Q6EWH2 (FYNA_DANRE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase fyna
EC=2.7.10.2

Alternative name(s):
Proto-oncogene c-Fyna

Gene names

Name:	fyna
Synonyms:	fyn

Organism

Danio rerio (Zebrafish) (Brachydanio rerio) [Reference proteome]

Taxonomic identifier

7955 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Actinopterygii › Actinopteri › Neopterygii › Teleostei › Elopocephala › Clupeocephala › Otocephala › Ostariophysi › Otophysi › Cypriniphysi › Cypriniformes › Cyprinoidea › Cyprinidae › Danio

Protein attributes

Sequence length	537 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tyrosine-protein kinase implicated in the control of cell growth. Plays a role in the regulation of intracellular calcium levels. Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension. Role in cntn1-mediated signaling By similarity. Required for convergent extension cell movements during gastrulation, acting with yes via rhoa. May be required for epiboly to occur, possibly through its effects in calcium signaling. Ref.1 Ref.2
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Cofactor	Manganese.
Enzyme regulation	Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site By similarity. Relatively inactive in the unfertilized oocyte, undergoes rapid activation immediately following fertilization. Total activity increases progressively during later development and remains elevated during sphere and epiboly stage. Ref.5
Subcellular location	Cytoplasm. Nucleus. Note: Transiently expressed in the nucleus at mid-blastula stage (3.3 hpf) in a large subset of cells. Nuclear localization is not observed from late blastula stage onward. Ref.5
Tissue specificity	Widely expressed. Ref.2 Ref.5
Developmental stage	Expressed in the pre-gastrula embryo (at protein level).
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.
Sequence caution	The sequence AAX47959.1 differs from that shown. Reason: Frameshift at positions 126 and 131.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
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	convergent extension involved in gastrulation Inferred from genetic interaction Ref.2. Source: ZFIN cytosolic calcium ion homeostasis Inferred from mutant phenotype Ref.1. Source: ZFIN gastrulation with mouth forming second Inferred from mutant phenotype Ref.1. Source: ZFIN protein autophosphorylation Inferred from direct assay Ref.1. Source: ZFIN regulation of protein kinase activity Inferred from genetic interaction PubMed 17611617PubMed 18550893. Source: ZFIN
Cellular_component	cytosol Inferred from direct assay Ref.5. Source: ZFIN nucleus Inferred from direct assay Ref.5. Source: ZFIN
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 protein kinase activity Inferred from direct assay Ref.1. Source: ZFIN
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6EWH2-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6EWH2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     293-293: N → H
     294-537: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 537	536	Tyrosine-protein kinase fyna		PRO_0000418878
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
Sites
	Active site	390	1	Proton acceptor By similarity
	Binding site	299	1	ATP By similarity
Amino acid modifications
	Modified residue	12	1	Phosphothreonine; by PKC By similarity
	Modified residue	420	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	531	1	Phosphotyrosine By similarity
	Lipidation	2	1	N-myristoyl glycine By similarity
	Lipidation	3	1	S-palmitoyl cysteine By similarity
	Lipidation	6	1	S-palmitoyl cysteine By similarity
Natural variations
	Alternative sequence	293	1	N → H in isoform 2.		VSP_044087
	Alternative sequence	294 – 537	244	Missing in isoform 2.		VSP_044088
Experimental info
	Mutagenesis	299	1	K → M: Loss of activity. Ref.1
	Sequence conflict	5	1	Q → R in AAH75763. Ref.4
	Sequence conflict	60 – 62	3	GVT → RVP in CAF06179. Ref.2
	Sequence conflict	148	1	D → E in AAX47959. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 5, 2012. Version 2. Checksum: 1C7CB34990049B96	FASTA	537	60,569
	10 20 30 40 50 60 MGCVQCKDKE ATKLTDERET SVSQHAGYRY GSDPTPQHYP SFGVTAIPNY NNFHAPVSQG 70 80 90 100 110 120 VTVFGGVNSS SHSGTLRSRG GTGVTLFVAL YDYEARSEDD LSFRKGEKFQ ILNSTEGDWW 130 140 150 160 170 180 EARSLTTGGT GYIPSNYVAP VDSIQAEDWY FGKLGRKDAE RQLLSNGNPR GTFLIRESET 190 200 210 220 230 240 TKGAYSLSIQ DWDETKGDHV KHYKIRKLDN GGYYITTRAQ FETLQQLVHH YSARAAGLCC 250 260 270 280 290 300 RLIVPCHKGM PRLADLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGNTKVAVKT 310 320 330 340 350 360 LKPGTMSPES FLEEAQIMKK LRHDKLVQLY AVVSEEPIYI VTEYMSKGSL LDFLKDGEGR 370 380 390 400 410 420 GLKLPNLVDM AAQVAAGMAY IERMNYIHRD LRSANILVGD SLVCKIADFG LARLIEDNEY 430 440 450 460 470 480 TARQGAKFPI KWTAPEAALY GRFTIKSDVW SFGILLTELV TKGRVPYPGM NNREVLEQVE 490 500 510 520 530 RGYRMPCPQD CPSSLHELML QCWKRDPEER PTFEYLQAFL EDYFTATEPQ YQPGDNL
	Isoform 2 [UniParc]. Checksum: CC69174A2FA24017	FASTA	293	32,799
	10 20 30 40 50 60 MGCVQCKDKE ATKLTDERET SVSQHAGYRY GSDPTPQHYP SFGVTAIPNY NNFHAPVSQG 70 80 90 100 110 120 VTVFGGVNSS SHSGTLRSRG GTGVTLFVAL YDYEARSEDD LSFRKGEKFQ ILNSTEGDWW 130 140 150 160 170 180 EARSLTTGGT GYIPSNYVAP VDSIQAEDWY FGKLGRKDAE RQLLSNGNPR GTFLIRESET 190 200 210 220 230 240 TKGAYSLSIQ DWDETKGDHV KHYKIRKLDN GGYYITTRAQ FETLQQLVHH YSARAAGLCC 250 260 270 280 290 RLIVPCHKGM PRLADLSVKT KDVWEIPRES LQLIKRLGNG QFGEVWMGTW NGH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Role of Fyn kinase in signaling associated with epiboly during zebrafish development." Sharma D., Holets L., Zhang X., Kinsey W.H. Dev. Biol. 285:462-476(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, MUTAGENESIS OF LYS-299. Tissue: Embryo.
[2]	"Fyn/Yes and non-canonical Wnt signalling converge on RhoA in vertebrate gastrulation cell movements." Jopling C., den Hertog J. EMBO Rep. 6:426-431(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[3]	The Danio rerio sequencing project at the Sanger Institute Submitted (JUL-2010) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Tuebingen.
[4]	NIH - Zebrafish Gene Collection (ZGC) project Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Embryo.
[5]	"Transient nuclear localization of Fyn kinase during development in zebrafish." Rongish B.J., Kinsey W.H. Anat. Rec. 260:115-123(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-153, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY948197 mRNA. Translation: AAX47959.1. Frameshift. AJ620748 mRNA. Translation: CAF06179.1. CU306817 Genomic DNA. No translation available. BC075763 mRNA. Translation: AAH75763.1. AF269145 mRNA. Translation: AAF81748.1.
IPI	IPI01024162.
RefSeq	NP_001007287.1. NM_001007286.1.
UniGene	Dr.118811.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	7955.ENSDARP00000003208.
Proteomic databases
PRIDE	Q6EWH2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSDART00000046414; ENSDARP00000046413; ENSDARG00000011370. ENSDART00000150232; ENSDARP00000123888; ENSDARG00000011370.
GeneID	373872.
KEGG	dre:373872.
Organism-specific databases
CTD	373872.
ZFIN	ZDB-GENE-030903-5. fyna.
Phylogenomic databases
GeneTree	ENSGT00620000087702.
HOVERGEN	HBG008761.
InParanoid	Q6EWH2.
KO	K05703.
OMA	TDERDGS.
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	20813409.

Entry information

Entry name

FYNA_DANRE

Accession

Primary (citable) accession number: Q6EWH2
Secondary accession number(s): F8W4M2 , Q58HR4, Q6DI27, Q9I8J8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2012
Last sequence update:	September 5, 2012
Last modified:	April 3, 2013
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program