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Protein

Tyrosine-protein kinase HCK

Gene

Hck

Organism
Rattus norvegicus (Rat)
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 similarity1 Publication

Catalytic activityi

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

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 (By similarity).By similarity

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

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 5301
ReactomeiR-RNO-2029481 FCGR activation
R-RNO-912631 Regulation of signaling by CBL

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
p56Hck
p59Hck
Gene namesi
Name:Hck
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi2785 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

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000881042 – 524Tyrosine-protein kinase HCKAdd BLAST523
Isoform 2 (identifier: P50545-2)
Initiator methionineiRemovedBy similarity

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Modified residuei50Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei200PhosphothreonineBy similarity1
Modified residuei207PhosphotyrosineBy similarity1
Modified residuei409Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei460PhosphoserineBy similarity1
Modified residuei520PhosphotyrosineBy similarity1
Isoform 2 (identifier: P50545-2)
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 (By similarity).By similarity
Ubiquitinated by CBL, leading to its degradation via the proteasome.By similarity
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

PaxDbiP50545
PRIDEiP50545

PTM databases

iPTMnetiP50545
PhosphoSitePlusiP50545

Expressioni

Tissue specificityi

Expressed strongly in spleen and at very low levels in thymus.1 Publication

Gene expression databases

BgeeiENSRNOG00000009331 Expressed in 10 organ(s), highest expression level in spleen

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012432

Structurei

3D structure databases

ProteinModelPortaliP50545
SMRiP50545
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
InParanoidiP50545
KOiK08893
OMAiRPEHCPE
PhylomeDBiP50545

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
Isoform 1 (identifier: P50545-1) [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 GCPRGEGRVP RMGCVKSRFL REGSKASKIE PNANQKGPVY
60 70 80 90 100
VPDPTSPKKL GPNSINSLPP GVVEGSEDTI VVALYDYEAI HREDLSFQKG
110 120 130 140 150
DQMVVLEESG EWWKARSLAT KKEGYIPSNY VARVNSLETE EWFFKGISRK
160 170 180 190 200
DAERHLLAPG NMLGSFMIRD SETTKGSYSL SVRDFDPQHG DTVKHYKIRT
210 220 230 240 250
LDSGGFYISP RSTFSSLQEL VVHYKKGKDG LCQKLSVPCV SPKPQKPWEK
260 270 280 290 300
DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF
310 320 330 340 350
LAEANLMKTL 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 PEELYSIMIR CWKNRPEERP
510 520
TFEYIQSVLD DFYTATESQY QQQP
Length:524
Mass (Da):59,154
Last modified:January 23, 2007 - v4
Checksum:iBBD928C9E717BF4B
GO
Isoform 2 (identifier: P50545-2) [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):56,968
Checksum:i4D4D0777FF3AAC99
GO

Sequence cautioni

The sequence AAA41312 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAB20754 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAA44218 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti72V → F in AAA41312 (PubMed:1764064).Curated1
Sequence conflicti72V → F in AAB20754 (PubMed:1764064).Curated1
Sequence conflicti226K → R in CAA44218 (Ref. 2) Curated1
Sequence conflicti327I → T in CAA44218 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0222481 – 21Missing in isoform 2. 3 PublicationsAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83666 mRNA Translation: AAA41312.1 Different initiation.
S74141 mRNA Translation: AAB20754.1 Different initiation.
X62345 mRNA Translation: CAA44218.1 Different initiation.
BC078890 mRNA Translation: AAH78890.2
PIRiJQ1321
RefSeqiNP_037317.2, NM_013185.3 [P50545-1]
UniGeneiRn.10945

Genome annotation databases

EnsembliENSRNOT00000012432; ENSRNOP00000012432; ENSRNOG00000009331 [P50545-2]
GeneIDi25734
KEGGirno:25734
UCSCiRGD:2785 rat [P50545-1]

Keywords - Coding sequence diversityi

Alternative initiation

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83666 mRNA Translation: AAA41312.1 Different initiation.
S74141 mRNA Translation: AAB20754.1 Different initiation.
X62345 mRNA Translation: CAA44218.1 Different initiation.
BC078890 mRNA Translation: AAH78890.2
PIRiJQ1321
RefSeqiNP_037317.2, NM_013185.3 [P50545-1]
UniGeneiRn.10945

3D structure databases

ProteinModelPortaliP50545
SMRiP50545
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000012432

PTM databases

iPTMnetiP50545
PhosphoSitePlusiP50545

Proteomic databases

PaxDbiP50545
PRIDEiP50545

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012432; ENSRNOP00000012432; ENSRNOG00000009331 [P50545-2]
GeneIDi25734
KEGGirno:25734
UCSCiRGD:2785 rat [P50545-1]

Organism-specific databases

CTDi3055
RGDi2785 Hck

Phylogenomic databases

eggNOGiKOG0197 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118938
HOGENOMiHOG000233858
HOVERGENiHBG008761
InParanoidiP50545
KOiK08893
OMAiRPEHCPE
PhylomeDBiP50545

Enzyme and pathway databases

BRENDAi2.7.10.2 5301
ReactomeiR-RNO-2029481 FCGR activation
R-RNO-912631 Regulation of signaling by CBL

Miscellaneous databases

PROiPR:P50545

Gene expression databases

BgeeiENSRNOG00000009331 Expressed in 10 organ(s), highest expression level in spleen

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_RAT
AccessioniPrimary (citable) accession number: P50545
Secondary accession number(s): Q64647, Q6AYV7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 171 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
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Main funding by: National Institutes of Health

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