Tyrosine-protein kinase HCK - Macaca fascicularis (Crab-eating macaque)

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Q95M30 (HCK_MACFA) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 83. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)

Taxonomic identifier

9541 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca

Protein attributes

Sequence length	504 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 vesicle › secretory vesicle By similarity. Cytoplasm › cytosol By similarity. Cell membrane; Lipid-anchor. Membrane › caveola; Lipid-anchor By similarity. Cell junction › focal adhesion By similarity. Cytoplasm › cytoskeleton 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 serveral 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. Palmytoylation requires prior myristoylation. Palmytoylation 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 process	Exocytosis Immunity Inflammatory response Innate immunity Phagocytosis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoplasmic vesicle Cytoskeleton Golgi apparatus Lysosome Membrane Nucleus
Disease	Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB 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 component	caveola Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB lysosome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

Removed By similarity

Chain

2 – 504

503

Tyrosine-protein kinase HCK

PRO_0000088103

Regions

Domain

56 – 116

SH3

Domain

122 – 219

SH2

Domain

240 – 493

254

Protein kinase

Nucleotide binding

246 – 254

ATP By similarity

Sites

Active site

359

Proton acceptor By similarity

Binding site

268

ATP By similarity

Amino acid modifications

Modified residue

Phosphothreonine By similarity

Modified residue

Phosphotyrosine By similarity

Modified residue

105

Phosphotyrosine By similarity

Modified residue

180

Phosphothreonine By similarity

Modified residue

187

Phosphotyrosine By similarity

Modified residue

308

Phosphotyrosine By similarity

Modified residue

389

Phosphotyrosine; by autocatalysis By similarity

Modified residue

440

Phosphoserine By similarity

Modified residue

493

Phosphotyrosine By similarity

Modified residue

498

Phosphoserine By similarity

Modified residue

500

Phosphotyrosine By similarity

Lipidation

N-myristoyl glycine By similarity

Lipidation

S-palmitoyl cysteine By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q95M30 [UniParc].

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

504

57,096

        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

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References

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

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ320181 mRNA. Translation: CAC44031.1.
3D structure databases
ProteinModelPortal	Q95M30.
SMR	Q95M30. Positions 56-504.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Phylogenomic databases
HOVERGEN	HBG008761.
Enzyme and pathway databases
BRENDA	2.7.10.2. 3121.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase. IPR000980. SH2. IPR001452. SH3_domain. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
Gene3D	G3DSA:3.30.505.10. SH2. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	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]
ProtoNet	Search...

Entry information

Entry name

HCK_MACFA

Accession

Primary (citable) accession number: Q95M30

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 23, 2002
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 83 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protocols and materials databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Entry information

Relevant documents