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Q95M30 (HCK_MACFA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 97. 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·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
Gene names
Name:HCK
OrganismMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Taxonomic identifier9541 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

Protein attributes

Sequence length504 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript 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.

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-389 is required for optimal activity. Phosphorylation at Tyr-500 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.

Subcellular location

Cytoplasmic vesiclesecretory vesicle By similarity. Cytoplasmcytosol By similarity. 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 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.

Post-translational modification

Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-389 increases kinase activity. Phosphorylation at Tyr-500 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-500, 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.

Palmitoylation requires prior myristoylation. Palmitoylation is required for caveolar localization 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.

Ontologies

Keywords
   Biological processExocytosis
Immunity
Inflammatory response
Innate immunity
Phagocytosis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoplasmic vesicle
Cytoskeleton
Golgi apparatus
Lysosome
Membrane
Nucleus
   DiseaseProto-oncogene
   DomainSH2 domain
SH3 domain
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
Ubl conjugation
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

peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

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

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...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 504503Tyrosine-protein kinase HCK
PRO_0000088103

Regions

Domain56 – 11661SH3
Domain122 – 21998SH2
Domain240 – 493254Protein kinase
Nucleotide binding246 – 2549ATP By similarity

Sites

Active site3591Proton acceptor By similarity
Binding site2681ATP By similarity

Amino acid modifications

Modified residue301Phosphotyrosine By similarity
Modified residue1801Phosphothreonine By similarity
Modified residue1871Phosphotyrosine By similarity
Modified residue3891Phosphotyrosine; by autocatalysis By similarity
Modified residue4401Phosphoserine By similarity
Modified residue5001Phosphotyrosine By similarity
Lipidation21N-myristoyl glycine By similarity
Lipidation31S-palmitoyl cysteine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q95M30 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 53B29322D2DE3423

FASTA50457,096
        10         20         30         40         50         60 
MGCMKSKFLQ AGGNTFSKTE TSANPHCPVY VPDPTSTIKP GPNSNNRNTP GIGEGSEDII 

        70         80         90        100        110        120 
VVALYDYEAI HHEDLSFQKG DQMVVLEESG EWWKARSLAT RKEGYIPSNY VARVDSLETE 

       130        140        150        160        170        180 
EWFFKGISRK DAERQLLAPG NMLGSFMIRD SETTKGSYSL SVRDYDPRQG DTVKHYKIRT 

       190        200        210        220        230        240 
LDNGGFYISP RSTFSTLQEL VDHYKKGSDG LCQKLSVPCV SSKPQKPWEK DAWEIPRESL 

       250        260        270        280        290        300 
KLEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF LAEANLMKTL QHDKLVKLHA 

       310        320        330        340        350        360 
VVTKEPIYII TEFMAKGSLL DFLKSDEGSK QPLPKLIDFS AQIAEGMAFI EQRNYIHRDL 

       370        380        390        400        410        420 
RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK WTAPEAINFG SSTIKSDVWS 

       430        440        450        460        470        480 
FGILLMEIVT YGRIPYPGMS NPEVIRALER GYRMPRPENC PEELYNIMMR CWKNRPEERP 

       490        500 
TFEYIQSVLD DFYTATESQY QQQP 

« Hide

References

[1]Picard C.
Thesis (2001), University of Marseille, France
Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ320181 mRNA. Translation: CAC44031.1.

3D structure databases

ProteinModelPortalQ95M30.
SMRQ95M30. Positions 56-504.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEQ95M30.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG008761.

Enzyme and pathway databases

BRENDA2.7.10.2. 3121.

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.
SSF55550. SSF55550. 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...

Entry information

Entry nameHCK_MACFA
AccessionPrimary (citable) accession number: Q95M30
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 97 of the entry and version 3 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