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P08631

- HCK_HUMAN

UniProt

P08631 - HCK_HUMAN

Protein

Tyrosine-protein kinase HCK

Gene

HCK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 196 (01 Oct 2014)
      Sequence version 5 (23 Jan 2007)
      Previous versions | rss
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    Functioni

    Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.19 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.8 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-411 is required for optimal activity. Phosphorylation at Tyr-522 inhibits kinase activity. Inhibited by PP1 and A-770041.9 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei290 – 2901ATP
    Active sitei381 – 3811Proton acceptor

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi268 – 2769ATP

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB-EC
    3. protein binding Source: UniProtKB
    4. protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. cell adhesion Source: UniProtKB
    2. cytokine-mediated signaling pathway Source: UniProtKB
    3. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
    4. inflammatory response Source: UniProtKB-KW
    5. innate immune response Source: Reactome
    6. innate immune response-activating signal transduction Source: UniProtKB
    7. integrin-mediated signaling pathway Source: UniProtKB
    8. interferon-gamma-mediated signaling pathway Source: UniProtKB
    9. leukocyte degranulation Source: UniProtKB
    10. leukocyte migration involved in immune response Source: UniProtKB
    11. lipopolysaccharide-mediated signaling pathway Source: UniProtKB
    12. mesoderm development Source: ProtInc
    13. negative regulation of apoptotic process Source: UniProtKB
    14. peptidyl-tyrosine phosphorylation Source: UniProtKB
    15. positive regulation of actin cytoskeleton reorganization Source: UniProtKB
    16. positive regulation of actin filament polymerization Source: UniProtKB
    17. positive regulation of cell proliferation Source: UniProtKB
    18. protein autophosphorylation Source: UniProtKB
    19. protein phosphorylation Source: ProtInc
    20. regulation of cell shape Source: UniProtKB
    21. regulation of defense response to virus by virus Source: Reactome
    22. regulation of inflammatory response Source: UniProtKB
    23. regulation of phagocytosis Source: UniProtKB
    24. regulation of podosome assembly Source: UniProtKB
    25. regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
    26. respiratory burst after phagocytosis Source: UniProtKB
    27. viral process Source: Reactome

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Exocytosis, Host-virus interaction, Immunity, Inflammatory response, Innate immunity, Phagocytosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 2681.
    ReactomeiREACT_11068. Nef and signal transduction.
    REACT_160274. FCGR activation.
    REACT_23787. Regulation of signaling by CBL.
    SignaLinkiP08631.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase HCK (EC:2.7.10.2)
    Alternative name(s):
    Hematopoietic cell kinase
    Hemopoietic cell kinase
    p59-HCK/p60-HCK
    p59Hck
    p61Hck
    Gene namesi
    Name:HCK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:4840. HCK.

    Subcellular locationi

    Isoform 1 : Lysosome. Membrane; Lipid-anchor. Cell projectionpodosome membrane; Lipid-anchor. Cytoplasmcytosol
    Note: Associated with specialized secretory lysosomes called azurophil granules. At least half of this isoform is found in the cytoplasm, some of this fraction is myristoylated.
    Isoform 2 : Cell membrane 1 Publication; Lipid-anchor 1 Publication. Membranecaveola 1 Publication; Lipid-anchor 1 Publication. Cell junctionfocal adhesion 1 Publication. Cytoplasmcytoskeleton 1 Publication. Golgi apparatus 1 Publication. Cytoplasmic vesicle 1 Publication. Lysosome 1 Publication. Nucleus 1 Publication
    Note: 20% of this isoform is associated with caveolae. Localization at the cell membrane and at caveolae requires palmitoylation at Cys-3. Colocalizes with the actin cytoskeleton at focal adhesions.

    GO - Cellular componenti

    1. caveola Source: UniProtKB
    2. cell projection Source: UniProtKB-KW
    3. cytoskeleton Source: UniProtKB-SubCell
    4. cytosol Source: Reactome
    5. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
    6. focal adhesion Source: UniProtKB
    7. Golgi apparatus Source: UniProtKB-SubCell
    8. lysosome Source: UniProtKB
    9. nucleus Source: UniProtKB-SubCell
    10. transport vesicle Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Golgi apparatus, Lysosome, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.
    Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi3 – 31G → C: Slight palmitoylation, cytoplasmic and caveolar localization; in isoform 1;. 2 Publications
    Mutagenesisi3 – 31G → S: Abolishes palmitoylation and localization at the cell membrane. 2 Publications
    Mutagenesisi23 – 231G → A: Myristoylation and palmitoylation are abolished, leading to entirely cytoplasmic localization; in isoform 2. 1 Publication
    Mutagenesisi24 – 241C → S: Palmitoylation is abolished, some cytoplasmic and no calveolar localization; in isoform 2. 1 Publication
    Mutagenesisi290 – 2901K → E: Loss of kinase activity. 1 Publication
    Mutagenesisi305 – 3051E → A: Loss of kinase activity. 1 Publication
    Mutagenesisi381 – 3811D → E: Loss of kinase activity. 1 Publication
    Mutagenesisi411 – 4111Y → A: Reduced catalytic activity and higher affinity for target peptides. 1 Publication
    Mutagenesisi522 – 5221Y → F: Constitutively activated kinase, leading to cellular transformation. 2 Publications

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA29216.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed
    Chaini2 – 526525Tyrosine-protein kinase HCKPRO_0000024433Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycine1 Publication
    Modified residuei51 – 511Phosphotyrosine; by autocatalysis1 Publication
    Modified residuei202 – 2021Phosphothreonine1 Publication
    Modified residuei209 – 2091PhosphotyrosineBy similarity
    Modified residuei411 – 4111Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei462 – 4621Phosphoserine1 Publication
    Modified residuei522 – 5221Phosphotyrosine5 Publications

    Post-translational modificationi

    Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation by the BCR-ABL fusion protein mediates activation of HCK. Phosphorylation at Tyr-411 increases kinase activity. Phosphorylation at Tyr-522 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-522, suggesting that this site is a target of other kinases.10 Publications
    Ubiquitinated by CBL, leading to its degradation via the proteasome.1 Publication
    Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.1 Publication

    Keywords - PTMi

    Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP08631.
    PaxDbiP08631.
    PRIDEiP08631.

    PTM databases

    PhosphoSiteiP08631.

    Expressioni

    Tissue specificityi

    Detected in monocytes and neutrophils (at protein level). Expressed predominantly in cells of the myeloid and B-lymphoid lineages. Highly expressed in granulocytes. Detected in tonsil.3 Publications

    Inductioni

    Up-regulated during myeloid cell differentiation. The highest levels are detected in fully differentiated phagocytes. Up-regulated by IL2.2 Publications

    Gene expression databases

    ArrayExpressiP08631.
    BgeeiP08631.
    GenevestigatoriP08631.

    Organism-specific databases

    HPAiCAB005195.

    Interactioni

    Subunit structurei

    Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with VAV1, WAS and RAPGEF1 By similarity. Interacts (via SH3 domain) with HIV-1 Nef and Vif. This interaction stimulates its tyrosine-kinase activity. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with ARRB1 and ARRB2. Interacts with ADAM15. Interacts with FASLG. Interacts with CBL. Interacts with FCGR1A; the interaction may be indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1. Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1.By similarity24 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    O929722EBI-346340,EBI-710506From a different organism.
    P279585EBI-346340,EBI-706378From a different organism.
    ADAM15Q134443EBI-346340,EBI-77818
    ALOX5P099172EBI-346340,EBI-79934
    ASAP1Q9ULH12EBI-346340,EBI-346622
    ELMO1Q925564EBI-346340,EBI-346417
    ERBB3P218602EBI-346340,EBI-720706
    FLT1P179482EBI-346340,EBI-1026718
    KHDRBS1Q076664EBI-346340,EBI-1364
    KITP107212EBI-346340,EBI-1379503
    nefQ90VU72EBI-346340,EBI-7460704From a different organism.
    PAK2Q131772EBI-346340,EBI-1045887
    PDCD6IPQ8WUM44EBI-346340,EBI-310624
    PIK3CBP423382EBI-346340,EBI-2609540
    PLCG1P191742EBI-346340,EBI-79387
    SOS1Q078894EBI-346340,EBI-297487
    vifP125043EBI-346340,EBI-779991From a different organism.
    WASP427689EBI-346340,EBI-346375
    WIPF1O435163EBI-346340,EBI-346356

    Protein-protein interaction databases

    BioGridi109305. 44 interactions.
    DIPiDIP-1051N.
    IntActiP08631. 58 interactions.
    MINTiMINT-135300.

    Structurei

    Secondary structure

    1
    526
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi82 – 876
    Beta strandi93 – 964
    Beta strandi104 – 1096
    Beta strandi114 – 1196
    Turni120 – 1223
    Beta strandi125 – 1295
    Helixi130 – 1323
    Beta strandi133 – 1353
    Helixi136 – 1383
    Helixi139 – 1413
    Beta strandi145 – 1484
    Helixi151 – 1599
    Beta strandi168 – 1725
    Beta strandi174 – 1763
    Beta strandi179 – 18810
    Turni189 – 1913
    Beta strandi192 – 20211
    Beta strandi204 – 2063
    Beta strandi208 – 2147
    Beta strandi216 – 2183
    Helixi219 – 2268
    Beta strandi233 – 2353
    Turni252 – 2554
    Helixi259 – 2613
    Beta strandi262 – 2698
    Beta strandi272 – 28110
    Turni282 – 2843
    Beta strandi285 – 2928
    Beta strandi294 – 2974
    Helixi299 – 30911
    Beta strandi320 – 3245
    Beta strandi326 – 3283
    Beta strandi330 – 3334
    Helixi341 – 3466
    Helixi348 – 3514
    Helixi355 – 37420
    Helixi384 – 3863
    Beta strandi387 – 3893
    Beta strandi395 – 3973
    Helixi402 – 4054
    Helixi409 – 4124
    Beta strandi416 – 4194
    Helixi421 – 4233
    Helixi426 – 4316
    Helixi436 – 45116
    Turni452 – 4543
    Beta strandi457 – 4604
    Helixi463 – 47210
    Beta strandi480 – 4823
    Helixi484 – 49310
    Helixi498 – 5003
    Helixi504 – 5129
    Beta strandi514 – 5185
    Beta strandi521 – 5233

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AD5X-ray2.60A/B79-526[»]
    1BU1X-ray2.60A/B/C/D/E/F81-137[»]
    1QCFX-ray2.00A81-526[»]
    2C0IX-ray2.30A/B81-526[»]
    2C0OX-ray2.85A/B81-526[»]
    2C0TX-ray2.15A/B81-526[»]
    2HCKX-ray3.00A/B79-526[»]
    2HK5X-ray2.00A247-514[»]
    2OI3NMR-A61-141[»]
    2OJ2NMR-A61-141[»]
    3HCKNMR-A140-245[»]
    3NHNX-ray2.61A72-256[»]
    3RBBX-ray2.35B/D79-138[»]
    3REAX-ray2.00B/D79-138[»]
    3REBX-ray3.45B/D79-138[»]
    3VRYX-ray2.48A/B81-526[»]
    3VRZX-ray2.22A/B81-526[»]
    3VS0X-ray2.93A/B81-526[»]
    3VS1X-ray2.46A/B81-526[»]
    3VS2X-ray2.61A/B81-526[»]
    3VS3X-ray2.17A/B81-526[»]
    3VS4X-ray2.75A/B81-526[»]
    3VS5X-ray2.85A/B81-526[»]
    3VS6X-ray2.37A/B81-526[»]
    3VS7X-ray3.00A/B81-526[»]
    4HCKNMR-A72-143[»]
    4LUDX-ray2.85A/B81-526[»]
    4LUEX-ray3.04A/B81-526[»]
    4ORZX-ray2.00A77-138[»]
    5HCKNMR-A72-143[»]
    ProteinModelPortaliP08631.
    SMRiP08631. Positions 49-526.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP08631.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini78 – 13861SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini144 – 24198SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini262 – 515254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The SH3 domain mediates binding to HIV-1 Nef.

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain, SH3 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233858.
    HOVERGENiHBG008761.
    InParanoidiP08631.
    KOiK08893.
    OrthoDBiEOG7GTT2V.
    PhylomeDBiP08631.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. Align

    Isoform 1 (identifier: P08631-1) [UniParc]FASTAAdd to Basket

    Also known as: p60-HCK, p61Hck

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGGRSSCEDP GCPRDEERAP RMGCMKSKFL QVGGNTFSKT ETSASPHCPV    50
    YVPDPTSTIK PGPNSHNSNT PGIREAGSED IIVVALYDYE AIHHEDLSFQ 100
    KGDQMVVLEE SGEWWKARSL ATRKEGYIPS NYVARVDSLE TEEWFFKGIS 150
    RKDAERQLLA PGNMLGSFMI RDSETTKGSY SLSVRDYDPR QGDTVKHYKI 200
    RTLDNGGFYI SPRSTFSTLQ ELVDHYKKGN DGLCQKLSVP CMSSKPQKPW 250
    EKDAWEIPRE SLKLEKKLGA GQFGEVWMAT YNKHTKVAVK TMKPGSMSVE 300
    AFLAEANVMK TLQHDKLVKL HAVVTKEPIY IITEFMAKGS LLDFLKSDEG 350
    SKQPLPKLID FSAQIAEGMA FIEQRNYIHR DLRAANILVS ASLVCKIADF 400
    GLARVIEDNE YTAREGAKFP IKWTAPEAIN FGSFTIKSDV WSFGILLMEI 450
    VTYGRIPYPG MSNPEVIRAL ERGYRMPRPE NCPEELYNIM MRCWKNRPEE 500
    RPTFEYIQSV LDDFYTATES QYQQQP 526

    Note: Initiates from a CTG codon.

    Length:526
    Mass (Da):59,600
    Last modified:January 23, 2007 - v5
    Checksum:i847E877A0A641725
    GO
    Isoform 2 (identifier: P08631-2) [UniParc]FASTAAdd to Basket

    Also known as: p59-HCK, p59Hck

    The sequence of this isoform differs from the canonical sequence as follows:
         1-21: Missing.

    Note: Initiator Met-1 is removed. Contains a N-myristoyl glycine at position 2. S-palmitoylated at Cys-3.

    Show »
    Length:505
    Mass (Da):57,312
    Checksum:i4F1EC1E8F3EDF9CA
    GO
    Isoform 3 (identifier: P08631-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-21: Missing.
         76-76: Missing.

    Show »
    Length:504
    Mass (Da):57,241
    Checksum:iC07FF5B8D3C1B862
    GO
    Isoform 4 (identifier: P08631-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         76-76: Missing.

    Note: Initiates from a CTG codon.

    Show »
    Length:525
    Mass (Da):59,529
    Checksum:i803967415A2F57FC
    GO

    Sequence cautioni

    The sequence AAA52643.1 differs from that shown. Reason: Frameshift at position 20.
    The sequence BAF82585.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti24 – 241C → S in AAA52643. (PubMed:3496523)Curated
    Sequence conflicti69 – 691N → D in BAF82585. (PubMed:14702039)Curated
    Sequence conflicti144 – 1441W → R in BAB15482. (PubMed:14702039)Curated
    Sequence conflicti168 – 1681F → Y in BAF82585. (PubMed:14702039)Curated
    Sequence conflicti378 – 3781I → T in AAI13855. (PubMed:15489334)Curated
    Sequence conflicti488 – 4881N → S in BAF82585. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti44 – 441A → T.1 Publication
    Corresponds to variant rs56029200 [ dbSNP | Ensembl ].
    VAR_041707
    Natural varianti105 – 1051M → L.2 Publications
    Corresponds to variant rs55722810 [ dbSNP | Ensembl ].
    VAR_041708
    Natural varianti399 – 3991D → G in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication
    VAR_041709
    Natural varianti502 – 5021P → Q.
    Corresponds to variant rs17093828 [ dbSNP | Ensembl ].
    VAR_033836

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 2121Missing in isoform 2 and isoform 3. 3 PublicationsVSP_018858Add
    BLAST
    Alternative sequencei76 – 761Missing in isoform 3 and isoform 4. 2 PublicationsVSP_041926

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M16591 mRNA. Translation: AAA52643.1. Frameshift.
    M16592 mRNA. Translation: AAA52644.1.
    AK026432 mRNA. Translation: BAB15482.1.
    AK289896 mRNA. Translation: BAF82585.1. Different initiation.
    AK298726 mRNA. Translation: BAG60878.1.
    AL353092, AL049539 Genomic DNA. Translation: CAI19694.1.
    AL353092, AL049539 Genomic DNA. Translation: CAI19695.1.
    AL049539, AL353092 Genomic DNA. Translation: CAI22966.1.
    AL049539, AL353092 Genomic DNA. Translation: CAI22967.1.
    CH471077 Genomic DNA. Translation: EAW76392.1.
    CH471077 Genomic DNA. Translation: EAW76393.1.
    BC014435 mRNA. Translation: AAH14435.2.
    BC094847 mRNA. Translation: AAH94847.2.
    BC108930 mRNA. Translation: AAI08931.2.
    BC108931 mRNA. Translation: AAI08932.2.
    BC113854 mRNA. Translation: AAI13855.2.
    BC114463 mRNA. Translation: AAI14464.2.
    X58741, X58742, X58743 Genomic DNA. Translation: CAA41565.2.
    CCDSiCCDS33460.1. [P08631-1]
    CCDS54453.1. [P08631-4]
    CCDS54455.1. [P08631-2]
    CCDS54456.1. [P08631-3]
    PIRiA27811. TVHUHC.
    A41263.
    RefSeqiNP_001165600.1. NM_001172129.1. [P08631-2]
    NP_001165601.1. NM_001172130.1. [P08631-4]
    NP_001165602.1. NM_001172131.1. [P08631-3]
    NP_001165604.1. NM_001172133.1. [P08631-2]
    NP_002101.2. NM_002110.3. [P08631-1]
    UniGeneiHs.655210.

    Genome annotation databases

    EnsembliENST00000518730; ENSP00000427757; ENSG00000101336. [P08631-3]
    ENST00000520553; ENSP00000429848; ENSG00000101336. [P08631-2]
    ENST00000538448; ENSP00000441169; ENSG00000101336. [P08631-2]
    GeneIDi3055.
    KEGGihsa:3055.
    UCSCiuc002wxh.3. human. [P08631-1]
    uc002wxi.3. human. [P08631-3]

    Polymorphism databases

    DMDMi20141296.

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M16591 mRNA. Translation: AAA52643.1 . Frameshift.
    M16592 mRNA. Translation: AAA52644.1 .
    AK026432 mRNA. Translation: BAB15482.1 .
    AK289896 mRNA. Translation: BAF82585.1 . Different initiation.
    AK298726 mRNA. Translation: BAG60878.1 .
    AL353092 , AL049539 Genomic DNA. Translation: CAI19694.1 .
    AL353092 , AL049539 Genomic DNA. Translation: CAI19695.1 .
    AL049539 , AL353092 Genomic DNA. Translation: CAI22966.1 .
    AL049539 , AL353092 Genomic DNA. Translation: CAI22967.1 .
    CH471077 Genomic DNA. Translation: EAW76392.1 .
    CH471077 Genomic DNA. Translation: EAW76393.1 .
    BC014435 mRNA. Translation: AAH14435.2 .
    BC094847 mRNA. Translation: AAH94847.2 .
    BC108930 mRNA. Translation: AAI08931.2 .
    BC108931 mRNA. Translation: AAI08932.2 .
    BC113854 mRNA. Translation: AAI13855.2 .
    BC114463 mRNA. Translation: AAI14464.2 .
    X58741 , X58742 , X58743 Genomic DNA. Translation: CAA41565.2 .
    CCDSi CCDS33460.1. [P08631-1 ]
    CCDS54453.1. [P08631-4 ]
    CCDS54455.1. [P08631-2 ]
    CCDS54456.1. [P08631-3 ]
    PIRi A27811. TVHUHC.
    A41263.
    RefSeqi NP_001165600.1. NM_001172129.1. [P08631-2 ]
    NP_001165601.1. NM_001172130.1. [P08631-4 ]
    NP_001165602.1. NM_001172131.1. [P08631-3 ]
    NP_001165604.1. NM_001172133.1. [P08631-2 ]
    NP_002101.2. NM_002110.3. [P08631-1 ]
    UniGenei Hs.655210.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AD5 X-ray 2.60 A/B 79-526 [» ]
    1BU1 X-ray 2.60 A/B/C/D/E/F 81-137 [» ]
    1QCF X-ray 2.00 A 81-526 [» ]
    2C0I X-ray 2.30 A/B 81-526 [» ]
    2C0O X-ray 2.85 A/B 81-526 [» ]
    2C0T X-ray 2.15 A/B 81-526 [» ]
    2HCK X-ray 3.00 A/B 79-526 [» ]
    2HK5 X-ray 2.00 A 247-514 [» ]
    2OI3 NMR - A 61-141 [» ]
    2OJ2 NMR - A 61-141 [» ]
    3HCK NMR - A 140-245 [» ]
    3NHN X-ray 2.61 A 72-256 [» ]
    3RBB X-ray 2.35 B/D 79-138 [» ]
    3REA X-ray 2.00 B/D 79-138 [» ]
    3REB X-ray 3.45 B/D 79-138 [» ]
    3VRY X-ray 2.48 A/B 81-526 [» ]
    3VRZ X-ray 2.22 A/B 81-526 [» ]
    3VS0 X-ray 2.93 A/B 81-526 [» ]
    3VS1 X-ray 2.46 A/B 81-526 [» ]
    3VS2 X-ray 2.61 A/B 81-526 [» ]
    3VS3 X-ray 2.17 A/B 81-526 [» ]
    3VS4 X-ray 2.75 A/B 81-526 [» ]
    3VS5 X-ray 2.85 A/B 81-526 [» ]
    3VS6 X-ray 2.37 A/B 81-526 [» ]
    3VS7 X-ray 3.00 A/B 81-526 [» ]
    4HCK NMR - A 72-143 [» ]
    4LUD X-ray 2.85 A/B 81-526 [» ]
    4LUE X-ray 3.04 A/B 81-526 [» ]
    4ORZ X-ray 2.00 A 77-138 [» ]
    5HCK NMR - A 72-143 [» ]
    ProteinModelPortali P08631.
    SMRi P08631. Positions 49-526.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109305. 44 interactions.
    DIPi DIP-1051N.
    IntActi P08631. 58 interactions.
    MINTi MINT-135300.

    Chemistry

    BindingDBi P08631.
    ChEMBLi CHEMBL3234.
    GuidetoPHARMACOLOGYi 2032.

    PTM databases

    PhosphoSitei P08631.

    Polymorphism databases

    DMDMi 20141296.

    Proteomic databases

    MaxQBi P08631.
    PaxDbi P08631.
    PRIDEi P08631.

    Protocols and materials databases

    DNASUi 3055.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000518730 ; ENSP00000427757 ; ENSG00000101336 . [P08631-3 ]
    ENST00000520553 ; ENSP00000429848 ; ENSG00000101336 . [P08631-2 ]
    ENST00000538448 ; ENSP00000441169 ; ENSG00000101336 . [P08631-2 ]
    GeneIDi 3055.
    KEGGi hsa:3055.
    UCSCi uc002wxh.3. human. [P08631-1 ]
    uc002wxi.3. human. [P08631-3 ]

    Organism-specific databases

    CTDi 3055.
    GeneCardsi GC20P030648.
    HGNCi HGNC:4840. HCK.
    HPAi CAB005195.
    MIMi 142370. gene.
    neXtProti NX_P08631.
    PharmGKBi PA29216.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi P08631.
    KOi K08893.
    OrthoDBi EOG7GTT2V.
    PhylomeDBi P08631.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    Reactomei REACT_11068. Nef and signal transduction.
    REACT_160274. FCGR activation.
    REACT_23787. Regulation of signaling by CBL.
    SignaLinki P08631.

    Miscellaneous databases

    ChiTaRSi HCK. human.
    EvolutionaryTracei P08631.
    GeneWikii HCK.
    GenomeRNAii 3055.
    NextBioi 12093.
    PROi P08631.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P08631.
    Bgeei P08631.
    Genevestigatori P08631.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells."
      Quintrell N., Lebo R., Varmus H., Bishop J.M., Pettenati M.J., le Beau M.M., Diaz M.O., Rowley J.D.
      Mol. Cell. Biol. 7:2267-2275(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin."
      Ziegler S.F., Marth J.D., Lewis D.B., Perlmutter R.M.
      Mol. Cell. Biol. 7:2276-2285(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), VARIANT LEU-105.
      Tissue: Corpus callosum and Ileal mucosa.
    4. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
      Tissue: B-cell and Lymph.
    7. "Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization."
      Lock P., Ralph S., Stanley E., Boulet I., Ramsay R., Dunn A.R.
      Mol. Cell. Biol. 11:4363-4370(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-21 (ISOFORM 1), ALTERNATIVE INITIATION.
      Tissue: Bone marrow.
    8. "The genomic locus of the human hemopoietic-specific cell protein tyrosine kinase (PTK)-encoding gene (HCK) confirms conservation of exon-intron structure among human PTKs of the src family."
      Hradetzky D., Strebhardt K., Ruesamen-Waigmann H.
      Gene 113:275-280(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-526.
      Tissue: Spleen.
    9. "Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells."
      Ghazizadeh S., Bolen J.B., Fleit H.B.
      J. Biol. Chem. 269:8878-8884(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FCGR2A, CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF FCGR2A.
    10. "Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn."
      Wang A.V., Scholl P.R., Geha R.S.
      J. Exp. Med. 180:1165-1170(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FCGR1A, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, PHOSPHORYLATION.
    11. "The Fc gamma RI receptor signals through the activation of hck and MAP kinase."
      Durden D.L., Kim H.M., Calore B., Liu Y.
      J. Immunol. 154:4039-4047(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN FCGR1A SIGNALING, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ENZYME REGULATION.
    12. "Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae."
      Robbins S.M., Quintrell N.A., Bishop J.M.
      Mol. Cell. Biol. 15:3507-3515(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, ALTERNATIVE INITIATION, MYRISTOYLATION AT GLY-2, PALMITOYLATION, MUTAGENESIS OF GLY-3; GLY-23 AND CYS-24.
    13. "Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines."
      Hallek M., Neumann C., Schaffer M., Danhauser-Riedl S., von Bubnoff N., de Vos G., Druker B.J., Yasukawa K., Griffin J.D., Emmerich B.
      Exp. Hematol. 25:1367-1377(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION, INTERACTION WITH IL6ST.
    14. "Hck is activated by opsonized zymosan and A23187 in distinct subcellular fractions of human granulocytes."
      Welch H., Maridonneau-Parini I.
      J. Biol. Chem. 272:102-109(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
    15. "SH3-mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1."
      Briggs S.D., Sharkey M., Stevenson M., Smithgall T.E.
      J. Biol. Chem. 272:17899-17902(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION, INTERACTION WITH HIV-1 NEF.
    16. "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr."
      Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M.
      J. Biol. Chem. 272:33260-33270(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF BCR, INTERACTION WITH BCR-ABL.
    17. "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase."
      Howlett C.J., Bisson S.A., Resek M.E., Tigley A.W., Robbins S.M.
      Biochem. Biophys. Res. Commun. 257:129-138(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CBL PHOSPHORYLATION; CELL PROLIFERATION AND REGULATION OF CELL SHAPE, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-522, INTERACTION WITH CBL.
    18. "IL-2 signaling in human monocytes involves the phosphorylation and activation of p59hck."
      Bosco M.C., Curiel R.E., Zea A.H., Malabarba M.G., Ortaldo J.R., Espinoza-Delgado I.
      J. Immunol. 164:4575-4585(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL2 SIGNALING, CATALYTIC ACTIVITY, INDUCTION, ENZYME REGULATION, PHOSPHORYLATION.
    19. "Reciprocal regulation of Hck activity by phosphorylation of Tyr(527) and Tyr(416). Effect of introducing a high affinity intramolecular SH2 ligand."
      Porter M., Schindler T., Kuriyan J., Miller W.T.
      J. Biol. Chem. 275:2721-2726(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-411 AND TYR-522, IDENTIFICATION BY MASS SPECTROMETRY, ENZYME REGULATION, MUTAGENESIS OF GLU-305 AND TYR-411.
    20. "Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI."
      Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E., Xu L., Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.
      Nat. Immunol. 1:227-233(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL8-MEDIATED DEGRANULATION, ENZYME REGULATION, INTERACTION WITH ARRB1 AND ARRB2.
    21. "The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral vif protein."
      Hassaine G., Courcoul M., Bessou G., Barthalay Y., Picard C., Olive D., Collette Y., Vigne R., Decroly E.
      J. Biol. Chem. 276:16885-16893(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV-1 VIF.
    22. "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK."
      Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.
      J. Biol. Chem. 276:42389-42400(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
    23. "The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells."
      Klejman A., Schreiner S.J., Nieborowska-Skorska M., Slupianek A., Wilson M., Smithgall T.E., Skorski T.
      EMBO J. 21:5766-5774(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS EFFECTOR OF THE BCR-ABL FUSION PROTEIN IN PHOSPHORYLATION OF STAT5B, INTERACTION WITH STAT5B AND THE BCR-ABL FUSION PROTEIN, PHOSPHORYLATION.
    24. "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases."
      Poghosyan Z., Robbins S.M., Houslay M.D., Webster A., Murphy G., Edwards D.R.
      J. Biol. Chem. 277:4999-5007(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ADAM15, FUNCTION IN PHOSPHORYLATION OF ADAM15.
    25. "p59Hck isoform induces F-actin reorganization to form protrusions of the plasma membrane in a Cdc42- and Rac-dependent manner."
      Carreno S., Caron E., Cougoule C., Emorine L.J., Maridonneau-Parini I.
      J. Biol. Chem. 277:21007-21016(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN REORGANIZATION OF THE ACTIN CYTOSKELETON; FORMATION OF CELL PROTRUSIONS AND PHAGOCYTOSIS (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), MUTAGENESIS OF GLY-3.
    26. "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation."
      Howlett C.J., Robbins S.M.
      Oncogene 21:1707-1716(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL PROLIFERATION, UBIQUITINATION, PHOSPHORYLATION AT TYR-51; TYR-411 AND TYR-522, SUBCELLULAR LOCATION, INTERACTION WITH CBL (ISOFORM 2), MUTAGENESIS OF LYS-290 AND TYR-522.
    27. "Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells."
      Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T., Catley L.P., Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.
      J. Biol. Chem. 279:21658-21665(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL6 SIGNALING CASCADE AND IN PHOSPHORYLATION OF GAB1 AND GAB2.
    28. "Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck."
      Yokoyama N., deBakker C.D., Zappacosta F., Huddleston M.J., Annan R.S., Ravichandran K.S., Miller W.T.
      Biochemistry 44:8841-8849(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF ELMO1, INTERACTION WITH ELMO1.
    29. "Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes."
      Cougoule C., Carreno S., Castandet J., Labrousse A., Astarie-Dequeker C., Poincloux R., Le Cabec V., Maridonneau-Parini I.
      Traffic 6:682-694(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-381.
    30. "HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction."
      Trible R.P., Emert-Sedlak L., Smithgall T.E.
      J. Biol. Chem. 281:27029-27038(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV-1 NEF, ENZYME REGULATION.
    31. "Regulation of p73 by Hck through kinase-dependent and independent mechanisms."
      Paliwal P., Radha V., Swarup G.
      BMC Mol. Biol. 8:45-45(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION AND INHIBITION OF TP73 ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH TP73 AND YAP1.
    32. "Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases."
      Hausherr A., Tavares R., Schaffer M., Obermeier A., Miksch C., Mitina O., Ellwart J., Hallek M., Krause G.
      Oncogene 26:4987-4998(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IL6ST.
    33. "Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
      Voss M., Lettau M., Janssen O.
      BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FASLG.
    34. "The oncogenic activity of the Src family kinase Hck requires the cooperative action of the plasma membrane- and lysosome-associated isoforms."
      Poincloux R., Al Saati T., Maridonneau-Parini I., Le Cabec V.
      Eur. J. Cancer 45:321-327(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN REORGANIZATION OF ACTIN CYTOSKELETON AND CELL PROLIFERATION, ROLE IN DISEASE.
    35. "Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins."
      Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.
      J. Cell. Biochem. 108:877-885(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ADAM15.
    36. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND SER-462, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    37. "c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration."
      Baruzzi A., Iacobucci I., Soverini S., Lowell C.A., Martinelli G., Berton G.
      FEBS Lett. 584:15-21(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ABL1-MEDIATED CELL MIGRATION, IDENTIFICATION IN A COMPLEX WITH ITGB1 AND WITH ABL1.
    38. "Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner."
      Pene-Dumitrescu T., Smithgall T.E.
      J. Biol. Chem. 285:21446-21457(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: ROLE IN DISEASE, FUNCTION IN PHOSPHORYLATION OF THE BCR-ABL FUSION PROTEIN.
    39. "Hematopoietic cell kinase (Hck) isoforms and phagocyte duties - from signaling and actin reorganization to migration and phagocytosis."
      Guiet R., Poincloux R., Castandet J., Marois L., Labrousse A., Le Cabec V., Maridonneau-Parini I.
      Eur. J. Cell Biol. 87:527-542(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON ROLE IN PHAGOCYTOSIS AND SUBSTRATES.
    40. "Protein tyrosine kinases in neutrophil activation and recruitment."
      Zarbock A., Ley K.
      Arch. Biochem. Biophys. 510:112-119(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: ROLE IN NEUTROPHIL FUNCTION, SIGNALING.
    41. "Sequential assignment and secondary structure determination for the Src homology 2 domain of hematopoietic cellular kinase."
      Zhang W., Smithgall T.E., Gmeiner W.H.
      FEBS Lett. 406:131-135(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 140-245.
    42. "Crystal structure of the Src family tyrosine kinase Hck."
      Sicheri F., Moarefi I., Kuriyan J.
      Nature 385:602-609(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 78-526 IN COMPLEX WITH CALCIUM, PHOSPHORYLATION AT TYR-522.
    43. "RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef."
      Arold S., O'Brien R., Franken P., Strub M.-P., Hoh F., Dumas C., Ladbury J.E.
      Biochemistry 37:14683-14691(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 81-137.
    44. "Solution structure of the human Hck SH3 domain and identification of its ligand binding site."
      Horita D.A., Baldisseri D.M., Zhang W., Altieri A.S., Smithgall T.E., Gmeiner W.H., Byrd R.A.
      J. Mol. Biol. 278:253-265(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 72-143.
    45. "Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor."
      Schindler T., Sicheri F., Pico A., Gazit A., Levitzki A., Kuriyan J.
      Mol. Cell 3:639-648(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 81-522 IN COMPLEX WITH THE PYRAZOLO PYRIMIDINE-TYPE INHIBITOR PP1, PHOSPHORYLATION AT TYR-522.
    46. "Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection."
      Burchat A., Borhani D.W., Calderwood D.J., Hirst G.C., Li B., Stachlewitz R.F.
      Bioorg. Med. Chem. Lett. 16:118-122(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 81-522 IN COMPLEXES WITH INHIBITORS A-420983; A-641359 AND A-770041, ENZYME REGULATION, PHOSPHORYLATION AT TYR-522.
    47. "The development of 2-benzimidazole substituted pyrimidine based inhibitors of lymphocyte specific kinase (Lck)."
      Sabat M., VanRens J.C., Laufersweiler M.J., Brugel T.A., Maier J., Golebiowski A., De B., Easwaran V., Hsieh L.C., Walter R.L., Mekel M.J., Evdokimov A., Janusz M.J.
      Bioorg. Med. Chem. Lett. 16:5973-5977(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 247-513 IN COMPLEX WITH INHIBITOR PG-1009247.
    48. "Solution structure of a Hck SH3 domain ligand complex reveals novel interaction modes."
      Schmidt H., Hoffmann S., Tran T., Stoldt M., Stangler T., Wiesehan K., Willbold D.
      J. Mol. Biol. 365:1517-1532(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 61-140 IN COMPLEX WITH PROLINE-RICH SYNTHETIC PEPTIDE.
    49. "Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism."
      Alvarado J.J., Betts L., Moroco J.A., Smithgall T.E., Yeh J.I.
      J. Biol. Chem. 285:35455-35461(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 72-256, ENZYME REGULATION, CATALYTIC ACTIVITY.
    50. "Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef."
      Breuer S., Schievink S.I., Schulte A., Blankenfeldt W., Fackler O.T., Geyer M.
      PLoS ONE 6:E20033-E20033(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 79-138 IN COMPLEX WITH HIV-1 NEF, INTERACTION WITH HIV-1 NEF.
    51. "Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by intermolecular domain assembly."
      Horenkamp F.A., Breuer S., Schulte A., Lulf S., Weyand M., Saksela K., Geyer M.
      Traffic 12:867-877(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 79-138 IN COMPLEX WITH HIV-1 NEF, INTERACTION WITH HIV-1 NEF.
    52. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-44; LEU-105 AND GLY-399.

    Entry informationi

    Entry nameiHCK_HUMAN
    AccessioniPrimary (citable) accession number: P08631
    Secondary accession number(s): A8K1I1
    , B4DQB6, E1P5M2, Q29RX1, Q2VPE2, Q504R5, Q5T7K1, Q5T7K2, Q96CC0, Q9H5Y5, Q9NUA4, Q9UMJ5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 196 of the entry and version 5 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3