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Q62844

- FYN_RAT

UniProt

Q62844 - FYN_RAT

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Protein
Tyrosine-protein kinase Fyn
Gene
Fyn
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.1 Publication

Cofactori

Manganese.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 – 2991ATP1 Publication
Active sitei390 – 3901Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi277 – 2859ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. CD4 receptor binding Source: RGD
  3. CD8 receptor binding Source: RGD
  4. T cell receptor binding Source: RGD
  5. glycoprotein binding Source: RGD
  6. metal ion binding Source: UniProtKB-KW
  7. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
  8. peptide hormone receptor binding Source: RGD
  9. phosphatidylinositol 3-kinase binding Source: RGD
  10. protein binding Source: RGD
  11. protein complex binding Source: RGD
  12. protein kinase activity Source: RGD
  13. protein tyrosine kinase activity Source: RGD
  14. receptor binding Source: RGD
Complete GO annotation...

GO - Biological processi

  1. T cell receptor signaling pathway Source: Ensembl
  2. activated T cell proliferation Source: Ensembl
  3. cellular response to growth factor stimulus Source: RGD
  4. cellular response to peptide hormone stimulus Source: RGD
  5. dendrite morphogenesis Source: Ensembl
  6. detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
  7. forebrain development Source: Ensembl
  8. ionotropic glutamate receptor signaling pathway Source: RGD
  9. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: UniProtKB
  10. negative regulation of gene expression Source: Ensembl
  11. negative regulation of neuron apoptotic process Source: UniProtKB
  12. negative regulation of protein catabolic process Source: Ensembl
  13. neuron migration Source: Ensembl
  14. peptidyl-tyrosine phosphorylation Source: RGD
  15. positive regulation of neuron projection development Source: Ensembl
  16. positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  17. positive regulation of protein localization to nucleus Source: Ensembl
  18. protein autophosphorylation Source: RGD
  19. regulation of cell shape Source: Ensembl
  20. response to drug Source: RGD
  21. response to ethanol Source: Ensembl
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_195025. Signaling by SCF-KIT.
REACT_196225. Regulation of signaling by CBL.
REACT_197451. Regulation of KIT signaling.
REACT_197531. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_198646. FCGR activation.
REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_211910. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_212418. DAP12 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:Fyn
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: 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.1 Publication

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. endosome Source: Ensembl
  3. intracellular membrane-bounded organelle Source: RGD
  4. membrane Source: RGD
  5. mitochondrion Source: RGD
  6. plasma membrane Source: UniProtKB-SubCell
  7. 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 – 11Removed By similarityBy similarity
Chaini2 – 537536Tyrosine-protein kinase FynBy similarity
PRO_0000282948Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine By similarityBy similarity
Lipidationi3 – 31S-palmitoyl cysteine By similarityBy similarity
Lipidationi6 – 61S-palmitoyl cysteine By similarityBy similarity
Modified residuei15 – 151Phosphothreonine By similarity
Modified residuei21 – 211Phosphoserine By similarityBy similarity
Modified residuei25 – 251Phosphoserine By similarity
Modified residuei185 – 1851Phosphotyrosine By similarity
Modified residuei213 – 2131Phosphotyrosine By similarity
Modified residuei214 – 2141Phosphotyrosine By similarity
Modified residuei257 – 2571Phosphoserine By similarity
Modified residuei420 – 4201Phosphotyrosine; by autocatalysis By similarityBy similarity
Modified residuei440 – 4401Phosphotyrosine By similarity
Modified residuei512 – 5121Phosphothreonine By similarity
Modified residuei531 – 5311Phosphotyrosine; by CSK By similarityBy 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.
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).1 Publication

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ62844.
SMRiQ62844. Positions 81-537.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini82 – 14362SH3
Add
BLAST
Domaini149 – 24698SH2
Add
BLAST
Domaini271 – 524254Protein kinase
Add
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SH3 domain.

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00620000087702.
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

MGCVQCKDKE AAKLTEERDG SLNQSSGYRY GTDPTPQHYP SFGVTSIPNY    50
NNFHAAGGQG LTVFGGVNSS SHTGTLRTRG GTGVTLFVAL YDYEARTEDD 100
LSFHKGEKFQ ILNSSEGDWW EARSLTTGET GYIPSNYVAP VDSIQAEEWY 150
FGKLGRKDAE RQLLSFGNPR GTFLIRESET TKGAYSLSIR DWDDMKGDHV 200
KHYKIRKLDN GGYYITTRAQ FETLQQLVQH YSERAAGLCC RLVVPCHKGM 250
PRLTDLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAIKT 300
LKPGTMSPES FLEEAQIMKK LKHDKLVQLY AVVSEEPIYI VTEYMNKGSL 350
LDFLKDGEGR ALKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGN 400
GLICKIADFG LARLIEDNEY TARQGAKFPI KWTAPEAALY GRFTIKSDVW 450
SFGILLTELV TKGRVPYPGM NNREVLEQVE RGYRMPCPQD CPISLHELMI 500
HCWKKDPEER PTFEYLQGFL EDYFTATEPQ YQPGENL 537
Length:537
Mass (Da):60,702
Last modified:November 1, 1996 - v1
Checksum:i11AE4420919DBF1C
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
U35365 mRNA. Translation: AAA82942.1 .
PIRi PT0199.
RefSeqi NP_036887.1. NM_012755.1.
UniGenei Rn.19361.
Rn.228993.

3D structure databases

ProteinModelPortali Q62844.
SMRi Q62844. Positions 81-537.
ModBasei Search...

Protein-protein interaction databases

BioGridi 247215. 2 interactions.
IntActi Q62844. 1 interaction.
STRINGi 10116.ENSRNOP00000000733.

PTM databases

PhosphoSitei Q62844.

Proteomic databases

PaxDbi Q62844.
PRIDEi Q62844.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000000733 ; ENSRNOP00000000733 ; ENSRNOG00000000596 .
GeneIDi 25150.
KEGGi rno:25150.
UCSCi RGD:2641. rat.

Organism-specific databases

CTDi 2534.
RGDi 2641. Fyn.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00620000087702.
HOGENOMi HOG000233858.
HOVERGENi HBG008761.
InParanoidi Q62844.
KOi K05703.
OMAi SHNSGYR.
OrthoDBi EOG7GTT2V.
PhylomeDBi Q62844.
TreeFami TF351634.

Enzyme and pathway databases

Reactomei REACT_195025. Signaling by SCF-KIT.
REACT_196225. Regulation of signaling by CBL.
REACT_197451. Regulation of KIT signaling.
REACT_197531. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_198646. FCGR activation.
REACT_198729. Constitutive PI3K/AKT Signaling in Cancer.
REACT_211910. Antigen activates B Cell Receptor (BCR) leading to generation of second messengers.
REACT_212418. DAP12 signaling.

Miscellaneous databases

NextBioi 605589.
PROi Q62844.

Gene expression databases

Genevestigatori Q62844.

Family and domain databases

Gene3Di 3.30.505.10. 1 hit.
InterProi IPR011009. 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 ]
Pfami PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTi SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view ]
SUPFAMi SSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

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: SHRSP.
    Tissue: Brain.
  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: September 3, 2014
This is version 119 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

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