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Q95M30

- HCK_MACFA

UniProt

Q95M30 - HCK_MACFA

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Protein

Tyrosine-protein kinase HCK

Gene

HCK

Organism
Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)
Status
Reviewed - 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.PROSITE-ProRule annotation

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei268 – 2681ATPPROSITE-ProRule annotation
Active sitei359 – 3591Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi246 – 2549ATPPROSITE-ProRule annotation

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. 3121.

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

Cytoplasmic vesiclesecretory vesicle By similarity. Cytoplasmcytosol By similarity. Cell membrane; Lipid-anchor. Membranecaveola By similarity; 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).By similarity

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. cytoplasmic vesicle Source: UniProtKB-KW
  3. cytoskeleton Source: UniProtKB-KW
  4. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  5. Golgi apparatus Source: UniProtKB-KW
  6. lysosome Source: UniProtKB
  7. nucleus Source: UniProtKB-KW
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 504503Tyrosine-protein kinase HCKPRO_0000088103Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Lipidationi3 – 31S-palmitoyl cysteineBy similarity
Modified residuei30 – 301PhosphotyrosineBy similarity
Modified residuei180 – 1801PhosphothreonineBy similarity
Modified residuei187 – 1871PhosphotyrosineBy similarity
Modified residuei389 – 3891Phosphotyrosine; by autocatalysisBy similarity
Modified residuei440 – 4401PhosphoserineBy similarity
Modified residuei500 – 5001PhosphotyrosineBy 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-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 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ95M30.
SMRiQ95M30. Positions 56-504.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini56 – 11661SH3PROSITE-ProRule annotationAdd
BLAST
Domaini122 – 21998SH2PROSITE-ProRule annotationAdd
BLAST
Domaini240 – 493254Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

HOVERGENiHBG008761.

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]

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortali Q95M30.
SMRi Q95M30. Positions 56-504.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PRIDEi Q95M30.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG008761.

Enzyme and pathway databases

BRENDAi 2.7.10.2. 3121.

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

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

Entry informationi

Entry nameiHCK_MACFA
AccessioniPrimary (citable) accession number: Q95M30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3