P09760 (FER_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Fer
EC=2.7.10.2

Alternative name(s):
Proto-oncogene c-Fer
Tyrosine-protein kinase FLK
p94-Fer

Gene names

Name:	Fer
Synonyms:	Fert2, Flk

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	823 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 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 clearly depends on cell type and stimulus By similarity. Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Ref.3
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Homotrimer. Interacts with IRS1, JAK1, NRP1, PIK3R1, PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320'. 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 By similarity. Interacts with ARHGDIA. Ref.4
Subcellular location	Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell projection By similarity. Cell junction By similarity. Membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Nucleus By similarity. Cytoplasm › cell cortex By similarity. 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 By similarity.
Domain	The coiled coil domains mediate homooligomerization and are required for location at microtubules By similarity. The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes By similarity.
Post-translational modification	Autophosphorylated By similarity. 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
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	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 electronic annotation. Source: Compara cell-cell adhesion mediated by cadherin Inferred from sequence or structural similarity. Source: UniProtKB cellular response to macrophage colony-stimulating factor stimulus Inferred from electronic annotation. Source: Compara 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 electronic annotation. Source: Compara microtubule cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB mitotic cell cycle Inferred from electronic annotation. Source: Compara negative regulation of mast cell activation involved in immune response Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-tyrosine phosphorylation 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 sequence or structural similarity. Source: UniProtKB positive regulation of actin filament polymerization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of epidermal growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of fibroblast migration Inferred from electronic annotation. Source: Compara regulation of lamellipodium assembly Inferred from sequence or structural similarity. 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 electronic annotation. Source: Compara
Cellular_component	actin cytoskeleton Inferred from electronic annotation. Source: Compara cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from electronic annotation. Source: Compara microtubule cytoskeleton Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW epidermal growth factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB lipid binding Inferred from sequence or structural similarity. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 823	823	Tyrosine-protein kinase Fer		PRO_0000088093
Regions
	Domain	1 – 58	58	FCH
	Domain	461 – 551	91	SH2
	Domain	564 – 815	252	Protein kinase
	Nucleotide binding	570 – 578	9	ATP By similarity
	Region	1 – 300	300	Important for interaction with membranes containing phosphoinositides By similarity
	Coiled coil	123 – 185	63	Potential
	Coiled coil	301 – 382	82	Potential
Sites
	Active site	685	1	Proton acceptor By similarity
	Binding site	592	1	ATP By similarity
Amino acid modifications
	Modified residue	402	1	Phosphotyrosine By similarity
	Modified residue	434	1	Phosphoserine By similarity
	Modified residue	616	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	715	1	Phosphotyrosine; by autocatalysis By similarity
Experimental info
	Sequence conflict	501	1	G → R in CAA31778. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P09760 [UniParc]. Last modified September 21, 2011. Version 2. Checksum: CA4F31E375F747DA	FASTA	823	94,314
	10 20 30 40 50 60 MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKDSTVQ 70 80 90 100 110 120 VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYVGIHQQ 130 140 150 160 170 180 IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER CDKATMKLHM 190 200 210 220 230 240 LHNQYVLALK GAQLHQSQYY DTTLPLLLDS VQKMQEEMIK ALKGIFDEYS EITSLVTEEI 250 260 270 280 290 300 VNVHKEIQMS VDQIDPSTEY NDFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 310 320 330 340 350 360 TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES SETCAKKSDI VLLLGQKQAL 370 380 390 400 410 420 EELKQSVQQL RCTEAKCAAQ KELLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 430 440 450 460 470 480 FESIRHSIAG IIKSPKSVLG SSTQLSDVIS VGEKPLAEHD WYHGAIPRIE AQELLKQQGD 490 500 510 520 530 540 FLVRESHGKP GEYVLSVYSD GQRRHFIIQF VDNLYRFEGT GFSNIPQLID HHFNTKQVIT 550 560 570 580 590 600 KKSGVVLLNP IPKDKKWVLN HEDVSLGELL GKGNFGEVYK GTLKDKTPVA VKTCKEDLPQ 610 620 630 640 650 660 ELKIKFLQEA KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VPGGDFLSFL RKRKDELKLK 670 680 690 700 710 720 QLVRFSLDVA AGMLYLEGKN CIHRDLAARN CLVGENNTLK ISDFGMSRQE DGGVYSSSGL 730 740 750 760 770 780 KQIPIKWTAP EALNYGRYSS ESDVWSFGIL LWETFSLGVC PYPGMTNQQA REQVERGYRM 790 800 810 820 SAPQNCPEEI FTIMMKCWDY KPENRPKFSD LHKELTAIKK KIT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[2]	"Novel protein-tyrosine kinase cDNAs related to fps/fes and eph cloned using anti-phosphotyrosine antibody." Letwin K., Yee S.P., Pawson T. Oncogene 3:621-627(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 501-823. Strain: Wistar. Tissue: Brain.
[3]	"Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and beta-catenin." Lee S.H., Peng I.F., Ng Y.G., Yanagisawa M., Bamji S.X., Elia L.P., Balsamo J., Lilien J., Anastasiadis P.Z., Ullian E.M., Reichardt L.F. J. Cell Biol. 183:893-908(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN SYNAPSE ORGANIZATION AND SYNAPTIC TRANSMISSION.
[4]	"The Fer tyrosine kinase regulates interactions of Rho GDP-Dissociation Inhibitor alpha with the small GTPase Rac." Fei F., Kweon S.M., Haataja L., De Sepulveda P., Groffen J., Heisterkamp N. BMC Biochem. 11:48-48(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ARHGDIA.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X13412 mRNA. Translation: CAA31778.1.
IPI	IPI00475852.
PIR	S04328.
UniGene	Rn.102629.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000021758.
PTM databases
PhosphoSite	P09760.
Proteomic databases
PaxDb	P09760.
PRIDE	P09760.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000021758; ENSRNOP00000021758; ENSRNOG00000015898.
Organism-specific databases
RGD	1306273. Fert2.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00600000084126.
HOGENOM	HOG000233858.
HOVERGEN	HBG001540.
InParanoid	P09760.
OMA	QYRFEGT.
OrthoDB	EOG4JM7P1.
Gene expression databases
ArrayExpress	P09760.
Genevestigator	P09760.
GermOnline	ENSRNOG00000015898. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR001060. FCH_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016250. Tyr_kinase_non-rcpt_Fes_subgr. [Graphical view]
Pfam	PF00611. FCH. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PIRSF	PIRSF000632. TyrPK_fps. 1 hit.
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
SMART	SM00055. FCH. 1 hit. SM00252. SH2. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50133. FCH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

FER_RAT

Accession

Primary (citable) accession number: P09760
Secondary accession number(s): F1MA12

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	September 21, 2011
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program