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Protein

Tyrosine-protein kinase Fer

Gene

Fer

Organism
Mus musculus (Mouse)
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). Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3 according to PubMed:10878010 and PubMed:19159681, but clearly plays a redundant role in STAT3 phosphorylation. According to PubMed:11134346, cells where wild type FER has been replaced by a kinase-dead mutant show no reduction in STAT3 phosphorylation. Phosphorylates TMF1. Isoform 3 lacks kinase activity.12 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

Enzyme regulationi

Activated by phosphatidic acid binding (By similarity). Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei592ATPPROSITE-ProRule annotation1
Active sitei685Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi570 – 578ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • actin cytoskeleton reorganization Source: UniProtKB
  • cell adhesion Source: MGI
  • cell-cell adhesion mediated by cadherin Source: UniProtKB
  • cell proliferation Source: MGI
  • cellular response to insulin stimulus Source: UniProtKB
  • cellular response to macrophage colony-stimulating factor stimulus Source: MGI
  • cellular response to reactive oxygen species Source: UniProtKB
  • chemotaxis Source: MGI
  • cytokine-mediated signaling pathway Source: UniProtKB
  • diapedesis Source: UniProtKB
  • epidermal growth factor receptor signaling pathway Source: GO_Central
  • 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: MGI
  • Kit signaling pathway Source: UniProtKB
  • microtubule cytoskeleton organization Source: UniProtKB
  • mitotic cell cycle Source: MGI
  • 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: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • protein autophosphorylation Source: MGI
  • protein phosphorylation Source: MGI
  • regulation of cell proliferation Source: GO_Central
  • regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
  • regulation of fibroblast migration Source: UniProtKB
  • 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
  • signal transduction Source: MGI
  • substrate adhesion-dependent cell spreading Source: UniProtKB
  • tyrosine phosphorylation of STAT protein Source: MGI

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-1433557 Signaling by SCF-KIT

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Fer (EC:2.7.10.2)
Alternative name(s):
Proto-oncogene c-Fer
p94-Fer
Gene namesi
Name:Fer
Synonyms:Fert2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:105917 Fer

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

Disruption phenotypei

No visible phenotype, and the mice are fertile. Mice have reduced CTTN phosphorylation. Mice lacking both Fps/Fes and Fer activity are viable and fertile, but produce slightly fewer pups per litter than normal. They display elevated levels of circulating neutrophils, erythrocytes and platelets, while other cell counts are normal.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi135 – 136KL → RP: Abolishes homooligomerization. 1 Publication2
Mutagenesisi322 – 323ML → RP: Abolishes homooligomerization. 1 Publication2
Mutagenesisi571G → R: Abolishes kinase activity. 1 Publication1
Mutagenesisi592K → R: Abolishes kinase activity. 1 Publication1
Mutagenesisi606F → A: Abolishes interaction with PPP1CA. 1 Publication1
Mutagenesisi616Y → F: Abolishes autophosphorylation. 1 Publication1
Mutagenesisi715Y → F: Abolishes autophosphorylation. 1 Publication1
Mutagenesisi743D → R: Abolishes kinase activity. 1 Publication1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002608251 – 823Tyrosine-protein kinase FerAdd BLAST823

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei402PhosphotyrosineCombined sources1
Modified residuei434PhosphoserineBy similarity1
Modified residuei616Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei715Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylated.4 Publications
Polyubiquitinated; this leads to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP70451
PaxDbiP70451
PeptideAtlasiP70451
PRIDEiP70451

PTM databases

iPTMnetiP70451
PhosphoSitePlusiP70451

Expressioni

Tissue specificityi

Detected in liver and testis. Isoform 4 is detected only in testis (at protein level). Widely expressed.3 Publications

Inductioni

Up-regulated by insulin in myogenic cells (in vitro).1 Publication

Gene expression databases

BgeeiENSMUSG00000000127
GenevisibleiP70451 MM

Interactioni

Subunit structurei

Homotrimer. Isoform 4 is a monomer, due to the absence of the N-terminal coiled coil domains. 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 (By similarity). Interacts with IRS1 and PIK3R1. Interacts with STAT3. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320'. Interacts with JAK1. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Interacts with ARHGDIA, NRP1, PLEC and TMF1.By similarity10 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi199633, 3 interactors
STRINGi10090.ENSMUSP00000000129

Structurei

3D structure databases

ProteinModelPortaliP70451
SMRiP70451
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 259F-BARPROSITE-ProRule annotationAdd BLAST259
Domaini461 – 551SH2PROSITE-ProRule annotationAdd BLAST91
Domaini564 – 817Protein kinasePROSITE-ProRule annotationAdd BLAST254

Region

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

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili123 – 185Sequence analysisAdd BLAST63
Coiled coili301 – 381Sequence analysisAdd BLAST81

Domaini

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

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
HOGENOMiHOG000233858
HOVERGENiHBG005655
InParanoidiP70451
KOiK08889
OMAiQFADNLY
OrthoDBiEOG091G01S4
PhylomeDBiP70451
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 (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P70451-1) [UniParc]FASTAAdd to basket

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 QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC
60 70 80 90 100
NQVDKESTVQ VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL
110 120 130 140 150
TMMIKDKQQV KKSYVGIHQQ IEAEMIKVTK TELEKLKSSY RQLIKEMNSA
160 170 180 190 200
KEKYKEALAK GKETEKAKER YDKATMKLHM LHNQYVLALK GAQLHQSQYY
210 220 230 240 250
DTTLPLLLDS VQKMQEEMIK ALKGIFDDYS QITSLVTEEI VNVHKEIQMS
260 270 280 290 300
VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL
310 320 330 340 350
TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES FETCEKKSDI
360 370 380 390 400
VLLLGQKQAL EELKQSVQQL RCTEAKCAAQ KALLEQKVQE NDGKEPPPVV
410 420 430 440 450
NYEEDARSVT SMERKERLSK FESIRHSIAG IIKSPKSVLG SSTQVCDVIS
460 470 480 490 500
VGERPLAEHD WYHGAIPRIE AQELLKQQGD FLVRESHGKP GEYVLSVYSD
510 520 530 540 550
GQRRHFIIQF VDNLYRFEGT GFSNIPQLID HHFNTKQVIT KKSGVVLLNP
560 570 580 590 600
IPKDKKWVLN HEDVSLGELL GKGNFGEVYK GTLKDKTPVA IKTCKEDLPQ
610 620 630 640 650
ELKIKFLQEA KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VPGGDFLTFL
660 670 680 690 700
RKRKDELKLK QLVRFSLDVA AGMLYLESKN CIHRDLAARN CLVGENNTLK
710 720 730 740 750
ISDFGMSRQE DGGVYSSSGL KQIPIKWTAP EALNYGRYSS ESDVWSFGIL
760 770 780 790 800
LWETFSLGVC PYPGMTNQQA REQVERGYRM SAPQNCPEEV FTIMMKCWDY
810 820
KPENRPKFND LHKELTVIKK MIT
Length:823
Mass (Da):94,579
Last modified:November 28, 2006 - v2
Checksum:iF4C22E1E63721663
GO
Isoform 2 (identifier: P70451-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-127: Missing.

Note: No experimental confirmation available.
Show »
Length:765
Mass (Da):87,762
Checksum:i91FCCCAAFEF1C283
GO
Isoform 3 (identifier: P70451-3) [UniParc]FASTAAdd to basket
Also known as: iFer

The sequence of this isoform differs from the canonical sequence as follows:
     491-542: GEYVLSVYSD...FNTKQVITKK → ESVSIRGHRV...GGSAQPHPKG
     543-823: Missing.

Show »
Length:532
Mass (Da):61,094
Checksum:i7468E01E9EB6F6E2
GO
Isoform 4 (identifier: P70451-4) [UniParc]FASTAAdd to basket
Also known as: FerT, p51FerT

The sequence of this isoform differs from the canonical sequence as follows:
     1-369: Missing.
     370-412: LRCTEAKCAA...EEDARSVTSM → MDKSMECPHC...PSSSEILRYK
     444-444: Missing.

Show »
Length:453
Mass (Da):51,601
Checksum:i1CDAA93ED40B6A1D
GO
Isoform 5 (identifier: P70451-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     444-444: Missing.

Show »
Length:822
Mass (Da):94,451
Checksum:iF08F6BB10161D738
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti328A → G in BAC38626 (PubMed:16141072).Curated1
Sequence conflicti373T → S in AAB18988 (Ref. 1) Curated1
Sequence conflicti373T → S in AAG40730 (PubMed:11006284).Curated1
Sequence conflicti730P → A in AAA37617 (PubMed:2294399).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0417661 – 369Missing in isoform 4. 1 PublicationAdd BLAST369
Alternative sequenceiVSP_02163470 – 127Missing in isoform 2. 1 PublicationAdd BLAST58
Alternative sequenceiVSP_041767370 – 412LRCTE…SVTSM → MDKSMECPHCEGVLEPESDP QFSKKCSIPLSPGPSSSEIL RYK in isoform 4. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_041768444Missing in isoform 4 and isoform 5. 2 Publications1
Alternative sequenceiVSP_041769491 – 542GEYVL…VITKK → ESVSIRGHRVFKHSPAYRSP LQYKASHHQEVWGGSAQPHP KG in isoform 3. 1 PublicationAdd BLAST52
Alternative sequenceiVSP_041770543 – 823Missing in isoform 3. 1 PublicationAdd BLAST281

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76762 mRNA Translation: AAB18988.1
M32054 mRNA Translation: AAA37617.1
AF286537 mRNA Translation: AAG40730.1
BC051249 mRNA Translation: AAH51249.1
BC058100 mRNA Translation: AAH58100.1
AK082799 mRNA Translation: BAC38626.1
CCDSiCCDS28936.1 [P70451-1]
CCDS28937.1 [P70451-4]
PIRiI49663
RefSeqiNP_001033086.2, NM_001037997.3 [P70451-1]
NP_001273344.1, NM_001286415.1 [P70451-2]
NP_032026.2, NM_008000.2 [P70451-4]
XP_006523703.1, XM_006523640.3 [P70451-1]
XP_006523704.1, XM_006523641.3 [P70451-1]
XP_006523706.1, XM_006523643.3 [P70451-5]
XP_011244595.1, XM_011246293.2 [P70451-5]
UniGeneiMm.151391
Mm.23039

Genome annotation databases

EnsembliENSMUST00000000129; ENSMUSP00000000129; ENSMUSG00000000127 [P70451-1]
ENSMUST00000038080; ENSMUSP00000037418; ENSMUSG00000000127 [P70451-4]
GeneIDi14158
KEGGimmu:14158
UCSCiuc008dfo.2 mouse [P70451-2]
uc008dfp.1 mouse [P70451-3]
uc008dfq.3 mouse [P70451-1]
uc008dfr.2 mouse [P70451-5]
uc008dfs.2 mouse [P70451-4]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiFER_MOUSE
AccessioniPrimary (citable) accession number: P70451
Secondary accession number(s): Q61561
, Q6PEE5, Q80UI3, Q8C481, Q9EQ77
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 28, 2006
Last modified: May 23, 2018
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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