HCK_HUMAN
ID HCK_HUMAN Reviewed; 526 AA.
AC P08631; A8K1I1; B4DQB6; E1P5M2; Q29RX1; Q2VPE2; Q504R5; Q5T7K1; Q5T7K2;
AC Q96CC0; Q9H5Y5; Q9NUA4; Q9UMJ5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 262.
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=p59-HCK/p60-HCK;
DE AltName: Full=p59Hck;
DE AltName: Full=p61Hck;
GN Name=HCK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3496523; DOI=10.1128/mcb.7.6.2267-2275.1987;
RA Quintrell N., Lebo R., Varmus H., Bishop J.M., Pettenati M.J.,
RA le Beau M.M., Diaz M.O., Rowley J.D.;
RT "Identification of a human gene (HCK) that encodes a protein-tyrosine
RT kinase and is expressed in hemopoietic cells.";
RL Mol. Cell. Biol. 7:2267-2275(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=3453117; DOI=10.1128/mcb.7.6.2276-2285.1987;
RA Ziegler S.F., Marth J.D., Lewis D.B., Perlmutter R.M.;
RT "Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells
RT of hematopoietic origin.";
RL Mol. Cell. Biol. 7:2276-2285(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), AND VARIANT
RP LEU-105.
RC TISSUE=Corpus callosum, and Ileal mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=B-cell, and Lymph;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-21 (ISOFORM 1), AND ALTERNATIVE INITIATION.
RC TISSUE=Bone marrow;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-526.
RC TISSUE=Spleen;
RX PubMed=1572549; DOI=10.1016/0378-1119(92)90407-g;
RA Hradetzky D., Strebhardt K., Ruesamen-Waigmann H.;
RT "The genomic locus of the human hemopoietic-specific cell protein tyrosine
RT kinase (PTK)-encoding gene (HCK) confirms conservation of exon-intron
RT structure among human PTKs of the src family.";
RL Gene 113:275-280(1992).
RN [9]
RP INTERACTION WITH FCGR2A, CATALYTIC ACTIVITY, AND FUNCTION IN
RP PHOSPHORYLATION OF FCGR2A.
RX PubMed=8132624; DOI=10.1016/s0021-9258(17)37050-3;
RA Ghazizadeh S., Bolen J.B., Fleit H.B.;
RT "Physical and functional association of Src-related protein tyrosine
RT kinases with Fc gamma RII in monocytic THP-1 cells.";
RL J. Biol. Chem. 269:8878-8884(1994).
RN [10]
RP INTERACTION WITH FCGR1A, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=8064233; DOI=10.1084/jem.180.3.1165;
RA Wang A.V., Scholl P.R., Geha R.S.;
RT "Physical and functional association of the high affinity immunoglobulin G
RT receptor (Fc gamma RI) with the kinases Hck and Lyn.";
RL J. Exp. Med. 180:1165-1170(1994).
RN [11]
RP FUNCTION IN FCGR1A SIGNALING, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND
RP ACTIVITY REGULATION.
RX PubMed=7535819;
RA Durden D.L., Kim H.M., Calore B., Liu Y.;
RT "The Fc gamma RI receptor signals through the activation of hck and MAP
RT kinase.";
RL J. Immunol. 154:4039-4047(1995).
RN [12]
RP SUBCELLULAR LOCATION, ALTERNATIVE INITIATION, MYRISTOYLATION AT GLY-2,
RP MYRISTOYLATION AT GLY-2 (ISOFORM 2), PALMITOYLATION AT CYS-3 (ISOFORM 2),
RP AND MUTAGENESIS OF GLY-3; GLY-23 AND CYS-24.
RX PubMed=7791757; DOI=10.1128/mcb.15.7.3507;
RA Robbins S.M., Quintrell N.A., Bishop J.M.;
RT "Myristoylation and differential palmitoylation of the HCK protein-tyrosine
RT kinases govern their attachment to membranes and association with
RT caveolae.";
RL Mol. Cell. Biol. 15:3507-3515(1995).
RN [13]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION, AND INTERACTION WITH IL6ST.
RX PubMed=9406996;
RA Hallek M., Neumann C., Schaffer M., Danhauser-Riedl S., von Bubnoff N.,
RA de Vos G., Druker B.J., Yasukawa K., Griffin J.D., Emmerich B.;
RT "Signal transduction of interleukin-6 involves tyrosine phosphorylation of
RT multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck,
RT and Lyn in multiple myeloma cell lines.";
RL Exp. Hematol. 25:1367-1377(1997).
RN [14]
RP INDUCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=8995234; DOI=10.1074/jbc.272.1.102;
RA Welch H., Maridonneau-Parini I.;
RT "Hck is activated by opsonized zymosan and A23187 in distinct subcellular
RT fractions of human granulocytes.";
RL J. Biol. Chem. 272:102-109(1997).
RN [15]
RP ACTIVITY REGULATION, AND INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION).
RX PubMed=9218412; DOI=10.1074/jbc.272.29.17899;
RA Briggs S.D., Sharkey M., Stevenson M., Smithgall T.E.;
RT "SH3-mediated Hck tyrosine kinase activation and fibroblast transformation
RT by the Nef protein of HIV-1.";
RL J. Biol. Chem. 272:17899-17902(1997).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF BCR, AND INTERACTION WITH BCR-ABL.
RX PubMed=9407116; DOI=10.1074/jbc.272.52.33260;
RA Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M.;
RT "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent
RT mechanism and phosphorylates the Grb2-binding site of Bcr.";
RL J. Biol. Chem. 272:33260-33270(1997).
RN [17]
RP FUNCTION IN CBL PHOSPHORYLATION; CELL PROLIFERATION AND REGULATION OF CELL
RP SHAPE, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-522, AND
RP INTERACTION WITH CBL.
RX PubMed=10092522; DOI=10.1006/bbrc.1999.0427;
RA Howlett C.J., Bisson S.A., Resek M.E., Tigley A.W., Robbins S.M.;
RT "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-
RT tyrosine kinase.";
RL Biochem. Biophys. Res. Commun. 257:129-138(1999).
RN [18]
RP FUNCTION IN IL2 SIGNALING, CATALYTIC ACTIVITY, INDUCTION, ACTIVITY
RP REGULATION, AND PHOSPHORYLATION.
RX PubMed=10779760; DOI=10.4049/jimmunol.164.9.4575;
RA Bosco M.C., Curiel R.E., Zea A.H., Malabarba M.G., Ortaldo J.R.,
RA Espinoza-Delgado I.;
RT "IL-2 signaling in human monocytes involves the phosphorylation and
RT activation of p59hck.";
RL J. Immunol. 164:4575-4585(2000).
RN [19]
RP PHOSPHORYLATION AT TYR-411 AND TYR-522, IDENTIFICATION BY MASS
RP SPECTROMETRY, ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-305 AND TYR-411.
RX PubMed=10644735; DOI=10.1074/jbc.275.4.2721;
RA Porter M., Schindler T., Kuriyan J., Miller W.T.;
RT "Reciprocal regulation of Hck activity by phosphorylation of Tyr(527) and
RT Tyr(416). Effect of introducing a high affinity intramolecular SH2
RT ligand.";
RL J. Biol. Chem. 275:2721-2726(2000).
RN [20]
RP FUNCTION IN IL8-MEDIATED DEGRANULATION, ACTIVITY REGULATION, AND
RP INTERACTION WITH ARRB1 AND ARRB2.
RX PubMed=10973280; DOI=10.1038/79767;
RA Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E., Xu L.,
RA Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.;
RT "Regulation of tyrosine kinase activation and granule release through beta-
RT arrestin by CXCRI.";
RL Nat. Immunol. 1:227-233(2000).
RN [21]
RP INTERACTION WITH HIV-1 VIF (MICROBIAL INFECTION).
RX PubMed=11278465; DOI=10.1074/jbc.m009076200;
RA Hassaine G., Courcoul M., Bessou G., Barthalay Y., Picard C., Olive D.,
RA Collette Y., Vigne R., Decroly E.;
RT "The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted
RT by the viral vif protein.";
RL J. Biol. Chem. 276:16885-16893(2001).
RN [22]
RP INTERACTION WITH HEV ORF3 PROTEIN (MICROBIAL INFECTION).
RX PubMed=11518702; DOI=10.1074/jbc.m101546200;
RA Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M.,
RA Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.;
RT "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and
RT activates MAPK.";
RL J. Biol. Chem. 276:42389-42400(2001).
RN [23]
RP FUNCTION AS EFFECTOR OF THE BCR-ABL FUSION PROTEIN IN PHOSPHORYLATION OF
RP STAT5B, INTERACTION WITH STAT5B AND THE BCR-ABL FUSION PROTEIN, AND
RP PHOSPHORYLATION.
RX PubMed=12411494; DOI=10.1093/emboj/cdf562;
RA Klejman A., Schreiner S.J., Nieborowska-Skorska M., Slupianek A.,
RA Wilson M., Smithgall T.E., Skorski T.;
RT "The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid
RT leukemia cells.";
RL EMBO J. 21:5766-5774(2002).
RN [24]
RP INTERACTION WITH ADAM15, AND FUNCTION IN PHOSPHORYLATION OF ADAM15.
RX PubMed=11741929; DOI=10.1074/jbc.m107430200;
RA Poghosyan Z., Robbins S.M., Houslay M.D., Webster A., Murphy G.,
RA Edwards D.R.;
RT "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain
RT and Src family protein-tyrosine kinases.";
RL J. Biol. Chem. 277:4999-5007(2002).
RN [25]
RP FUNCTION IN REORGANIZATION OF THE ACTIN CYTOSKELETON; FORMATION OF CELL
RP PROTRUSIONS AND PHAGOCYTOSIS (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2),
RP AND MUTAGENESIS OF GLY-3.
RX PubMed=11904303; DOI=10.1074/jbc.m201212200;
RA Carreno S., Caron E., Cougoule C., Emorine L.J., Maridonneau-Parini I.;
RT "p59Hck isoform induces F-actin reorganization to form protrusions of the
RT plasma membrane in a Cdc42- and Rac-dependent manner.";
RL J. Biol. Chem. 277:21007-21016(2002).
RN [26]
RP FUNCTION IN CELL PROLIFERATION, UBIQUITINATION, PHOSPHORYLATION AT TYR-51;
RP TYR-411 AND TYR-522, SUBCELLULAR LOCATION, INTERACTION WITH CBL (ISOFORM
RP 2), AND MUTAGENESIS OF LYS-290 AND TYR-522.
RX PubMed=11896602; DOI=10.1038/sj.onc.1205228;
RA Howlett C.J., Robbins S.M.;
RT "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated
RT cellular transformation.";
RL Oncogene 21:1707-1716(2002).
RN [27]
RP FUNCTION IN IL6 SIGNALING CASCADE AND IN PHOSPHORYLATION OF GAB1 AND GAB2.
RX PubMed=15010462; DOI=10.1074/jbc.m305783200;
RA Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T., Catley L.P.,
RA Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.;
RT "Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation
RT of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation
RT and survival of multiple myeloma cells.";
RL J. Biol. Chem. 279:21658-21665(2004).
RN [28]
RP FUNCTION IN PHOSPHORYLATION OF ELMO1, AND INTERACTION WITH ELMO1.
RX PubMed=15952790; DOI=10.1021/bi0500832;
RA Yokoyama N., deBakker C.D., Zappacosta F., Huddleston M.J., Annan R.S.,
RA Ravichandran K.S., Miller W.T.;
RT "Identification of tyrosine residues on ELMO1 that are phosphorylated by
RT the Src-family kinase Hck.";
RL Biochemistry 44:8841-8849(2005).
RN [29]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-381.
RX PubMed=15998323; DOI=10.1111/j.1600-0854.2005.00307.x;
RA Cougoule C., Carreno S., Castandet J., Labrousse A., Astarie-Dequeker C.,
RA Poincloux R., Le Cabec V., Maridonneau-Parini I.;
RT "Activation of the lysosome-associated p61Hck isoform triggers the
RT biogenesis of podosomes.";
RL Traffic 6:682-694(2005).
RN [30]
RP INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION), AND ACTIVITY REGULATION.
RX PubMed=16849330; DOI=10.1074/jbc.m601128200;
RA Trible R.P., Emert-Sedlak L., Smithgall T.E.;
RT "HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src
RT through direct SH3 domain interaction.";
RL J. Biol. Chem. 281:27029-27038(2006).
RN [31]
RP FUNCTION IN PHOSPHORYLATION AND INHIBITION OF TP73 ACTIVITY, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH TP73 AND YAP1.
RX PubMed=17535448; DOI=10.1186/1471-2199-8-45;
RA Paliwal P., Radha V., Swarup G.;
RT "Regulation of p73 by Hck through kinase-dependent and independent
RT mechanisms.";
RL BMC Mol. Biol. 8:45-45(2007).
RN [32]
RP FUNCTION, AND INTERACTION WITH IL6ST.
RX PubMed=17310994; DOI=10.1038/sj.onc.1210306;
RA Hausherr A., Tavares R., Schaffer M., Obermeier A., Miksch C., Mitina O.,
RA Ellwart J., Hallek M., Krause G.;
RT "Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide
RT repressing the gp130-mediated activation of Src family kinases.";
RL Oncogene 26:4987-4998(2007).
RN [33]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL (CD178) by
RT phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [34]
RP FUNCTION IN REORGANIZATION OF ACTIN CYTOSKELETON AND CELL PROLIFERATION,
RP AND ROLE IN DISEASE.
RX PubMed=19114024; DOI=10.1016/j.ejca.2008.11.020;
RA Poincloux R., Al Saati T., Maridonneau-Parini I., Le Cabec V.;
RT "The oncogenic activity of the Src family kinase Hck requires the
RT cooperative action of the plasma membrane- and lysosome-associated
RT isoforms.";
RL Eur. J. Cancer 45:321-327(2009).
RN [35]
RP INTERACTION WITH ADAM15.
RX PubMed=19718658; DOI=10.1002/jcb.22317;
RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.;
RT "Alternative splicing of ADAM15 regulates its interactions with cellular
RT SH3 proteins.";
RL J. Cell. Biochem. 108:877-885(2009).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND SER-462, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [37]
RP FUNCTION IN ABL1-MEDIATED CELL MIGRATION, AND IDENTIFICATION IN A COMPLEX
RP WITH ITGB1 AND 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).
RN [38]
RP ROLE IN DISEASE, AND FUNCTION IN PHOSPHORYLATION OF THE BCR-ABL FUSION
RP PROTEIN.
RX PubMed=20452982; DOI=10.1074/jbc.m109.090043;
RA Pene-Dumitrescu T., Smithgall T.E.;
RT "Expression of a Src family kinase in chronic myelogenous leukemia cells
RT induces resistance to imatinib in a kinase-dependent manner.";
RL J. Biol. Chem. 285:21446-21457(2010).
RN [39]
RP REVIEW ON ROLE IN PHAGOCYTOSIS AND SUBSTRATES.
RX PubMed=18538446; DOI=10.1016/j.ejcb.2008.03.008;
RA Guiet R., Poincloux R., Castandet J., Marois L., Labrousse A., Le Cabec V.,
RA Maridonneau-Parini I.;
RT "Hematopoietic cell kinase (Hck) isoforms and phagocyte duties - from
RT signaling and actin reorganization to migration and phagocytosis.";
RL Eur. J. Cell Biol. 87:527-542(2008).
RN [40]
RP ROLE IN NEUTROPHIL FUNCTION, AND SIGNALING.
RX PubMed=21338576; DOI=10.1016/j.abb.2011.02.009;
RA Zarbock A., Ley K.;
RT "Protein tyrosine kinases in neutrophil activation and recruitment.";
RL Arch. Biochem. Biophys. 510:112-119(2011).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [42]
RP INTERACTION WITH WDCP.
RX PubMed=25469238; DOI=10.3892/br.2014.374;
RA Yokoyama N., Miller W.T.;
RT "Molecular characterization of WDCP, a novel fusion partner for the
RT anaplastic lymphoma tyrosine kinase ALK.";
RL Biomed. Rep. 3:9-13(2015).
RN [43]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [44]
RP STRUCTURE BY NMR OF 140-245.
RX PubMed=9109402; DOI=10.1016/s0014-5793(97)00255-x;
RA Zhang W., Smithgall T.E., Gmeiner W.H.;
RT "Sequential assignment and secondary structure determination for the Src
RT homology 2 domain of hematopoietic cellular kinase.";
RL FEBS Lett. 406:131-135(1997).
RN [45]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 78-526 IN COMPLEX WITH CALCIUM,
RP AND PHOSPHORYLATION AT TYR-522.
RX PubMed=9024658; DOI=10.1038/385602a0;
RA Sicheri F., Moarefi I., Kuriyan J.;
RT "Crystal structure of the Src family tyrosine kinase Hck.";
RL Nature 385:602-609(1997).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 81-137.
RX PubMed=9778343; DOI=10.1021/bi980989q;
RA Arold S., O'Brien R., Franken P., Strub M.-P., Hoh F., Dumas C.,
RA Ladbury J.E.;
RT "RT loop flexibility enhances the specificity of Src family SH3 domains for
RT HIV-1 Nef.";
RL Biochemistry 37:14683-14691(1998).
RN [47]
RP STRUCTURE BY NMR OF 72-143.
RX PubMed=9571048; DOI=10.1006/jmbi.1998.1690;
RA Horita D.A., Baldisseri D.M., Zhang W., Altieri A.S., Smithgall T.E.,
RA Gmeiner W.H., Byrd R.A.;
RT "Solution structure of the human Hck SH3 domain and identification of its
RT ligand binding site.";
RL J. Mol. Biol. 278:253-265(1998).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 81-522 IN COMPLEX WITH THE
RP PYRAZOLO PYRIMIDINE-TYPE INHIBITOR PP1, AND PHOSPHORYLATION AT TYR-522.
RX PubMed=10360180; DOI=10.1016/s1097-2765(00)80357-3;
RA Schindler T., Sicheri F., Pico A., Gazit A., Levitzki A., Kuriyan J.;
RT "Crystal structure of Hck in complex with a Src family-selective tyrosine
RT kinase inhibitor.";
RL Mol. Cell 3:639-648(1999).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 81-522 IN COMPLEXES WITH
RP INHIBITORS A-420983; A-641359 AND A-770041, ACTIVITY REGULATION, AND
RP PHOSPHORYLATION AT TYR-522.
RX PubMed=16216497; DOI=10.1016/j.bmcl.2005.09.039;
RA Burchat A., Borhani D.W., Calderwood D.J., Hirst G.C., Li B.,
RA Stachlewitz R.F.;
RT "Discovery of A-770041, a src-family selective orally active lck inhibitor
RT that prevents organ allograft rejection.";
RL Bioorg. Med. Chem. Lett. 16:118-122(2006).
RN [50]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 247-513 IN COMPLEX WITH INHIBITOR
RP PG-1009247.
RX PubMed=16997556; DOI=10.1016/j.bmcl.2006.08.132;
RA Sabat M., VanRens J.C., Laufersweiler M.J., Brugel T.A., Maier J.,
RA Golebiowski A., De B., Easwaran V., Hsieh L.C., Walter R.L., Mekel M.J.,
RA Evdokimov A., Janusz M.J.;
RT "The development of 2-benzimidazole substituted pyrimidine based inhibitors
RT of lymphocyte specific kinase (Lck).";
RL Bioorg. Med. Chem. Lett. 16:5973-5977(2006).
RN [51]
RP STRUCTURE BY NMR OF 61-140 IN COMPLEX WITH PROLINE-RICH SYNTHETIC PEPTIDE.
RX PubMed=17141806; DOI=10.1016/j.jmb.2006.11.013;
RA Schmidt H., Hoffmann S., Tran T., Stoldt M., Stangler T., Wiesehan K.,
RA Willbold D.;
RT "Solution structure of a Hck SH3 domain ligand complex reveals novel
RT interaction modes.";
RL J. Mol. Biol. 365:1517-1532(2007).
RN [52]
RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 72-256, ACTIVITY REGULATION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=20810664; DOI=10.1074/jbc.m110.145102;
RA Alvarado J.J., Betts L., Moroco J.A., Smithgall T.E., Yeh J.I.;
RT "Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory
RT region supports an SH3-dominant activation mechanism.";
RL J. Biol. Chem. 285:35455-35461(2010).
RN [53]
RP X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 79-138 IN COMPLEX WITH HIV-1 NEF,
RP AND INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION).
RX PubMed=21625496; DOI=10.1371/journal.pone.0020033;
RA Breuer S., Schievink S.I., Schulte A., Blankenfeldt W., Fackler O.T.,
RA Geyer M.;
RT "Molecular design, functional characterization and structural basis of a
RT protein inhibitor against the HIV-1 pathogenicity factor Nef.";
RL PLoS ONE 6:E20033-E20033(2011).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 79-138 IN COMPLEX WITH HIV-1 NEF,
RP AND INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION).
RX PubMed=21477083; DOI=10.1111/j.1600-0854.2011.01205.x;
RA Horenkamp F.A., Breuer S., Schulte A., Lulf S., Weyand M., Saksela K.,
RA Geyer M.;
RT "Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by
RT intermolecular domain assembly.";
RL Traffic 12:867-877(2011).
RN [55]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-44; LEU-105 AND GLY-399.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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.
CC {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760,
CC ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929,
CC ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494,
CC ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790,
CC ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994,
CC ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024,
CC ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982,
CC ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819,
CC ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996,
CC ECO:0000269|PubMed:9407116}.
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:10092522, ECO:0000269|PubMed:10779760,
CC ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:20810664,
CC ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8064233,
CC ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:8995234};
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-411 is required for optimal activity.
CC Phosphorylation at Tyr-522 inhibits kinase activity. Inhibited by PP1
CC and A-770041. {ECO:0000269|PubMed:10644735,
CC ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280,
CC ECO:0000269|PubMed:16216497, ECO:0000269|PubMed:16849330,
CC ECO:0000269|PubMed:20810664, ECO:0000269|PubMed:7535819,
CC ECO:0000269|PubMed:9218412, ECO:0000269|PubMed:9406996}.
CC -!- SUBUNIT: Interacts (via SH2 domain) with FLT3 (tyrosine
CC phosphorylated). Interacts with VAV1, WAS and RAPGEF1 (By similarity).
CC This interaction stimulates its tyrosine-kinase activity. Interacts
CC with ARRB1 and ARRB2. Interacts with ADAM15. Interacts with FASLG.
CC Interacts with CBL. 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 SH3 domain) with WDCP. {ECO:0000250,
CC ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10360180,
CC ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929,
CC ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15952790,
CC ECO:0000269|PubMed:16997556, ECO:0000269|PubMed:17141806,
CC ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448,
CC ECO:0000269|PubMed:19718658, ECO:0000269|PubMed:19807924,
CC ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:25469238,
CC ECO:0000269|PubMed:8064233, ECO:0000269|PubMed:8132624,
CC ECO:0000269|PubMed:9024658, ECO:0000269|PubMed:9406996,
CC ECO:0000269|PubMed:9407116}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via SH3 domain) with HEV ORF3
CC protein. {ECO:0000269|PubMed:11518702}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via SH3 domain) with HIV-1
CC Nef and Vif. {ECO:0000269|PubMed:11278465, ECO:0000269|PubMed:16849330,
CC ECO:0000269|PubMed:21477083, ECO:0000269|PubMed:21625496,
CC ECO:0000269|PubMed:9218412}.
CC -!- INTERACTION:
CC P08631; O14672: ADAM10; NbExp=2; IntAct=EBI-346340, EBI-1536151;
CC P08631; O43184: ADAM12; NbExp=2; IntAct=EBI-346340, EBI-2625825;
CC P08631; Q13444: ADAM15; NbExp=4; IntAct=EBI-346340, EBI-77818;
CC P08631; P09917: ALOX5; NbExp=2; IntAct=EBI-346340, EBI-79934;
CC P08631; Q9ULH1: ASAP1; NbExp=2; IntAct=EBI-346340, EBI-346622;
CC P08631; P00533: EGFR; NbExp=3; IntAct=EBI-346340, EBI-297353;
CC P08631; Q92556: ELMO1; NbExp=4; IntAct=EBI-346340, EBI-346417;
CC P08631; P21860: ERBB3; NbExp=2; IntAct=EBI-346340, EBI-720706;
CC P08631; Q9HD26: GOPC; NbExp=3; IntAct=EBI-346340, EBI-349832;
CC P08631; P08238: HSP90AB1; NbExp=4; IntAct=EBI-346340, EBI-352572;
CC P08631; Q07666: KHDRBS1; NbExp=4; IntAct=EBI-346340, EBI-1364;
CC P08631; P10721: KIT; NbExp=2; IntAct=EBI-346340, EBI-1379503;
CC P08631; Q6A162: KRT40; NbExp=3; IntAct=EBI-346340, EBI-10171697;
CC P08631; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-346340, EBI-10172052;
CC P08631; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-346340, EBI-742948;
CC P08631; P59046: NLRP12; NbExp=4; IntAct=EBI-346340, EBI-6374637;
CC P08631; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-346340, EBI-945833;
CC P08631; Q13177: PAK2; NbExp=2; IntAct=EBI-346340, EBI-1045887;
CC P08631; Q8WUM4: PDCD6IP; NbExp=4; IntAct=EBI-346340, EBI-310624;
CC P08631; Q07889: SOS1; NbExp=4; IntAct=EBI-346340, EBI-297487;
CC P08631; P42768: WAS; NbExp=9; IntAct=EBI-346340, EBI-346375;
CC P08631; O43516: WIPF1; NbExp=3; IntAct=EBI-346340, EBI-346356;
CC P08631; P03406: nef; Xeno; NbExp=2; IntAct=EBI-346340, EBI-15672419;
CC P08631; Q90VU7: nef; Xeno; NbExp=2; IntAct=EBI-346340, EBI-7460704;
CC P08631; P12504: vif; Xeno; NbExp=3; IntAct=EBI-346340, EBI-779991;
CC P08631; O92972; Xeno; NbExp=2; IntAct=EBI-346340, EBI-710506;
CC P08631; P27958; Xeno; NbExp=5; IntAct=EBI-346340, EBI-706378;
CC P08631-2; O95994: AGR2; NbExp=3; IntAct=EBI-9834454, EBI-712648;
CC P08631-2; Q9NP55: BPIFA1; NbExp=3; IntAct=EBI-9834454, EBI-953896;
CC P08631-2; P22681: CBL; NbExp=2; IntAct=EBI-9834454, EBI-518228;
CC P08631-2; A6NC98: CCDC88B; NbExp=3; IntAct=EBI-9834454, EBI-347573;
CC P08631-2; P78358: CTAG1B; NbExp=3; IntAct=EBI-9834454, EBI-1188472;
CC P08631-2; Q8WUJ1: CYB5D2; NbExp=3; IntAct=EBI-9834454, EBI-19113794;
CC P08631-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-9834454, EBI-3867333;
CC P08631-2; Q5TD97: FHL5; NbExp=3; IntAct=EBI-9834454, EBI-750641;
CC P08631-2; O43559: FRS3; NbExp=2; IntAct=EBI-9834454, EBI-725515;
CC P08631-2; Q9HD26-2: GOPC; NbExp=3; IntAct=EBI-9834454, EBI-11102276;
CC P08631-2; O75031: HSF2BP; NbExp=3; IntAct=EBI-9834454, EBI-7116203;
CC P08631-2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-9834454, EBI-6509505;
CC P08631-2; Q5T749: KPRP; NbExp=3; IntAct=EBI-9834454, EBI-10981970;
CC P08631-2; Q15323: KRT31; NbExp=3; IntAct=EBI-9834454, EBI-948001;
CC P08631-2; O76011: KRT34; NbExp=3; IntAct=EBI-9834454, EBI-1047093;
CC P08631-2; Q92764: KRT35; NbExp=3; IntAct=EBI-9834454, EBI-1058674;
CC P08631-2; O76013-2: KRT36; NbExp=3; IntAct=EBI-9834454, EBI-11958506;
CC P08631-2; Q6A162: KRT40; NbExp=3; IntAct=EBI-9834454, EBI-10171697;
CC P08631-2; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-9834454, EBI-11959885;
CC P08631-2; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-9834454, EBI-11749135;
CC P08631-2; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-9834454, EBI-10172290;
CC P08631-2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-9834454, EBI-10171774;
CC P08631-2; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-9834454, EBI-10172052;
CC P08631-2; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-9834454, EBI-9996449;
CC P08631-2; P21741: MDK; NbExp=3; IntAct=EBI-9834454, EBI-722444;
CC P08631-2; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-9834454, EBI-10172526;
CC P08631-2; Q13064: MKRN3; NbExp=3; IntAct=EBI-9834454, EBI-2340269;
CC P08631-2; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-9834454, EBI-11522433;
CC P08631-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-9834454, EBI-22310682;
CC P08631-2; Q8TAK6: OLIG1; NbExp=2; IntAct=EBI-9834454, EBI-3867416;
CC P08631-2; Q92569: PIK3R3; NbExp=4; IntAct=EBI-9834454, EBI-79893;
CC P08631-2; Q58EX7: PLEKHG4; NbExp=3; IntAct=EBI-9834454, EBI-949255;
CC P08631-2; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-9834454, EBI-302345;
CC P08631-2; Q05397: PTK2; NbExp=2; IntAct=EBI-9834454, EBI-702142;
CC P08631-2; Q93062-3: RBPMS; NbExp=3; IntAct=EBI-9834454, EBI-740343;
CC P08631-2; O14492-2: SH2B2; NbExp=3; IntAct=EBI-9834454, EBI-19952306;
CC P08631-2; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-9834454, EBI-750487;
CC P08631-2; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-9834454, EBI-11139477;
CC P08631-2; Q96NM4-3: TOX2; NbExp=3; IntAct=EBI-9834454, EBI-12815137;
CC P08631-2; P14373: TRIM27; NbExp=3; IntAct=EBI-9834454, EBI-719493;
CC P08631-2; Q15654: TRIP6; NbExp=3; IntAct=EBI-9834454, EBI-742327;
CC P08631-2; O76024: WFS1; NbExp=3; IntAct=EBI-9834454, EBI-720609;
CC P08631-2; Q8NAM6: ZSCAN4; NbExp=3; IntAct=EBI-9834454, EBI-7252920;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Lysosome. Membrane; Lipid-anchor.
CC Cell projection, podosome membrane; Lipid-anchor. Cytoplasm, cytosol.
CC Note=Associated with specialized secretory lysosomes called azurophil
CC granules. At least half of this isoform is found in the cytoplasm, some
CC of this fraction is myristoylated.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane
CC {ECO:0000269|PubMed:11904303}; Lipid-anchor
CC {ECO:0000269|PubMed:11904303}. Membrane, caveola
CC {ECO:0000269|PubMed:11904303}; Lipid-anchor
CC {ECO:0000269|PubMed:11904303}. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:11904303}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:11904303}. Golgi apparatus
CC {ECO:0000269|PubMed:11904303}. Cytoplasmic vesicle
CC {ECO:0000269|PubMed:11904303}. Lysosome {ECO:0000269|PubMed:11904303}.
CC Nucleus {ECO:0000269|PubMed:11904303}. Note=20% of this isoform is
CC associated with caveolae. Localization at the cell membrane and at
CC caveolae requires palmitoylation at Cys-3. Colocalizes with the actin
CC cytoskeleton at focal adhesions.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle.
CC Cytoplasm, cytosol.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=1; Synonyms=p60-HCK, p61Hck;
CC IsoId=P08631-1; Sequence=Displayed;
CC Name=2; Synonyms=p59-HCK, p59Hck;
CC IsoId=P08631-2; Sequence=VSP_018858;
CC Name=3;
CC IsoId=P08631-3; Sequence=VSP_018858, VSP_041926;
CC Name=4;
CC IsoId=P08631-4; Sequence=VSP_041926;
CC -!- TISSUE SPECIFICITY: Detected in monocytes and neutrophils (at protein
CC level). Expressed predominantly in cells of the myeloid and B-lymphoid
CC lineages. Highly expressed in granulocytes. Detected in tonsil.
CC {ECO:0000269|PubMed:3453117, ECO:0000269|PubMed:8064233,
CC ECO:0000269|PubMed:8995234}.
CC -!- INDUCTION: Up-regulated during myeloid cell differentiation. The
CC highest levels are detected in fully differentiated phagocytes. Up-
CC regulated by IL2. {ECO:0000269|PubMed:10779760,
CC ECO:0000269|PubMed:8995234}.
CC -!- DOMAIN: The SH3 domain mediates binding to HIV-1 Nef.
CC -!- PTM: Phosphorylated on several tyrosine residues. Autophosphorylated.
CC Becomes rapidly phosphorylated upon activation of the immunoglobulin
CC receptors FCGR1A and FCGR2A. Phosphorylation by the BCR-ABL fusion
CC protein mediates activation of HCK. Phosphorylation at Tyr-411
CC increases kinase activity. Phosphorylation at Tyr-522 inhibits kinase
CC activity. Kinase activity is not required for phosphorylation at Tyr-
CC 522, suggesting that this site is a target of other kinases.
CC {ECO:0000269|PubMed:10360180, ECO:0000269|PubMed:10644735,
CC ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:11896602,
CC ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:16216497,
CC ECO:0000269|PubMed:8064233, ECO:0000269|PubMed:9024658,
CC ECO:0000269|PubMed:9406996}.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation via the
CC proteasome. {ECO:0000269|PubMed:11896602}.
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:0000269|PubMed:7791757}.
CC -!- DISEASE: Note=Aberrant activation of HCK by HIV-1 protein Nef enhances
CC HIV-1 replication and contributes to HIV-1 pathogenicity.
CC -!- DISEASE: Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion
CC protein, promotes cancer cell proliferation.
CC -!- MISCELLANEOUS: [Isoform 1]: Initiates from a CTG codon.
CC -!- MISCELLANEOUS: [Isoform 4]: Initiates from a CTG codon. {ECO:0000305}.
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=AAA52643.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAF82585.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M16591; AAA52643.1; ALT_FRAME; mRNA.
DR EMBL; M16592; AAA52644.1; -; mRNA.
DR EMBL; AK026432; BAB15482.1; -; mRNA.
DR EMBL; AK289896; BAF82585.1; ALT_INIT; mRNA.
DR EMBL; AK298726; BAG60878.1; -; mRNA.
DR EMBL; AL353092; CAI19694.1; -; Genomic_DNA.
DR EMBL; AL049539; CAI19694.1; JOINED; Genomic_DNA.
DR EMBL; AL353092; CAI19695.1; -; Genomic_DNA.
DR EMBL; AL049539; CAI19695.1; JOINED; Genomic_DNA.
DR EMBL; AL049539; CAI22966.1; -; Genomic_DNA.
DR EMBL; AL353092; CAI22966.1; JOINED; Genomic_DNA.
DR EMBL; AL049539; CAI22967.1; -; Genomic_DNA.
DR EMBL; AL353092; CAI22967.1; JOINED; Genomic_DNA.
DR EMBL; CH471077; EAW76392.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76393.1; -; Genomic_DNA.
DR EMBL; BC014435; AAH14435.2; -; mRNA.
DR EMBL; BC094847; AAH94847.2; -; mRNA.
DR EMBL; BC108930; AAI08931.2; -; mRNA.
DR EMBL; BC108931; AAI08932.2; -; mRNA.
DR EMBL; BC113854; AAI13855.2; -; mRNA.
DR EMBL; BC114463; AAI14464.2; -; mRNA.
DR EMBL; X58741; CAA41565.2; -; Genomic_DNA.
DR EMBL; X58742; CAA41565.2; JOINED; Genomic_DNA.
DR EMBL; X58743; CAA41565.2; JOINED; Genomic_DNA.
DR CCDS; CCDS33460.1; -. [P08631-1]
DR CCDS; CCDS54453.1; -. [P08631-4]
DR CCDS; CCDS54455.1; -. [P08631-2]
DR CCDS; CCDS54456.1; -. [P08631-3]
DR PIR; A27811; TVHUHC.
DR PIR; A41263; A41263.
DR RefSeq; NP_001165600.1; NM_001172129.1. [P08631-2]
DR RefSeq; NP_001165601.1; NM_001172130.1. [P08631-4]
DR RefSeq; NP_001165602.1; NM_001172131.1. [P08631-3]
DR RefSeq; NP_001165604.1; NM_001172133.1. [P08631-2]
DR RefSeq; NP_002101.2; NM_002110.3. [P08631-1]
DR PDB; 1AD5; X-ray; 2.60 A; A/B=79-526.
DR PDB; 1BU1; X-ray; 2.60 A; A/B/C/D/E/F=81-137.
DR PDB; 1QCF; X-ray; 2.00 A; A=81-526.
DR PDB; 2C0I; X-ray; 2.30 A; A/B=81-526.
DR PDB; 2C0O; X-ray; 2.85 A; A/B=81-526.
DR PDB; 2C0T; X-ray; 2.15 A; A/B=81-526.
DR PDB; 2HCK; X-ray; 3.00 A; A/B=79-526.
DR PDB; 2HK5; X-ray; 2.00 A; A=247-514.
DR PDB; 2OI3; NMR; -; A=61-141.
DR PDB; 2OJ2; NMR; -; A=61-141.
DR PDB; 3HCK; NMR; -; A=140-245.
DR PDB; 3NHN; X-ray; 2.61 A; A=72-256.
DR PDB; 3RBB; X-ray; 2.35 A; B/D=79-138.
DR PDB; 3REA; X-ray; 2.00 A; B/D=79-138.
DR PDB; 3REB; X-ray; 3.45 A; B/D=79-138.
DR PDB; 3VRY; X-ray; 2.48 A; A/B=81-526.
DR PDB; 3VRZ; X-ray; 2.22 A; A/B=81-526.
DR PDB; 3VS0; X-ray; 2.93 A; A/B=81-526.
DR PDB; 3VS1; X-ray; 2.46 A; A/B=81-526.
DR PDB; 3VS2; X-ray; 2.61 A; A/B=81-526.
DR PDB; 3VS3; X-ray; 2.17 A; A/B=81-526.
DR PDB; 3VS4; X-ray; 2.75 A; A/B=81-526.
DR PDB; 3VS5; X-ray; 2.85 A; A/B=81-526.
DR PDB; 3VS6; X-ray; 2.37 A; A/B=81-526.
DR PDB; 3VS7; X-ray; 3.00 A; A/B=81-526.
DR PDB; 4HCK; NMR; -; A=72-143.
DR PDB; 4LUD; X-ray; 2.85 A; A/B=81-526.
DR PDB; 4LUE; X-ray; 3.04 A; A/B=81-526.
DR PDB; 4ORZ; X-ray; 2.00 A; A=77-138.
DR PDB; 4U5W; X-ray; 1.86 A; B/D=72-242.
DR PDB; 5H09; X-ray; 1.95 A; A=81-526.
DR PDB; 5H0B; X-ray; 1.65 A; A=81-526.
DR PDB; 5H0E; X-ray; 2.10 A; A=81-526.
DR PDB; 5H0G; X-ray; 1.80 A; A=81-526.
DR PDB; 5H0H; X-ray; 1.72 A; A=81-526.
DR PDB; 5HCK; NMR; -; A=72-143.
DR PDB; 5NUH; X-ray; 2.78 A; C/D=79-138.
DR PDB; 5ZJ6; X-ray; 1.70 A; A/B=242-521.
DR PDBsum; 1AD5; -.
DR PDBsum; 1BU1; -.
DR PDBsum; 1QCF; -.
DR PDBsum; 2C0I; -.
DR PDBsum; 2C0O; -.
DR PDBsum; 2C0T; -.
DR PDBsum; 2HCK; -.
DR PDBsum; 2HK5; -.
DR PDBsum; 2OI3; -.
DR PDBsum; 2OJ2; -.
DR PDBsum; 3HCK; -.
DR PDBsum; 3NHN; -.
DR PDBsum; 3RBB; -.
DR PDBsum; 3REA; -.
DR PDBsum; 3REB; -.
DR PDBsum; 3VRY; -.
DR PDBsum; 3VRZ; -.
DR PDBsum; 3VS0; -.
DR PDBsum; 3VS1; -.
DR PDBsum; 3VS2; -.
DR PDBsum; 3VS3; -.
DR PDBsum; 3VS4; -.
DR PDBsum; 3VS5; -.
DR PDBsum; 3VS6; -.
DR PDBsum; 3VS7; -.
DR PDBsum; 4HCK; -.
DR PDBsum; 4LUD; -.
DR PDBsum; 4LUE; -.
DR PDBsum; 4ORZ; -.
DR PDBsum; 4U5W; -.
DR PDBsum; 5H09; -.
DR PDBsum; 5H0B; -.
DR PDBsum; 5H0E; -.
DR PDBsum; 5H0G; -.
DR PDBsum; 5H0H; -.
DR PDBsum; 5HCK; -.
DR PDBsum; 5NUH; -.
DR PDBsum; 5ZJ6; -.
DR AlphaFoldDB; P08631; -.
DR BMRB; P08631; -.
DR SMR; P08631; -.
DR BioGRID; 109305; 153.
DR DIP; DIP-1051N; -.
DR ELM; P08631; -.
DR IntAct; P08631; 155.
DR MINT; P08631; -.
DR STRING; 9606.ENSP00000444986; -.
DR BindingDB; P08631; -.
DR ChEMBL; CHEMBL3234; -.
DR DrugBank; DB01809; 1-Ter-Butyl-3-P-Tolyl-1h-Pyrazolo[3,4-D]Pyrimidin-4-Ylamine.
DR DrugBank; DB06616; Bosutinib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB01962; Phosphonotyrosine.
DR DrugBank; DB04216; Quercetin.
DR DrugCentral; P08631; -.
DR GuidetoPHARMACOLOGY; 2032; -.
DR GlyGen; P08631; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P08631; -.
DR PhosphoSitePlus; P08631; -.
DR SwissPalm; P08631; -.
DR BioMuta; HCK; -.
DR DMDM; 20141296; -.
DR EPD; P08631; -.
DR jPOST; P08631; -.
DR MassIVE; P08631; -.
DR MaxQB; P08631; -.
DR PaxDb; P08631; -.
DR PeptideAtlas; P08631; -.
DR PRIDE; P08631; -.
DR ProteomicsDB; 52142; -. [P08631-1]
DR ProteomicsDB; 52143; -. [P08631-2]
DR ProteomicsDB; 52144; -. [P08631-3]
DR ProteomicsDB; 52145; -. [P08631-4]
DR Antibodypedia; 3921; 606 antibodies from 37 providers.
DR DNASU; 3055; -.
DR Ensembl; ENST00000375852.5; ENSP00000365012.3; ENSG00000101336.18. [P08631-1]
DR Ensembl; ENST00000375862.7; ENSP00000365022.3; ENSG00000101336.18. [P08631-4]
DR Ensembl; ENST00000518730.5; ENSP00000427757.1; ENSG00000101336.18. [P08631-3]
DR Ensembl; ENST00000520553.5; ENSP00000429848.1; ENSG00000101336.18. [P08631-2]
DR Ensembl; ENST00000629881.2; ENSP00000486627.1; ENSG00000101336.18. [P08631-2]
DR GeneID; 3055; -.
DR KEGG; hsa:3055; -.
DR MANE-Select; ENST00000375852.5; ENSP00000365012.3; NM_002110.5; NP_002101.2.
DR UCSC; uc002wxi.4; human. [P08631-1]
DR CTD; 3055; -.
DR DisGeNET; 3055; -.
DR GeneCards; HCK; -.
DR HGNC; HGNC:4840; HCK.
DR HPA; ENSG00000101336; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 142370; gene.
DR neXtProt; NX_P08631; -.
DR OpenTargets; ENSG00000101336; -.
DR PharmGKB; PA29216; -.
DR VEuPathDB; HostDB:ENSG00000101336; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000158738; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; P08631; -.
DR OMA; QKLTFPC; -.
DR PhylomeDB; P08631; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P08631; -.
DR Reactome; R-HSA-164944; Nef and signal transduction.
DR Reactome; R-HSA-2029481; FCGR activation.
DR Reactome; R-HSA-912631; Regulation of signaling by CBL.
DR Reactome; R-HSA-9664323; FCGR3A-mediated IL10 synthesis.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-9706374; FLT3 signaling through SRC family kinases.
DR SignaLink; P08631; -.
DR SIGNOR; P08631; -.
DR BioGRID-ORCS; 3055; 12 hits in 1101 CRISPR screens.
DR ChiTaRS; HCK; human.
DR EvolutionaryTrace; P08631; -.
DR GeneWiki; HCK; -.
DR GenomeRNAi; 3055; -.
DR Pharos; P08631; Tclin.
DR PRO; PR:P08631; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P08631; protein.
DR Bgee; ENSG00000101336; Expressed in monocyte and 175 other tissues.
DR ExpressionAtlas; P08631; baseline and differential.
DR Genevisible; P08631; HS.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IMP:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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; IPI:CAFA.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IMP:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; TAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:UniProtKB.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0002758; P:innate immune response-activating signal transduction; TAS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:UniProtKB.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:UniProtKB.
DR GO; GO:0043299; P:leukocyte degranulation; TAS:UniProtKB.
DR GO; GO:0002522; P:leukocyte migration involved in immune response; TAS:UniProtKB.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; TAS:UniProtKB.
DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0002862; P:negative regulation of inflammatory response to antigenic stimulus; TAS:Reactome.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IDA:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; TAS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; TAS:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; IMP:UniProtKB.
DR GO; GO:0071801; P:regulation of podosome assembly; IDA:UniProtKB.
DR GO; GO:0045728; P:respiratory burst after phagocytosis; TAS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10363; SH2_Src_HCK; 1.
DR DisProt; DP02383; -.
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 3D-structure; Alternative initiation; Alternative splicing; ATP-binding;
KW Cell junction; Cell membrane; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Exocytosis; Golgi apparatus;
KW Host-virus interaction; Immunity; Inflammatory response; Innate immunity;
KW Kinase; Lipoprotein; Lysosome; Membrane; Myristate; Nucleotide-binding;
KW Nucleus; 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 CHAIN 2..526
FT /note="Tyrosine-protein kinase HCK"
FT /id="PRO_0000024433"
FT DOMAIN 78..138
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 144..241
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 262..515
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 ACT_SITE 381
FT /note="Proton acceptor"
FT BINDING 268..276
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 36
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 51
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11896602"
FT MOD_RES 202
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 209
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P08103"
FT MOD_RES 411
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:10644735,
FT ECO:0000269|PubMed:11896602"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 522
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10360180,
FT ECO:0000269|PubMed:10644735, ECO:0000269|PubMed:11896602,
FT ECO:0000269|PubMed:16216497, ECO:0000269|PubMed:9024658"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:7791757"
FT VAR_SEQ 1..21
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:3453117"
FT /id="VSP_018858"
FT VAR_SEQ 76
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_041926"
FT VARIANT 44
FT /note="A -> T (in dbSNP:rs56029200)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041707"
FT VARIANT 105
FT /note="M -> L (in dbSNP:rs55722810)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_041708"
FT VARIANT 399
FT /note="D -> G (in an ovarian mucinous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041709"
FT VARIANT 502
FT /note="P -> Q (in dbSNP:rs17093828)"
FT /id="VAR_033836"
FT MUTAGEN 3
FT /note="G->C: Slight palmitoylation, cytoplasmic and
FT caveolar localization; in isoform 1;."
FT /evidence="ECO:0000269|PubMed:11904303,
FT ECO:0000269|PubMed:7791757"
FT MUTAGEN 3
FT /note="G->S: Abolishes palmitoylation and localization at
FT the cell membrane."
FT /evidence="ECO:0000269|PubMed:11904303,
FT ECO:0000269|PubMed:7791757"
FT MUTAGEN 23
FT /note="G->A: Myristoylation and palmitoylation are
FT abolished, leading to entirely cytoplasmic localization; in
FT isoform 2."
FT /evidence="ECO:0000269|PubMed:7791757"
FT MUTAGEN 24
FT /note="C->S: Palmitoylation is abolished, some cytoplasmic
FT and no calveolar localization; in isoform 2."
FT /evidence="ECO:0000269|PubMed:7791757"
FT MUTAGEN 290
FT /note="K->E: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:11896602"
FT MUTAGEN 305
FT /note="E->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:10644735"
FT MUTAGEN 381
FT /note="D->E: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:15998323"
FT MUTAGEN 411
FT /note="Y->A: Reduced catalytic activity and higher affinity
FT for target peptides."
FT /evidence="ECO:0000269|PubMed:10644735"
FT MUTAGEN 522
FT /note="Y->F: Constitutively activated kinase, leading to
FT cellular transformation."
FT /evidence="ECO:0000269|PubMed:10092522,
FT ECO:0000269|PubMed:11896602"
FT CONFLICT 24
FT /note="C -> S (in Ref. 1; AAA52643)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="N -> D (in Ref. 3; BAF82585)"
FT /evidence="ECO:0000305"
FT CONFLICT 144
FT /note="W -> R (in Ref. 3; BAB15482)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="F -> Y (in Ref. 3; BAF82585)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="I -> T (in Ref. 6; AAI13855)"
FT /evidence="ECO:0000305"
FT CONFLICT 488
FT /note="N -> S (in Ref. 3; BAF82585)"
FT /evidence="ECO:0000305"
FT STRAND 82..85
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:5H0H"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 114..122
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:2OI3"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:3VS2"
FT HELIX 151..159
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 168..172
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 180..188
FT /evidence="ECO:0007829|PDB:5H0B"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 192..202
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:4U5W"
FT STRAND 208..211
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 233..235
FT /evidence="ECO:0007829|PDB:5H0B"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:2HCK"
FT HELIX 259..261
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 262..270
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 272..281
FT /evidence="ECO:0007829|PDB:5H0B"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 285..292
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 294..297
FT /evidence="ECO:0007829|PDB:3VS3"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 330..333
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 341..345
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 355..374
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 402..405
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 410..413
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 416..419
FT /evidence="ECO:0007829|PDB:1QCF"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 426..431
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 436..451
FT /evidence="ECO:0007829|PDB:5H0B"
FT TURN 452..454
FT /evidence="ECO:0007829|PDB:2HK5"
FT STRAND 457..460
FT /evidence="ECO:0007829|PDB:1AD5"
FT HELIX 463..471
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 480..482
FT /evidence="ECO:0007829|PDB:3VS6"
FT HELIX 484..493
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 498..500
FT /evidence="ECO:0007829|PDB:5H0B"
FT HELIX 504..512
FT /evidence="ECO:0007829|PDB:5H0B"
FT TURN 513..518
FT /evidence="ECO:0007829|PDB:5H0B"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:1QCF"
FT INIT_MET P08631-2:1
FT /note="Removed"
FT /evidence="ECO:0000305"
FT LIPID P08631-2:2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:7791757"
FT LIPID P08631-2:3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:7791757"
SQ SEQUENCE 526 AA; 59600 MW; 847E877A0A641725 CRC64;
MGGRSSCEDP GCPRDEERAP RMGCMKSKFL QVGGNTFSKT ETSASPHCPV YVPDPTSTIK
PGPNSHNSNT PGIREAGSED IIVVALYDYE AIHHEDLSFQ KGDQMVVLEE SGEWWKARSL
ATRKEGYIPS NYVARVDSLE TEEWFFKGIS RKDAERQLLA PGNMLGSFMI RDSETTKGSY
SLSVRDYDPR QGDTVKHYKI RTLDNGGFYI SPRSTFSTLQ ELVDHYKKGN DGLCQKLSVP
CMSSKPQKPW EKDAWEIPRE SLKLEKKLGA GQFGEVWMAT YNKHTKVAVK TMKPGSMSVE
AFLAEANVMK TLQHDKLVKL HAVVTKEPIY IITEFMAKGS LLDFLKSDEG SKQPLPKLID
FSAQIAEGMA FIEQRNYIHR DLRAANILVS ASLVCKIADF GLARVIEDNE YTAREGAKFP
IKWTAPEAIN FGSFTIKSDV WSFGILLMEI VTYGRIPYPG MSNPEVIRAL ERGYRMPRPE
NCPEELYNIM MRCWKNRPEE RPTFEYIQSV LDDFYTATES QYQQQP
