P50545 (HCK_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

Hck

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	524 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	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.
Subunit structure	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
Subcellular location	Cytoplasmic vesicle › secretory vesicle By similarity. Cytoplasm › cytosol By similarity. 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.
Tissue specificity	Expressed strongly in spleen and at very low levels in thymus. Ref.2
Post-translational modification	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. Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. Contains 1 protein kinase domain. Contains 1 SH2 domain. Contains 1 SH3 domain.
Sequence caution	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.

Ontologies

Keywords
Biological process	Exocytosis Immunity Inflammatory response Innate immunity Phagocytosis
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoplasmic vesicle Cytoskeleton Golgi apparatus Lysosome Membrane Nucleus
Coding sequence diversity	Alternative initiation
Disease	Proto-oncogene
Domain	SH2 domain SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	exocytosis Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB phagocytosis Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of actin cytoskeleton reorganization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of cell shape Inferred from sequence or structural similarity. Source: UniProtKB regulation of phagocytosis Inferred from sequence or structural similarity. Source: UniProtKB regulation of podosome assembly Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell caveola Inferred from electronic annotation. Source: UniProtKB-SubCell cell projection Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB focal adhesion Inferred from electronic annotation. Source: UniProtKB-SubCell lysosome Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell transport vesicle Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW non-membrane spanning protein tyrosine kinase activity Inferred from electronic annotation. Source: EC protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

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:
     1-21: Missing.

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
Molecule processing
	Chain	1 – 524	524	Tyrosine-protein kinase HCK		PRO_0000088104
Regions
	Domain	76 – 136	61	SH3
	Domain	142 – 239	98	SH2
	Domain	260 – 513	254	Protein kinase
	Nucleotide binding	266 – 274	9	ATP By similarity
Sites
	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
Natural variations
	Alternative sequence	1 – 21	21	Missing in isoform 2.		VSP_022248
Experimental info
	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

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (p59-HCK) [UniParc]. Last modified January 23, 2007. Version 4. Checksum: BBD928C9E717BF4B	FASTA	524	59,154
	10 20 30 40 50 60 MGGRSSCEDP GCPRGEGRVP RMGCVKSRFL REGSKASKIE PNANQKGPVY VPDPTSPKKL 70 80 90 100 110 120 GPNSINSLPP GVVEGSEDTI VVALYDYEAI HREDLSFQKG DQMVVLEESG EWWKARSLAT 130 140 150 160 170 180 KKEGYIPSNY VARVNSLETE EWFFKGISRK DAERHLLAPG NMLGSFMIRD SETTKGSYSL 190 200 210 220 230 240 SVRDFDPQHG DTVKHYKIRT LDSGGFYISP RSTFSSLQEL VVHYKKGKDG LCQKLSVPCV 250 260 270 280 290 300 SPKPQKPWEK DAWEIPRESL QMEKKLGAGQ FGEVWMATYN KHTKVAVKTM KPGSMSVEAF 310 320 330 340 350 360 LAEANLMKTL QHDKLVKLHA VVSQEPIFIV TEFMAKGSLL DFLKSEEGSK QPLPKLIDFS 370 380 390 400 410 420 AQISEGMAFI EQRNYIHRDL RAANILVSAS LVCKIADFGL ARIIEDNEYT AREGAKFPIK 430 440 450 460 470 480 WTAPEAINFG SFTIKSDVWS FGILLMEIVT YGRIPYPGMS NPEVIRALEH GYRMPRPDNC 490 500 510 520 PEELYSIMIR CWKNRPEERP TFEYIQSVLD DFYTATESQY QQQP
	Isoform 2 (p56-HCK) [UniParc]. Checksum: 4D4D0777FF3AAC99	FASTA	503	56,968
	10 20 30 40 50 60 MGCVKSRFLR EGSKASKIEP NANQKGPVYV PDPTSPKKLG PNSINSLPPG VVEGSEDTIV 70 80 90 100 110 120 VALYDYEAIH REDLSFQKGD QMVVLEESGE WWKARSLATK KEGYIPSNYV ARVNSLETEE 130 140 150 160 170 180 WFFKGISRKD AERHLLAPGN MLGSFMIRDS ETTKGSYSLS VRDFDPQHGD TVKHYKIRTL 190 200 210 220 230 240 DSGGFYISPR STFSSLQELV VHYKKGKDGL CQKLSVPCVS PKPQKPWEKD AWEIPRESLQ 250 260 270 280 290 300 MEKKLGAGQF GEVWMATYNK HTKVAVKTMK PGSMSVEAFL AEANLMKTLQ HDKLVKLHAV 310 320 330 340 350 360 VSQEPIFIVT EFMAKGSLLD FLKSEEGSKQ PLPKLIDFSA QISEGMAFIE QRNYIHRDLR 370 380 390 400 410 420 AANILVSASL VCKIADFGLA RIIEDNEYTA REGAKFPIKW TAPEAINFGS FTIKSDVWSF 430 440 450 460 470 480 GILLMEIVTY GRIPYPGMSN PEVIRALEHG YRMPRPDNCP EELYSIMIRC WKNRPEERPT 490 500 FEYIQSVLDD FYTATESQYQ QQP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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). Tissue: Megakaryocyte.
[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. Strain: Wistar. Tissue: Spleen.
[3]	"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. Tissue: Lung.
[4]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00325226. IPI00817068.
PIR	JQ1321.
RefSeq	NP_037317.2. NM_013185.3.
UniGene	Rn.10945.
3D structure databases
ProteinModelPortal	P50545.
SMR	P50545. Positions 80-524.
ModBase	Search...
PTM databases
PhosphoSite	P50545.
Proteomic databases
PaxDb	P50545.
PRIDE	P50545.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	25734.
KEGG	rno:25734.
UCSC	RGD:2785. rat.
Organism-specific databases
CTD	3055.
RGD	2785. Hck.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233858.
HOVERGEN	HBG008761.
InParanoid	P50545.
KO	K08893.
OrthoDB	EOG4N04DP.
Enzyme and pathway databases
BRENDA	2.7.10.2. 5301.
Reactome	REACT_109781. Immune System.
Gene expression databases
ArrayExpress	P50545.
Genevestigator	P50545.
GermOnline	ENSRNOG00000009331. Rattus norvegicus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00252. SH2. 1 hit. SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
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. [Graphical view]
ProtoNet	Search...
Other
NextBio	607867.

Entry information

Entry name

HCK_RAT

Accession

Primary (citable) accession number: P50545
Secondary accession number(s): Q64647, Q6AYV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 125 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program