CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002688
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tyrosine-protein kinase HCK 
Protein Synonyms/Alias
 Hematopoietic cell kinase; Hemopoietic cell kinase; p59-HCK/p60-HCK; p59Hck; p61Hck 
Gene Name
 HCK 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
28RMGCMKSKFLQVGGNubiquitination[1, 2]
124ARSLATRKEGYIPSNubiquitination[1, 2]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 
Functional Description
 Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS. 
Sequence Annotation
 DOMAIN 78 138 SH3.
 DOMAIN 144 241 SH2.
 DOMAIN 262 515 Protein kinase.
 NP_BIND 268 276 ATP.
 ACT_SITE 381 381 Proton acceptor.
 BINDING 290 290 ATP.
 MOD_RES 51 51 Phosphotyrosine; by autocatalysis.
 MOD_RES 202 202 Phosphothreonine.
 MOD_RES 209 209 Phosphotyrosine (By similarity).
 MOD_RES 411 411 Phosphotyrosine; by autocatalysis.
 MOD_RES 462 462 Phosphoserine.
 MOD_RES 522 522 Phosphotyrosine.
 LIPID 2 2 N-myristoyl glycine.  
Keyword
 3D-structure; Alternative initiation; Alternative splicing; ATP-binding; Cell junction; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Exocytosis; Golgi apparatus; Host-virus interaction; Immunity; Inflammatory response; Innate immunity; Kinase; Lipoprotein; Lysosome; Membrane; Myristate; Nucleotide-binding; Nucleus; Palmitate; Phagocytosis; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 526 AA 
Protein Sequence
MGGRSSCEDP GCPRDEERAP RMGCMKSKFL QVGGNTFSKT ETSASPHCPV YVPDPTSTIK 60
PGPNSHNSNT PGIREAGSED IIVVALYDYE AIHHEDLSFQ KGDQMVVLEE SGEWWKARSL 120
ATRKEGYIPS NYVARVDSLE TEEWFFKGIS RKDAERQLLA PGNMLGSFMI RDSETTKGSY 180
SLSVRDYDPR QGDTVKHYKI RTLDNGGFYI SPRSTFSTLQ ELVDHYKKGN DGLCQKLSVP 240
CMSSKPQKPW EKDAWEIPRE SLKLEKKLGA GQFGEVWMAT YNKHTKVAVK TMKPGSMSVE 300
AFLAEANVMK TLQHDKLVKL HAVVTKEPIY IITEFMAKGS LLDFLKSDEG SKQPLPKLID 360
FSAQIAEGMA FIEQRNYIHR DLRAANILVS ASLVCKIADF GLARVIEDNE YTAREGAKFP 420
IKWTAPEAIN FGSFTIKSDV WSFGILLMEI VTYGRIPYPG MSNPEVIRAL ERGYRMPRPE 480
NCPEELYNIM MRCWKNRPEE RPTFEYIQSV LDDFYTATES QYQQQP 526 
Gene Ontology
 GO:0005901; C:caveola; IDA:UniProtKB.
 GO:0042995; C:cell projection; IEA:UniProtKB-KW.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0031234; C:extrinsic to internal side of plasma membrane; IMP:UniProtKB.
 GO:0005925; C:focal adhesion; IMP:UniProtKB.
 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
 GO:0005764; C:lysosome; IDA:UniProtKB.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0004713; F:protein tyrosine kinase activity; IMP:UniProtKB.
 GO:0007155; P:cell adhesion; TAS:UniProtKB.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0002758; P:innate immune response-activating signal transduction; TAS:UniProtKB.
 GO:0007229; P:integrin-mediated signaling pathway; TAS:UniProtKB.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:UniProtKB.
 GO:0043299; P:leukocyte degranulation; TAS:UniProtKB.
 GO:0002522; P:leukocyte migration involved in immune response; TAS:UniProtKB.
 GO:0031663; P:lipopolysaccharide-mediated signaling pathway; TAS:UniProtKB.
 GO:0007498; P:mesoderm development; TAS:ProtInc.
 GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
 GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:UniProtKB.
 GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IDA:UniProtKB.
 GO:0030838; P:positive regulation of actin filament polymerization; TAS:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
 GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
 GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
 GO:0050727; P:regulation of inflammatory response; TAS:UniProtKB.
 GO:0050764; P:regulation of phagocytosis; IMP:UniProtKB.
 GO:0071801; P:regulation of podosome assembly; IDA:UniProtKB.
 GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; IMP:UniProtKB.
 GO:0045728; P:respiratory burst after phagocytosis; TAS:UniProtKB.
 GO:0016032; P:viral reproduction; TAS:Reactome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
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. 
Pfam
 PF07714; Pkinase_Tyr
 PF00017; SH2
 PF00018; SH3_1 
SMART
 SM00252; SH2
 SM00326; SH3
 SM00219; TyrKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50001; SH2
 PS50002; SH3 
PRINTS
 PR00401; SH2DOMAIN.
 PR00452; SH3DOMAIN.
 PR00109; TYRKINASE.