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 27-MAR-2024, entry version 271. 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). RN [56] RP VARIANT AIPCV 515-TYR--PRO-526 DEL, CHARACTERIZATION OF VARIANT AIPCV RP 515-TYR--PRO-526 DEL, AND INVOLVEMENT IN AIPCV. RX PubMed=34536415; DOI=10.1016/j.jaci.2021.07.046; RA Kanderova V., Svobodova T., Borna S., Fejtkova M., Martinu V., Paderova J., RA Svaton M., Kralova J., Fronkova E., Klocperk A., Pruhova S., RA Lee-Kirsch M.A., Hornofova L., Koblizek M., Novak P., Zimmermannova O., RA Parackova Z., Sediva A., Kalina T., Janda A., Kayserova J., Dvorakova M., RA Macek M., Pohunek P., Sedlacek P., Poh A., Ernst M., Brdicka T., Hrusak O., RA Lebl J.; RT "Early-onset pulmonary and cutaneous vasculitis driven by constitutively RT active SRC-family kinase HCK."; RL J. Allergy Clin. Immunol. 149:1464-1472(2022). 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 -!- DISEASE: Autoinflammation with pulmonary and cutaneous vasculitis CC (AIPCV) [MIM:620296]: An autosomal dominant disorder characterized by CC cutaneous vasculitis and chronic pulmonary inflammation that evolves to CC fibrosis. AIPCV manifests soon after birth with petechial skin lesions, CC followed by progressive pulmonary involvement causing restrictive lung CC disease and respiratory insufficiency. {ECO:0000269|PubMed:34536415}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8F2P; X-ray; 2.63 A; B=77-140. 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 PDBsum; 8F2P; -. DR AlphaFoldDB; P08631; -. DR BMRB; P08631; -. DR SMR; P08631; -. DR BioGRID; 109305; 166. DR DIP; DIP-1051N; -. DR ELM; P08631; -. DR IntAct; P08631; 155. DR MINT; P08631; -. DR STRING; 9606.ENSP00000365012; -. 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 GlyCosmos; P08631; 2 sites, 1 glycan. 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; 9606-ENSP00000444986; -. DR PeptideAtlas; P08631; -. DR ProteomicsDB; 52142; -. [P08631-1] DR ProteomicsDB; 52143; -. [P08631-2] DR ProteomicsDB; 52144; -. [P08631-3] DR ProteomicsDB; 52145; -. [P08631-4] DR Antibodypedia; 3921; 669 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 AGR; HGNC:4840; -. DR CTD; 3055; -. DR DisGeNET; 3055; -. DR GeneCards; HCK; -. DR HGNC; HGNC:4840; HCK. DR HPA; ENSG00000101336; Tissue enhanced (lymphoid). DR MalaCards; HCK; -. DR MIM; 142370; gene. DR MIM; 620296; phenotype. 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; RGGAVKH; -. DR OrthoDB; 1614410at2759; -. 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-9680350; Signaling by CSF1 (M-CSF) in myeloid cells. 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; 13 hits in 1180 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 177 other cell types or tissues. DR ExpressionAtlas; P08631; baseline and differential. DR GO; GO:0005901; C:caveola; IDA:UniProtKB. DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IMP:UniProtKB. 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; IBA:GO_Central. 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:0008289; F:lipid binding; EXP:DisProt. 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 signaling pathway; TAS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IMP: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:0051179; P:localization; EXP:DisProt. 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: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:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB. 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 GO; GO:0060333; P:type II interferon-mediated signaling pathway; TAS:UniProtKB. DR CDD; cd10363; SH2_Src_HCK; 1. DR DisProt; DP02383; -. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF245; TYROSINE-PROTEIN KINASE HCK; 1. 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR SUPFAM; SSF50044; SH3-domain; 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. DR Genevisible; P08631; HS. 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 VARIANT 515..526 FT /note="Missing (in AIPCV; results in increased activation FT of inflammatory response; decreased protein abundance in FT patient cells; increased protein degradation; results in FT increased kinase activity and autophosphorylation)" FT /evidence="ECO:0000269|PubMed:34536415" FT /id="VAR_088298" 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 //