P16591 (FER_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Fer
EC=2.7.10.2

Alternative name(s):
Feline encephalitis virus-related kinase FER
Fujinami poultry sarcoma/Feline sarcoma-related protein Fer
Proto-oncogene c-Fer
Tyrosine kinase 3
p94-Fer

Gene names

Name:	FER
Synonyms:	TYK3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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 for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell attachment and cell migration. Acts downstream of EGFR, PDGFRa and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. Ref.8 Ref.9 Ref.10 Ref.16 Ref.18 Ref.19 Ref.20
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.10 Ref.18
Enzyme regulation	Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS). Ref.18
Subunit structure	Homotrimer. Interacts with IRS1 and PIK3R1 By similarity. Interacts with CTNND1, EGFR, FLT3, PECAM1 and PDGFR. Interacts (via SH2 domain) with CTTN. Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Ref.8 Ref.9 Ref.10 Ref.16 Ref.19 Ref.20
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection. Cell junction. Membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Cytoplasm › cell cortex. Note: Associated with the chromatin. Detected on microtubles in polarized and motile vascular endothelial cells. Colocalizes with F-actin at the cell cortex. Colocalizes with PECAM1 and CTNND1 at nascent cell-cell contacts. Ref.7 Ref.9 Ref.10 Ref.11
Tissue specificity	Widely expressed. Ref.6
Domain	The coiled coil domains mediate homooligomerization and are required for location at microtubules. Ref.11 Ref.18 The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes. Ref.11 Ref.18
Post-translational modification	Autophosphorylated. Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19 Ref.20
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 Cell projection Cytoplasm Cytoskeleton Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
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	intracellular signal transduction Traceable author statement. Source: ProtInc microtubule cytoskeleton organization Inferred from mutant phenotype Ref.10. Source: UniProtKB negative regulation of mast cell activation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from direct assay Ref.10Ref.18. Source: UniProtKB platelet-derived growth factor receptor signaling pathway Traceable author statement Ref.22. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.20. Source: UniProtKB positive regulation of actin filament polymerization Inferred from mutant phenotype Ref.18. Source: UniProtKB positive regulation of cell migration Inferred from mutant phenotype Ref.18. Source: UniProtKB positive regulation of cell proliferation Traceable author statement Ref.19. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.8. Source: UniProtKB regulation of epidermal growth factor receptor signaling pathway Inferred from mutant phenotype Ref.20. Source: UniProtKB regulation of lamellipodium assembly Inferred from direct assay Ref.18. Source: UniProtKB
Cellular component	cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cell projection Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to internal side of plasma membrane Inferred from direct assay Ref.18. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW epidermal growth factor receptor binding Inferred from direct assay Ref.20. Source: UniProtKB lipid binding Inferred from direct assay Ref.18. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.10Ref.18. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P16591-1)

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: P16591-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-175: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 822

822

Tyrosine-protein kinase Fer

PRO_0000088084

Regions

Domain

1 – 58

58

FCH

Domain

460 – 550

91

SH2

Domain

563 – 816

254

Protein kinase

Nucleotide binding

569 – 577

9

ATP By similarity

Region

1 – 300

300

Important for interaction with membranes containing phosphoinositides

Coiled coil

123 – 185

63

Potential

Coiled coil

301 – 390

90

Potential

Sites

Active site

684

1

Proton acceptor By similarity

Binding site

591

1

ATP By similarity

Amino acid modifications

Modified residue

402

1

Phosphotyrosine Ref.12 Ref.13 Ref.14 Ref.15 Ref.17

Modified residue

410

1

Phosphothreonine Ref.17

Modified residue

411

1

Phosphoserine Ref.15 Ref.17

Modified residue

434

1

Phosphoserine Ref.13 Ref.15 Ref.17

Modified residue

714

1

Phosphotyrosine; by autocatalysis Ref.12 Ref.13 Ref.15 Ref.17

Natural variations

Alternative sequence

1 – 175

175

Missing in isoform 2.

VSP_041765

Natural variant

128

1

V → F. [dbSNP:rs35150210] Ref.24

VAR_041691

Natural variant

404

1

E → Q in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.24

VAR_041692

Natural variant

412

1

M → V. [dbSNP:rs33940843] Ref.24

VAR_041693

Natural variant

439

1

L → V. [dbSNP:rs34499946] Ref.1 Ref.23 Ref.24

VAR_006282

Natural variant

443

1

A → P. [dbSNP:rs34259824] Ref.24

VAR_041694

Natural variant

460

1

W → C in a lung small cell carcinoma sample; somatic mutation. Ref.24

VAR_041695

Natural variant

507

1

I → T. [dbSNP:rs34204308]

VAR_051695

Natural variant

813

1

E → Q. [dbSNP:rs56097357] Ref.24

VAR_041696

Experimental info

Mutagenesis

483

1

R → Q: Abolishes kinase activity. Abolishes location at microtubules. Ref.10

Mutagenesis

591

1

K → R: Abolishes kinase activity. Ref.9

Sequence conflict

219

1

I → L in BAG61714. Ref.2

Sequence conflict

234

1

S → N in BAG61714. Ref.2

Sequence conflict

426

1

H → Q in BAG61714. Ref.2

Sequence conflict

505

1

F → L in BAG61714. Ref.2

Sequence conflict

730

1

E → G in BAG61714. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

822

Helix Strand Turn

Details...

Turn

455 – 457

3

Helix

467 – 472

6

Beta strand

480 – 484

5

Beta strand

492 – 497

6

Beta strand

502 – 510

9

Beta strand

513 – 515

3

Helix

524 – 533

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 16, 2006. Version 2. Checksum: BD42DF6C03419C76	FASTA	822	94,638
	10 20 30 40 50 60 MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC NQVDKESTVQ 70 80 90 100 110 120 MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYIGVHQQ 130 140 150 160 170 180 IEAEMIKVTK TELEKLKCSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM 190 200 210 220 230 240 LHNQYVLALK GAQLHQNQYY DITLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI 250 260 270 280 290 300 VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 310 320 330 340 350 360 TAESLQVMLK TLAEELMQTQ QMLLNKEEAV LELEKRIEES SETCEKKSDI VLLLSQKQAL 370 380 390 400 410 420 EELKQSVQQL RCTEAKFSAQ KELLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 430 440 450 460 470 480 FESIRHSIAG IIRSPKSALG SSALSDMISI SEKPLAEQDW YHGAIPRIEA QELLKKQGDF 490 500 510 520 530 540 LVRESHGKPG EYVLSVYSDG QRRHFIIQYV DNMYRFEGTG FSNIPQLIDH HYTTKQVITK 550 560 570 580 590 600 KSGVVLLNPI PKDKKWILSH EDVILGELLG KGNFGEVYKG TLKDKTSVAV KTCKEDLPQE 610 620 630 640 650 660 LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV SGGDFLTFLR RKKDELKLKQ 670 680 690 700 710 720 LVKFSLDAAA GMLYLESKNC IHRDLAARNC LVGENNVLKI SDFGMSRQED GGVYSSSGLK 730 740 750 760 770 780 QIPIKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGVCP YPGMTNQQAR EQVERGYRMS 790 800 810 820 APQHCPEDIS KIMMKCWDYK PENRPKFSEL QKELTIIKRK LT
	Isoform 2 [UniParc]. Checksum: F05F6497716D7D36	FASTA	647	74,266
	10 20 30 40 50 60 MKLHMLHNQY VLALKGAQLH QNQYYDITLP LLLDSLQKMQ EEMIKALKGI FDEYSQITSL 70 80 90 100 110 120 VTEEIVNVHK EIQMSVEQID PSTEYNNFID VHRTTAAKEQ EIEFDTSLLE ENENLQANEI 130 140 150 160 170 180 MWNNLTAESL QVMLKTLAEE LMQTQQMLLN KEEAVLELEK RIEESSETCE KKSDIVLLLS 190 200 210 220 230 240 QKQALEELKQ SVQQLRCTEA KFSAQKELLE QKVQENDGKE PPPVVNYEED ARSVTSMERK 250 260 270 280 290 300 ERLSKFESIR HSIAGIIRSP KSALGSSALS DMISISEKPL AEQDWYHGAI PRIEAQELLK 310 320 330 340 350 360 KQGDFLVRES HGKPGEYVLS VYSDGQRRHF IIQYVDNMYR FEGTGFSNIP QLIDHHYTTK 370 380 390 400 410 420 QVITKKSGVV LLNPIPKDKK WILSHEDVIL GELLGKGNFG EVYKGTLKDK TSVAVKTCKE 430 440 450 460 470 480 DLPQELKIKF LQEAKILKQY DHPNIVKLIG VCTQRQPVYI IMELVSGGDF LTFLRRKKDE 490 500 510 520 530 540 LKLKQLVKFS LDAAAGMLYL ESKNCIHRDL AARNCLVGEN NVLKISDFGM SRQEDGGVYS 550 560 570 580 590 600 SSGLKQIPIK WTAPEALNYG RYSSESDVWS FGILLWETFS LGVCPYPGMT NQQAREQVER 610 620 630 640 GYRMSAPQHC PEDISKIMMK CWDYKPENRP KFSELQKELT IIKRKLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and sequence analysis of a novel human tyrosine kinase gene." Hao Q.-L., Heisterkamp N., Groffen J. Mol. Cell. Biol. 9:1587-1593(1989) [PubMed: 2725517] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-439.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain.
[3]	"The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M. Nature 431:268-274(2004) [PubMed: 15372022] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes." Lee S.-T., Strunk K.M., Spritz R.A. Oncogene 8:3403-3410(1993) [PubMed: 8247543] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 686-741.
[6]	"Identification and chromosomal mapping of new human tyrosine kinase genes." Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R. Oncogene 5:277-282(1990) [PubMed: 2156206] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Nuclear and cytoplasmic location of the FER tyrosine kinase." Hao Q.-L., Ferris D.K., White G., Heisterkamp N., Groffen J. Mol. Cell. Biol. 11:1180-1183(1991) [PubMed: 1990274] [Abstract] Cited for: SUBCELLULAR LOCATION.
[8]	"The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors." Kim L., Wong T.W. Mol. Cell. Biol. 15:4553-4561(1995) [PubMed: 7623846] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CTNND1, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH CTNND1.
[9]	"Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the cytoplasmic tyrosine kinase FER." Kim L., Wong T.W. J. Biol. Chem. 273:23542-23548(1998) [PubMed: 9722593] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CTTN, INTERACTION WITH CTTN; CTNND1 AND PDGFR, MUTAGENESIS OF LYS-591, SUBCELLULAR LOCATION.
[10]	"Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells." Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M., Mochizuki N. Mol. Biol. Cell 14:3553-3564(2003) [PubMed: 12972546] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PECAM1; PTPN11 AND GAB1, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-483, INTERACTION WITH PECAM1.
[11]	"Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis." Tsujita K., Suetsugu S., Sasaki N., Furutani M., Oikawa T., Takenawa T. J. Cell Biol. 172:269-279(2006) [PubMed: 16418535] [Abstract] Cited for: SUBCELLULAR LOCATION, LIPID-BINDING, DOMAIN.
[12]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND TYR-714, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[13]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402; SER-434 AND TYR-714, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402; SER-411; SER-434 AND TYR-714, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes." Oh M.A., Choi S., Lee M.J., Choi M.C., Lee S.A., Ko W., Cance W.G., Oh E.S., Buday L., Kim S.H., Lee J.W. Biochim. Biophys. Acta 1793:781-791(2009) [PubMed: 19339212] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PTK2/FAK1, FUNCTION IN REGULATION OF ACTIN CYTOSKELETON, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH CTTN AND PTK2/FAK1.
[17]	"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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402; THR-410; SER-411; SER-434 AND TYR-714, MASS SPECTROMETRY.
[18]	"The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration." Itoh T., Hasegawa J., Tsujita K., Kanaho Y., Takenawa T. Sci. Signal. 2:RA52-RA52(2009) [PubMed: 19738202] [Abstract] Cited for: FUNCTION IN REGULATION OF ACTIN CYTOSKELETON AND CELL MIGRATION, CATALYTIC ACTIVITY, DOMAIN, LIPID-BINDING, ENZYME REGULATION.
[19]	"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: 20111072] [Abstract] Cited for: FUNCTION IN CELL PROLIFERATION, PHOSPHORYLATION, INTERACTION WITH FLT3.
[20]	"FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB." Guo C., Stark G.R. Proc. Natl. Acad. Sci. U.S.A. 108:7968-7973(2011) [PubMed: 21518868] [Abstract] Cited for: FUNCTION IN ACTIVATION OF NF-KAPPA-B DOWNSTREAM OF EGFR AND CELL PROLIFERATION, INTERACTION WITH EGFR, PHOSPHORYLATION.
[21]	"Solution structure of SH2 domain of proto-oncogene tyrosine-protein kinase FER from Homo sapiens, Northeast structural genomics consortium (NESG) target HR3461D." Northeast structural genomics consortium (NESG) Submitted (AUG-2009) to the PDB data bank Cited for: STRUCTURE BY NMR OF 453-557.
[22]	"Closing in on the biological functions of Fps/Fes and Fer." Greer P. Nat. Rev. Mol. Cell Biol. 3:278-289(2002) [PubMed: 11994747] [Abstract] Cited for: REVIEW.
[23]	"Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients." Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P., Markham A., Krush A.J., Petersen G.M., Hamilton S.R., Nilbert M.C., Levy D.B., Bryan T.M., Preisinger A.C. , Smith K.J., Su L.-K., Kinzler K.W., Vogelstein B. Science 253:665-669(1991) [PubMed: 1651563] [Abstract] Cited for: VARIANT VAL-439.
[24]	"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: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-128; GLN-404; VAL-412; VAL-439; PRO-443; CYS-460 AND GLN-813.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03358 mRNA. Translation: AAA61190.1.
AK299855 mRNA. Translation: BAG61714.1.
AK315234 mRNA. Translation: BAG37661.1.
AC034207 Genomic DNA. No translation available.
AC008871 Genomic DNA. No translation available.
AC109481 Genomic DNA. No translation available.
AC008955 Genomic DNA. No translation available.
AC010228 Genomic DNA. No translation available.
AC011421 Genomic DNA. No translation available.
AC116428 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW49055.1.

IPI

IPI00029263.
IPI01010324.

PIR

TVHUFE. A31943.

RefSeq

NP_005237.2. NM_005246.2.

UniGene

Hs.221472.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KK6	NMR	-	A	453-557	[»]

ProteinModelPortal

P16591.

SMR

P16591. Positions 452-820.

ModBase

Search...

Protein-protein interaction databases

IntAct

P16591. 1 interaction.

MINT

MINT-261636.

STRING

P16591.

PTM databases

PhosphoSite

P16591.

Polymorphism databases

DMDM

97536202.

Proteomic databases

PeptideAtlas

P16591.

PRIDE

P16591.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000281092; ENSP00000281092; ENSG00000151422.
ENST00000438717; ENSP00000394297; ENSG00000151422.

GeneID

2241.

KEGG

hsa:2241.

UCSC

uc003kop.1. human.

Organism-specific databases

CTD

2241.

GeneCards

GC05P108111.

H-InvDB

HIX0032042.

HGNC

HGNC:3655. FER.

HPA

CAB022464.
HPA007641.

MIM

176942. gene.

neXtProt

NX_P16591.

PharmGKB

PA28095.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05339.

HOGENOM

HBG446727.

HOVERGEN

HBG005655.

InParanoid

P16591.

OMA

RHFIIQY.

OrthoDB

EOG4JM7P1.

PhylomeDB

P16591.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
pdgfrbpathway. PDGFR-beta signaling pathway.
ptp1bpathway. Signaling events mediated by PTP1B.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P16591.

Bgee

P16591.

CleanEx

HS_FER.

Genevestigator

P16591.

Family and domain databases

InterPro

IPR001060. FCH.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR000980. SH2.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016250. Tyr_kinase_non-rcpt_Fes_subgr.
[Graphical view]

Gene3D

G3DSA:3.30.505.10. SH2. 1 hit.

KO

K08889.

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

9065.

SOURCE

Search...

Entry information

Entry name

FER_HUMAN

Accession

Primary (citable) accession number: P16591
Secondary accession number(s): B2RCR4, B4DSQ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	May 16, 2006
Last modified:	January 25, 2012
This is version 132 of the entry and version 2 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.