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Protein

Tyrosine-protein kinase HCK

Gene

Hck

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 similarity13 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation1 Publication

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-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity. Inhibited by PP1.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei288 – 2881ATPPROSITE-ProRule annotation
Active sitei379 – 3791Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi266 – 2749ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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. 3474.
ReactomeiR-MMU-2029481. FCGR activation.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase HCK (EC:2.7.10.2)
Alternative name(s):
B-cell/myeloid kinase
Short name:
BMK
Hematopoietic cell kinase
Hemopoietic cell kinase
p56-HCK/p59-HCK
Gene namesi
Name:Hck
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:96052. Hck.

Subcellular locationi

Isoform 1 :
Isoform 2 :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

No visible phenotype, but macrophages have impaired phagocytosis. Mice lacking both HCK and FGR are extremely sensitive to infections by L.monocytogenes.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi409 – 4091Y → F: Reduced autophosphorylation. 1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 524523Tyrosine-protein kinase HCKPRO_0000024435Add
BLAST
Isoform 2 (identifier: P08103-2)
Initiator methionineiRemovedBy similarity

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Modified residuei50 – 501Phosphotyrosine; by autocatalysis1 Publication
Modified residuei200 – 2001PhosphothreonineBy similarity
Modified residuei207 – 2071PhosphotyrosineCombined sources
Modified residuei409 – 4091Phosphotyrosine; by autocatalysis1 Publication
Modified residuei460 – 4601PhosphoserineBy similarity
Modified residuei520 – 5201PhosphotyrosineCombined sources
Isoform 2 (identifier: P08103-2)
Lipidationi2 – 21N-myristoyl glycine By similarityBy similarity
Lipidationi3 – 31S-palmitoyl cysteine By similarityBy 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-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.1 Publication
Ubiquitinated by CBL, leading to its degradation via the proteasome.
Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2 (By similarity).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP08103.
PaxDbiP08103.
PeptideAtlasiP08103.
PRIDEiP08103.

PTM databases

iPTMnetiP08103.
PhosphoSiteiP08103.
SwissPalmiP08103.

Expressioni

Tissue specificityi

Expressed predominantly in cells of the myeloid and B-lymphoid lineages.

Gene expression databases

BgeeiENSMUSG00000003283.
CleanExiMM_HCK.
ExpressionAtlasiP08103. baseline and differential.
GenevisibleiP08103. MM.

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 (By similarity). 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).By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
WASP427683EBI-6248894,EBI-346375From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200249. 4 interactions.
IntActiP08103. 5 interactions.
MINTiMINT-4097288.
STRINGi10090.ENSMUSP00000003370.

Structurei

3D structure databases

ProteinModelPortaliP08103.
SMRiP08103. Positions 80-524.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini76 – 13661SH3PROSITE-ProRule annotationAdd
BLAST
Domaini142 – 23998SH2PROSITE-ProRule annotationAdd
BLAST
Domaini260 – 513254Protein 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

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP08103.
KOiK08893.
PhylomeDBiP08103.

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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P08103-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGGRSSCEDP GCPRSEGRAP RMGCVKSRFL RDGSKASKTE PSANQKGPVY
60 70 80 90 100
VPDPTSSSKL GPNNSNSMPP GFVEGSEDTI VVALYDYEAI HREDLSFQKG
110 120 130 140 150
DQMVVLEEAG EWWKARSLAT KKEGYIPSNY VARVNSLETE EWFFKGISRK
160 170 180 190 200
DAERHLLAPG NMLGSFMIRD SETTKGSYSL SVRDFDPQHG DTVKHYKIRT
210 220 230 240 250
LDSGGFYISP RSTFSSLQEL VLHYKKGKDG LCQKLSVPCV SPKPQKPWEK
260 270 280 290 300
DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF
310 320 330 340 350
LAEANLMKSL QHDKLVKLHA VVSQEPIFIV TEFMAKGSLL DFLKSEEGSK
360 370 380 390 400
QPLPKLIDFS AQISEGMAFI EQRNYIHRDL RAANILVSAS LVCKIADFGL
410 420 430 440 450
ARIIEDNEYT AREGAKFPIK WTAPEAINFG SFTIKSDVWS FGILLMEIVT
460 470 480 490 500
YGRIPYPGMS NPEVIRALEH GYRMPRPDNC PEELYNIMIR CWKNRPEERP
510 520
TFEYIQSVLD DFYTATESQY QQQP
Note: Initiates from a CTG codon.
Length:524
Mass (Da):59,129
Last modified:January 23, 2007 - v4
Checksum:iDF72FD69B38C9706
GO
Isoform 2 (identifier: P08103-2) [UniParc]FASTAAdd to basket
Also known as: p56-HCK

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Show »
Length:503
Mass (Da):56,942
Checksum:i29E004E0ABA7DF40
GO

Sequence cautioni

The sequence AAA37305 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence BAE29054 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence BAE29445 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence BAE29787 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence BAE33532 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence BAE38133 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence CAA68544 differs from that shown.Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2121Missing in isoform 2. CuratedVSP_018859Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00487 mRNA. Translation: CAA68544.1. Sequence problems.
J03023 mRNA. Translation: AAA37305.1. Sequence problems.
AK149736 mRNA. Translation: BAE29054.1. Sequence problems.
AK150290 mRNA. Translation: BAE29445.1. Sequence problems.
AK150709 mRNA. Translation: BAE29787.1. Sequence problems.
AK155975 mRNA. Translation: BAE33532.1. Sequence problems.
AK165315 mRNA. Translation: BAE38133.1. Sequence problems.
BC010478 mRNA. Translation: AAH10478.2.
CCDSiCCDS38284.1. [P08103-1]
CCDS50756.1. [P08103-2]
PIRiA27282. TVMSHC.
RefSeqiNP_001165588.1. NM_001172117.1. [P08103-2]
NP_034537.2. NM_010407.4. [P08103-1]
XP_011250107.1. XM_011251805.1. [P08103-2]
XP_011250108.1. XM_011251806.1. [P08103-2]
UniGeneiMm.715.

Genome annotation databases

EnsembliENSMUST00000109799; ENSMUSP00000105423; ENSMUSG00000003283. [P08103-2]
ENSMUST00000189688; ENSMUSP00000141030; ENSMUSG00000003283. [P08103-2]
GeneIDi15162.
KEGGimmu:15162.
UCSCiuc008nhc.3. mouse. [P08103-1]

Keywords - Coding sequence diversityi

Alternative initiation

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y00487 mRNA. Translation: CAA68544.1. Sequence problems.
J03023 mRNA. Translation: AAA37305.1. Sequence problems.
AK149736 mRNA. Translation: BAE29054.1. Sequence problems.
AK150290 mRNA. Translation: BAE29445.1. Sequence problems.
AK150709 mRNA. Translation: BAE29787.1. Sequence problems.
AK155975 mRNA. Translation: BAE33532.1. Sequence problems.
AK165315 mRNA. Translation: BAE38133.1. Sequence problems.
BC010478 mRNA. Translation: AAH10478.2.
CCDSiCCDS38284.1. [P08103-1]
CCDS50756.1. [P08103-2]
PIRiA27282. TVMSHC.
RefSeqiNP_001165588.1. NM_001172117.1. [P08103-2]
NP_034537.2. NM_010407.4. [P08103-1]
XP_011250107.1. XM_011251805.1. [P08103-2]
XP_011250108.1. XM_011251806.1. [P08103-2]
UniGeneiMm.715.

3D structure databases

ProteinModelPortaliP08103.
SMRiP08103. Positions 80-524.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200249. 4 interactions.
IntActiP08103. 5 interactions.
MINTiMINT-4097288.
STRINGi10090.ENSMUSP00000003370.

PTM databases

iPTMnetiP08103.
PhosphoSiteiP08103.
SwissPalmiP08103.

Proteomic databases

MaxQBiP08103.
PaxDbiP08103.
PeptideAtlasiP08103.
PRIDEiP08103.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000109799; ENSMUSP00000105423; ENSMUSG00000003283. [P08103-2]
ENSMUST00000189688; ENSMUSP00000141030; ENSMUSG00000003283. [P08103-2]
GeneIDi15162.
KEGGimmu:15162.
UCSCiuc008nhc.3. mouse. [P08103-1]

Organism-specific databases

CTDi3055.
MGIiMGI:96052. Hck.

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP08103.
KOiK08893.
PhylomeDBiP08103.

Enzyme and pathway databases

BRENDAi2.7.10.2. 3474.
ReactomeiR-MMU-2029481. FCGR activation.

Miscellaneous databases

PROiP08103.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003283.
CleanExiMM_HCK.
ExpressionAtlasiP08103. baseline and differential.
GenevisibleiP08103. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiHCK_MOUSE
AccessioniPrimary (citable) accession number: P08103
Secondary accession number(s): Q0VH03, Q3UD17
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 180 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.