HCK_MOUSE
ID HCK_MOUSE Reviewed; 524 AA.
AC P08103; Q0VH03; Q3UD17;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Tyrosine-protein kinase HCK;
DE EC=2.7.10.2;
DE AltName: Full=B-cell/myeloid kinase;
DE Short=BMK;
DE AltName: Full=Hematopoietic cell kinase;
DE AltName: Full=Hemopoietic cell kinase;
DE AltName: Full=p56-HCK/p59-HCK;
GN Name=Hck;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Macrophage;
RX PubMed=3684607; DOI=10.1093/nar/15.22.9600;
RA Klemsz M.J., McKercher S.R., Maki R.A.;
RT "Nucleotide sequence of the mouse hck gene.";
RL Nucleic Acids Res. 15:9600-9600(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Macrophage;
RX PubMed=3317404; DOI=10.1073/pnas.84.23.8325;
RA Holtzman D.A., Cook W.D., Dunn A.R.;
RT "Isolation and sequence of a cDNA corresponding to a src-related gene
RT expressed in murine hemopoietic cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8325-8329(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow macrophage, and Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-21 (ISOFORM 1), SUBCELLULAR LOCATION,
RP IDENTIFICATION OF ISOFORM 2, AND ALTERNATIVE INITIATION.
RX PubMed=1875927; DOI=10.1128/mcb.11.9.4363-4370.1991;
RA Lock P., Ralph S., Stanley E., Boulet I., Ramsay R., Dunn A.R.;
RT "Two isoforms of murine hck, generated by utilization of alternative
RT translational initiation codons, exhibit different patterns of subcellular
RT localization.";
RL Mol. Cell. Biol. 11:4363-4370(1991).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=8125254; DOI=10.1101/gad.8.4.387;
RA Lowell C.A., Soriano P., Varmus H.E.;
RT "Functional overlap in the src gene family: inactivation of hck and fgr
RT impairs natural immunity.";
RL Genes Dev. 8:387-398(1994).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=8666673; DOI=10.1083/jcb.133.4.895;
RA Lowell C.A., Fumagalli L., Berton G.;
RT "Deficiency of Src family kinases p59/61hck and p58c-fgr results in
RT defective adhesion-dependent neutrophil functions.";
RL J. Cell Biol. 133:895-910(1996).
RN [8]
RP FUNCTION, AND INTERACTION WITH VAV1.
RX PubMed=9400828; DOI=10.1002/jlb.62.6.859;
RA English B.K., Orlicek S.L., Mei Z., Meals E.A.;
RT "Bacterial LPS and IFN-gamma trigger the tyrosine phosphorylation of vav in
RT macrophages: evidence for involvement of the hck tyrosine kinase.";
RL J. Leukoc. Biol. 62:859-864(1997).
RN [9]
RP FUNCTION.
RX PubMed=10547366; DOI=10.1242/jcs.112.22.4067;
RA Suen P.W., Ilic D., Caveggion E., Berton G., Damsky C.H., Lowell C.A.;
RT "Impaired integrin-mediated signal transduction, altered cytoskeletal
RT structure and reduced motility in Hck/Fgr deficient macrophages.";
RL J. Cell Sci. 112:4067-4078(1999).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=9916742;
RA Mocsai A., Ligeti E., Lowell C.A., Berton G.;
RT "Adhesion-dependent degranulation of neutrophils requires the Src family
RT kinases Fgr and Hck.";
RL J. Immunol. 162:1120-1126(1999).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF CBL, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH CBL.
RX PubMed=10799548; DOI=10.1074/jbc.275.19.14615;
RA Scholz G., Cartledge K., Dunn A.R.;
RT "Hck enhances the adherence of lipopolysaccharide-stimulated macrophages
RT via Cbl and phosphatidylinositol 3-kinase.";
RL J. Biol. Chem. 275:14615-14623(2000).
RN [12]
RP PHOSPHORYLATION AT TYR-50 AND TYR-409, MUTAGENESIS OF TYR-409, AND ACTIVITY
RP REGULATION.
RX PubMed=10934191; DOI=10.1074/jbc.m002022200;
RA Johnson T.M., Williamson N.A., Scholz G., Jaworowski A., Wettenhall R.E.,
RA Dunn A.R., Cheng H.C.;
RT "Modulation of the catalytic activity of the Src family tyrosine kinase Hck
RT by autophosphorylation at a novel site in the unique domain.";
RL J. Biol. Chem. 275:33353-33364(2000).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF WAS, AND INTERACTION WITH WAS.
RX PubMed=12235133; DOI=10.1074/jbc.m203346200;
RA Cory G.O., Garg R., Cramer R., Ridley A.J.;
RT "Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate
RT actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome
RT protein.";
RL J. Biol. Chem. 277:45115-45121(2002).
RN [14]
RP INTERACTION WITH RAPGEF1, AND FUNCTION IN REGULATION OF APOPTOSIS.
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 [15]
RP INTERACTION WITH FLT3.
RX PubMed=16684964; DOI=10.1182/blood-2005-07-008896;
RA Heiss E., Masson K., Sundberg C., Pedersen M., Sun J., Bengtsson S.,
RA Ronnstrand L.;
RT "Identification of Y589 and Y599 in the juxtamembrane domain of Flt3 as
RT ligand-induced autophosphorylation sites involved in binding of Src family
RT kinases and the protein tyrosine phosphatase SHP2.";
RL Blood 108:1542-1550(2006).
RN [16]
RP FUNCTION.
RX PubMed=16809022; DOI=10.1016/j.cellsig.2006.05.007;
RA Achuthan A., Elsegood C., Masendycz P., Hamilton J.A., Scholz G.M.;
RT "CpG DNA enhances macrophage cell spreading by promoting the Src-family
RT kinase-mediated phosphorylation of paxillin.";
RL Cell. Signal. 18:2252-2261(2006).
RN [17]
RP FUNCTION.
RX PubMed=17513616; DOI=10.1182/blood-2007-01-066092;
RA Hong H., Kitaura J., Xiao W., Horejsi V., Ra C., Lowell C.A., Kawakami Y.,
RA Kawakami T.;
RT "The Src family kinase Hck regulates mast cell activation by suppressing an
RT inhibitory Src family kinase Lyn.";
RL Blood 110:2511-2519(2007).
RN [18]
RP FUNCTION.
RX PubMed=18246197; DOI=10.1172/jci34013;
RA Xiao W., Hong H., Kawakami Y., Lowell C.A., Kawakami T.;
RT "Regulation of myeloproliferation and M2 macrophage programming in mice by
RT Lyn/Hck, SHIP, and Stat5.";
RL J. Clin. Invest. 118:924-934(2008).
RN [19]
RP FUNCTION.
RX PubMed=18625913; DOI=10.1189/jlb.0208118;
RA Paul R., Obermaier B., Van Ziffle J., Angele B., Pfister H.W., Lowell C.A.,
RA Koedel U.;
RT "Myeloid Src kinases regulate phagocytosis and oxidative burst in
RT pneumococcal meningitis by activating NADPH oxidase.";
RL J. Leukoc. Biol. 84:1141-1150(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-207 AND TYR-520, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [21]
RP FUNCTION.
RX PubMed=19897576; DOI=10.1182/blood-2009-04-218735;
RA Cougoule C., Le Cabec V., Poincloux R., Al Saati T., Mege J.L.,
RA Tabouret G., Lowell C.A., Laviolette-Malirat N., Maridonneau-Parini I.;
RT "Three-dimensional migration of macrophages requires Hck for podosome
RT organization and extracellular matrix proteolysis.";
RL Blood 115:1444-1452(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [23]
RP FUNCTION IN MYELOID CELL MIGRATION, AND INTERACTION WITH ABL1.
RX PubMed=19903482; DOI=10.1016/j.febslet.2009.11.009;
RA Baruzzi A., Iacobucci I., Soverini S., Lowell C.A., Martinelli G.,
RA Berton G.;
RT "c-Abl and Src-family kinases cross-talk in regulation of myeloid cell
RT migration.";
RL FEBS Lett. 584:15-21(2010).
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:10547366, ECO:0000269|PubMed:10799548,
CC ECO:0000269|PubMed:12235133, ECO:0000269|PubMed:14551197,
CC ECO:0000269|PubMed:16809022, ECO:0000269|PubMed:17513616,
CC ECO:0000269|PubMed:18246197, ECO:0000269|PubMed:18625913,
CC ECO:0000269|PubMed:19897576, ECO:0000269|PubMed:19903482,
CC ECO:0000269|PubMed:8125254, ECO:0000269|PubMed:9400828,
CC ECO:0000269|PubMed:9916742}.
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 ECO:0000269|PubMed:9916742};
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. Inhibited by PP1.
CC {ECO:0000269|PubMed:10934191, ECO:0000269|PubMed:9916742}.
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 (By
CC similarity). Interacts (via SH2 domain) with FLT3 (tyrosine
CC phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and
CC RAPGEF1. Interacts (via SH3 domain) with WDCP (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P08631,
CC ECO:0000269|PubMed:10799548, ECO:0000269|PubMed:12235133,
CC ECO:0000269|PubMed:14551197, ECO:0000269|PubMed:16684964,
CC ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:9400828}.
CC -!- INTERACTION:
CC P08103; P42768: WAS; Xeno; NbExp=3; IntAct=EBI-6248894, EBI-346375;
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=20%
CC of this isoform 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=p59-HCK;
CC IsoId=P08103-1; Sequence=Displayed;
CC Name=2; Synonyms=p56-HCK;
CC IsoId=P08103-2; Sequence=VSP_018859;
CC -!- TISSUE SPECIFICITY: Expressed predominantly in cells of the myeloid and
CC B-lymphoid lineages.
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.
CC {ECO:0000269|PubMed:10934191}.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation via the
CC proteasome.
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 -!- DISRUPTION PHENOTYPE: No visible phenotype, but macrophages have
CC impaired phagocytosis. Mice lacking both HCK and FGR are extremely
CC sensitive to infections by L.monocytogenes.
CC {ECO:0000269|PubMed:8125254, ECO:0000269|PubMed:8666673}.
CC -!- MISCELLANEOUS: [Isoform 1]: Initiates from a CTG codon.
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=AAA37305.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=BAE29054.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=BAE29445.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=BAE29787.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=BAE33532.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=BAE38133.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
CC Sequence=CAA68544.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.; Evidence={ECO:0000305};
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DR EMBL; Y00487; CAA68544.1; ALT_SEQ; mRNA.
DR EMBL; J03023; AAA37305.1; ALT_SEQ; mRNA.
DR EMBL; AK149736; BAE29054.1; ALT_SEQ; mRNA.
DR EMBL; AK150290; BAE29445.1; ALT_SEQ; mRNA.
DR EMBL; AK150709; BAE29787.1; ALT_SEQ; mRNA.
DR EMBL; AK155975; BAE33532.1; ALT_SEQ; mRNA.
DR EMBL; AK165315; BAE38133.1; ALT_SEQ; mRNA.
DR EMBL; BC010478; AAH10478.2; -; mRNA.
DR CCDS; CCDS38284.1; -. [P08103-1]
DR CCDS; CCDS50756.1; -. [P08103-2]
DR PIR; A27282; TVMSHC.
DR RefSeq; NP_001165588.1; NM_001172117.1. [P08103-2]
DR RefSeq; NP_034537.2; NM_010407.4. [P08103-1]
DR AlphaFoldDB; P08103; -.
DR SMR; P08103; -.
DR BioGRID; 200249; 11.
DR IntAct; P08103; 5.
DR MINT; P08103; -.
DR STRING; 10090.ENSMUSP00000003370; -.
DR iPTMnet; P08103; -.
DR PhosphoSitePlus; P08103; -.
DR SwissPalm; P08103; -.
DR jPOST; P08103; -.
DR MaxQB; P08103; -.
DR PaxDb; P08103; -.
DR PeptideAtlas; P08103; -.
DR PRIDE; P08103; -.
DR ProteomicsDB; 270949; -. [P08103-1]
DR ProteomicsDB; 270950; -. [P08103-2]
DR Antibodypedia; 3921; 606 antibodies from 37 providers.
DR DNASU; 15162; -.
DR Ensembl; ENSMUST00000109799; ENSMUSP00000105423; ENSMUSG00000003283. [P08103-2]
DR Ensembl; ENSMUST00000189688; ENSMUSP00000141030; ENSMUSG00000003283. [P08103-2]
DR GeneID; 15162; -.
DR KEGG; mmu:15162; -.
DR UCSC; uc008nhc.3; mouse. [P08103-1]
DR CTD; 3055; -.
DR MGI; MGI:96052; Hck.
DR VEuPathDB; HostDB:ENSMUSG00000003283; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158738; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P08103; -.
DR OMA; QKLTFPC; -.
DR PhylomeDB; P08103; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-2029481; FCGR activation.
DR Reactome; R-MMU-912631; Regulation of signaling by CBL.
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-MMU-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR BioGRID-ORCS; 15162; 1 hit in 73 CRISPR screens.
DR PRO; PR:P08103; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P08103; protein.
DR Bgee; ENSMUSG00000003283; Expressed in granulocyte and 142 other tissues.
DR ExpressionAtlas; P08103; baseline and differential.
DR Genevisible; P08103; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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:MGI.
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; IGI:MGI.
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:MGI.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IMP:MGI.
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:MGI.
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_0000024435"
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..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 37..72
FT /note="Polar residues"
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:0000269|PubMed:10934191"
FT MOD_RES 200
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 207
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 409
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10934191"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT MOD_RES 520
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19144319"
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:0000305"
FT /id="VSP_018859"
FT MUTAGEN 409
FT /note="Y->F: Reduced autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10934191"
FT INIT_MET P08103-2:1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT LIPID P08103-2:2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
FT LIPID P08103-2:3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P08631"
SQ SEQUENCE 524 AA; 59129 MW; DF72FD69B38C9706 CRC64;
MGGRSSCEDP GCPRSEGRAP RMGCVKSRFL RDGSKASKTE PSANQKGPVY VPDPTSSSKL
GPNNSNSMPP GFVEGSEDTI VVALYDYEAI HREDLSFQKG DQMVVLEEAG EWWKARSLAT
KKEGYIPSNY VARVNSLETE EWFFKGISRK DAERHLLAPG NMLGSFMIRD SETTKGSYSL
SVRDFDPQHG DTVKHYKIRT LDSGGFYISP RSTFSSLQEL VLHYKKGKDG LCQKLSVPCV
SPKPQKPWEK DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF
LAEANLMKSL QHDKLVKLHA VVSQEPIFIV TEFMAKGSLL DFLKSEEGSK QPLPKLIDFS
AQISEGMAFI EQRNYIHRDL RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK
WTAPEAINFG SFTIKSDVWS FGILLMEIVT YGRIPYPGMS NPEVIRALEH GYRMPRPDNC
PEELYNIMIR CWKNRPEERP TFEYIQSVLD DFYTATESQY QQQP
