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Protein

Tyrosine-protein kinase Fyn

Gene

Fyn

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1 (By similarity). Interacts with UNC119 (By similarity).By similarity1 Publication

Catalytic activityi

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

Cofactori

Mn2+1 Publication

Enzyme regulationi

Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei299ATPPROSITE-ProRule annotation1 Publication1
Active sitei390Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi277 – 285ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • CD4 receptor binding Source: RGD
  • CD8 receptor binding Source: RGD
  • disordered domain specific binding Source: Ensembl
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: Ensembl
  • growth factor receptor binding Source: Ensembl
  • identical protein binding Source: Ensembl
  • ion channel binding Source: Ensembl
  • metal ion binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • peptide hormone receptor binding Source: RGD
  • phosphatidylinositol 3-kinase binding Source: RGD
  • protein complex binding Source: RGD
  • protein kinase activity Source: RGD
  • protein tyrosine kinase activity Source: RGD
  • receptor binding Source: RGD
  • signal transducer activity Source: Ensembl
  • T cell receptor binding Source: RGD
  • tubulin binding Source: Ensembl
  • type 5 metabotropic glutamate receptor binding Source: ARUK-UCL

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-114604. GPVI-mediated activation cascade.
R-RNO-1257604. PIP3 activates AKT signaling.
R-RNO-1266695. Interleukin-7 signaling.
R-RNO-1433557. Signaling by SCF-KIT.
R-RNO-1433559. Regulation of KIT signaling.
R-RNO-202733. Cell surface interactions at the vascular wall.
R-RNO-2029481. FCGR activation.
R-RNO-2424491. DAP12 signaling.
R-RNO-373753. Nephrin family interactions.
R-RNO-375165. NCAM signaling for neurite out-growth.
R-RNO-389356. CD28 co-stimulation.
R-RNO-389357. CD28 dependent PI3K/Akt signaling.
R-RNO-389359. CD28 dependent Vav1 pathway.
R-RNO-389513. CTLA4 inhibitory signaling.
R-RNO-3928662. EPHB-mediated forward signaling.
R-RNO-3928663. EPHA-mediated growth cone collapse.
R-RNO-3928664. Ephrin signaling.
R-RNO-3928665. EPH-ephrin mediated repulsion of cells.
R-RNO-399954. Sema3A PAK dependent Axon repulsion.
R-RNO-399955. SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
R-RNO-399956. CRMPs in Sema3A signaling.
R-RNO-418885. DCC mediated attractive signaling.
R-RNO-4420097. VEGFA-VEGFR2 Pathway.
R-RNO-5621575. CD209 (DC-SIGN) signaling.
R-RNO-5673001. RAF/MAP kinase cascade.
R-RNO-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-RNO-75892. Platelet Adhesion to exposed collagen.
R-RNO-8866376. Reelin signalling pathway.
R-RNO-912631. Regulation of signaling by CBL.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase Fyn (EC:2.7.10.2)
Alternative name(s):
Proto-oncogene c-Fyn
p59-Fyn
Gene namesi
Name:FynImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi2641. Fyn.

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 membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi299K → M: Loss of kinase activity and reduction in oligodendrocyte process extension and myelin membrane formation. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002829482 – 537Tyrosine-protein kinase FynAdd BLAST536

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteineBy similarity1
Lipidationi6S-palmitoyl cysteineBy similarity1
Modified residuei21PhosphoserineBy similarity1
Modified residuei26PhosphoserineBy similarity1
Modified residuei124PhosphoserineBy similarity1
Modified residuei181PhosphothreonineBy similarity1
Modified residuei185PhosphotyrosineBy similarity1
Modified residuei214PhosphotyrosineBy similarity1
Modified residuei420Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei531PhosphotyrosineCombined sources1

Post-translational modificationi

Autophosphorylated at Tyr-420. Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state. PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling (By similarity).By similarity
Palmitoylation at Cys-3 and Cys-6 regulate subcellular location.By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ62844.
PRIDEiQ62844.

PTM databases

iPTMnetiQ62844.
PhosphoSitePlusiQ62844.

Expressioni

Tissue specificityi

Detected in spinal cord oligodendrocytes (at protein level).1 Publication

Developmental stagei

Up-regulated during oligodendrocyte differentiation.1 Publication

Gene expression databases

BgeeiENSRNOG00000000596.
ExpressionAtlasiQ62844. baseline and differential.
GenevisibleiQ62844. RN.

Interactioni

Subunit structurei

Interacts (via its SH3 domain) with PIK3R1 and PRMT8 (By similarity). Interacts with FYB1, PAG1, and SH2D1A (By similarity). Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity (By similarity). Interacts with TOM1L1 (phosphorylated form) (By similarity). Interacts with SH2D1A and SLAMF1 (By similarity). Interacts with and phosphorylates ITCH, down-regulating its activity (By similarity). Interacts with FASLG (By similarity). Interacts with RUNX3 (By similarity). Interacts with KIT (By similarity). Interacts with KDR (tyrosine phosphorylated) (By similarity). Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion (By similarity). Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation (By similarity). Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity). Interacts (via SH3 domain) with KLHL2 (via N-terminus) (PubMed:15715669). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form). Interacts with FYB2 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • CD4 receptor binding Source: RGD
  • CD8 receptor binding Source: RGD
  • disordered domain specific binding Source: Ensembl
  • enzyme binding Source: RGD
  • ephrin receptor binding Source: Ensembl
  • growth factor receptor binding Source: Ensembl
  • identical protein binding Source: Ensembl
  • ion channel binding Source: Ensembl
  • peptide hormone receptor binding Source: RGD
  • phosphatidylinositol 3-kinase binding Source: RGD
  • protein complex binding Source: RGD
  • receptor binding Source: RGD
  • T cell receptor binding Source: RGD
  • tubulin binding Source: Ensembl
  • type 5 metabotropic glutamate receptor binding Source: ARUK-UCL

Protein-protein interaction databases

BioGridi247215. 3 interactors.
CORUMiQ62844.
IntActiQ62844. 1 interactor.
STRINGi10116.ENSRNOP00000000733.

Structurei

3D structure databases

ProteinModelPortaliQ62844.
SMRiQ62844.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 143SH3PROSITE-ProRule annotationAdd BLAST62
Domaini149 – 246SH2PROSITE-ProRule annotationAdd BLAST98
Domaini271 – 524Protein kinasePROSITE-ProRule annotationAdd BLAST254

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ62844.
KOiK05703.
OMAiSHNSGYR.
OrthoDBiEOG091G0D46.
PhylomeDBiQ62844.
TreeFamiTF351634.

Family and domain databases

CDDicd12006. SH3_Fyn_Yrk. 1 hit.
Gene3Di3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR035750. Fyn/Yrk_SH3.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR036860. SH2_dom_sf.
IPR036028. SH3-like_dom.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiView protein in SMART
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62844-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCVQCKDKE AAKLTEERDG SLNQSSGYRY GTDPTPQHYP SFGVTSIPNY
60 70 80 90 100
NNFHAAGGQG LTVFGGVNSS SHTGTLRTRG GTGVTLFVAL YDYEARTEDD
110 120 130 140 150
LSFHKGEKFQ ILNSSEGDWW EARSLTTGET GYIPSNYVAP VDSIQAEEWY
160 170 180 190 200
FGKLGRKDAE RQLLSFGNPR GTFLIRESET TKGAYSLSIR DWDDMKGDHV
210 220 230 240 250
KHYKIRKLDN GGYYITTRAQ FETLQQLVQH YSERAAGLCC RLVVPCHKGM
260 270 280 290 300
PRLTDLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAIKT
310 320 330 340 350
LKPGTMSPES FLEEAQIMKK LKHDKLVQLY AVVSEEPIYI VTEYMNKGSL
360 370 380 390 400
LDFLKDGEGR ALKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGN
410 420 430 440 450
GLICKIADFG LARLIEDNEY TARQGAKFPI KWTAPEAALY GRFTIKSDVW
460 470 480 490 500
SFGILLTELV TKGRVPYPGM NNREVLEQVE RGYRMPCPQD CPISLHELMI
510 520 530
HCWKKDPEER PTFEYLQGFL EDYFTATEPQ YQPGENL
Length:537
Mass (Da):60,702
Last modified:November 1, 1996 - v1
Checksum:i11AE4420919DBF1C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U35365 mRNA. Translation: AAA82942.1.
PIRiPT0199.
RefSeqiNP_036887.1. NM_012755.1.
UniGeneiRn.19361.
Rn.228993.

Genome annotation databases

EnsembliENSRNOT00000000733; ENSRNOP00000000733; ENSRNOG00000000596.
GeneIDi25150.
KEGGirno:25150.
UCSCiRGD:2641. rat.

Similar proteinsi

Entry informationi

Entry nameiFYN_RAT
AccessioniPrimary (citable) accession number: Q62844
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: November 1, 1996
Last modified: October 25, 2017
This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families