A1Y2K1 (FYN_PIG) 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

Sus scrofa (Pig) [Reference proteome]

Taxonomic identifier

9823 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Laurasiatheria › Cetartiodactyla › Suina › Suidae › Sus

Protein attributes

Sequence length	537 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. UniProtKB P06241
Cofactor	Manganese By similarity. UniProtKB P06241
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). Interacts (via SH3 domain) with KLHL2 (via N-terminus) By similarity.
Subcellular location	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.
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. ultraviolet B (UVB) strongly increase phosphorylation at Thr-12 and kinase activity, and promotes translocation from the cytoplasm to the nucleus 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
Biological process	Adaptive immunity Immunity
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
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 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 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 electronic annotation. Source: Compara positive regulation of neuron projection development Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of cell shape Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara
Cellular_component	endosome Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
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_0000282943
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 By similarity UniProtKB Q62844
Amino acid modifications
	Modified residue	12	1	Phosphothreonine; by PKC By similarity UniProtKB P06241
	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

Sequences

	Sequence		Length	Mass (Da)
	A1Y2K1 [UniParc]. Last modified February 20, 2007. Version 2. Checksum: 1CD6E4665939438F	FASTA	537	60,689
	10 20 30 40 50 60 MGCVQCKDKE ATKLTEERDG SLNQSSGFRY GTDPTPQHYP SFGVTSIPNY NNFHAAGGQG 70 80 90 100 110 120 LTVFGGVSSS 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]	"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].

Cross-references

Sequence databases
EMBL GenBank DDBJ	DQ836055 mRNA. Translation: ABI33874.2.
RefSeq	NP_001073675.2. NM_001080206.2.
UniGene	Ssc.44857.
3D structure databases
ProteinModelPortal	A1Y2K1.
SMR	A1Y2K1. Positions 81-537.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSSSCT00000004884; ENSSSCP00000004769; ENSSSCG00000004421.
GeneID	791125.
KEGG	ssc:791125.
Organism-specific databases
CTD	2534.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00620000087702.
HOGENOM	HOG000233858.
HOVERGEN	HBG008761.
KO	K05703.
OMA	TDERDGS.
OrthoDB	EOG41ZF9H.
Gene expression databases
ArrayExpress	A1Y2K1.
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...

Entry information

Entry name

FYN_PIG

Accession

Primary (citable) accession number: A1Y2K1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 3, 2007
Last sequence update:	February 20, 2007
Last modified:	May 1, 2013
This is version 57 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program