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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, KIRREL 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 similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei299 – 2991ATPPROSITE-ProRule annotation1 Publication
Active sitei390 – 3901Proton acceptorPROSITE-ProRule annotationBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi277 – 2859ATPPROSITE-ProRule annotationBy similarity

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • CD4 receptor binding Source: RGD
  • CD8 receptor binding Source: RGD
  • glycoprotein binding Source: RGD
  • 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
  • T cell receptor binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_276807. CD28 dependent PI3K/Akt signaling.
REACT_277188. EPHB-mediated forward signaling.
REACT_282745. NCAM signaling for neurite out-growth.
REACT_286909. Platelet Adhesion to exposed collagen.
REACT_289444. CD28 co-stimulation.
REACT_292219. FCGR activation.
REACT_297589. GPVI-mediated activation cascade.
REACT_299102. PIP3 activates AKT signaling.
REACT_299172. Ephrin signaling.
REACT_299454. DCC mediated attractive signaling.
REACT_301102. CRMPs in Sema3A signaling.
REACT_301330. VEGFA-VEGFR2 Pathway.
REACT_302394. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_305922. CTLA4 inhibitory signaling.
REACT_308505. Netrin mediated repulsion signals.
REACT_313117. EPH-ephrin mediated repulsion of cells.
REACT_313573. Regulation of KIT signaling.
REACT_316519. CD28 dependent Vav1 pathway.
REACT_320606. Regulation of signaling by CBL.
REACT_326461. Nephrin interactions.
REACT_332169. DAP12 signaling.
REACT_335137. Signaling by SCF-KIT.
REACT_335402. EPHA-mediated growth cone collapse.
REACT_341785. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_343260. Cell surface interactions at the vascular wall.
REACT_346770. SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
REACT_347274. Sema3A PAK dependent Axon repulsion.
REACT_348379. EPH-Ephrin signaling.
REACT_359326. Dectin-2 family.
REACT_359478. CD209 (DC-SIGN) signaling.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi2641. Fyn.

Subcellular locationi

  • Cell membrane By similarity

  • Note: Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking (By similarity).By similarity

GO - Cellular componenti

  • actin filament Source: Ensembl
  • cytosol Source: Reactome
  • endosome Source: Ensembl
  • extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  • intracellular membrane-bounded organelle Source: RGD
  • membrane Source: RGD
  • membrane raft Source: Ensembl
  • mitochondrion Source: RGD
  • postsynaptic density Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi299 – 2991K → M: Loss of kinase activity and reduction in oligodendrocyte process extension and myelin membrane formation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 537536Tyrosine-protein kinase FynPRO_0000282948Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Lipidationi3 – 31S-palmitoyl cysteineBy similarity
Lipidationi6 – 61S-palmitoyl cysteineBy similarity
Modified residuei21 – 211PhosphoserineBy similarity
Modified residuei185 – 1851PhosphotyrosineBy similarity
Modified residuei420 – 4201Phosphotyrosine; by autocatalysisBy similarity
Modified residuei531 – 5311Phosphotyrosine; by CSKBy similarity

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

PhosphoSiteiQ62844.

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

GenevestigatoriQ62844.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi247215. 2 interactions.
IntActiQ62844. 1 interaction.
STRINGi10116.ENSRNOP00000000733.

Structurei

3D structure databases

ProteinModelPortaliQ62844.
SMRiQ62844. Positions 81-537.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 14362SH3PROSITE-ProRule annotationAdd
BLAST
Domaini149 – 24698SH2PROSITE-ProRule annotationAdd
BLAST
Domaini271 – 524254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ62844.
KOiK05703.
OMAiSHNSGYR.
OrthoDBiEOG7GTT2V.
PhylomeDBiQ62844.
TreeFamiTF351634.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ62844.
SMRiQ62844. Positions 81-537.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247215. 2 interactions.
IntActiQ62844. 1 interaction.
STRINGi10116.ENSRNOP00000000733.

PTM databases

PhosphoSiteiQ62844.

Proteomic databases

PaxDbiQ62844.
PRIDEiQ62844.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2534.
RGDi2641. Fyn.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiQ62844.
KOiK05703.
OMAiSHNSGYR.
OrthoDBiEOG7GTT2V.
PhylomeDBiQ62844.
TreeFamiTF351634.

Enzyme and pathway databases

ReactomeiREACT_276807. CD28 dependent PI3K/Akt signaling.
REACT_277188. EPHB-mediated forward signaling.
REACT_282745. NCAM signaling for neurite out-growth.
REACT_286909. Platelet Adhesion to exposed collagen.
REACT_289444. CD28 co-stimulation.
REACT_292219. FCGR activation.
REACT_297589. GPVI-mediated activation cascade.
REACT_299102. PIP3 activates AKT signaling.
REACT_299172. Ephrin signaling.
REACT_299454. DCC mediated attractive signaling.
REACT_301102. CRMPs in Sema3A signaling.
REACT_301330. VEGFA-VEGFR2 Pathway.
REACT_302394. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_305922. CTLA4 inhibitory signaling.
REACT_308505. Netrin mediated repulsion signals.
REACT_313117. EPH-ephrin mediated repulsion of cells.
REACT_313573. Regulation of KIT signaling.
REACT_316519. CD28 dependent Vav1 pathway.
REACT_320606. Regulation of signaling by CBL.
REACT_326461. Nephrin interactions.
REACT_332169. DAP12 signaling.
REACT_335137. Signaling by SCF-KIT.
REACT_335402. EPHA-mediated growth cone collapse.
REACT_341785. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_343260. Cell surface interactions at the vascular wall.
REACT_346770. SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
REACT_347274. Sema3A PAK dependent Axon repulsion.
REACT_348379. EPH-Ephrin signaling.
REACT_359326. Dectin-2 family.
REACT_359478. CD209 (DC-SIGN) signaling.

Miscellaneous databases

NextBioi605589.
PROiQ62844.

Gene expression databases

GenevestigatoriQ62844.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Expression of three type mRNAs encoding rat FYN by alternative splicing within 5' untranslated region."
    Nemoto K., Sekimoto M., Kageyama H., Fukamachi K., Nemoto F., Ueyama T., Senba E., Tomita I.
    Submitted (SEP-1995) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: SHRSPImported.
    Tissue: BrainImported.
  2. "Novel putative protein kinase clones from a rat large granular lymphocyte tumor cell line."
    Yue C.C.
    Mol. Immunol. 28:399-408(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Morphological differentiation of oligodendrocytes requires activation of Fyn tyrosine kinase."
    Osterhout D.J., Wolven A., Wolf R.M., Resh M.D., Chao M.V.
    J. Cell Biol. 145:1209-1218(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF LYS-299.
  4. "Process elongation of oligodendrocytes is promoted by the Kelch-related actin-binding protein Mayven."
    Jiang S., Avraham H.K., Park S.Y., Kim T.A., Bu X., Seng S., Avraham S.
    J. Neurochem. 92:1191-1203(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLHL2, TISSUE SPECIFICITY.

Entry informationi

Entry nameiFYN_RAT
AccessioniPrimary (citable) accession number: Q62844
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: November 1, 1996
Last modified: May 27, 2015
This is version 128 of the entry and version 1 of the sequence. [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

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.