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Protein

Tyrosine-protein kinase Fer

Gene

FER

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.10 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation2 Publications

Enzyme regulationi

Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei591ATPPROSITE-ProRule annotation1
Active sitei684Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi569 – 577ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • epidermal growth factor receptor binding Source: UniProtKB
  • lipid binding Source: UniProtKB
  • non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
  • protein phosphatase 1 binding Source: Ensembl
  • protein tyrosine kinase activity Source: ProtInc

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • cell adhesion Source: GO_Central
  • cell-cell adhesion mediated by cadherin Source: UniProtKB
  • cell differentiation Source: GO_Central
  • cell proliferation Source: UniProtKB
  • cellular response to insulin stimulus Source: UniProtKB
  • cellular response to macrophage colony-stimulating factor stimulus Source: UniProtKB
  • cellular response to reactive oxygen species Source: UniProtKB
  • chemotaxis Source: GO_Central
  • cytokine-mediated signaling pathway Source: UniProtKB
  • diapedesis Source: UniProtKB
  • extracellular matrix-cell signaling Source: UniProtKB
  • Fc-epsilon receptor signaling pathway Source: UniProtKB
  • innate immune response Source: GO_Central
  • insulin receptor signaling pathway via phosphatidylinositol 3-kinase Source: UniProtKB
  • interleukin-6-mediated signaling pathway Source: UniProtKB
  • intracellular signal transduction Source: ProtInc
  • Kit signaling pathway Source: UniProtKB
  • microtubule cytoskeleton organization Source: UniProtKB
  • mitotic cell cycle Source: UniProtKB
  • negative regulation of mast cell activation involved in immune response Source: UniProtKB
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of actin filament polymerization Source: UniProtKB
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: CACAO
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
  • regulation of fibroblast migration Source: Ensembl
  • regulation of lamellipodium assembly Source: UniProtKB
  • regulation of mast cell degranulation Source: GO_Central
  • regulation of protein phosphorylation Source: UniProtKB
  • response to lipopolysaccharide Source: UniProtKB
  • response to platelet-derived growth factor Source: UniProtKB
  • substrate adhesion-dependent cell spreading Source: UniProtKB
  • tyrosine phosphorylation of STAT protein Source: UniProtKB

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Lipid-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2 2681
ReactomeiR-HSA-1433557 Signaling by SCF-KIT
SignaLinkiP16591
SIGNORiP16591

Names & Taxonomyi

Protein namesi
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 namesi
Name:FER
Synonyms:TYK3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000151422.12
HGNCiHGNC:3655 FER
MIMi176942 gene
neXtProtiNX_P16591

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi483R → Q: Abolishes kinase activity. Abolishes location at microtubules. 1 Publication1
Mutagenesisi591K → R: Abolishes kinase activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi2241
OpenTargetsiENSG00000151422
PharmGKBiPA28095

Chemistry databases

ChEMBLiCHEMBL3982
GuidetoPHARMACOLOGYi2022

Polymorphism and mutation databases

BioMutaiFER
DMDMi97536202

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000880841 – 822Tyrosine-protein kinase FerAdd BLAST822

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei402PhosphotyrosineCombined sources1
Modified residuei434PhosphoserineCombined sources1
Modified residuei615Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei714Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Autophosphorylated.2 Publications
Polyubiquitinated; this leads to proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP16591
PaxDbiP16591
PeptideAtlasiP16591
PRIDEiP16591
ProteomicsDBi53382
53383 [P16591-2]
53384 [P16591-3]

PTM databases

iPTMnetiP16591
PhosphoSitePlusiP16591

Expressioni

Tissue specificityi

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.3 Publications

Gene expression databases

BgeeiENSG00000151422
CleanExiHS_FER
ExpressionAtlasiP16591 baseline and differential
GenevisibleiP16591 HS

Organism-specific databases

HPAiCAB022464
HPA007641

Interactioni

Subunit structurei

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.By similarity8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • epidermal growth factor receptor binding Source: UniProtKB
  • protein phosphatase 1 binding Source: Ensembl

Protein-protein interaction databases

BioGridi108532, 21 interactors
IntActiP16591, 18 interactors
MINTiP16591
STRINGi9606.ENSP00000281092

Chemistry databases

BindingDBiP16591

Structurei

Secondary structure

1822
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni455 – 457Combined sources3
Beta strandi461 – 464Combined sources4
Helixi467 – 472Combined sources6
Beta strandi480 – 484Combined sources5
Beta strandi492 – 498Combined sources7
Beta strandi501 – 510Combined sources10
Beta strandi513 – 518Combined sources6
Beta strandi520 – 522Combined sources3
Helixi524 – 533Combined sources10
Turni540 – 542Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KK6NMR-A453-557[»]
ProteinModelPortaliP16591
SMRiP16591
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16591

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 259F-BARPROSITE-ProRule annotationAdd BLAST259
Domaini460 – 550SH2PROSITE-ProRule annotationAdd BLAST91
Domaini563 – 816Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 300Important for interaction with membranes containing phosphoinositidesAdd BLAST300

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili123 – 185Sequence analysisAdd BLAST63
Coiled coili301 – 390Sequence analysisAdd BLAST90

Domaini

The coiled coil domains mediate homooligomerization and are required for location at microtubules.
The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, SH2 domain

Phylogenomic databases

eggNOGiKOG0194 Eukaryota
ENOG410Y6RP LUCA
GeneTreeiENSGT00760000119011
HOGENOMiHOG000059550
HOVERGENiHBG005655
InParanoidiP16591
KOiK08889
OMAiQFADNLY
OrthoDBiEOG091G01S4
PhylomeDBiP16591
TreeFamiTF315363

Family and domain databases

CDDicd07686 F-BAR_Fer, 1 hit
cd10361 SH2_Fps_family, 1 hit
Gene3Di1.20.1270.60, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR031160 F_BAR
IPR001060 FCH_dom
IPR028539 Fer
IPR037452 Fer_F-BAR
IPR035849 Fes/Fps/Fer_SH2
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR016250 Tyr-prot_kinase_Fes/Fps
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PANTHERiPTHR24418:SF227 PTHR24418:SF227, 1 hit
PfamiView protein in Pfam
PF00611 FCH, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00017 SH2, 1 hit
PIRSFiPIRSF000632 TyrPK_fps, 1 hit
PRINTSiPR00401 SH2DOMAIN
PR00109 TYRKINASE
SMARTiView protein in SMART
SM00055 FCH, 1 hit
SM00252 SH2, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF55550 SSF55550, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51741 F_BAR, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS50001 SH2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16591-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC
60 70 80 90 100
NQVDKESTVQ MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL
110 120 130 140 150
TMMIKDKQQV KKSYIGVHQQ IEAEMIKVTK TELEKLKCSY RQLIKEMNSA
160 170 180 190 200
KEKYKEALAK GKETEKAKER YDKATMKLHM LHNQYVLALK GAQLHQNQYY
210 220 230 240 250
DITLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI VNVHKEIQMS
260 270 280 290 300
VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL
310 320 330 340 350
TAESLQVMLK TLAEELMQTQ QMLLNKEEAV LELEKRIEES SETCEKKSDI
360 370 380 390 400
VLLLSQKQAL EELKQSVQQL RCTEAKFSAQ KELLEQKVQE NDGKEPPPVV
410 420 430 440 450
NYEEDARSVT SMERKERLSK FESIRHSIAG IIRSPKSALG SSALSDMISI
460 470 480 490 500
SEKPLAEQDW YHGAIPRIEA QELLKKQGDF LVRESHGKPG EYVLSVYSDG
510 520 530 540 550
QRRHFIIQYV DNMYRFEGTG FSNIPQLIDH HYTTKQVITK KSGVVLLNPI
560 570 580 590 600
PKDKKWILSH EDVILGELLG KGNFGEVYKG TLKDKTSVAV KTCKEDLPQE
610 620 630 640 650
LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV SGGDFLTFLR
660 670 680 690 700
RKKDELKLKQ LVKFSLDAAA GMLYLESKNC IHRDLAARNC LVGENNVLKI
710 720 730 740 750
SDFGMSRQED GGVYSSSGLK QIPIKWTAPE ALNYGRYSSE SDVWSFGILL
760 770 780 790 800
WETFSLGVCP YPGMTNQQAR EQVERGYRMS APQHCPEDIS KIMMKCWDYK
810 820
PENRPKFSEL QKELTIIKRK LT
Length:822
Mass (Da):94,638
Last modified:May 16, 2006 - v2
Checksum:iBD42DF6C03419C76
GO
Isoform 2 (identifier: P16591-2) [UniParc]FASTAAdd to basket

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

Show »
Length:647
Mass (Da):74,266
Checksum:iF05F6497716D7D36
GO
Isoform 3 (identifier: P16591-3) [UniParc]FASTAAdd to basket
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.
Show »
Length:453
Mass (Da):51,643
Checksum:iE9B8AD1A2DD0A7DC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti219I → L in BAG61714 (PubMed:14702039).Curated1
Sequence conflicti234S → N in BAG61714 (PubMed:14702039).Curated1
Sequence conflicti426H → Q in BAG61714 (PubMed:14702039).Curated1
Sequence conflicti447M → L in AEY69041 (PubMed:22223638).Curated1
Sequence conflicti485S → G in AEY69041 (PubMed:22223638).Curated1
Sequence conflicti492Y → H in AEY69041 (PubMed:22223638).Curated1
Sequence conflicti505F → L in BAG61714 (PubMed:14702039).Curated1
Sequence conflicti558L → F in AEY69041 (PubMed:22223638).Curated1
Sequence conflicti730E → G in BAG61714 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041691128V → F1 PublicationCorresponds to variant dbSNP:rs35150210Ensembl.1
Natural variantiVAR_041692404E → Q in an ovarian Endometrioid carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041693412M → V1 PublicationCorresponds to variant dbSNP:rs33940843Ensembl.1
Natural variantiVAR_006282439L → V3 PublicationsCorresponds to variant dbSNP:rs2229086Ensembl.1
Natural variantiVAR_041694443A → P1 PublicationCorresponds to variant dbSNP:rs34259824Ensembl.1
Natural variantiVAR_041695460W → C in a lung small cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_051695507I → T. Corresponds to variant dbSNP:rs34204308Ensembl.1
Natural variantiVAR_041696813E → Q1 PublicationCorresponds to variant dbSNP:rs56097357Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0438461 – 369Missing in isoform 3. 1 PublicationAdd BLAST369
Alternative sequenceiVSP_0417651 – 175Missing in isoform 2. 1 PublicationAdd BLAST175
Alternative sequenceiVSP_043847370 – 412LRCTE…SVTSM → MEQKMKCPHCKDQLESGFGS QSCKTCALMFSSEPSTSEVH RDQ in isoform 3. 1 PublicationAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS4098.1 [P16591-1]
CCDS78044.1 [P16591-3]
PIRiA31943 TVHUFE
RefSeqiNP_001294957.1, NM_001308028.1 [P16591-2]
NP_001294960.1, NM_001308031.1 [P16591-3]
NP_001294967.1, NM_001308038.1
NP_005237.2, NM_005246.3 [P16591-1]
XP_011541573.1, XM_011543271.2 [P16591-1]
XP_016864719.1, XM_017009230.1 [P16591-1]
XP_016864720.1, XM_017009231.1 [P16591-1]
UniGeneiHs.107418
Hs.221472
Hs.625304

Genome annotation databases

EnsembliENST00000281092; ENSP00000281092; ENSG00000151422 [P16591-1]
ENST00000618353; ENSP00000484767; ENSG00000151422 [P16591-3]
GeneIDi2241
KEGGihsa:2241
UCSCiuc031skp.2 human [P16591-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiFER_HUMAN
AccessioniPrimary (citable) accession number: P16591
Secondary accession number(s): B2RCR4, B4DSQ2, H2FLB8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: May 16, 2006
Last modified: June 20, 2018
This is version 197 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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