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Protein

Tyrosine-protein kinase Fyn

Gene

FYN

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 similarity1 Publication

Catalytic activityi

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

Cofactori

Mn2+By similarity

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 annotationBy similarity1
Active sitei390Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Adaptive immunity, Immunity

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiR-BTA-114604. GPVI-mediated activation cascade.
R-BTA-1257604. PIP3 activates AKT signaling.
R-BTA-1433557. Signaling by SCF-KIT.
R-BTA-1433559. Regulation of KIT signaling.
R-BTA-202733. Cell surface interactions at the vascular wall.
R-BTA-2424491. DAP12 signaling.
R-BTA-373753. Nephrin interactions.
R-BTA-375165. NCAM signaling for neurite out-growth.
R-BTA-389356. CD28 co-stimulation.
R-BTA-389357. CD28 dependent PI3K/Akt signaling.
R-BTA-389359. CD28 dependent Vav1 pathway.
R-BTA-389513. CTLA4 inhibitory signaling.
R-BTA-3928662. EPHB-mediated forward signaling.
R-BTA-3928663. EPHA-mediated growth cone collapse.
R-BTA-3928664. Ephrin signaling.
R-BTA-3928665. EPH-ephrin mediated repulsion of cells.
R-BTA-399954. Sema3A PAK dependent Axon repulsion.
R-BTA-399956. CRMPs in Sema3A signaling.
R-BTA-418885. DCC mediated attractive signaling.
R-BTA-4420097. VEGFA-VEGFR2 Pathway.
R-BTA-5621575. CD209 (DC-SIGN) signaling.
R-BTA-5673001. RAF/MAP kinase cascade.
R-BTA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-BTA-75892. Platelet Adhesion to exposed collagen.
R-BTA-8866376. Reelin signalling pathway.
R-BTA-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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 9

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity
  • Cell membrane By similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002823142 – 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 residuei12Phosphothreonine; by PKCBy similarity1
Modified residuei21PhosphoserineBy similarity1
Modified residuei26PhosphoserineBy similarity1
Modified residuei185PhosphotyrosineBy similarity1
Modified residuei420Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei531Phosphotyrosine; by CSKBy similarity1

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. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-12 and kinase activity, and promotes translocation from the cytoplasm to the nucleus. 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

PaxDbiA0JNB0.
PRIDEiA0JNB0.

Expressioni

Gene expression databases

BgeeiENSBTAG00000011851.

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). Interacts (via SH3 domain) with KLHL2 (via N-terminus). Interacts (via SH2 domain) with PTPRH (phosphorylated form). Interacts with PTPRO (phosphorylated form). Interacts with PTPRB (phosphorylated form).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000015730.

Structurei

3D structure databases

ProteinModelPortaliA0JNB0.
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
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

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiA0JNB0.
KOiK05703.
OMAiSHNSGYR.
OrthoDBiEOG091G0D46.
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.

A0JNB0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCVQCKDKE ATKLTEERDG SLNQSSGYRY GTDPTPQHYP SFGVTSIPNY
60 70 80 90 100
NNFHGAGGQG 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):60,718
Last modified:December 12, 2006 - v1
Checksum:iA048E0F5193D7CFF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC126591 mRNA. Translation: AAI26592.1.
RefSeqiNP_001071440.1. NM_001077972.1.
XP_005210845.1. XM_005210788.2.
XP_005210846.1. XM_005210789.3.
XP_005210847.1. XM_005210790.3.
UniGeneiBt.6838.

Genome annotation databases

EnsembliENSBTAT00000015730; ENSBTAP00000015730; ENSBTAG00000011851.
GeneIDi527263.
KEGGibta:527263.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC126591 mRNA. Translation: AAI26592.1.
RefSeqiNP_001071440.1. NM_001077972.1.
XP_005210845.1. XM_005210788.2.
XP_005210846.1. XM_005210789.3.
XP_005210847.1. XM_005210790.3.
UniGeneiBt.6838.

3D structure databases

ProteinModelPortaliA0JNB0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000015730.

Proteomic databases

PaxDbiA0JNB0.
PRIDEiA0JNB0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000015730; ENSBTAP00000015730; ENSBTAG00000011851.
GeneIDi527263.
KEGGibta:527263.

Organism-specific databases

CTDi2534.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiA0JNB0.
KOiK05703.
OMAiSHNSGYR.
OrthoDBiEOG091G0D46.
TreeFamiTF351634.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSBTAG00000011851.

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...

Entry informationi

Entry nameiFYN_BOVIN
AccessioniPrimary (citable) accession number: A0JNB0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: December 12, 2006
Last modified: November 30, 2016
This is version 96 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

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 one 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.