P50545 (HCK_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 125. History...
Names and origin
|Protein names||Recommended name:|
Tyrosine-protein kinase HCK
Hematopoietic cell kinase
Hemopoietic cell kinase
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||524 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.4
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
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.
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. Ref.4
Isoform 1: Membrane; Lipid-anchor. Membrane › caveola By similarity. Lysosome By similarity. Cell projection › podosome membrane; Lipid-anchor By similarity. Cytoplasm › cytosol By similarity. Note: Associated with specialized secretory lysosomes called azurophil granules. A fraction of this isoform is found in the cytoplasm, some of this fraction is myristoylated By similarity.
Isoform 2: Cell membrane; Lipid-anchor. Membrane › caveola; Lipid-anchor By similarity. Cell junction › focal adhesion By similarity. Cytoplasm › cytoskeleton By similarity. Golgi apparatus By similarity. Cytoplasmic vesicle By similarity. Lysosome By similarity. Nucleus By similarity. Note: A small fraction of this isoform 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.
Expressed strongly in spleen and at very low levels in thymus. Ref.2
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.
Ubiquitinated by CBL, leading to its degradation via the proteasome By similarity.
Contains 1 protein kinase domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.
The sequence AAA41312.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
The sequence AAB20754.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
The sequence CAA44218.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.
|This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]|
|Isoform 1 (identifier: P50545-1) |
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.
|Isoform 2 (identifier: P50545-2) |
Also known as: p56-HCK;
The sequence of this isoform differs from the canonical sequence as follows:
|Note: Initiator Met-1 is removed. Contains a N-myristoyl glycine at position 2 (By similarity). Contains a S-palmitoyl cysteine at position 3 (By similarity).|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 524||524||Tyrosine-protein kinase HCK||PRO_0000088104|
|Domain||76 – 136||61||SH3|
|Domain||142 – 239||98||SH2|
|Domain||260 – 513||254||Protein kinase|
|Nucleotide binding||266 – 274||9||ATP By similarity|
|Active site||379||1||Proton acceptor By similarity|
|Binding site||288||1||ATP By similarity|
Amino acid modifications
|Modified residue||34||1||Phosphoserine By similarity|
|Modified residue||50||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||200||1||Phosphothreonine By similarity|
|Modified residue||207||1||Phosphotyrosine By similarity|
|Modified residue||409||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||460||1||Phosphoserine By similarity|
|Modified residue||520||1||Phosphotyrosine By similarity|
|Lipidation||2||1||N-myristoyl glycine By similarity|
|Alternative sequence||1 – 21||21||Missing in isoform 2.||VSP_022248|
|Sequence conflict||72||1||V → F in AAA41312. Ref.1|
|Sequence conflict||72||1||V → F in AAB20754. Ref.1|
|Sequence conflict||226||1||K → R in CAA44218. Ref.2|
|Sequence conflict||327||1||I → T in CAA44218. Ref.2|
|||"Identification of rat cDNA encoding hck tyrosine kinase from megakaryocytes."|
Okano Y., Sugimoto Y., Fukuoka M., Matsui A., Nagata K., Nozawa Y.
Biochem. Biophys. Res. Commun. 181:1137-1144(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
|||"Nucleotide sequence of a cDNA coding for rat hck tyrosine kinase and characterization of its gene product."|
Vijaya Gouri B.S., Rema V., Kamatkar S., Swarup G.
J. Biosci. 19:117-129(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: Brown Norway.
|||"Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain."|
Shivakrupa R., Radha V., Sudhakar C., Swarup G.
J. Biol. Chem. 278:52188-52194(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAPGEF1, FUNCTION IN PHOSPHORYLATION OF RAPGEF1.
|+||Additional computationally mapped references.|
|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.
|RefSeq||NP_037317.2. NM_013185.3. |
3D structure databases
|SMR||P50545. Positions 80-524. |
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:2785. rat. |
|RGD||2785. Hck. |
Enzyme and pathway databases
|BRENDA||18.104.22.168. 5301. |
|Reactome||REACT_109781. Immune System. |
Gene expression databases
|GermOnline||ENSRNOG00000009331. Rattus norvegicus. |
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF07714. Pkinase_Tyr. 1 hit. |
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00252. SH2. 1 hit. |
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
|SUPFAM||SSF56112. Kinase_like. 1 hit. |
SSF50044. SH3. 1 hit.
|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.
|Accession||Primary (citable) accession number: P50545|
Secondary accession number(s): Q64647, Q6AYV7
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families