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Protein

Neuronal proto-oncogene tyrosine-protein kinase Src

Gene

Src

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1. Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors. Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation. Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of ADRBK1, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor. 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. Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase. Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-731'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-132'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity.4 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

Phosphorylation by CSK at Tyr-535 inhibits kinase activity. Inhibitory phosphorylation at Tyr-535 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-424 increases kinase activity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei303 – 3031ATPPROSITE-ProRule annotation
Active sitei394 – 3941Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi281 – 2899ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. enzyme binding Source: MGI
  3. ephrin receptor binding Source: UniProtKB
  4. growth factor receptor binding Source: MGI
  5. heme binding Source: UniProtKB
  6. hormone receptor binding Source: GO_Central
  7. ion channel binding Source: MGI
  8. kinase activity Source: MGI
  9. non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  10. phosphoprotein binding Source: MGI
  11. protein domain specific binding Source: MGI
  12. protein kinase activity Source: MGI
  13. protein tyrosine kinase activity Source: BHF-UCL
  14. receptor binding Source: MGI
  15. scaffold protein binding Source: BHF-UCL
  16. SH2 domain binding Source: MGI

GO - Biological processi

  1. activation of protein kinase B activity Source: Ensembl
  2. adherens junction organization Source: Ensembl
  3. angiotensin-activated signaling pathway involved in heart process Source: BHF-UCL
  4. bone resorption Source: UniProtKB
  5. branching involved in mammary gland duct morphogenesis Source: MGI
  6. cell cycle Source: UniProtKB-KW
  7. cell migration Source: MGI
  8. cell proliferation Source: Ensembl
  9. cellular response to fatty acid Source: Ensembl
  10. cellular response to fluid shear stress Source: MGI
  11. cellular response to hypoxia Source: Ensembl
  12. cellular response to insulin stimulus Source: Ensembl
  13. cellular response to lipopolysaccharide Source: Ensembl
  14. cellular response to peptide hormone stimulus Source: BHF-UCL
  15. cellular response to platelet-derived growth factor stimulus Source: MGI
  16. cellular response to progesterone stimulus Source: Ensembl
  17. cellular response to transforming growth factor beta stimulus Source: MGI
  18. epidermal growth factor receptor signaling pathway Source: GO_Central
  19. forebrain development Source: MGI
  20. innate immune response Source: GO_Central
  21. integrin-mediated signaling pathway Source: MGI
  22. intracellular signal transduction Source: MGI
  23. negative regulation of anoikis Source: MGI
  24. negative regulation of apoptotic process Source: MGI
  25. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  26. negative regulation of extrinsic apoptotic signaling pathway Source: MGI
  27. negative regulation of focal adhesion assembly Source: Ensembl
  28. negative regulation of intrinsic apoptotic signaling pathway Source: MGI
  29. negative regulation of mitochondrial depolarization Source: MGI
  30. negative regulation of protein homooligomerization Source: MGI
  31. negative regulation of transcription, DNA-templated Source: Ensembl
  32. neurotrophin TRK receptor signaling pathway Source: Ensembl
  33. oogenesis Source: MGI
  34. osteoclast development Source: MGI
  35. peptidyl-serine phosphorylation Source: Ensembl
  36. peptidyl-tyrosine autophosphorylation Source: GO_Central
  37. peptidyl-tyrosine phosphorylation Source: MGI
  38. phosphorylation Source: BHF-UCL
  39. platelet-derived growth factor receptor signaling pathway Source: GO_Central
  40. positive regulation of apoptotic process Source: Ensembl
  41. positive regulation of canonical Wnt signaling pathway Source: MGI
  42. positive regulation of cell adhesion Source: Ensembl
  43. positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
  44. positive regulation of cytokine secretion Source: Ensembl
  45. positive regulation of DNA biosynthetic process Source: Ensembl
  46. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  47. positive regulation of glucose metabolic process Source: Ensembl
  48. positive regulation of insulin receptor signaling pathway Source: Ensembl
  49. positive regulation of MAP kinase activity Source: Ensembl
  50. positive regulation of phosphatidylinositol 3-kinase activity Source: Ensembl
  51. positive regulation of platelet-derived growth factor receptor signaling pathway Source: Ensembl
  52. positive regulation of podosome assembly Source: MGI
  53. positive regulation of protein autophosphorylation Source: Ensembl
  54. positive regulation of protein kinase B signaling Source: MGI
  55. positive regulation of smooth muscle cell migration Source: Ensembl
  56. positive regulation of transcription, DNA-templated Source: Ensembl
  57. progesterone receptor signaling pathway Source: GO_Central
  58. protein autophosphorylation Source: MGI
  59. protein destabilization Source: CACAO
  60. protein phosphorylation Source: MGI
  61. regulation of caveolin-mediated endocytosis Source: MGI
  62. regulation of cell-cell adhesion Source: MGI
  63. regulation of cell cycle Source: GO_Central
  64. regulation of cell projection assembly Source: MGI
  65. regulation of cell proliferation Source: GO_Central
  66. regulation of early endosome to late endosome transport Source: MGI
  67. regulation of epithelial cell migration Source: MGI
  68. regulation of intracellular estrogen receptor signaling pathway Source: MGI
  69. regulation of protein binding Source: MGI
  70. response to acidic pH Source: Ensembl
  71. response to drug Source: Ensembl
  72. response to electrical stimulus Source: Ensembl
  73. response to hydrogen peroxide Source: Ensembl
  74. response to interleukin-1 Source: MGI
  75. response to mechanical stimulus Source: Ensembl
  76. response to mineralocorticoid Source: Ensembl
  77. response to nutrient levels Source: Ensembl
  78. response to virus Source: Ensembl
  79. single organismal cell-cell adhesion Source: Ensembl
  80. stress fiber assembly Source: MGI
  81. substrate adhesion-dependent cell spreading Source: MGI
  82. transcytosis Source: Ensembl
  83. transforming growth factor beta receptor signaling pathway Source: MGI
  84. uterus development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell adhesion, Cell cycle, Immunity

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiREACT_271763. DSCAM interactions.
REACT_275222. Thrombin signalling through proteinase activated receptors (PARs).
REACT_278281. Ephrin signaling.
REACT_278498. Downstream signal transduction.
REACT_280640. EPHA-mediated growth cone collapse.
REACT_284350. Signaling by EGFR.
REACT_292566. EPH-Ephrin signaling.
REACT_295531. DCC mediated attractive signaling.
REACT_296095. p38MAPK events.
REACT_298419. Spry regulation of FGF signaling.
REACT_299722. VEGFR2 mediated cell proliferation.
REACT_304203. GP1b-IX-V activation signalling.
REACT_306499. GAB1 signalosome.
REACT_311393. CTLA4 inhibitory signaling.
REACT_313804. EPHB-mediated forward signaling.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_315885. VEGFA-VEGFR2 Pathway.
REACT_316753. p130Cas linkage to MAPK signaling for integrins.
REACT_327841. Signaling by SCF-KIT.
REACT_330010. Integrin alphaIIb beta3 signaling.
REACT_332492. GRB2:SOS provides linkage to MAPK signaling for Integrins.
REACT_333749. FCGR activation.
REACT_334244. ADP signalling through P2Y purinoceptor 1.
REACT_334921. CD28 co-stimulation.
REACT_337259. Netrin mediated repulsion signals.
REACT_339798. NCAM signaling for neurite out-growth.
REACT_342354. c-src mediated regulation of Cx43 function and closure of gap junctions.
REACT_348099. Signaling by ERBB2.
REACT_353475. Recycling pathway of L1.
REACT_354765. Regulation of KIT signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Neuronal 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 namesi
Name:Src
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:98397. Src.

Subcellular locationi

  1. Cell membrane 1 Publication
  2. Mitochondrion inner membrane 1 Publication
  3. Nucleus 1 Publication
  4. Cytoplasmcytoskeleton 1 Publication

  5. Note: Localizes to focal adhesion sites after integrin engagement. Localization to focal adhesion sites requires myristoylation and the SH3 domain.

GO - Cellular componenti

  1. actin filament Source: MGI
  2. caveola Source: BHF-UCL
  3. cytoplasm Source: MGI
  4. cytosol Source: MGI
  5. extracellular vesicular exosome Source: MGI
  6. extrinsic component of cytoplasmic side of plasma membrane Source: GO_Central
  7. late endosome Source: MGI
  8. lysosome Source: MGI
  9. mitochondrial inner membrane Source: MGI
  10. mitochondrion Source: MGI
  11. neuron projection Source: Ensembl
  12. nucleus Source: MGI
  13. perinuclear region of cytoplasm Source: MGI
  14. plasma membrane Source: MGI
  15. postsynaptic density Source: Ensembl
  16. ruffle membrane Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Mitochondrion, Mitochondrion inner membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 541540Neuronal proto-oncogene tyrosine-protein kinase SrcPRO_0000088142Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Modified residuei17 – 171PhosphoserineBy similarity
Modified residuei34 – 341PhosphoserineBy similarity
Modified residuei68 – 681PhosphoserineBy similarity
Modified residuei73 – 731PhosphothreonineBy similarity
Modified residuei74 – 741Phosphoserine; by CDK5By similarity
Modified residuei192 – 1921Phosphotyrosine1 Publication
Modified residuei424 – 4241Phosphotyrosine; by autocatalysis; alternateBy similarity
Modified residuei424 – 4241Phosphotyrosine; by FAK2; alternateBy similarity
Modified residuei444 – 4441PhosphotyrosineBy similarity
Modified residuei516 – 5161PhosphothreonineBy similarity
Modified residuei527 – 5271PhosphotyrosineBy similarity
Modified residuei535 – 5351Phosphotyrosine; by CSKBy similarity

Post-translational modificationi

Myristoylated at Gly-2, and this is essential for targeting to membranes.By similarity
Dephosphorylated at Tyr-535 by PTPRJ (By similarity). Phosphorylated on Tyr-535 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-424. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-535, the SH3 domain engaged with the SH2-kinase linker, and Tyr-424 dephosphorylated. Dephosphorylation of Tyr-535 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-535, Tyr-424 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-535 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-74 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity (By similarity).By similarity
S-nitrosylation is important for activation of its kinase activity.By similarity
Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-424 and may lead to lysosomal degradation (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP05480.
PaxDbiP05480.
PRIDEiP05480.

PTM databases

PhosphoSiteiP05480.

Expressioni

Gene expression databases

BgeeiP05480.
CleanExiMM_SRC.
ExpressionAtlasiP05480. baseline and differential.
GenevestigatoriP05480.

Interactioni

Subunit structurei

Interacts with CDCP1, PELP1, TGFB1I1 and TOM1L2. Interacts with DDEF1/ASAP1 via its SH3 domain. Interacts with CCPG1. Interacts with the cytoplasmic domain of MUC1, phosphorylates it and increases binding of MUC1 with beta-catenin. Interacts with RALGPS1 via its SH3 domain. Interacts with CAV2 (tyrosine phosphorylated form). Interacts (via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation state of SRC C-terminus. Interacts with FCAMR and PXN. Interacts with ARRB2. Interacts with ARRB1. Interacts with SRCIN1. Interacts with SRCIN1. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1, ESR1 (dimethylated on arginine) and FAK. Interacts (via SH2 and SH3 domain) with TNK2. Interacts (via protein kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt domain). Interacts with TRAF3 (via RING-type zinc finger domain). Interacts with DDX58, MAVS and TBK1. Interacts (via SH2 domain) with GNB2L1/RACK1; the interaction is enhanced by tyrosine phosphorylation of GNB2L1 and inhibits SRC activity. Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with ERBB2 and STAT1. Interacts with PDGFRA (tyrosine phosphorylated). Interacts with CSF1R. Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. Interacts with DDR2. Interacts with AMOTL2; this interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites. Interacts with DDR1 and DAB2. Interacts with TRAP1. Interacts with CBLC; the interaction is enhanced when SRC is phosphorylated at 'Tyr-424'.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Bcar1Q637672EBI-298680,EBI-1176801From a different organism.
Csf1P071412EBI-298680,EBI-777188
Dlg4P310169EBI-298680,EBI-375655From a different organism.
enaQ8T4F72EBI-298680,EBI-466810From a different organism.
Ephb2P547633EBI-298680,EBI-537711
Grin2aQ009595EBI-298680,EBI-630970From a different organism.
ITGB3P051065EBI-298680,EBI-702847From a different organism.
PTK2Q053975EBI-298680,EBI-702142From a different organism.
PtpraP180522EBI-298680,EBI-6597520
PXNP490232EBI-298680,EBI-702209From a different organism.
ROR1Q019733EBI-298680,EBI-6082337From a different organism.
WasP703152EBI-298680,EBI-644195

Protein-protein interaction databases

BioGridi203491. 41 interactions.
DIPiDIP-31071N.
IntActiP05480. 28 interactions.
MINTiMINT-85032.
STRINGi10090.ENSMUSP00000105155.

Structurei

3D structure databases

ProteinModelPortaliP05480.
SMRiP05480. Positions 56-541.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini83 – 15068SH3PROSITE-ProRule annotationAdd
BLAST
Domaini156 – 25398SH2PROSITE-ProRule annotationAdd
BLAST
Domaini275 – 528254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP05480.
KOiK05704.
OMAiCHRLTNV.
OrthoDBiEOG7GTT2V.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P05480-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSNKSKPKD ASQRRRSLEP SENVHGAGGA FPASQTPSKP ASADGHRGPS
60 70 80 90 100
AAFVPPAAEP KLFGGFNSSD TVTSPQRAGP LAGGVTTFVA LYDYESRTET
110 120 130 140 150
DLSFKKGERL QIVNNTRKVD VREGDWWLAH SLSTGQTGYI PSNYVAPSDS
160 170 180 190 200
IQAEEWYFGK ITRRESERLL LNAENPRGTF LVRESETTKG AYCLSVSDFD
210 220 230 240 250
NAKGLNVKHY KIRKLDSGGF YITSRTQFNS LQQLVAYYSK HADGLCHRLT
260 270 280 290 300
TVCPTSKPQT QGLAKDAWEI PRESLRLEVK LGQGCFGEVW MGTWNGTTRV
310 320 330 340 350
AIKTLKPGTM SPEAFLQEAQ VMKKLRHEKL VQLYAVVSEE PIYIVTEYMN
360 370 380 390 400
KGSLLDFLKG ETGKYLRLPQ LVDMSAQIAS GMAYVERMNY VHRDLRAANI
410 420 430 440 450
LVGENLVCKV ADFGLARLIE DNEYTARQGA KFPIKWTAPE AALYGRFTIK
460 470 480 490 500
SDVWSFGILL TELTTKGRVP YPGMVNREVL DQVERGYRMP CPPECPESLH
510 520 530 540
DLMCQCWRKE PEERPTFEYL QAFLEDYFTS TEPQYQPGEN L
Length:541
Mass (Da):60,645
Last modified:July 27, 2011 - v4
Checksum:i0534AF027783BCCF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti80 – 801P → A in AAA40135 (PubMed:2440106).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17031 mRNA. Translation: AAA40135.1.
AY902331 Genomic DNA. Translation: AAX90616.1.
AL672259 Genomic DNA. Translation: CAM16141.1.
CH466551 Genomic DNA. Translation: EDL06234.1.
CCDSiCCDS38305.1.
PIRiA43610.
RefSeqiNP_001020566.1. NM_001025395.2.
NP_033297.2. NM_009271.3.
UniGeneiMm.22845.

Genome annotation databases

EnsembliENSMUST00000092576; ENSMUSP00000090237; ENSMUSG00000027646.
ENSMUST00000109529; ENSMUSP00000105155; ENSMUSG00000027646.
GeneIDi20779.
KEGGimmu:20779.
UCSCiuc008npa.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17031 mRNA. Translation: AAA40135.1.
AY902331 Genomic DNA. Translation: AAX90616.1.
AL672259 Genomic DNA. Translation: CAM16141.1.
CH466551 Genomic DNA. Translation: EDL06234.1.
CCDSiCCDS38305.1.
PIRiA43610.
RefSeqiNP_001020566.1. NM_001025395.2.
NP_033297.2. NM_009271.3.
UniGeneiMm.22845.

3D structure databases

ProteinModelPortaliP05480.
SMRiP05480. Positions 56-541.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203491. 41 interactions.
DIPiDIP-31071N.
IntActiP05480. 28 interactions.
MINTiMINT-85032.
STRINGi10090.ENSMUSP00000105155.

Chemistry

BindingDBiP05480.
ChEMBLiCHEMBL3074.

PTM databases

PhosphoSiteiP05480.

Proteomic databases

MaxQBiP05480.
PaxDbiP05480.
PRIDEiP05480.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000092576; ENSMUSP00000090237; ENSMUSG00000027646.
ENSMUST00000109529; ENSMUSP00000105155; ENSMUSG00000027646.
GeneIDi20779.
KEGGimmu:20779.
UCSCiuc008npa.1. mouse.

Organism-specific databases

CTDi6714.
MGIiMGI:98397. Src.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP05480.
KOiK05704.
OMAiCHRLTNV.
OrthoDBiEOG7GTT2V.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiREACT_271763. DSCAM interactions.
REACT_275222. Thrombin signalling through proteinase activated receptors (PARs).
REACT_278281. Ephrin signaling.
REACT_278498. Downstream signal transduction.
REACT_280640. EPHA-mediated growth cone collapse.
REACT_284350. Signaling by EGFR.
REACT_292566. EPH-Ephrin signaling.
REACT_295531. DCC mediated attractive signaling.
REACT_296095. p38MAPK events.
REACT_298419. Spry regulation of FGF signaling.
REACT_299722. VEGFR2 mediated cell proliferation.
REACT_304203. GP1b-IX-V activation signalling.
REACT_306499. GAB1 signalosome.
REACT_311393. CTLA4 inhibitory signaling.
REACT_313804. EPHB-mediated forward signaling.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_315885. VEGFA-VEGFR2 Pathway.
REACT_316753. p130Cas linkage to MAPK signaling for integrins.
REACT_327841. Signaling by SCF-KIT.
REACT_330010. Integrin alphaIIb beta3 signaling.
REACT_332492. GRB2:SOS provides linkage to MAPK signaling for Integrins.
REACT_333749. FCGR activation.
REACT_334244. ADP signalling through P2Y purinoceptor 1.
REACT_334921. CD28 co-stimulation.
REACT_337259. Netrin mediated repulsion signals.
REACT_339798. NCAM signaling for neurite out-growth.
REACT_342354. c-src mediated regulation of Cx43 function and closure of gap junctions.
REACT_348099. Signaling by ERBB2.
REACT_353475. Recycling pathway of L1.
REACT_354765. Regulation of KIT signaling.

Miscellaneous databases

ChiTaRSiSrc. mouse.
NextBioi299503.
PROiP05480.
SOURCEiSearch...

Gene expression databases

BgeeiP05480.
CleanExiMM_SRC.
ExpressionAtlasiP05480. baseline and differential.
GenevestigatoriP05480.

Family and domain databases

Gene3Di3.30.505.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Neuronal pp60c-src contains a six-amino acid insertion relative to its non-neuronal counterpart."
    Martinez R., Mathey-Prevot B., Bernards A., Baltimore D.
    Science 237:411-415(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
  2. "Characterization of quantitative trait loci influencing growth and adiposity using congenic mouse strains."
    Farber C.R., Corva P.M., Medrano J.F.
    Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: CAST/EiJ.
    Tissue: Brain.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor."
    Courtneidge S.A., Dhand R., Pilat D., Twamley G.M., Waterfield M.D., Roussel M.F.
    EMBO J. 12:943-950(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CSF1R.
  6. "Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor."
    Muthuswamy S.K., Muller W.J.
    Oncogene 11:271-279(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ERBB2.
  7. "Activation of Src-family protein tyrosine kinases and phosphatidylinositol 3-kinase in 3T3-L1 mouse preadipocytes by interleukin-11."
    Fuhrer D.K., Yang Y.C.
    Exp. Hematol. 24:195-203(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN IL11-SIGNALING.
  8. "Bombesin, bradykinin, vasopressin, and phorbol esters rapidly and transiently activate Src family tyrosine kinases in Swiss 3T3 cells. Dissociation from tyrosine phosphorylation of p125 focal adhesion kinase."
    Rodriguez-Fernandez J.L., Rozengurt E.
    J. Biol. Chem. 271:27895-27901(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION.
  9. "c-Src activates both STAT1 and STAT3 in PDGF-stimulated NIH3T3 cells."
    Cirri P., Chiarugi P., Marra F., Raugei G., Camici G., Manao G., Ramponi G.
    Biochem. Biophys. Res. Commun. 239:493-497(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH STAT1.
  10. "ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src."
    Brown M.T., Andrade J., Radhakrishna H., Donaldson J.G., Cooper J.A., Randazzo P.A.
    Mol. Cell. Biol. 18:7038-7051(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DDEF1/ASAP1.
  11. "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling."
    Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.
    Nat. Cell Biol. 3:650-657(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; FGFR4; SHC1; GAP43 AND CTTN.
  12. "The role of c-Src in platelet-derived growth factor alpha receptor internalization."
    Avrov K., Kazlauskas A.
    Exp. Cell Res. 291:426-434(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PDGFRA.
  13. "Regulation of cytochrome c oxidase activity by c-Src in osteoclasts."
    Miyazaki T., Neff L., Tanaka S., Horne W.C., Baron R.
    J. Cell Biol. 160:709-718(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  14. "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis."
    Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.
    J. Cell Biol. 162:661-671(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH EPHB1.
  15. "Src kinase activity is essential for osteoclast function."
    Miyazaki T., Sanjay A., Neff L., Tanaka S., Horne W.C., Baron R.
    J. Biol. Chem. 279:17660-17666(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PTK2B/PYK2.
  16. "Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as ligand-induced autophosphorylation sites involved in binding of Src family kinases and the protein tyrosine phosphatase SHP2."
    Heiss E., Masson K., Sundberg C., Pedersen M., Sun J., Bengtsson S., Ronnstrand L.
    Blood 108:1542-1550(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FLT3.
  17. "Ccpg1, a novel scaffold protein that regulates the activity of the Rho guanine nucleotide exchange factor Dbs."
    Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P.
    Mol. Cell. Biol. 26:8964-8975(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CCPG1.
  18. "Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain."
    Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.
    J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-192, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain.
  19. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  20. "Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance."
    Luan B., Zhao J., Wu H., Duan B., Shu G., Wang X., Li D., Jia W., Kang J., Pei G.
    Nature 457:1146-1149(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ARRB2.
  21. "Collagen stimulates discoidin domain receptor 1-mediated migration of smooth muscle cells through Src."
    Lu K.K., Trcka D., Bendeck M.P.
    Cardiovasc. Pathol. 20:71-76(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DDR1.
  22. Cited for: REVIEW ON FUNCTION.
  23. "Cellular functions regulated by Src family kinases."
    Thomas S.M., Brugge J.S.
    Annu. Rev. Cell Dev. Biol. 13:513-609(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  24. "Novel regulation and function of Src tyrosine kinase."
    Ma Y.C., Huang X.Y.
    Cell. Mol. Life Sci. 59:456-462(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.

Entry informationi

Entry nameiSRC_MOUSE
AccessioniPrimary (citable) accession number: P05480
Secondary accession number(s): Q2M4I4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: July 27, 2011
Last modified: April 29, 2015
This is version 170 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.