Q1JPZ3 (SRC_DANRE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 64. History...
Names and origin
|Protein names||Recommended name:|
Proto-oncogene tyrosine-protein kinase 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|
|Sequence length||534 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
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.
Interacts with amotl2; this interaction promotes the translocation of phosphorylated src to peripheral cell-matrix adhesion sites. Ref.4
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.
Widely expressed. Ref.1
The SH2 and SH3 domains are important for the intramolecular and intermolecular interactions that regulate catalytic activity, localization, and substrate recruitment By similarity.
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.
Contains 1 protein kinase domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 534||533||Proto-oncogene tyrosine-protein kinase Src||PRO_0000418880|
|Domain||82 – 143||62||SH3|
|Domain||149 – 253||105||SH2|
|Domain||268 – 521||254||Protein kinase|
|Nucleotide binding||274 – 282||9||ATP By similarity|
|Active site||387||1||Proton acceptor By similarity|
|Binding site||296||1||ATP By similarity|
Amino acid modifications
|Modified residue||17||1||Phosphoserine By similarity|
|Modified residue||34||1||Phosphoserine By similarity|
|Modified residue||67||1||Phosphoserine By similarity|
|Modified residue||73||1||Phosphothreonine By similarity|
|Modified residue||74||1||Phosphoserine; by CDK5 By similarity|
|Modified residue||185||1||Phosphotyrosine By similarity|
|Modified residue||417||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||417||1||Phosphotyrosine; by FAK2 By similarity|
|Modified residue||437||1||Phosphotyrosine By similarity|
|Modified residue||499||1||S-nitrosocysteine By similarity|
|Modified residue||509||1||Phosphothreonine By similarity|
|Modified residue||520||1||Phosphotyrosine By similarity|
|Modified residue||528||1||Phosphotyrosine; by CSK By similarity|
|Lipidation||2||1||N-myristoyl glycine By similarity|
|Mutagenesis||528||1||Y → F: Lower affinity for AMOTL2-binding compared with wild-type. Ref.4|
|Sequence conflict||4||1||V → A in AAI16545. Ref.3|
|Sequence conflict||166||1||L → M in AAI16545. Ref.3|
|||"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.
|||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].
|||NIH - Zebrafish Gene Collection (ZGC) project|
Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"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.|
|AJ620750 mRNA. Translation: CAF06181.1.|
BX548066 Genomic DNA. No translation available.
CU302205 Genomic DNA. No translation available.
BC116544 mRNA. Translation: AAI16545.1.
|RefSeq||NP_001003837.2. NM_001003837.2. |
3D structure databases
|SMR||Q1JPZ3. Positions 84-534. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSDART00000102843; ENSDARP00000093618; ENSDARG00000008107. |
ENSDART00000112198; ENSDARP00000097596; ENSDARG00000008107.
|ZFIN||ZDB-GENE-030131-3809. src. |
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF07714. Pkinase_Tyr. 1 hit. |
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00252. SH2. 1 hit. |
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
|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.
|Accession||Primary (citable) accession number: Q1JPZ3|
Secondary accession number(s): Q6EWH0
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families