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Protein

Tyrosine-protein kinase Fyn

Gene

FYN

Organism
Sus scrofa (Pig)
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).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotationBy similarity

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

Regions

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

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

ReactomeiREACT_273163. Sema3A PAK dependent Axon repulsion.
REACT_277405. GPVI-mediated activation cascade.
REACT_282287. PIP3 activates AKT signaling.
REACT_282805. CTLA4 inhibitory signaling.
REACT_287497. CD28 dependent Vav1 pathway.
REACT_291059. Regulation of KIT signaling.
REACT_296312. EPHA-mediated growth cone collapse.
REACT_298611. SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
REACT_301177. DAP12 signaling.
REACT_305564. CD28 co-stimulation.
REACT_306821. Ephrin signaling.
REACT_310115. NCAM signaling for neurite out-growth.
REACT_314517. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_315142. CD28 dependent PI3K/Akt signaling.
REACT_317814. Netrin mediated repulsion signals.
REACT_318286. Signaling by SCF-KIT.
REACT_321052. Regulation of signaling by CBL.
REACT_324924. EPH-ephrin mediated repulsion of cells.
REACT_328852. EPH-Ephrin signaling.
REACT_332790. CRMPs in Sema3A signaling.
REACT_333875. Nephrin interactions.
REACT_336627. DCC mediated attractive signaling.
REACT_340931. Platelet Adhesion to exposed collagen.
REACT_343850. EPHB-mediated forward signaling.
REACT_351345. VEGFA-VEGFR2 Pathway.
REACT_360745. 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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227 Componenti: Chromosome 1

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 537536Tyrosine-protein kinase FynPRO_0000282943Add
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 residuei12 – 121Phosphothreonine; by PKCBy 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. 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

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) (By similarity). Interacts with UNC119 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliA1Y2K1.
SMRiA1Y2K1. 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.
InParanoidiA1Y2K1.
KOiK05703.
OMAiSHNSGYR.
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.

A1Y2K1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCVQCKDKE ATKLTEERDG SLNQSSGFRY GTDPTPQHYP SFGVTSIPNY
60 70 80 90 100
NNFHAAGGQG LTVFGGVSSS 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):60,689
Last modified:February 20, 2007 - v2
Checksum:i1CD6E4665939438F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ836055 mRNA. Translation: ABI33874.2.
RefSeqiNP_001073675.2. NM_001080206.2.
UniGeneiSsc.44857.

Genome annotation databases

EnsembliENSSSCT00000004884; ENSSSCP00000004769; ENSSSCG00000004421.
GeneIDi791125.
KEGGissc:791125.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ836055 mRNA. Translation: ABI33874.2.
RefSeqiNP_001073675.2. NM_001080206.2.
UniGeneiSsc.44857.

3D structure databases

ProteinModelPortaliA1Y2K1.
SMRiA1Y2K1. Positions 81-537.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000004884; ENSSSCP00000004769; ENSSSCG00000004421.
GeneIDi791125.
KEGGissc:791125.

Organism-specific databases

CTDi2534.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiA1Y2K1.
KOiK05703.
OMAiSHNSGYR.
TreeFamiTF351634.

Enzyme and pathway databases

ReactomeiREACT_273163. Sema3A PAK dependent Axon repulsion.
REACT_277405. GPVI-mediated activation cascade.
REACT_282287. PIP3 activates AKT signaling.
REACT_282805. CTLA4 inhibitory signaling.
REACT_287497. CD28 dependent Vav1 pathway.
REACT_291059. Regulation of KIT signaling.
REACT_296312. EPHA-mediated growth cone collapse.
REACT_298611. SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion.
REACT_301177. DAP12 signaling.
REACT_305564. CD28 co-stimulation.
REACT_306821. Ephrin signaling.
REACT_310115. NCAM signaling for neurite out-growth.
REACT_314517. Role of LAT2/NTAL/LAB on calcium mobilization.
REACT_315142. CD28 dependent PI3K/Akt signaling.
REACT_317814. Netrin mediated repulsion signals.
REACT_318286. Signaling by SCF-KIT.
REACT_321052. Regulation of signaling by CBL.
REACT_324924. EPH-ephrin mediated repulsion of cells.
REACT_328852. EPH-Ephrin signaling.
REACT_332790. CRMPs in Sema3A signaling.
REACT_333875. Nephrin interactions.
REACT_336627. DCC mediated attractive signaling.
REACT_340931. Platelet Adhesion to exposed collagen.
REACT_343850. EPHB-mediated forward signaling.
REACT_351345. VEGFA-VEGFR2 Pathway.
REACT_360745. CD209 (DC-SIGN) signaling.

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. "Cloning and expression of porcine FYN gene."
    Long H., Yang Z.
    Submitted (JAN-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiFYN_PIG
AccessioniPrimary (citable) accession number: A1Y2K1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: February 20, 2007
Last modified: May 27, 2015
This is version 76 of the entry and version 2 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.