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) [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 for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. 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. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus. Ref.2 Ref.9 Ref.10 Ref.11 Ref.12 Ref.16 Ref.18 Ref.20 Ref.21 Ref.22
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.11 Ref.20
Enzyme regulation	Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS). Ref.20
Subunit structure	Homotrimer. Interacts with ARHGDIA, IRS1, JAK1, NRP1, PIK3R1, PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320' By similarity. Interacts with CTNND1, EGFR, FLT3, PECAM1, PDGFR and STAT3. Interacts (via SH2 domain) with CTTN. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Ref.9 Ref.10 Ref.11 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22
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 microtubules 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.8 Ref.10 Ref.11 Ref.13
Tissue specificity	Isoform 1 is detected in normal colon and in fibroblasts (at protein level). Isoform 3 is detected in normal testis, in colon carcinoma-derived metastases in lung, liver and ovary, and in colon carcinoma and hepato carcinoma cell lines (at protein level). Isoform 3 is not detected in normal colon or in normal fibroblasts (at protein level). Widely expressed. Ref.2 Ref.7 Ref.14
Domain	The coiled coil domains mediate homooligomerization and are required for location at microtubules. Ref.13 Ref.20 The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes. Ref.13 Ref.20
Post-translational modification	Autophosphorylated. Ref.9 Ref.21 Ref.22 Polyubiquitinated; this leads to proteasomal degradation 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 Cell projection Cytoplasm Cytoskeleton Membrane Nucleus
Coding sequence diversity	Alternative promoter usage 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 Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Fc-epsilon receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB Kit signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB cell proliferation Inferred from mutant phenotype Ref.2. Source: UniProtKB cell-cell adhesion mediated by cadherin Inferred from sequence or structural similarity. Source: UniProtKB cellular response to macrophage colony-stimulating factor stimulus Inferred from mutant phenotype Ref.10. Source: UniProtKB cellular response to reactive oxygen species Inferred from sequence or structural similarity. Source: UniProtKB chemotaxis Inferred from electronic annotation. Source: Compara diapedesis Inferred from sequence or structural similarity. Source: UniProtKB extracellular matrix-cell signaling Inferred from sequence or structural similarity. Source: UniProtKB insulin receptor signaling pathway via phosphatidylinositol 3-kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB interleukin-6-mediated signaling pathway Inferred from mutant phenotype Ref.18. Source: UniProtKB microtubule cytoskeleton organization Inferred from mutant phenotype Ref.11. Source: UniProtKB mitotic cell cycle Inferred from mutant phenotype Ref.2. Source: UniProtKB negative regulation of mast cell activation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB platelet-derived growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.22. Source: UniProtKB positive regulation of actin filament polymerization Inferred from mutant phenotype Ref.20. Source: UniProtKB positive regulation of cell migration Inferred from mutant phenotype Ref.20. Source: UniProtKB positive regulation of cell proliferation Traceable author statement Ref.21. Source: UniProtKB protein autophosphorylation Inferred from direct assay Ref.9. Source: UniProtKB regulation of epidermal growth factor receptor signaling pathway Inferred from mutant phenotype Ref.22. Source: UniProtKB regulation of fibroblast migration Inferred from electronic annotation. Source: Compara regulation of lamellipodium assembly Inferred from direct assay Ref.20. Source: UniProtKB regulation of protein phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB response to platelet-derived growth factor stimulus Inferred from sequence or structural similarity. Source: UniProtKB substrate adhesion-dependent cell spreading Inferred from sequence or structural similarity. Source: UniProtKB tyrosine phosphorylation of Stat3 protein 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 cytosol Traceable author statement. Source: Reactome extrinsic to internal side of plasma membrane Inferred from direct assay Ref.20. Source: UniProtKB nucleus Inferred from direct assay Ref.18. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW epidermal growth factor receptor binding Inferred from direct assay Ref.22. Source: UniProtKB lipid binding Inferred from direct assay Ref.20. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from direct assay Ref.11Ref.20. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform 1 (identifier: P16591-1)

Also known as: p94;

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.

Isoform 3 (identifier: P16591-3)

Also known as: FerT; p47;

The sequence of this isoform differs from the canonical sequence as follows:
     1-369: Missing.
     370-412: LRCTEAKFSA...EEDARSVTSM → MEQKMKCPHC...PSTSEVHRDQ

Note: Produced by alternative promoter usage.

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.15 Ref.19

Modified residue

434

1

Phosphoserine Ref.15 Ref.19

Modified residue

615

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

714

1

Phosphotyrosine; by autocatalysis

Natural variations

Alternative sequence

1 – 369

369

Missing in isoform 3.

VSP_043846

Alternative sequence

1 – 175

175

Missing in isoform 2.

VSP_041765

Alternative sequence

370 – 412

43

LRCTE…SVTSM → MEQKMKCPHCKDQLESGFGS QSCKTCALMFSSEPSTSEVH RDQ in isoform 3.

VSP_043847

Natural variant

128

1

V → F. Ref.26
Corresponds to variant rs35150210 [ dbSNP | Ensembl ].

VAR_041691

Natural variant

404

1

E → Q in an ovarian Endometrioid carcinoma sample; somatic mutation. Ref.26

VAR_041692

Natural variant

412

1

M → V. Ref.26
Corresponds to variant rs33940843 [ dbSNP | Ensembl ].

VAR_041693

Natural variant

439

1

L → V. Ref.1 Ref.25 Ref.26
Corresponds to variant rs34499946 [ dbSNP | Ensembl ].

VAR_006282

Natural variant

443

1

A → P. Ref.26
Corresponds to variant rs34259824 [ dbSNP | Ensembl ].

VAR_041694

Natural variant

460

1

W → C in a lung small cell carcinoma sample; somatic mutation. Ref.26

VAR_041695

Natural variant

507

1

I → T.
Corresponds to variant rs34204308 [ dbSNP | Ensembl ].

VAR_051695

Natural variant

813

1

E → Q. Ref.26
Corresponds to variant rs56097357 [ dbSNP | Ensembl ].

VAR_041696

Experimental info

Mutagenesis

483

1

R → Q: Abolishes kinase activity. Abolishes location at microtubules. Ref.11

Mutagenesis

591

1

K → R: Abolishes kinase activity. Ref.10

Sequence conflict

219

1

I → L in BAG61714. Ref.3

Sequence conflict

234

1

S → N in BAG61714. Ref.3

Sequence conflict

426

1

H → Q in BAG61714. Ref.3

Sequence conflict

447

1

M → L in AEY69041. Ref.2

Sequence conflict

485

1

S → G in AEY69041. Ref.2

Sequence conflict

492

1

Y → H in AEY69041. Ref.2

Sequence conflict

505

1

F → L in BAG61714. Ref.3

Sequence conflict

558

1

L → F in AEY69041. Ref.2

Sequence conflict

730

1

E → G in BAG61714. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

822

Helix Strand Turn

Details...

Turn

455 – 457

3

Beta strand

461 – 464

4

Helix

467 – 472

6

Beta strand

480 – 484

5

Beta strand

492 – 498

7

Beta strand

501 – 510

10

Beta strand

513 – 518

6

Beta strand

520 – 522

3

Helix

524 – 533

10

Turn

540 – 542

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p94) [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
	Isoform 3 (FerT) (p47) [UniParc]. Checksum: E9B8AD1A2DD0A7DC	FASTA	453	51,643
	10 20 30 40 50 60 MEQKMKCPHC KDQLESGFGS QSCKTCALMF SSEPSTSEVH RDQERKERLS KFESIRHSIA 70 80 90 100 110 120 GIIRSPKSAL GSSALSDMIS ISEKPLAEQD WYHGAIPRIE AQELLKKQGD FLVRESHGKP 130 140 150 160 170 180 GEYVLSVYSD GQRRHFIIQY VDNMYRFEGT GFSNIPQLID HHYTTKQVIT KKSGVVLLNP 190 200 210 220 230 240 IPKDKKWILS HEDVILGELL GKGNFGEVYK GTLKDKTSVA VKTCKEDLPQ ELKIKFLQEA 250 260 270 280 290 300 KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VSGGDFLTFL RRKKDELKLK QLVKFSLDAA 310 320 330 340 350 360 AGMLYLESKN CIHRDLAARN CLVGENNVLK ISDFGMSRQE DGGVYSSSGL KQIPIKWTAP 370 380 390 400 410 420 EALNYGRYSS ESDVWSFGIL LWETFSLGVC PYPGMTNQQA REQVERGYRM SAPQHCPEDI 430 440 450 SKIMMKCWDY KPENRPKFSE LQKELTIIKR KLT

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-439.
[2]	"Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells." Makovski A., Yaffe E., Shpungin S., Nir U. J. Biol. Chem. 287:6100-6112(2012) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE PROMOTER USAGE, FUNCTION, MASS SPECTROMETRY, TISSUE SPECIFICITY. Tissue: Testis.
[3]	"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: Brain.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 686-741.
[7]	"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] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CTNND1, AUTOPHOSPHORYLATION, SUBUNIT, INTERACTION WITH CTNND1.
[10]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CTTN, INTERACTION WITH CTTN; CTNND1 AND PDGFR, MUTAGENESIS OF LYS-591, SUBCELLULAR LOCATION.
[11]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PECAM1; PTPN11 AND GAB1, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-483, INTERACTION WITH PECAM1.
[12]	"Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription." Miravet S., Piedra J., Castano J., Raurell I., Franci C., Dunach M., Garcia de Herreros A. Mol. Cell. Biol. 23:7391-7402(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF JUP AND IN REGULATION OF PROTEIN PHOSPHORYLATION.
[13]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, LIPID-BINDING, DOMAIN.
[14]	"Expression of Fer testis (FerT) tyrosine kinase transcript variants and distribution sites of FerT during the development of the acrosome-acroplaxome-manchette complex in rat spermatids." Kierszenbaum A.L., Rivkin E., Tres L.L. Dev. Dyn. 237:3882-3891(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF ISOFORM 3, TISSUE SPECIFICITY.
[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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND SER-434, 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] [Europe PMC] [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]	"Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required for the Fer tyrosine kinase activity." Hikri E., Shpungin S., Nir U. Cell. Signal. 21:588-596(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HSP90.
[18]	"The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth." Zoubeidi A., Rocha J., Zouanat F.Z., Hamel L., Scarlata E., Aprikian A.G., Chevalier S. Mol. Cancer Res. 7:142-155(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN IL6 SIGNALING PATHWAY; CELL PROLIFERATION AND IN PHOSPHORYLATION OF STAT3, INTERACTION WITH STAT3.
[19]	"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 TYR-402 AND SER-434, MASS SPECTROMETRY.
[20]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN REGULATION OF ACTIN CYTOSKELETON AND CELL MIGRATION, CATALYTIC ACTIVITY, DOMAIN, LIPID-BINDING, ENZYME REGULATION.
[21]	"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 IN CELL PROLIFERATION, PHOSPHORYLATION, INTERACTION WITH FLT3.
[22]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF NF-KAPPA-B DOWNSTREAM OF EGFR AND CELL PROLIFERATION, INTERACTION WITH EGFR, PHOSPHORYLATION.
[23]	"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.
[24]	"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.
[25]	"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] [Europe PMC] [Abstract] Cited for: VARIANT VAL-439.
[26]	"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] 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.
JQ412173 mRNA. Translation: AEY69041.1.
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.

ModBase

Search...

Protein-protein interaction databases

IntAct

P16591. 3 interactions.

MINT

MINT-261636.

STRING

9606.ENSP00000281092.

PTM databases

PhosphoSite

P16591.

Polymorphism databases

DMDM

97536202.

Proteomic databases

PaxDb

P16591.

PeptideAtlas

P16591.

PRIDE

P16591.

Protocols and materials databases

DNASU

2241.

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.

HGNC

HGNC:3655. FER.

HPA

CAB022464.
HPA007641.

MIM

176942. gene.

neXtProt

NX_P16591.

PharmGKB

PA28095.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000059550.

HOVERGEN

HBG005655.

InParanoid

P16591.

KO

K08889.

OMA

QYRFEGT.

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.

SignaLink

P16591.

Gene expression databases

ArrayExpress

P16591.

Bgee

P16591.

CleanEx

HS_FER.

Genevestigator

P16591.

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

P16591.

ChEMBL

CHEMBL3982.

EvolutionaryTrace

P16591.

GenomeRNAi

2241.

NextBio

9065.

SOURCE

Search...

Entry information

Entry name

FER_HUMAN

Accession

Primary (citable) accession number: P16591
Secondary accession number(s): B2RCR4, B4DSQ2, H2FLB8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	May 16, 2006
Last modified:	May 29, 2013
This is version 147 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.