Proto-oncogene tyrosine-protein kinase Src

Contribute

Send feedback

Read comments (?) or add your own

Q1JPZ3 (SRC_DANRE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 64. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Proto-oncogene tyrosine-protein kinase Src
EC=2.7.10.2

Alternative name(s):
Proto-oncogene c-Src
pp60c-src
Short name=p60-Src

Gene names

Name:

src

Organism

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

Taxonomic identifier

7955 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Actinopterygii › Neopterygii › Teleostei › Ostariophysi › Cypriniformes › Cyprinidae › Danio

Protein attributes

Sequence length	534 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	Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each src kinase is very difficult. Src appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of src to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including ptk2/fak1 and paxillin (pxn). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus By similarity.
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations. Heme regulates its activity by enhancing the phosphorylation on Tyr-528 By similarity.
Subunit structure	Interacts with amotl2; this interaction promotes the translocation of phosphorylated src to peripheral cell-matrix adhesion sites. Ref.4
Subcellular location	Cell membrane By similarity. Mitochondrion inner membrane By similarity. Nucleus By similarity. Cytoplasm › cytoskeleton By similarity. Note: Localizes to focal adhesion sites following integrin engagement. Localization to focal adhesion sites requires myristoylation and the SH3 domain By similarity.
Tissue specificity	Widely expressed. Ref.1
Domain	The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment By similarity.
Post-translational modification	Myristoylated at Gly-2, and this is essential for targeting to membranes By similarity. Dephosphorylated at Tyr-528 by PTPRJ. Phosphorylated on Tyr-528 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-417. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-528, the SH3 domain engaged with the SH2-kinase linker, and Tyr-417 dephosphorylated. Dephosphorylation of Tyr-528 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-528, Tyr-417 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-528 by CSK allows this interaction to reform, resulting in SRC inactivation By similarity. S-nitrosylation is important for activation of kinase activity 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	Cell adhesion Cell cycle
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Mitochondrion Mitochondrion inner membrane Nucleus
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Phosphoprotein S-nitrosylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial inner membrane Inferred from electronic annotation. Source: UniProtKB-SubCell 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 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

Initiator methionine

Removed By similarity

Chain

2 – 534

533

Proto-oncogene tyrosine-protein kinase Src

PRO_0000418880

Regions

Domain

82 – 143

SH3

Domain

149 – 253

105

SH2

Domain

268 – 521

254

Protein kinase

Nucleotide binding

274 – 282

ATP By similarity

Sites

Active site

387

Proton acceptor By similarity

Binding site

296

ATP By similarity

Amino acid modifications

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphoserine By similarity

Modified residue

Phosphothreonine By similarity

Modified residue

Phosphoserine; by CDK5 By similarity

Modified residue

185

Phosphotyrosine By similarity

Modified residue

417

Phosphotyrosine; by autocatalysis By similarity

Modified residue

417

Phosphotyrosine; by FAK2 By similarity

Modified residue

437

Phosphotyrosine By similarity

Modified residue

499

S-nitrosocysteine By similarity

Modified residue

509

Phosphothreonine By similarity

Modified residue

520

Phosphotyrosine By similarity

Modified residue

528

Phosphotyrosine; by CSK By similarity

Lipidation

N-myristoyl glycine By similarity

Experimental info

Mutagenesis

528

Y → F: Lower affinity for AMOTL2-binding compared with wild-type. Ref.4

Sequence conflict

V → A in AAI16545. Ref.3

Sequence conflict

166

L → M in AAI16545. Ref.3

Sequences

Sequence

Length

Mass (Da)

Tools

Q1JPZ3 [UniParc].

Last modified September 5, 2012. Version 2.
Checksum: EC09B5A1BC01A38A
Show »

FASTA

534

60,147

        10         20         30         40         50         60 
MGGVKSKPKE LGQRSRSLDD GTGGHHHHTP NPTSFTPNRS PPVEGSRRGT QPNIINAEQA 

        70         80         90        100        110        120 
LFGGVNSTTN SITSPNRIGI LGGVTTFVAL YDYESRTASD LSFRKGERLQ IVNNTEGDWW 

       130        140        150        160        170        180 
LARSLTTGES GYIPSNYVAP SDSIQAEEWY FGKITRRDSE RLLLNLENRR GTFLVRESET 

       190        200        210        220        230        240 
TKGAYCLSVL DYDNVKGLNV KHYKIRKLDS GGFYITSRTQ FSTLQQLVNH YRQHADGLCH 

       250        260        270        280        290        300 
SLTDVCPVLK PPTQGLARDA WEIPRDSLRL DVKLGQGCFG EVWMGTWNGT TRVAIKTLKP 

       310        320        330        340        350        360 
GTMSPEAFLQ EAQVMKKLRH EKLVQLYAVV SEEPIYIVTE YMGQGSLLDF LKGDMGKMLR 

       370        380        390        400        410        420 
LPQLVDMASQ IASGMAYVER MNYVHRDLRA ANILVGDNLV CKVADFGLAR LIEDNEYTAR 

       430        440        450        460        470        480 
QGAKFPIKWT APEAALYGRF TIKSDVWSFG ILLTELTTKG RVPYPGMVNR EVLDQVERGY 

       490        500        510        520        530 
RMPCPAECPD SLHELMLTCW RKEPEERPTF EYLQGFLEDY FTSTEPQYQP GENL

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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], TISSUE SPECIFICITY.
[2]	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.
[3]	NIH - Zebrafish Gene Collection (ZGC) project Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[4]	"Amotl2 is essential for cell movements in zebrafish embryo and regulates c-Src translocation." Huang H., Lu F.I., Jia S., Meng S., Cao Y., Wang Y., Ma W., Yin K., Wen Z., Peng J., Thisse C., Thisse B., Meng A. Development 134:979-988(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AMOTL2, MUTAGENESIS OF TYR-528.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ620750 mRNA. Translation: CAF06181.1. BX548066 Genomic DNA. No translation available. CU302205 Genomic DNA. No translation available. BC116544 mRNA. Translation: AAI16545.1.
IPI	IPI00489784.
RefSeq	NP_001003837.2. NM_001003837.2.
UniGene	Dr.2731.
3D structure databases
ProteinModelPortal	Q1JPZ3.
SMR	Q1JPZ3. Positions 84-534.
ModBase	Search...
Protein-protein interaction databases
STRING	7955.ENSDARP00000093618.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSDART00000102843; ENSDARP00000093618; ENSDARG00000008107. ENSDART00000112198; ENSDARP00000097596; ENSDARG00000008107.
GeneID	325084.
KEGG	dre:325084.
Organism-specific databases
CTD	6714.
ZFIN	ZDB-GENE-030131-3809. src.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00620000087702.
HOGENOM	HOG000233858.
HOVERGEN	HBG008761.
KO	K05704.
OMA	CQCWRKD.
OrthoDB	EOG4K6G41.
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	20809110.

Entry information

Entry name

SRC_DANRE

Accession

Primary (citable) accession number: Q1JPZ3
Secondary accession number(s): Q6EWH0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2012
Last sequence update:	September 5, 2012
Last modified:	April 3, 2013
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents