SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

P50545

- HCK_RAT

UniProt

P50545 - HCK_RAT

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein
Tyrosine-protein kinase HCK
Gene
Hck
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei288 – 2881ATP By similarity
Active sitei379 – 3791Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi266 – 2749ATP By similarity

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
Complete GO annotation...

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; 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.
Isoform 2 : Cell membrane; Lipid-anchor. Membranecaveola; 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.

GO - Cellular componenti

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

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 – 11Removed By similarity
Chaini2 – 524523Tyrosine-protein kinase HCK
PRO_0000088104Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine By similarity
Modified residuei50 – 501Phosphotyrosine; by autocatalysis By similarity
Modified residuei200 – 2001Phosphothreonine By similarity
Modified residuei207 – 2071Phosphotyrosine By similarity
Modified residuei409 – 4091Phosphotyrosine; by autocatalysis By similarity
Modified residuei460 – 4601Phosphoserine By similarity
Modified residuei520 – 5201Phosphotyrosine By 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.
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.

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.1 Publication

Structurei

3D structure databases

ProteinModelPortaliP50545.
SMRiP50545. Positions 80-524.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini76 – 13661SH3
Add
BLAST
Domaini142 – 23998SH2
Add
BLAST
Domaini260 – 513254Protein kinase
Add
BLAST

Sequence similaritiesi

Contains 1 SH2 domain.
Contains 1 SH3 domain.

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).

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.

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2 – 2120Missing in isoform 2.
VSP_022248Add
BLAST

Sequence conflict

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

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 137 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

Similar proteinsi