LOCUS       NP_004374                450 aa            linear   PRI 30-APR-2025
DEFINITION  tyrosine-protein kinase CSK isoform 1 [Homo sapiens].
ACCESSION   NP_004374
VERSION     NP_004374.1
DBSOURCE    REFSEQ: accession NM_004383.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 450)
  AUTHORS   Brian,B.F. 4th, Sjaastad,F.V. and Freedman,T.S.
  TITLE     SH3-domain mutations selectively disrupt Csk homodimerization or
            PTPN22 binding
  JOURNAL   Sci Rep 12 (1), 5875 (2022)
   PUBMED   35393453
  REMARK    GeneRIF: SH3-domain mutations selectively disrupt Csk
            homodimerization or PTPN22 binding.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 450)
  AUTHORS   Chiva-Blanch,G., Pena,E., Cubedo,J., Garcia-Arguinzonis,M.,
            Pane,A., Gil,P.A., Perez,A., Ortega,E., Padro,T. and Badimon,L.
  TITLE     Molecular mapping of platelet hyperreactivity in diabetes: the
            stress proteins complex HSPA8/Hsp90/CSK2alpha and platelet
            aggregation in diabetic and normal platelets
  JOURNAL   Transl Res 235, 1-14 (2021)
   PUBMED   33887528
  REMARK    GeneRIF: Molecular mapping of platelet hyperreactivity in diabetes:
            the stress proteins complex HSPA8/Hsp90/CSK2alpha and platelet
            aggregation in diabetic and normal platelets.
REFERENCE   3  (residues 1 to 450)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   4  (residues 1 to 450)
  AUTHORS   Buljan,M., Ciuffa,R., van Drogen,A., Vichalkovski,A., Mehnert,M.,
            Rosenberger,G., Lee,S., Varjosalo,M., Pernas,L.E., Spegg,V.,
            Snijder,B., Aebersold,R. and Gstaiger,M.
  TITLE     Kinase Interaction Network Expands Functional and Disease Roles of
            Human Kinases
  JOURNAL   Mol Cell 79 (3), 504-520 (2020)
   PUBMED   32707033
REFERENCE   5  (residues 1 to 450)
  AUTHORS   Yao,Q., Liu,B.Q., Li,H., McGarrigle,D., Xing,B.W., Zhou,M.T.,
            Wang,Z., Zhang,J.J., Huang,X.Y. and Guo,L.
  TITLE     C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic
            elongation factor 2 (eEF2) promotes proteolytic cleavage and
            nuclear translocation of eEF2
  JOURNAL   J Biol Chem 289 (18), 12666-12678 (2014)
   PUBMED   24648518
  REMARK    GeneRIF: Data indicate that the accumulation of the cleaved
            C-terminal small fragment of eukaryotic elongation factor 2 (eEF2)
            in the nucleus, and C-terminal Src kinase (Csk) could enhance the
            proteolytic cleavage of eEF2.
REFERENCE   6  (residues 1 to 450)
  AUTHORS   Manjarrez-Orduno,N., Marasco,E., Chung,S.A., Katz,M.S.,
            Kiridly,J.F., Simpfendorfer,K.R., Freudenberg,J., Ballard,D.H.,
            Nashi,E., Hopkins,T.J., Cunninghame Graham,D.S., Lee,A.T.,
            Coenen,M.J., Franke,B., Swinkels,D.W., Graham,R.R., Kimberly,R.P.,
            Gaffney,P.M., Vyse,T.J., Behrens,T.W., Criswell,L.A., Diamond,B.
            and Gregersen,P.K.
  TITLE     CSK regulatory polymorphism is associated with systemic lupus
            erythematosus and influences B-cell signaling and activation
  JOURNAL   Nat Genet 44 (11), 1227-1230 (2012)
   PUBMED   23042117
  REMARK    GeneRIF: This suggests that the Lyp-Csk complex increases
            susceptibility to lupus at multiple maturation and activation
            points in B cells.
REFERENCE   7  (residues 1 to 450)
  AUTHORS   Brauninger,A., Holtrich,U., Strebhardt,K. and Rubsamen-Waigmann,H.
  TITLE     Isolation and characterization of a human gene that encodes a new
            subclass of protein tyrosine kinases
  JOURNAL   Gene 110 (2), 205-211 (1992)
   PUBMED   1371489
REFERENCE   8  (residues 1 to 450)
  AUTHORS   Armstrong,E., Cannizzaro,L., Bergman,M., Huebner,K. and Alitalo,K.
  TITLE     The c-src tyrosine kinase (CSK) gene, a potential antioncogene,
            localizes to human chromosome region 15q23----q25
  JOURNAL   Cytogenet Cell Genet 60 (2), 119-120 (1992)
   PUBMED   1377109
REFERENCE   9  (residues 1 to 450)
  AUTHORS   Holtrich,U., Brauninger,A., Strebhardt,K. and Rubsamen-Waigmann,H.
  TITLE     Two additional protein-tyrosine kinases expressed in human lung:
            fourth member of the fibroblast growth factor receptor family and
            an intracellular protein-tyrosine kinase
  JOURNAL   Proc Natl Acad Sci U S A 88 (23), 10411-10415 (1991)
   PUBMED   1720539
REFERENCE   10 (residues 1 to 450)
  AUTHORS   Partanen,J., Armstrong,E., Bergman,M., Makela,T.P., Hirvonen,H.,
            Huebner,K. and Alitalo,K.
  TITLE     cyl encodes a putative cytoplasmic tyrosine kinase lacking the
            conserved tyrosine autophosphorylation site (Y416src)
  JOURNAL   Oncogene 6 (11), 2013-2018 (1991)
   PUBMED   1945408
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC091230.23.
            
            Summary: The protein encoded by this gene is involved in multiple
            pathways, including the regulation of Src family kinases. It plays
            an important role in T-cell activation through its association with
            the protein encoded by the protein tyrosine phosphatase,
            non-receptor type 22 (PTPN22) gene. This protein also
            phosphorylates C-terminal tyrosine residues on multiple substrates,
            including the protein encoded by the SRC proto-oncogene,
            non-receptor tyrosine kinase gene. Phosphorylation suppresses the
            kinase activity of the Src family tyrosine kinases. An intronic
            polymorphism (rs34933034) in this gene has been found to affect
            B-cell activation and is associated with systemic lupus
            erythematosus (SLE). Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Aug 2017].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X59932.1, BC106073.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000220003.14/ ENSP00000220003.9
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..450
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q24.1"
     Protein         1..450
                     /product="tyrosine-protein kinase CSK isoform 1"
                     /EC_number="2.7.10.2"
                     /note="tyrosine-protein kinase CSK; C-Src kinase;
                     protein-tyrosine kinase CYL; c-src tyrosine kinase; CSK,
                     non-receptor tyrosine kinase"
                     /calculated_mol_wt=50573
     Site            2
                     /site_type="acetylation"
                     /note="N-acetylserine.
                     /evidence=ECO:0007744|PubMed:19413330; propagated from
                     UniProtKB/Swiss-Prot (P41240.1)"
     Region          9..70
                     /region_name="Interaction with PTPN22.
                     /evidence=ECO:0000250|UniProtKB:P41241"
                     /note="propagated from UniProtKB/Swiss-Prot (P41240.1)"
     Region          11..67
                     /region_name="SH3_CSK"
                     /note="Src Homology 3 domain of C-terminal Src kinase;
                     cd11769"
                     /db_xref="CDD:212703"
     Site            order(20,23..24,26,40..41,43..44,46..47,49,59,61..64)
                     /site_type="other"
                     /note="peptide ligand binding site [polypeptide binding]"
                     /db_xref="CDD:212703"
     Region          78..175
                     /region_name="SH2_csk_like"
                     /note="Src homology 2 (SH2) domain found in
                     Carboxyl-Terminal Src Kinase (Csk); cd09937"
                     /db_xref="CDD:198190"
     Site            order(89,107,128,130)
                     /site_type="other"
                     /note="phosphotyrosine binding pocket [polypeptide
                     binding]"
                     /db_xref="CDD:198190"
     Site            order(129,156)
                     /site_type="other"
                     /note="hydrophobic binding pocket [polypeptide binding]"
                     /db_xref="CDD:198190"
     Site            184
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0000269|PubMed:9148770; propagated from
                     UniProtKB/Swiss-Prot (P41240.1)"
     Region          188..443
                     /region_name="PTKc_Csk"
                     /note="Catalytic domain of the Protein Tyrosine Kinase,
                     C-terminal Src kinase; cd05082"
                     /db_xref="CDD:133213"
     Site            order(201..203,209,220,222,249,266..269,272..273,314,
                     318..319,321,331..332,345..349,358,392)
                     /site_type="active"
                     /db_xref="CDD:133213"
     Site            order(201..203,209,220,222,249,266..269,272..273,318..319,
                     321,331..332)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:133213"
     Site            order(215,226,238,241..242,244,259)
                     /site_type="other"
                     /note="SH3/SH2 domain interface [polypeptide binding]"
                     /db_xref="CDD:133213"
     Site            order(279..283,351,384..385,388..390)
                     /site_type="other"
                     /note="c-Src interface [polypeptide binding]"
                     /db_xref="CDD:133213"
     Site            304
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine.
                     /evidence=ECO:0000269|PubMed:9148770; propagated from
                     UniProtKB/Swiss-Prot (P41240.1)"
     Site            order(314,318,345..349,358,392)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:133213"
     Site            331..351
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:133213"
     Site            364
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by PKA.
                     /evidence=ECO:0000269|PubMed:11181701; propagated from
                     UniProtKB/Swiss-Prot (P41240.1)"
     Site            416
                     /site_type="phosphorylation"
                     /note="Phosphotyrosine, by autocatalysis.
                     /evidence=ECO:0000269|PubMed:1945408; propagated from
                     UniProtKB/Swiss-Prot (P41240.1)"
     CDS             1..450
                     /gene="CSK"
                     /coded_by="NM_004383.3:707..2059"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS10269.1"
                     /db_xref="GeneID:1445"
                     /db_xref="HGNC:HGNC:2444"
                     /db_xref="MIM:124095"
ORIGIN      
        1 msaiqaawps gteciakynf hgtaeqdlpf ckgdvltiva vtkdpnwyka knkvgregii
       61 panyvqkreg vkagtklslm pwfhgkitre qaerllyppe tglflvrest nypgdytlcv
      121 scdgkvehyr imyhasklsi deevyfenlm qlvehytsda dglctrlikp kvmegtvaaq
      181 defyrsgwal nmkelkllqt igkgefgdvm lgdyrgnkva vkcikndata qaflaeasvm
      241 tqlrhsnlvq llgviveekg glyivteyma kgslvdylrs rgrsvlggdc llkfsldvce
      301 ameylegnnf vhrdlaarnv lvsednvakv sdfgltkeas stqdtgklpv kwtapealre
      361 kkfstksdvw sfgillweiy sfgrvpypri plkdvvprve kgykmdapdg cppavyevmk
      421 ncwhldaamr psflqlreql ehikthelhl
//
