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UniProtKB - P08103 (HCK_MOUSE)

Protein

Tyrosine-protein kinase HCK

Gene

Hck

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei288ATPPROSITE-ProRule annotation1
Active sitei379Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi266 – 274ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

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 3474
ReactomeiR-MMU-2029481 FCGR activation
R-MMU-912631 Regulation of signaling by CBL

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:96052 Hck

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, 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)DescriptionActionsGraphical viewLength
Mutagenesisi409Y → F: Reduced autophosphorylation. 1 Publication1

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000244352 – 524Tyrosine-protein kinase HCKAdd BLAST523
Isoform 2 (identifier: P08103-2)
Initiator methionineiRemovedBy similarity

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei50Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei200PhosphothreonineBy similarity1
Modified residuei207PhosphotyrosineCombined sources1
Modified residuei409Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei460PhosphoserineBy similarity1
Modified residuei520PhosphotyrosineCombined sources1
Isoform 2 (identifier: P08103-2)
Lipidationi2N-myristoyl glycine By similarityBy similarity1
Lipidationi3S-palmitoyl cysteine By similarityBy 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-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

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP08103
PaxDbiP08103
PeptideAtlasiP08103
PRIDEiP08103

PTM databases

iPTMnetiP08103
PhosphoSitePlusiP08103
SwissPalmiP08103

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000003283 Expressed in 144 organ(s), highest expression level in spleen
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 Homo sapiens.

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi200249, 5 interactors
IntActiP08103, 5 interactors
MINTiP08103
STRINGi10090.ENSMUSP00000003370

Structurei

3D structure databases

ProteinModelPortaliP08103
SMRiP08103
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 136SH3PROSITE-ProRule annotationAdd BLAST61
Domaini142 – 239SH2PROSITE-ProRule annotationAdd BLAST98
Domaini260 – 513Protein kinasePROSITE-ProRule annotationAdd BLAST254

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP08103
KOiK08893
OMAiMMRCWKN
PhylomeDBiP08103

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

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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F6UND7F6UND7_MOUSE
Tyrosine-protein kinase
Hck
524Annotation score:
A0A087WQ04A0A087WQ04_MOUSE
Tyrosine-protein kinase
Hck
524Annotation score:

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)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0188591 – 21Missing in isoform 2. CuratedAdd BLAST21

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]
UniGeneiMm.715

Genome annotation databases

EnsembliENSMUST00000109799; ENSMUSP00000105423; ENSMUSG00000003283 [P08103-2]
ENSMUST00000189688; ENSMUSP00000141030; ENSMUSG00000003283 [P08103-2]
ENSMUST00000191431; ENSMUSP00000139988; ENSMUSG00000003283 [P08103-1]
GeneIDi15162
KEGGimmu:15162
UCSCiuc008nhc.3 mouse [P08103-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

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]
UniGeneiMm.715

3D structure databases

ProteinModelPortaliP08103
SMRiP08103
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200249, 5 interactors
IntActiP08103, 5 interactors
MINTiP08103
STRINGi10090.ENSMUSP00000003370

PTM databases

iPTMnetiP08103
PhosphoSitePlusiP08103
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]
ENSMUST00000191431; ENSMUSP00000139988; ENSMUSG00000003283 [P08103-1]
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
OMAiMMRCWKN
PhylomeDBiP08103

Enzyme and pathway databases

BRENDAi2.7.10.2 3474
ReactomeiR-MMU-2029481 FCGR activation
R-MMU-912631 Regulation of signaling by CBL

Miscellaneous databases

PROiPR:P08103
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000003283 Expressed in 144 organ(s), highest expression level in spleen
CleanExiMM_HCK
ExpressionAtlasiP08103 baseline and differential
GenevisibleiP08103 MM

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
ProtoNetiSearch...

Entry informationi

Entry nameiHCK_MOUSE
AccessioniPrimary (citable) accession number: P08103
Secondary accession number(s): Q0VH03, Q3UD17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 196 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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