Q07014 (LYN_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 132. History...
Names and origin
|Protein names||Recommended name:|
Tyrosine-protein kinase Lyn
V-yes-1 Yamaguchi sarcoma viral related oncogene homolog
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||512 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B By similarity. Phosphorylates LPXN on 'Tyr-72' By similarity.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.4
Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Ref.4
Interacts with TEC. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via proline-rich region) By similarity. Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation By similarity. Interacts (via ankyrin repeat region) with LYN (via SH3-domain) in an activation-independent status of LYN By similarity. Forms a multiprotein complex with LYN and HS1 By similarity.
Cell membrane By similarity. Nucleus By similarity. Cytoplasm By similarity. Cytoplasm › perinuclear region By similarity. Golgi apparatus By similarity. Note: Accumulates in the nucleus by inhibition of Crm1-mediated nuclear export. Nuclear accumulation is increased by inhibition of its kinase activity. The trafficking from the Golgi apparatus to the cell membrane occurs in a kinase domain-dependent but kinase activity independent manner and is mediated by exocytic vesicular transport By similarity.
Detected in spleen (at protein level). Expressed predominantly in B-lymphoid and myeloid cells. Ref.4
The protein kinase domain plays an important role in its localization in the cell membrane By similarity.
Ubiquitinated. Ubiquitination is SH3-dependent By similarity.
Phosphorylated on tyrosine residues in response to KIT signaling By similarity. Autophosphorylated. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A By similarity. Ref.4
Contains 1 protein kinase domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform LYN A (identifier: Q07014-1) |
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 LYN B (identifier: Q07014-2) |
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 512||512||Tyrosine-protein kinase Lyn||PRO_0000088131|
|Domain||63 – 123||61||SH3|
|Domain||129 – 226||98||SH2|
|Domain||247 – 501||255||Protein kinase|
|Nucleotide binding||253 – 261||9||ATP By similarity|
|Active site||367||1||Proton acceptor By similarity|
|Binding site||275||1||ATP By similarity|
Amino acid modifications
|Modified residue||6||1||Phosphoserine By similarity|
|Modified residue||30||1||Phosphothreonine By similarity|
|Modified residue||32||1||Phosphotyrosine By similarity|
|Modified residue||37||1||Phosphothreonine By similarity|
|Modified residue||193||1||Phosphotyrosine By similarity|
|Modified residue||194||1||Phosphotyrosine By similarity|
|Modified residue||228||1||Phosphoserine By similarity|
|Modified residue||265||1||Phosphotyrosine By similarity|
|Modified residue||306||1||Phosphotyrosine By similarity|
|Modified residue||316||1||Phosphotyrosine By similarity|
|Modified residue||397||1||Phosphotyrosine; by autocatalysis Ref.4|
|Modified residue||460||1||Phosphotyrosine By similarity|
|Modified residue||473||1||Phosphotyrosine By similarity|
|Modified residue||489||1||Phosphothreonine By similarity|
|Modified residue||502||1||Phosphothreonine By similarity|
|Modified residue||508||1||Phosphotyrosine; by autocatalysis, CSK and MATK Ref.4|
|Lipidation||2||1||N-myristoyl glycine By similarity|
|Lipidation||3||1||S-palmitoyl cysteine By similarity|
|Alternative sequence||25 – 45||21||Missing in isoform LYN B.||VSP_005004|
|Sequence conflict||231||1||P → L in AAA20944. Ref.2|
|Sequence conflict||231||1||P → L in AAA20945. Ref.2|
|Sequence conflict||308||1||V → A in AAA20944. Ref.2|
|Sequence conflict||308||1||V → A in AAA20945. Ref.2|
|Sequence conflict||419||1||C → Y in AAA20944. Ref.2|
|Sequence conflict||419||1||C → Y in AAA20945. Ref.2|
|||"Bacterially expressed rat p56lyn binds several proteins in rat basophilic leukemia cells including pp72, a tyrosine phosphorylated protein prominent in activated cells."|
Minoguchi K., Nishikata H., Siraganian R.P.
J. Immunol. 150:222-222(1993)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The cDNAs encoding two forms of the LYN protein tyrosine kinase are expressed in rat mast cells and human myeloid cells."|
Rider L.G., Raben N., Miller L., Jelsema C.
Gene 138:219-222(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"The unique domain as the site on Lyn kinase for its constitutive association with the high affinity receptor for IgE."|
Vonakis B.M., Chen H., Haleem-Smith H., Metzger H.
J. Biol. Chem. 272:24072-24080(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Spontaneous autophosphorylation of Lyn tyrosine kinase at both its activation segment and C-terminal tail confers altered substrate specificity."|
Donella-Deana A., Cesaro L., Ruzzene M., Brunati A.M., Marin O., Pinna L.A.
Biochemistry 37:1438-1446(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-397 AND TYR-508, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ENZYME REGULATION, TISSUE SPECIFICITY.
|+||Additional computationally mapped references.|
|L14951 mRNA. Translation: AAA41549.1.|
L14782 mRNA. Translation: AAA20944.1.
L14823 mRNA. Translation: AAA20945.1.
AF000300 mRNA. Translation: AAB71344.1.
AF000301 mRNA. Translation: AAB71345.1.
AF000302 mRNA. Translation: AAB71346.1.
|RefSeq||NP_001104568.1. NM_001111098.1. |
3D structure databases
|SMR||Q07014. Positions 67-512. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000011130; ENSRNOP00000011130; ENSRNOG00000008180. |
|UCSC||RGD:621017. rat. |
|RGD||621017. Lyn. |
Enzyme and pathway databases
|BRENDA||18.104.22.168. 5301. |
|Reactome||REACT_109781. Immune System. |
Gene expression databases
|GermOnline||ENSRNOG00000008180. Rattus norvegicus. |
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: Q07014|
Secondary accession number(s): Q63320
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families