HCK_RAT
ID HCK_RAT Reviewed; 524 AA.
AC P50545; Q64647; Q6AYV7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 191.
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;
DE AltName: Full=p56Hck;
DE AltName: Full=p59Hck;
GN Name=Hck;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Megakaryocyte;
RX PubMed=1764064; DOI=10.1016/0006-291x(91)92057-q;
RA Okano Y., Sugimoto Y., Fukuoka M., Matsui A., Nagata K., Nozawa Y.;
RT "Identification of rat cDNA encoding hck tyrosine kinase from
RT megakaryocytes.";
RL Biochem. Biophys. Res. Commun. 181:1137-1144(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC STRAIN=Wistar; TISSUE=Spleen;
RA Vijaya Gouri B.S., Rema V., Kamatkar S., Swarup G.;
RT "Nucleotide sequence of a cDNA coding for rat hck tyrosine kinase and
RT characterization of its gene product.";
RL J. Biosci. 19:117-129(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Brown Norway; TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH RAPGEF1, AND FUNCTION IN PHOSPHORYLATION OF RAPGEF1.
RX PubMed=14551197; DOI=10.1074/jbc.m310656200;
RA Shivakrupa R., Radha V., Sudhakar C., Swarup G.;
RT "Physical and functional interaction between Hck tyrosine kinase and
RT guanine nucleotide exchange factor C3G results in apoptosis, which is
RT independent of C3G catalytic domain.";
RL J. Biol. Chem. 278:52188-52194(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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, ECO:0000269|PubMed:14551197}.
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-409 is required for optimal activity.
CC Phosphorylation at Tyr-520 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 (via
CC 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}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Membrane; Lipid-anchor. Membrane,
CC caveola {ECO:0000250}. Lysosome {ECO:0000250}. Cell projection,
CC podosome membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}. Cytoplasm,
CC cytosol {ECO:0000250}. Note=Associated with specialized secretory
CC lysosomes called azurophil granules. A fraction of this isoform is
CC found in the cytoplasm, some of this fraction is myristoylated (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Lipid-anchor.
CC Membrane, caveola {ECO:0000250}; Lipid-anchor {ECO:0000250}. Cell
CC 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 of this isoform is associated with caveolae.
CC Localization at the cell membrane and at caveolae requires
CC palmitoylation at Cys-3. Colocalizes with the actin cytoskeleton at
CC focal adhesions (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=p59-HCK;
CC IsoId=P50545-1; Sequence=Displayed;
CC Name=2; Synonyms=p56-HCK;
CC IsoId=P50545-2; Sequence=VSP_022248;
CC -!- TISSUE SPECIFICITY: Expressed strongly in spleen and at very low levels
CC in thymus. {ECO:0000269|Ref.2}.
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-409 increases
CC kinase activity. Phosphorylation at Tyr-520 inhibits kinase activity.
CC Kinase activity is not required for phosphorylation at Tyr-520,
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: Isoform 2 palmitoylation at position 2 requires prior
CC myristoylation. Palmitoylation at position 3 is required for caveolar
CC localization of isoform 2. {ECO:0000250|UniProtKB:P08631}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA41312.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAB20754.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA44218.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M83666; AAA41312.1; ALT_INIT; mRNA.
DR EMBL; S74141; AAB20754.1; ALT_INIT; mRNA.
DR EMBL; X62345; CAA44218.1; ALT_INIT; mRNA.
DR EMBL; BC078890; AAH78890.2; -; mRNA.
DR PIR; JQ1321; JQ1321.
DR RefSeq; NP_037317.2; NM_013185.3. [P50545-1]
DR AlphaFoldDB; P50545; -.
DR SMR; P50545; -.
DR IntAct; P50545; 2.
DR STRING; 10116.ENSRNOP00000012432; -.
DR iPTMnet; P50545; -.
DR PhosphoSitePlus; P50545; -.
DR jPOST; P50545; -.
DR PaxDb; P50545; -.
DR PRIDE; P50545; -.
DR GeneID; 25734; -.
DR KEGG; rno:25734; -.
DR UCSC; RGD:2785; rat. [P50545-1]
DR CTD; 3055; -.
DR RGD; 2785; Hck.
DR VEuPathDB; HostDB:ENSRNOG00000009331; -.
DR eggNOG; KOG0197; Eukaryota.
DR InParanoid; P50545; -.
DR OMA; QKLTFPC; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; P50545; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-2029481; FCGR activation.
DR Reactome; R-RNO-912631; Regulation of signaling by CBL.
DR Reactome; R-RNO-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-RNO-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR PRO; PR:P50545; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000009331; Expressed in spleen and 19 other tissues.
DR GO; GO:0005884; C:actin filament; IEA:Ensembl.
DR GO; GO:0005901; C:caveola; ISO:RGD.
DR GO; GO:0042995; C:cell projection; 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; ISO:RGD.
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; IBA:GO_Central.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
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; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; ISO:RGD.
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:0051090; P:regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0071801; P:regulation of podosome assembly; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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 1: Evidence at protein level;
KW Alternative initiation; ATP-binding; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Exocytosis;
KW Golgi apparatus; Immunity; Inflammatory response; Innate immunity; Kinase;
KW Lipoprotein; Lysosome; Membrane; Myristate; Nucleotide-binding; Nucleus;
KW Palmitate; Phagocytosis; Phosphoprotein; Proto-oncogene;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT CHAIN 2..524
FT /note="Tyrosine-protein kinase HCK"
FT /id="PRO_0000088104"
FT DOMAIN 76..136
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 142..239
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 260..513
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 35..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 379
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 266..274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 288
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 50
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 207
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08103"
FT MOD_RES 409
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 520
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1764064, ECO:0000303|Ref.2"
FT /id="VSP_022248"
FT CONFLICT 72
FT /note="V -> F (in Ref. 1; AAA41312/AAB20754)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="K -> R (in Ref. 2; CAA44218)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="I -> T (in Ref. 2; CAA44218)"
FT /evidence="ECO:0000305"
FT INIT_MET P50545-2:1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT LIPID P50545-2:2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT LIPID P50545-2:3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
SQ SEQUENCE 524 AA; 59154 MW; BBD928C9E717BF4B CRC64;
MGGRSSCEDP GCPRGEGRVP RMGCVKSRFL REGSKASKIE PNANQKGPVY VPDPTSPKKL
GPNSINSLPP GVVEGSEDTI VVALYDYEAI HREDLSFQKG DQMVVLEESG EWWKARSLAT
KKEGYIPSNY VARVNSLETE EWFFKGISRK DAERHLLAPG NMLGSFMIRD SETTKGSYSL
SVRDFDPQHG DTVKHYKIRT LDSGGFYISP RSTFSSLQEL VVHYKKGKDG LCQKLSVPCV
SPKPQKPWEK DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF
LAEANLMKTL QHDKLVKLHA VVSQEPIFIV TEFMAKGSLL DFLKSEEGSK QPLPKLIDFS
AQISEGMAFI EQRNYIHRDL RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK
WTAPEAINFG SFTIKSDVWS FGILLMEIVT YGRIPYPGMS NPEVIRALEH GYRMPRPDNC
PEELYSIMIR CWKNRPEERP TFEYIQSVLD DFYTATESQY QQQP
