTATIVE ROLE IN RENAL CARCINOMA.
[25]	"Contributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for coupling to the FcepsilonRI pathway in mast cells." McPherson V.A., Everingham S., Karisch R., Smith J.A., Udell C.M., Zheng J., Jia Z., Craig A.W. Mol. Cell. Biol. 29:389-401(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MS4A2/FCER1B AND HCLS1/HS1, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH PHOSPHOINOSITIDE-CONTAINING MEMBRANES, MUTAGENESIS OF 113-ARG-LYS-114.
[26]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64; SER-67; TYR-261; TYR-713 AND SER-716, MASS SPECTROMETRY.
[27]	"FES kinases are required for oncogenic FLT3 signaling." Voisset E., Lopez S., Chaix A., Georges C., Hanssens K., Prebet T., Dubreuil P., De Sepulveda P. Leukemia 24:721-728(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT THR-421, INTERACTION WITH FLT3.
[28]	"Structure and regulation of the c-Fes protein-tyrosine kinase." Hellwig S., Smithgall T.E. Front. Biosci. 17:3146-3155(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[29]	"Pathological significance and predictive value for biochemical recurrence of c-Fes expression in prostate cancer." Miyata Y., Watanabe S.I., Matsuo T., Hayashi T., Sakai H., Xuan J.W., Greer P.A., Kanda S. Prostate 72:201-208(2012) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE ROLE IN PROSTATE CANCER.
[30]	"Solution structure of the Src homology 2 domain from the human feline sarcoma oncogene Fes." Scott A., Pantoja-Uceda D., Koshiba S., Inoue M., Kigawa T., Terada T., Shirouzu M., Tanaka A., Sugano S., Yokoyama S., Guentert P. J. Biomol. NMR 31:357-361(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 450-550.
[31]	"Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation." Filippakopoulos P., Kofler M., Hantschel O., Gish G.D., Grebien F., Salah E., Neudecker P., Kay L.E., Turk B.E., Superti-Furga G., Pawson T., Knapp S. Cell 134:793-803(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 448-822 OF UNPHOSPHORYLATED APOPROTEIN AND IN COMPLEX WITH STAUROSPORINE AND A SUBSTRATE PEPTIDE, CATALYTIC ACTIVITY, ENZYME REGULATION, PHOSPHORYLATION AT TYR-713, NMR SPECTROSCOPY, MUTAGENESIS OF GLY-463 AND ARG-483.
[32]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-85; GLN-246 AND VAL-323.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X52192 mRNA. Translation: CAA36438.1.
X06292 Genomic DNA. Translation: CAA29619.1.
AY513654 mRNA. Translation: AAS82866.1.
AY513656 mRNA. Translation: AAS82868.1.
AY513657 mRNA. Translation: AAS82869.1.
AK300595 mRNA. Translation: BAG62292.1.
AK312545 mRNA. Translation: BAG35443.1.
AC124248 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02114.1.
BC035357 mRNA. Translation: AAH35357.1.

IPI

IPI00294344.
IPI00658077.
IPI00658126.
IPI01015757.

PIR

TVHUFF. A24673.

RefSeq

NP_001137255.1. NM_001143783.1.
NP_001137256.1. NM_001143784.1.
NP_001137257.1. NM_001143785.1.
NP_001996.1. NM_002005.3.

UniGene

Hs.7636.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WQU	NMR	-	A	450-550	[»]
2DCR	NMR	-	A	450-550	[»]
3BKB	X-ray	1.78	A	448-822	[»]
3CBL	X-ray	1.75	A	448-822	[»]
3CD3	X-ray	1.98	A	448-822	[»]
4DYL	X-ray	2.18	A	1-405	[»]
4E93	X-ray	1.84	A	448-822	[»]

ProteinModelPortal

P07332.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07332. 6 interactions.

MINT

MINT-1497714.

STRING

9606.ENSP00000331504.

PTM databases

PhosphoSite

P07332.

Polymorphism databases

DMDM

115502390.

Proteomic databases

PaxDb

P07332.

PRIDE

P07332.

Protocols and materials databases

DNASU

2242.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000328850; ENSP00000331504; ENSG00000182511.
ENST00000394300; ENSP00000377837; ENSG00000182511.
ENST00000414248; ENSP00000414629; ENSG00000182511.
ENST00000444422; ENSP00000400868; ENSG00000182511.
ENST00000450438; ENSP00000409915; ENSG00000182511.

GeneID

2242.

KEGG

hsa:2242.

UCSC

uc002bpv.3. human.
uc002bpx.3. human.
uc002bpy.3. human.
uc010uqj.2. human.

Organism-specific databases

CTD

2242.

GeneCards

GC15P091426.

HGNC

HGNC:3657. FES.

HPA

HPA001376.

MIM

190030. gene.

neXtProt

NX_P07332.

PharmGKB

PA28098.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG005655.

InParanoid

P07332.

KO

K07527.

OMA

GAIPRAE.

OrthoDB

EOG4VDPXW.

PhylomeDB

P07332.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

angiopoietinreceptor_pathway. Angiopoietin receptor Tie2-mediated signaling.
il4_2pathway. IL4-mediated signaling events.
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P07332.

Bgee

P07332.

CleanEx

HS_FES.

Genevestigator

P07332.

GermOnline

ENSG00000182511. Homo sapiens.

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

BindingDB

P07332.

ChEMBL

CHEMBL5455.

EvolutionaryTrace

P07332.

GenomeRNAi

2242.

NextBio

9069.

SOURCE

Search...

Entry information

Entry name

FES_HUMAN

Accession

Primary (citable) accession number: P07332
Secondary accession number(s): B2R6E6 , B4DUD0, E9PC94, E9PC95, Q2VXS7, Q2VXS8, Q2VXT0, Q6GTU5

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	October 3, 2006
Last modified:	May 1, 2013
This is version 152 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.