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Protein

Tyrosine-protein kinase HCK

Gene

HCK

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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).By similarity

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-389 is required for optimal activity. Phosphorylation at Tyr-500 inhibits kinase activity (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei268ATP1
Active sitei359Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi246 – 254ATP9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase, Tyrosine-protein kinase
Biological processExocytosis, Immunity, Inflammatory response, Innate immunity, Phagocytosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.2. 1793.

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
Gene namesi
Name:HCK
OrganismiMacaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Taxonomic identifieri9541 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Golgi apparatus, Lysosome, Membrane, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000881032 – 504Tyrosine-protein kinase HCKAdd BLAST503

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteineBy similarity1
Modified residuei15PhosphothreonineBy similarity1
Modified residuei30PhosphotyrosineBy similarity1
Modified residuei180PhosphothreonineBy similarity1
Modified residuei187PhosphotyrosineBy similarity1
Modified residuei389Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei440PhosphoserineBy similarity1
Modified residuei500PhosphotyrosineBy similarity1

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ95M30.

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. Interacts (via SH3 domain) with WDCP.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ95M30.
SMRiQ95M30.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 116SH3Add BLAST61
Domaini122 – 219SH2Add BLAST98
Domaini240 – 493Protein kinaseAdd BLAST254

Sequence similaritiesi

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

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

HOVERGENiHBG008761.
KOiK08893.

Family and domain databases

CDDicd10363. SH2_Src_HCK. 1 hit.
Gene3Di3.30.505.10. 1 hit.
InterProiView protein in InterPro
IPR035851. HCK_SH2.
IPR011009. Kinase-like_dom_sf.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR000980. SH2.
IPR036860. SH2_dom_sf.
IPR036028. SH3-like_dom_sf.
IPR001452. SH3_domain.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
PfamiView protein in Pfam
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
PRINTSiPR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
PR00109. TYRKINASE.
SMARTiView protein in SMART
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
SUPFAMiSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiView protein in 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.

Sequencei

Sequence statusi: Complete.

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

Q95M30-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGCMKSKFLQ AGGNTFSKTE TSANPHCPVY VPDPTSTIKP GPNSNNRNTP
60 70 80 90 100
GIGEGSEDII VVALYDYEAI HHEDLSFQKG DQMVVLEESG EWWKARSLAT
110 120 130 140 150
RKEGYIPSNY VARVDSLETE EWFFKGISRK DAERQLLAPG NMLGSFMIRD
160 170 180 190 200
SETTKGSYSL SVRDYDPRQG DTVKHYKIRT LDNGGFYISP RSTFSTLQEL
210 220 230 240 250
VDHYKKGSDG LCQKLSVPCV SSKPQKPWEK DAWEIPRESL KLEKKLGAGQ
260 270 280 290 300
FGEVWMATYN KHTKVAVKTM KPGSMSVEAF LAEANLMKTL QHDKLVKLHA
310 320 330 340 350
VVTKEPIYII TEFMAKGSLL DFLKSDEGSK QPLPKLIDFS AQIAEGMAFI
360 370 380 390 400
EQRNYIHRDL RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK
410 420 430 440 450
WTAPEAINFG SSTIKSDVWS FGILLMEIVT YGRIPYPGMS NPEVIRALER
460 470 480 490 500
GYRMPRPENC PEELYNIMMR CWKNRPEERP TFEYIQSVLD DFYTATESQY

QQQP
Length:504
Mass (Da):57,096
Last modified:January 23, 2007 - v3
Checksum:i53B29322D2DE3423
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ320181 mRNA. Translation: CAC44031.1.
RefSeqiNP_001306372.1. NM_001319443.1.
UniGeneiMfa.6652.

Genome annotation databases

GeneIDi102115729.
KEGGimcf:102115729.

Similar proteinsi

Entry informationi

Entry nameiHCK_MACFA
AccessioniPrimary (citable) accession number: Q95M30
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: January 23, 2007
Last modified: November 22, 2017
This is version 115 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families