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P50545

- HCK_RAT

UniProt

P50545 - HCK_RAT

Protein

Tyrosine-protein kinase HCK

Gene

Hck

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 4 (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 By similarity.By similarity

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-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-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei288 – 2881ATPPROSITE-ProRule annotation
    Active sitei379 – 3791Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi266 – 2749ATPPROSITE-ProRule annotation

    GO - Molecular functioni

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

    GO - Biological processi

    1. exocytosis Source: UniProtKB-KW
    2. inflammatory response Source: UniProtKB-KW
    3. innate immune response Source: UniProtKB-KW
    4. peptidyl-tyrosine phosphorylation Source: UniProtKB
    5. phagocytosis Source: UniProtKB-KW
    6. positive regulation of actin cytoskeleton reorganization Source: UniProtKB
    7. positive regulation of cell proliferation Source: UniProtKB
    8. protein autophosphorylation Source: UniProtKB
    9. regulation of cell shape Source: UniProtKB
    10. regulation of phagocytosis Source: UniProtKB
    11. regulation of podosome assembly Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Exocytosis, Immunity, Inflammatory response, Innate immunity, Phagocytosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 5301.
    ReactomeiREACT_196225. Regulation of signaling by CBL.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase HCK (EC:2.7.10.2)
    Alternative name(s):
    Hematopoietic cell kinase
    Hemopoietic cell kinase
    p56-HCK
    p56Hck
    p59Hck
    Gene namesi
    Name:Hck
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi2785. Hck.

    Subcellular locationi

    Cytoplasmic vesiclesecretory vesicle By similarity. Cytoplasmcytosol By similarity
    Isoform 1 : Membrane; Lipid-anchor. Membranecaveola By similarity. Lysosome By similarity. Cell projectionpodosome membrane By similarity; Lipid-anchor By similarity. Cytoplasmcytosol By similarity
    Note: Associated with specialized secretory lysosomes called azurophil granules. A fraction of this isoform is found in the cytoplasm, some of this fraction is myristoylated By similarity.By similarity
    Isoform 2 : Cell membrane; Lipid-anchor. Membranecaveola By similarity; Lipid-anchor By similarity. Cell junctionfocal adhesion By similarity. Cytoplasmcytoskeleton By similarity. Golgi apparatus By similarity. Cytoplasmic vesicle By similarity. Lysosome By similarity. Nucleus By similarity
    Note: A small fraction 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 By similarity.By similarity

    GO - Cellular componenti

    1. caveola Source: UniProtKB-SubCell
    2. cell projection Source: UniProtKB-KW
    3. cytoskeleton Source: UniProtKB-SubCell
    4. cytosol Source: UniProtKB-SubCell
    5. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
    6. focal adhesion Source: UniProtKB-SubCell
    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

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 524523Tyrosine-protein kinase HCKPRO_0000088104Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity
    Modified residuei50 – 501Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei200 – 2001PhosphothreonineBy similarity
    Modified residuei207 – 2071PhosphotyrosineBy similarity
    Modified residuei409 – 4091Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei460 – 4601PhosphoserineBy similarity
    Modified residuei520 – 5201PhosphotyrosineBy similarity

    Post-translational modificationi

    Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-409 increases kinase activity. Phosphorylation at Tyr-520 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-520, suggesting that this site may be a target of other kinases By similarity.By similarity
    Ubiquitinated by CBL, leading to its degradation via the proteasome.By similarity
    Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2 By similarity.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiP50545.
    PRIDEiP50545.

    PTM databases

    PhosphoSiteiP50545.

    Expressioni

    Tissue specificityi

    Expressed strongly in spleen and at very low levels in thymus.1 Publication

    Gene expression databases

    GenevestigatoriP50545.

    Interactioni

    Subunit structurei

    Interacts with ADAM15. Interacts with FASLG. Interacts with ARRB1 and ARRB2. 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. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP50545.
    SMRiP50545. Positions 80-524.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini76 – 13661SH3PROSITE-ProRule annotationAdd
    BLAST
    Domaini142 – 23998SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini260 – 513254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    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.
    InParanoidiP50545.
    KOiK08893.
    PhylomeDBiP50545.

    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 (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative initiation. Align

    Isoform 1 (identifier: P50545-1) [UniParc]FASTAAdd to Basket

    Also known as: p59-HCK

    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 GCPRGEGRVP RMGCVKSRFL REGSKASKIE PNANQKGPVY    50
    VPDPTSPKKL GPNSINSLPP GVVEGSEDTI VVALYDYEAI HREDLSFQKG 100
    DQMVVLEESG EWWKARSLAT KKEGYIPSNY VARVNSLETE EWFFKGISRK 150
    DAERHLLAPG NMLGSFMIRD SETTKGSYSL SVRDFDPQHG DTVKHYKIRT 200
    LDSGGFYISP RSTFSSLQEL VVHYKKGKDG LCQKLSVPCV SPKPQKPWEK 250
    DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF 300
    LAEANLMKTL QHDKLVKLHA VVSQEPIFIV TEFMAKGSLL DFLKSEEGSK 350
    QPLPKLIDFS AQISEGMAFI EQRNYIHRDL RAANILVSAS LVCKIADFGL 400
    ARIIEDNEYT AREGAKFPIK WTAPEAINFG SFTIKSDVWS FGILLMEIVT 450
    YGRIPYPGMS NPEVIRALEH GYRMPRPDNC PEELYSIMIR CWKNRPEERP 500
    TFEYIQSVLD DFYTATESQY QQQP 524
    Length:524
    Mass (Da):59,154
    Last modified:January 23, 2007 - v4
    Checksum:iBBD928C9E717BF4B
    GO
    Isoform 2 (identifier: P50545-2) [UniParc]FASTAAdd to Basket

    Also known as: p56-HCK

    The sequence of this isoform differs from the canonical sequence as follows:
         2-21: Missing.

    Note: Initiator Met-1 is removed. Contains a N-myristoyl glycine at position 2 (By similarity). Contains a S-palmitoyl cysteine at position 3 (By similarity).By similarity

    Show »
    Length:504
    Mass (Da):57,099
    Checksum:iA8E00777FF3AAC8C
    GO

    Sequence cautioni

    The sequence AAA41312.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence AAB20754.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
    The sequence CAA44218.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti72 – 721V → F in AAA41312. (PubMed:1764064)Curated
    Sequence conflicti72 – 721V → F in AAB20754. (PubMed:1764064)Curated
    Sequence conflicti226 – 2261K → R in CAA44218. 1 PublicationCurated
    Sequence conflicti327 – 3271I → T in CAA44218. 1 PublicationCurated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei2 – 2120Missing in isoform 2. 3 PublicationsVSP_022248Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M83666 mRNA. Translation: AAA41312.1. Different initiation.
    S74141 mRNA. Translation: AAB20754.1. Different initiation.
    X62345 mRNA. Translation: CAA44218.1. Different initiation.
    BC078890 mRNA. Translation: AAH78890.2.
    PIRiJQ1321.
    RefSeqiNP_037317.2. NM_013185.3. [P50545-1]
    UniGeneiRn.10945.

    Genome annotation databases

    GeneIDi25734.
    KEGGirno:25734.
    UCSCiRGD:2785. rat. [P50545-1]

    Keywords - Coding sequence diversityi

    Alternative initiation

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M83666 mRNA. Translation: AAA41312.1 . Different initiation.
    S74141 mRNA. Translation: AAB20754.1 . Different initiation.
    X62345 mRNA. Translation: CAA44218.1 . Different initiation.
    BC078890 mRNA. Translation: AAH78890.2 .
    PIRi JQ1321.
    RefSeqi NP_037317.2. NM_013185.3. [P50545-1 ]
    UniGenei Rn.10945.

    3D structure databases

    ProteinModelPortali P50545.
    SMRi P50545. Positions 80-524.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei P50545.

    Proteomic databases

    PaxDbi P50545.
    PRIDEi P50545.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 25734.
    KEGGi rno:25734.
    UCSCi RGD:2785. rat. [P50545-1 ]

    Organism-specific databases

    CTDi 3055.
    RGDi 2785. Hck.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233858.
    HOVERGENi HBG008761.
    InParanoidi P50545.
    KOi K08893.
    PhylomeDBi P50545.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 5301.
    Reactomei REACT_196225. Regulation of signaling by CBL.

    Miscellaneous databases

    NextBioi 607867.
    PROi P50545.

    Gene expression databases

    Genevestigatori P50545.

    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 rat cDNA encoding hck tyrosine kinase from megakaryocytes."
      Okano Y., Sugimoto Y., Fukuoka M., Matsui A., Nagata K., Nozawa Y.
      Biochem. Biophys. Res. Commun. 181:1137-1144(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Megakaryocyte.
    2. "Nucleotide sequence of a cDNA coding for rat hck tyrosine kinase and characterization of its gene product."
      Vijaya Gouri B.S., Rema V., Kamatkar S., Swarup G.
      J. Biosci. 19:117-129(1994)
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
      Strain: Wistar.
      Tissue: Spleen.
    3. "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] (ISOFORM 2).
      Strain: Brown Norway.
      Tissue: Lung.
    4. "Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain."
      Shivakrupa R., Radha V., Sudhakar C., Swarup G.
      J. Biol. Chem. 278:52188-52194(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RAPGEF1, FUNCTION IN PHOSPHORYLATION OF RAPGEF1.

    Entry informationi

    Entry nameiHCK_RAT
    AccessioniPrimary (citable) accession number: P50545
    Secondary accession number(s): Q64647, Q6AYV7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 138 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3