HCK_MACFA
ID HCK_MACFA Reviewed; 504 AA.
AC Q95M30;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Tyrosine-protein kinase HCK;
DE EC=2.7.10.2;
DE AltName: Full=Hematopoietic cell kinase;
DE AltName: Full=Hemopoietic cell kinase;
DE AltName: Full=p56-HCK;
GN Name=HCK;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Picard C.;
RL Thesis (2001), University of Marseille, France.
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase found in hematopoietic
CC cells that transmits signals from cell surface receptors and plays an
CC important role in the regulation of innate immune responses, including
CC neutrophil, monocyte, macrophage and mast cell functions, phagocytosis,
CC cell survival and proliferation, cell adhesion and migration. Acts
CC downstream of receptors that bind the Fc region of immunoglobulins,
CC such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for
CC IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During
CC the phagocytic process, mediates mobilization of secretory lysosomes,
CC degranulation, and activation of NADPH oxidase to bring about the
CC respiratory burst. Plays a role in the release of inflammatory
CC molecules. Promotes reorganization of the actin cytoskeleton and actin
CC polymerization, formation of podosomes and cell protrusions. Inhibits
CC TP73-mediated transcription activation and TP73-mediated apoptosis.
CC Phosphorylates CBL in response to activation of immunoglobulin gamma Fc
CC region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1,
CC GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Subject to autoinhibition, mediated by
CC intramolecular interactions involving the SH2 and SH3 domains. Kinase
CC activity is also regulated by phosphorylation at regulatory tyrosine
CC residues. Phosphorylation at Tyr-389 is required for optimal activity.
CC Phosphorylation at Tyr-500 inhibits kinase activity (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts with ADAM15. Interacts with FASLG. Interacts with
CC ARRB1 and ARRB2. Interacts with FCGR1A; the interaction may be
CC indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1.
CC Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts
CC with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1.
CC Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated).
CC Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1. Interacts
CC (via SH3 domain) with WDCP. {ECO:0000250|UniProtKB:P08103,
CC ECO:0000250|UniProtKB:P08631}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}. Cell membrane; Lipid-
CC anchor. Membrane, caveola {ECO:0000250}; Lipid-anchor {ECO:0000250}.
CC Cell junction, focal adhesion {ECO:0000250}. Cytoplasm, cytoskeleton
CC {ECO:0000250}. Golgi apparatus {ECO:0000250}. Cytoplasmic vesicle
CC {ECO:0000250}. Lysosome {ECO:0000250}. Nucleus {ECO:0000250}. Note=A
CC small fraction is associated with caveolae. Localization at the cell
CC membrane and at caveolae requires palmitoylation at Cys-3. Colocalizes
CC with the actin cytoskeleton at focal adhesions (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on several tyrosine residues. Autophosphorylated.
CC Becomes rapidly phosphorylated upon activation of the immunoglobulin
CC receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-389 increases
CC kinase activity. Phosphorylation at Tyr-500 inhibits kinase activity.
CC Kinase activity is not required for phosphorylation at Tyr-500,
CC suggesting that this site may be a target of other kinases (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation via the
CC proteasome. {ECO:0000250}.
CC -!- PTM: Palmitoylation requires prior myristoylation. Palmitoylation is
CC required for caveolar localization (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AJ320181; CAC44031.1; -; mRNA.
DR RefSeq; NP_001306372.1; NM_001319443.1.
DR AlphaFoldDB; Q95M30; -.
DR BMRB; Q95M30; -.
DR SMR; Q95M30; -.
DR STRING; 9541.XP_005568712.1; -.
DR PRIDE; Q95M30; -.
DR GeneID; 102115729; -.
DR CTD; 3055; -.
DR eggNOG; KOG0197; Eukaryota.
DR BRENDA; 2.7.10.2; 1793.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IEA:UniProtKB-KW.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0071801; P:regulation of podosome assembly; ISS:UniProtKB.
DR CDD; cd10363; SH2_Src_HCK; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035851; HCK_SH2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell junction; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; Exocytosis; Golgi apparatus; Immunity; Inflammatory response;
KW Innate immunity; Kinase; Lipoprotein; Lysosome; Membrane; Myristate;
KW Nucleotide-binding; Nucleus; Palmitate; Phagocytosis; Phosphoprotein;
KW Proto-oncogene; Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..504
FT /note="Tyrosine-protein kinase HCK"
FT /id="PRO_0000088103"
FT DOMAIN 56..116
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 122..219
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 240..493
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 34..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 37..52
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 359
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 246..254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 268
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 15
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 30
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 180
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 187
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08103"
FT MOD_RES 389
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 500
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 504 AA; 57096 MW; 53B29322D2DE3423 CRC64;
MGCMKSKFLQ AGGNTFSKTE TSANPHCPVY VPDPTSTIKP GPNSNNRNTP GIGEGSEDII
VVALYDYEAI HHEDLSFQKG DQMVVLEESG EWWKARSLAT RKEGYIPSNY VARVDSLETE
EWFFKGISRK DAERQLLAPG NMLGSFMIRD SETTKGSYSL SVRDYDPRQG DTVKHYKIRT
LDNGGFYISP RSTFSTLQEL VDHYKKGSDG LCQKLSVPCV SSKPQKPWEK DAWEIPRESL
KLEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF LAEANLMKTL QHDKLVKLHA
VVTKEPIYII TEFMAKGSLL DFLKSDEGSK QPLPKLIDFS AQIAEGMAFI EQRNYIHRDL
RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK WTAPEAINFG SSTIKSDVWS
FGILLMEIVT YGRIPYPGMS NPEVIRALER GYRMPRPENC PEELYNIMMR CWKNRPEERP
TFEYIQSVLD DFYTATESQY QQQP
