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P50545 (HCK_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase HCK

EC=2.7.10.2
Alternative name(s):
Hematopoietic cell kinase
Hemopoietic cell kinase
p56-HCK
p56Hck
p59Hck
Gene names
Name:Hck
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length524 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

Catalytic activity

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

Enzyme regulation

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.

Subunit structure

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. Ref.4

Subcellular location

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 isfound 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 isassociated 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.

Tissue specificity

Expressed strongly in spleen and at very low levels in thymus. Ref.2

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Sequence caution

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.

Ontologies

Keywords
   Biological processExocytosis
Immunity
Inflammatory response
Innate immunity
Phagocytosis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Golgi apparatus
Lysosome
Membrane
Nucleus
   Coding sequence diversityAlternative initiation
   DiseaseProto-oncogene
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processexocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

phagocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell shape

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of phagocytosis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of podosome assembly

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell projection

Inferred from electronic annotation. Source: UniProtKB-KW

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

extrinsic component of cytoplasmic side of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

focal adhesion

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosome

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

transport vesicle

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein tyrosine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform 1 (identifier: P50545-1)

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.
Isoform 2 (identifier: P50545-2)

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).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 524523Tyrosine-protein kinase HCK
PRO_0000088104

Regions

Domain76 – 13661SH3
Domain142 – 23998SH2
Domain260 – 513254Protein kinase
Nucleotide binding266 – 2749ATP By similarity

Sites

Active site3791Proton acceptor By similarity
Binding site2881ATP By similarity

Amino acid modifications

Modified residue501Phosphotyrosine; by autocatalysis By similarity
Modified residue2001Phosphothreonine By similarity
Modified residue2071Phosphotyrosine By similarity
Modified residue4091Phosphotyrosine; by autocatalysis By similarity
Modified residue4601Phosphoserine By similarity
Modified residue5201Phosphotyrosine By similarity
Lipidation21N-myristoyl glycine By similarity

Natural variations

Alternative sequence2 – 2120Missing in isoform 2.
VSP_022248

Experimental info

Sequence conflict721V → F in AAA41312. Ref.1
Sequence conflict721V → F in AAB20754. Ref.1
Sequence conflict2261K → R in CAA44218. Ref.2
Sequence conflict3271I → T in CAA44218. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (p59-HCK) [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: BBD928C9E717BF4B

FASTA52459,154
        10         20         30         40         50         60 
MGGRSSCEDP GCPRGEGRVP RMGCVKSRFL REGSKASKIE PNANQKGPVY VPDPTSPKKL 

        70         80         90        100        110        120 
GPNSINSLPP GVVEGSEDTI VVALYDYEAI HREDLSFQKG DQMVVLEESG EWWKARSLAT 

       130        140        150        160        170        180 
KKEGYIPSNY VARVNSLETE EWFFKGISRK DAERHLLAPG NMLGSFMIRD SETTKGSYSL 

       190        200        210        220        230        240 
SVRDFDPQHG DTVKHYKIRT LDSGGFYISP RSTFSSLQEL VVHYKKGKDG LCQKLSVPCV 

       250        260        270        280        290        300 
SPKPQKPWEK DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF 

       310        320        330        340        350        360 
LAEANLMKTL QHDKLVKLHA VVSQEPIFIV TEFMAKGSLL DFLKSEEGSK QPLPKLIDFS 

       370        380        390        400        410        420 
AQISEGMAFI EQRNYIHRDL RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK 

       430        440        450        460        470        480 
WTAPEAINFG SFTIKSDVWS FGILLMEIVT YGRIPYPGMS NPEVIRALEH GYRMPRPDNC 

       490        500        510        520 
PEELYSIMIR CWKNRPEERP TFEYIQSVLD DFYTATESQY QQQP 

« Hide

Isoform 2 (p56-HCK) [UniParc].

Checksum: A8E00777FF3AAC8C
Show »

FASTA50457,099

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRJQ1321.
RefSeqNP_037317.2. NM_013185.3.
UniGeneRn.10945.

3D structure databases

ProteinModelPortalP50545.
SMRP50545. Positions 80-524.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP50545.

Proteomic databases

PaxDbP50545.
PRIDEP50545.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25734.
KEGGrno:25734.
UCSCRGD:2785. rat. [P50545-1]

Organism-specific databases

CTD3055.
RGD2785. Hck.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233858.
HOVERGENHBG008761.
InParanoidP50545.
KOK08893.

Enzyme and pathway databases

BRENDA2.7.10.2. 5301.

Gene expression databases

GenevestigatorP50545.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR011009. 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]
PfamPF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTSM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. 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]
ProtoNetSearch...

Other

NextBio607867.
PROP50545.

Entry information

Entry nameHCK_RAT
AccessionPrimary (citable) accession number: P50545
Secondary accession number(s): Q64647, Q6AYV7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 134 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families