Q62844 (FYN_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Fyn
EC=2.7.10.2

Alternative name(s):
Proto-oncogene c-Fyn
p59-Fyn

Gene names

Name:

Fyn

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	537 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.3
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.3
Cofactor	Manganese. Ref.3
Enzyme regulation	Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site By similarity.
Subunit structure	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). Ref.4
Subcellular location	Cell membrane By similarity. Note: Present and active in lipid rafts. Palmitoylation is crucial for proper trafficking By similarity. Ref.3
Tissue specificity	Detected in spinal cord oligodendrocytes (at protein level). Ref.4
Developmental stage	Up-regulated during oligodendrocyte differentiation. Ref.3
Post-translational modification	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 By similarity. Palmitoylation at Cys-3 and Cys-6 regulate subcellular location By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Manganese Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara activated T cell proliferation Inferred from electronic annotation. Source: Compara cellular response to growth factor stimulus Inferred from expression pattern PubMed 11236902. Source: RGD cellular response to peptide hormone stimulus Inferred from expression pattern PubMed 9460655. Source: RGD dendrite morphogenesis Inferred from electronic annotation. Source: Compara detection of mechanical stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara forebrain development Inferred from electronic annotation. Source: Compara ionotropic glutamate receptor signaling pathway Traceable author statement PubMed 12736333. Source: RGD negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Inferred from mutant phenotype PubMed 18469807. Source: UniProtKB negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of protein catabolic process Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara peptidyl-tyrosine phosphorylation Inferred from direct assay PubMed 9460655. Source: RGD positive regulation of neuron projection development Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay PubMed 12353920. Source: RGD regulation of cell shape Inferred from electronic annotation. Source: Compara response to drug Inferred from expression pattern PubMed 14625475PubMed 9551931. Source: RGD response to ethanol Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome endosome Inferred from electronic annotation. Source: Compara membrane Inferred from direct assay PubMed 12882964. Source: RGD mitochondrion Inferred from direct assay PubMed 12007793. Source: RGD plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic density Inferred from direct assay PubMed 11226670. Source: RGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW T cell receptor binding Inferred from direct assay PubMed 1372996. Source: RGD metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC phosphatidylinositol 3-kinase binding Inferred from direct assay PubMed 9460655. Source: RGD protein tyrosine kinase activity Inferred from direct assay PubMed 12007793PubMed 12231245PubMed 8870703. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 537	537	Tyrosine-protein kinase Fyn		PRO_0000282948
Regions
	Domain	82 – 143	62	SH3
	Domain	149 – 246	98	SH2
	Domain	271 – 524	254	Protein kinase
	Nucleotide binding	277 – 285	9	ATP By similarity UniProtKB P28523
Sites
	Active site	390	1	Proton acceptor By similarity UniProtKB P28523
	Binding site	299	1	ATP Ref.3
Amino acid modifications
	Modified residue	15	1	Phosphothreonine By similarity
	Modified residue	21	1	Phosphoserine By similarity UniProtKB P06241
	Modified residue	25	1	Phosphoserine By similarity
	Modified residue	185	1	Phosphotyrosine By similarity
	Modified residue	213	1	Phosphotyrosine By similarity
	Modified residue	214	1	Phosphotyrosine By similarity
	Modified residue	254	1	Phosphothreonine By similarity
	Modified residue	257	1	Phosphoserine By similarity
	Modified residue	420	1	Phosphotyrosine; by autocatalysis By similarity UniProtKB P06241
	Modified residue	440	1	Phosphotyrosine By similarity
	Modified residue	512	1	Phosphothreonine By similarity
	Modified residue	531	1	Phosphotyrosine; by CSK By similarity UniProtKB P39688
	Lipidation	2	1	N-myristoyl glycine By similarity UniProtKB P39688
	Lipidation	3	1	S-palmitoyl cysteine By similarity UniProtKB P39688
	Lipidation	6	1	S-palmitoyl cysteine By similarity UniProtKB P39688
Experimental info
	Mutagenesis	299	1	K → M: Loss of kinase activity and reduction in oligodendrocyte process extension and myelin membrane formation. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q62844 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 11AE4420919DBF1C	FASTA	537	60,702
	10 20 30 40 50 60 MGCVQCKDKE AAKLTEERDG SLNQSSGYRY GTDPTPQHYP SFGVTSIPNY NNFHAAGGQG 70 80 90 100 110 120 LTVFGGVNSS SHTGTLRTRG GTGVTLFVAL YDYEARTEDD LSFHKGEKFQ ILNSSEGDWW 130 140 150 160 170 180 EARSLTTGET GYIPSNYVAP VDSIQAEEWY FGKLGRKDAE RQLLSFGNPR GTFLIRESET 190 200 210 220 230 240 TKGAYSLSIR DWDDMKGDHV KHYKIRKLDN GGYYITTRAQ FETLQQLVQH YSERAAGLCC 250 260 270 280 290 300 RLVVPCHKGM PRLTDLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAIKT 310 320 330 340 350 360 LKPGTMSPES FLEEAQIMKK LKHDKLVQLY AVVSEEPIYI VTEYMNKGSL LDFLKDGEGR 370 380 390 400 410 420 ALKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGN GLICKIADFG LARLIEDNEY 430 440 450 460 470 480 TARQGAKFPI KWTAPEAALY GRFTIKSDVW SFGILLTELV TKGRVPYPGM NNREVLEQVE 490 500 510 520 530 RGYRMPCPQD CPISLHELMI HCWKKDPEER PTFEYLQGFL EDYFTATEPQ YQPGENL

References

[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U35365 mRNA. Translation: AAA82942.1.
IPI	IPI00209210.
PIR	PT0199.
RefSeq	NP_036887.1. NM_012755.1.
UniGene	Rn.19361.
3D structure databases
HSSP	HSSP built from PDB template 1FYN based on UniProtKB P06241.
ProteinModelPortal	Q62844.
SMR	Q62844. Positions 81-537.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000000733.
PTM databases
PhosphoSite	Q62844.
Proteomic databases
PaxDb	Q62844.
PRIDE	Q62844.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000000733; ENSRNOP00000000733; ENSRNOG00000000596.
GeneID	25150.
KEGG	rno:25150.
UCSC	RGD:2641. rat.
Organism-specific databases
CTD	2534.
RGD	2641. Fyn.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00620000087702.
HOGENOM	HOG000233858.
HOVERGEN	HBG008761.
InParanoid	Q62844.
KO	K05703.
OMA	TDERDGS.
OrthoDB	EOG41ZF9H.
Enzyme and pathway databases
Reactome	REACT_109781. Immune System.
Gene expression databases
ArrayExpress	Q62844.
Genevestigator	Q62844.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
NextBio	605589.

Entry information

Entry name

FYN_RAT

Accession

Primary (citable) accession number: Q62844

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program