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Protein

Tyrosine-protein kinase HCK

Gene

HCK

Organism
Homo sapiens (Human)
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.19 Publications

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation8 Publications

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-411 is required for optimal activity. Phosphorylation at Tyr-522 inhibits kinase activity. Inhibited by PP1 and A-770041.9 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei290ATP1
Active sitei381Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi268 – 276ATP9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: UniProtKB
  • receptor binding Source: GO_Central

GO - Biological processi

  • cell adhesion Source: UniProtKB
  • cell differentiation Source: GO_Central
  • cytokine-mediated signaling pathway Source: UniProtKB
  • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  • inflammatory response Source: UniProtKB-KW
  • innate immune response-activating signal transduction Source: UniProtKB
  • integrin-mediated signaling pathway Source: UniProtKB
  • interferon-gamma-mediated signaling pathway Source: UniProtKB
  • leukocyte degranulation Source: UniProtKB
  • leukocyte migration involved in immune response Source: UniProtKB
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • mesoderm development Source: ProtInc
  • negative regulation of apoptotic process Source: UniProtKB
  • peptidyl-tyrosine autophosphorylation Source: GO_Central
  • peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of actin cytoskeleton reorganization Source: UniProtKB
  • positive regulation of actin filament polymerization Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • regulation of cell shape Source: UniProtKB
  • regulation of defense response to virus by virus Source: Reactome
  • regulation of inflammatory response Source: UniProtKB
  • regulation of phagocytosis Source: UniProtKB
  • regulation of podosome assembly Source: UniProtKB
  • regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  • respiratory burst after phagocytosis Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Exocytosis, Host-virus interaction, Immunity, Inflammatory response, Innate immunity, Phagocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02246-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-164944. Nef and signal transduction.
R-HSA-2029481. FCGR activation.
R-HSA-912631. Regulation of signaling by CBL.
SignaLinkiP08631.
SIGNORiP08631.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase HCK (EC:2.7.10.2)
Alternative name(s):
Hematopoietic cell kinase
Hemopoietic cell kinase
p59-HCK/p60-HCK
p59Hck
p61Hck
Gene namesi
Name:HCK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:4840. HCK.

Subcellular locationi

Isoform 1 :
Isoform 2 :
  • Cell membrane 1 Publication; Lipid-anchor 1 Publication
  • Membranecaveola 1 Publication; Lipid-anchor 1 Publication
  • Cell junctionfocal adhesion 1 Publication
  • Cytoplasmcytoskeleton 1 Publication
  • Golgi apparatus 1 Publication
  • Cytoplasmic vesicle 1 Publication
  • Lysosome 1 Publication
  • Nucleus 1 Publication

  • Note: 20% 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.

GO - Cellular componenti

  • caveola Source: UniProtKB
  • cell projection Source: UniProtKB-KW
  • cytoskeleton Source: UniProtKB-SubCell
  • cytosol Source: Reactome
  • extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: UniProtKB-SubCell
  • lysosome Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • transport vesicle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.

Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3G → C: Slight palmitoylation, cytoplasmic and caveolar localization; in isoform 1;. 2 Publications1
Mutagenesisi3G → S: Abolishes palmitoylation and localization at the cell membrane. 2 Publications1
Mutagenesisi23G → A: Myristoylation and palmitoylation are abolished, leading to entirely cytoplasmic localization; in isoform 2. 1 Publication1
Mutagenesisi24C → S: Palmitoylation is abolished, some cytoplasmic and no calveolar localization; in isoform 2. 1 Publication1
Mutagenesisi290K → E: Loss of kinase activity. 1 Publication1
Mutagenesisi305E → A: Loss of kinase activity. 1 Publication1
Mutagenesisi381D → E: Loss of kinase activity. 1 Publication1
Mutagenesisi411Y → A: Reduced catalytic activity and higher affinity for target peptides. 1 Publication1
Mutagenesisi522Y → F: Constitutively activated kinase, leading to cellular transformation. 2 Publications1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi3055.
OpenTargetsiENSG00000101336.
PharmGKBiPA29216.

Chemistry databases

ChEMBLiCHEMBL3234.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2032.

Polymorphism and mutation databases

BioMutaiHCK.
DMDMi20141296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved
ChainiPRO_00000244332 – 526Tyrosine-protein kinase HCKAdd BLAST525
Isoform 2 (identifier: P08631-2)
Initiator methionineiRemoved

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Modified residuei36PhosphothreonineCombined sources1
Modified residuei51Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei202PhosphothreonineCombined sources1
Modified residuei209PhosphotyrosineBy similarity1
Modified residuei411Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei462PhosphoserineCombined sources1
Modified residuei522Phosphotyrosine5 Publications1
Isoform 2 (identifier: P08631-2)
Lipidationi2N-myristoyl glycine1

Post-translational modificationi

Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation by the BCR-ABL fusion protein mediates activation of HCK. Phosphorylation at Tyr-411 increases kinase activity. Phosphorylation at Tyr-522 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-522, suggesting that this site is a target of other kinases.9 Publications
Ubiquitinated by CBL, leading to its degradation via the proteasome.1 Publication
Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP08631.
PaxDbiP08631.
PeptideAtlasiP08631.
PRIDEiP08631.

PTM databases

iPTMnetiP08631.
PhosphoSitePlusiP08631.
SwissPalmiP08631.

Expressioni

Tissue specificityi

Detected in monocytes and neutrophils (at protein level). Expressed predominantly in cells of the myeloid and B-lymphoid lineages. Highly expressed in granulocytes. Detected in tonsil.3 Publications

Inductioni

Up-regulated during myeloid cell differentiation. The highest levels are detected in fully differentiated phagocytes. Up-regulated by IL2.2 Publications

Gene expression databases

BgeeiENSG00000101336.
ExpressionAtlasiP08631. baseline and differential.
GenevisibleiP08631. HS.

Organism-specific databases

HPAiCAB005195.

Interactioni

Subunit structurei

Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with VAV1, WAS and RAPGEF1 (By similarity). Interacts (via SH3 domain) with HIV-1 Nef and Vif. This interaction stimulates its tyrosine-kinase activity. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with ARRB1 and ARRB2. Interacts with ADAM15. Interacts with FASLG. Interacts with CBL. 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 SH3 domain) with WDCP.By similarity25 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
O929722EBI-346340,EBI-710506From a different organism.
P279585EBI-346340,EBI-706378From a different organism.
ADAM15Q134443EBI-346340,EBI-77818
ALOX5P099172EBI-346340,EBI-79934
ASAP1Q9ULH12EBI-346340,EBI-346622
CBLP226812EBI-9834454,EBI-518228
EGFRP005332EBI-346340,EBI-297353
ELMO1Q925564EBI-346340,EBI-346417
ERBB3P218602EBI-346340,EBI-720706
FLT1P179482EBI-346340,EBI-1026718
FRS3O435592EBI-9834454,EBI-725515
GOPCQ9HD263EBI-346340,EBI-349832
KHDRBS1Q076664EBI-346340,EBI-1364
KITP107212EBI-346340,EBI-1379503
KRT40Q6A1623EBI-346340,EBI-10171697
KRTAP10-9P604113EBI-346340,EBI-10172052
MTUS2Q5JR593EBI-346340,EBI-742948
nefQ90VU72EBI-346340,EBI-7460704From a different organism.
NOTCH2NLQ7Z3S93EBI-346340,EBI-945833
OLIG1Q8TAK62EBI-9834454,EBI-3867416
PAK2Q131772EBI-346340,EBI-1045887
PDCD6IPQ8WUM44EBI-346340,EBI-310624
PIK3CBP423382EBI-346340,EBI-2609540
PIK3R3Q925694EBI-9834454,EBI-79893
PLCG1P191742EBI-346340,EBI-79387
PTK2Q053972EBI-9834454,EBI-702142
SOS1Q078894EBI-346340,EBI-297487
vifP125043EBI-346340,EBI-779991From a different organism.
WASP427689EBI-346340,EBI-346375
WIPF1O435163EBI-346340,EBI-346356

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109305. 61 interactors.
DIPiDIP-1051N.
IntActiP08631. 87 interactors.
MINTiMINT-135300.
STRINGi9606.ENSP00000365012.

Chemistry databases

BindingDBiP08631.

Structurei

Secondary structure

1526
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi81 – 87Combined sources7
Beta strandi93 – 96Combined sources4
Beta strandi104 – 109Combined sources6
Beta strandi114 – 119Combined sources6
Turni120 – 122Combined sources3
Beta strandi125 – 129Combined sources5
Helixi130 – 132Combined sources3
Beta strandi133 – 135Combined sources3
Helixi136 – 138Combined sources3
Helixi139 – 141Combined sources3
Beta strandi145 – 148Combined sources4
Helixi151 – 159Combined sources9
Beta strandi168 – 172Combined sources5
Beta strandi174 – 176Combined sources3
Beta strandi180 – 188Combined sources9
Turni189 – 191Combined sources3
Beta strandi192 – 202Combined sources11
Beta strandi204 – 206Combined sources3
Beta strandi208 – 211Combined sources4
Beta strandi214 – 218Combined sources5
Helixi219 – 228Combined sources10
Beta strandi233 – 235Combined sources3
Turni252 – 255Combined sources4
Helixi259 – 261Combined sources3
Beta strandi262 – 269Combined sources8
Beta strandi272 – 281Combined sources10
Turni282 – 284Combined sources3
Beta strandi285 – 292Combined sources8
Beta strandi294 – 297Combined sources4
Helixi299 – 309Combined sources11
Beta strandi320 – 324Combined sources5
Beta strandi326 – 328Combined sources3
Beta strandi330 – 333Combined sources4
Helixi341 – 346Combined sources6
Helixi348 – 351Combined sources4
Helixi355 – 374Combined sources20
Helixi384 – 386Combined sources3
Beta strandi387 – 389Combined sources3
Beta strandi395 – 397Combined sources3
Helixi402 – 405Combined sources4
Helixi409 – 412Combined sources4
Beta strandi416 – 419Combined sources4
Helixi421 – 423Combined sources3
Helixi426 – 431Combined sources6
Helixi436 – 451Combined sources16
Turni452 – 454Combined sources3
Beta strandi457 – 460Combined sources4
Helixi463 – 472Combined sources10
Beta strandi480 – 482Combined sources3
Helixi484 – 493Combined sources10
Helixi498 – 500Combined sources3
Helixi504 – 512Combined sources9
Beta strandi514 – 518Combined sources5
Beta strandi521 – 523Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AD5X-ray2.60A/B79-526[»]
1BU1X-ray2.60A/B/C/D/E/F81-137[»]
1QCFX-ray2.00A81-526[»]
2C0IX-ray2.30A/B81-526[»]
2C0OX-ray2.85A/B81-526[»]
2C0TX-ray2.15A/B81-526[»]
2HCKX-ray3.00A/B79-526[»]
2HK5X-ray2.00A247-514[»]
2OI3NMR-A61-141[»]
2OJ2NMR-A61-141[»]
3HCKNMR-A140-245[»]
3NHNX-ray2.61A72-256[»]
3RBBX-ray2.35B/D79-138[»]
3REAX-ray2.00B/D79-138[»]
3REBX-ray3.45B/D79-138[»]
3VRYX-ray2.48A/B81-526[»]
3VRZX-ray2.22A/B81-526[»]
3VS0X-ray2.93A/B81-526[»]
3VS1X-ray2.46A/B81-526[»]
3VS2X-ray2.61A/B81-526[»]
3VS3X-ray2.17A/B81-526[»]
3VS4X-ray2.75A/B81-526[»]
3VS5X-ray2.85A/B81-526[»]
3VS6X-ray2.37A/B81-526[»]
3VS7X-ray3.00A/B81-526[»]
4HCKNMR-A72-143[»]
4LUDX-ray2.85A/B81-526[»]
4LUEX-ray3.04A/B81-526[»]
4ORZX-ray2.00A77-138[»]
4U5WX-ray1.86B/D72-242[»]
5HCKNMR-A72-143[»]
ProteinModelPortaliP08631.
SMRiP08631.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08631.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini78 – 138SH3PROSITE-ProRule annotationAdd BLAST61
Domaini144 – 241SH2PROSITE-ProRule annotationAdd BLAST98
Domaini262 – 515Protein kinasePROSITE-ProRule annotationAdd BLAST254

Domaini

The SH3 domain mediates binding to HIV-1 Nef.

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.
InParanoidiP08631.
KOiK08893.
PhylomeDBiP08631.

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 (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: P08631-1) [UniParc]FASTAAdd to basket
Also known as: p60-HCK, p61Hck

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 GCPRDEERAP RMGCMKSKFL QVGGNTFSKT ETSASPHCPV
60 70 80 90 100
YVPDPTSTIK PGPNSHNSNT PGIREAGSED IIVVALYDYE AIHHEDLSFQ
110 120 130 140 150
KGDQMVVLEE SGEWWKARSL ATRKEGYIPS NYVARVDSLE TEEWFFKGIS
160 170 180 190 200
RKDAERQLLA PGNMLGSFMI RDSETTKGSY SLSVRDYDPR QGDTVKHYKI
210 220 230 240 250
RTLDNGGFYI SPRSTFSTLQ ELVDHYKKGN DGLCQKLSVP CMSSKPQKPW
260 270 280 290 300
EKDAWEIPRE SLKLEKKLGA GQFGEVWMAT YNKHTKVAVK TMKPGSMSVE
310 320 330 340 350
AFLAEANVMK TLQHDKLVKL HAVVTKEPIY IITEFMAKGS LLDFLKSDEG
360 370 380 390 400
SKQPLPKLID FSAQIAEGMA FIEQRNYIHR DLRAANILVS ASLVCKIADF
410 420 430 440 450
GLARVIEDNE YTAREGAKFP IKWTAPEAIN FGSFTIKSDV WSFGILLMEI
460 470 480 490 500
VTYGRIPYPG MSNPEVIRAL ERGYRMPRPE NCPEELYNIM MRCWKNRPEE
510 520
RPTFEYIQSV LDDFYTATES QYQQQP
Note: Initiates from a CTG codon.
Length:526
Mass (Da):59,600
Last modified:January 23, 2007 - v5
Checksum:i847E877A0A641725
GO
Isoform 2 (identifier: P08631-2) [UniParc]FASTAAdd to basket
Also known as: p59-HCK, p59Hck

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

Note: S-palmitoylated at Cys-3.
Show »
Length:505
Mass (Da):57,312
Checksum:i4F1EC1E8F3EDF9CA
GO
Isoform 3 (identifier: P08631-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.
     76-76: Missing.

Show »
Length:504
Mass (Da):57,241
Checksum:iC07FF5B8D3C1B862
GO
Isoform 4 (identifier: P08631-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-76: Missing.

Note: Initiates from a CTG codon.
Show »
Length:525
Mass (Da):59,529
Checksum:i803967415A2F57FC
GO

Sequence cautioni

The sequence AAA52643 differs from that shown. Reason: Frameshift at position 20.Curated
The sequence BAF82585 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24C → S in AAA52643 (PubMed:3496523).Curated1
Sequence conflicti69N → D in BAF82585 (PubMed:14702039).Curated1
Sequence conflicti144W → R in BAB15482 (PubMed:14702039).Curated1
Sequence conflicti168F → Y in BAF82585 (PubMed:14702039).Curated1
Sequence conflicti378I → T in AAI13855 (PubMed:15489334).Curated1
Sequence conflicti488N → S in BAF82585 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04170744A → T.1 PublicationCorresponds to variant rs56029200dbSNPEnsembl.1
Natural variantiVAR_041708105M → L.2 PublicationsCorresponds to variant rs55722810dbSNPEnsembl.1
Natural variantiVAR_041709399D → G in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_033836502P → Q.Corresponds to variant rs17093828dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0188581 – 21Missing in isoform 2 and isoform 3. 3 PublicationsAdd BLAST21
Alternative sequenceiVSP_04192676Missing in isoform 3 and isoform 4. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16591 mRNA. Translation: AAA52643.1. Frameshift.
M16592 mRNA. Translation: AAA52644.1.
AK026432 mRNA. Translation: BAB15482.1.
AK289896 mRNA. Translation: BAF82585.1. Different initiation.
AK298726 mRNA. Translation: BAG60878.1.
AL353092, AL049539 Genomic DNA. Translation: CAI19694.1.
AL353092, AL049539 Genomic DNA. Translation: CAI19695.1.
AL049539, AL353092 Genomic DNA. Translation: CAI22966.1.
AL049539, AL353092 Genomic DNA. Translation: CAI22967.1.
CH471077 Genomic DNA. Translation: EAW76392.1.
CH471077 Genomic DNA. Translation: EAW76393.1.
BC014435 mRNA. Translation: AAH14435.2.
BC094847 mRNA. Translation: AAH94847.2.
BC108930 mRNA. Translation: AAI08931.2.
BC108931 mRNA. Translation: AAI08932.2.
BC113854 mRNA. Translation: AAI13855.2.
BC114463 mRNA. Translation: AAI14464.2.
X58741, X58742, X58743 Genomic DNA. Translation: CAA41565.2.
CCDSiCCDS33460.1. [P08631-1]
CCDS54453.1. [P08631-4]
CCDS54455.1. [P08631-2]
CCDS54456.1. [P08631-3]
PIRiA27811. TVHUHC.
A41263.
RefSeqiNP_001165600.1. NM_001172129.1. [P08631-2]
NP_001165601.1. NM_001172130.1. [P08631-4]
NP_001165602.1. NM_001172131.1. [P08631-3]
NP_001165604.1. NM_001172133.1. [P08631-2]
NP_002101.2. NM_002110.3. [P08631-1]
UniGeneiHs.655210.

Genome annotation databases

EnsembliENST00000518730; ENSP00000427757; ENSG00000101336. [P08631-3]
ENST00000520553; ENSP00000429848; ENSG00000101336. [P08631-2]
ENST00000538448; ENSP00000441169; ENSG00000101336. [P08631-2]
ENST00000629881; ENSP00000486627; ENSG00000101336. [P08631-2]
GeneIDi3055.
KEGGihsa:3055.
UCSCiuc002wxi.4. human. [P08631-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M16591 mRNA. Translation: AAA52643.1. Frameshift.
M16592 mRNA. Translation: AAA52644.1.
AK026432 mRNA. Translation: BAB15482.1.
AK289896 mRNA. Translation: BAF82585.1. Different initiation.
AK298726 mRNA. Translation: BAG60878.1.
AL353092, AL049539 Genomic DNA. Translation: CAI19694.1.
AL353092, AL049539 Genomic DNA. Translation: CAI19695.1.
AL049539, AL353092 Genomic DNA. Translation: CAI22966.1.
AL049539, AL353092 Genomic DNA. Translation: CAI22967.1.
CH471077 Genomic DNA. Translation: EAW76392.1.
CH471077 Genomic DNA. Translation: EAW76393.1.
BC014435 mRNA. Translation: AAH14435.2.
BC094847 mRNA. Translation: AAH94847.2.
BC108930 mRNA. Translation: AAI08931.2.
BC108931 mRNA. Translation: AAI08932.2.
BC113854 mRNA. Translation: AAI13855.2.
BC114463 mRNA. Translation: AAI14464.2.
X58741, X58742, X58743 Genomic DNA. Translation: CAA41565.2.
CCDSiCCDS33460.1. [P08631-1]
CCDS54453.1. [P08631-4]
CCDS54455.1. [P08631-2]
CCDS54456.1. [P08631-3]
PIRiA27811. TVHUHC.
A41263.
RefSeqiNP_001165600.1. NM_001172129.1. [P08631-2]
NP_001165601.1. NM_001172130.1. [P08631-4]
NP_001165602.1. NM_001172131.1. [P08631-3]
NP_001165604.1. NM_001172133.1. [P08631-2]
NP_002101.2. NM_002110.3. [P08631-1]
UniGeneiHs.655210.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AD5X-ray2.60A/B79-526[»]
1BU1X-ray2.60A/B/C/D/E/F81-137[»]
1QCFX-ray2.00A81-526[»]
2C0IX-ray2.30A/B81-526[»]
2C0OX-ray2.85A/B81-526[»]
2C0TX-ray2.15A/B81-526[»]
2HCKX-ray3.00A/B79-526[»]
2HK5X-ray2.00A247-514[»]
2OI3NMR-A61-141[»]
2OJ2NMR-A61-141[»]
3HCKNMR-A140-245[»]
3NHNX-ray2.61A72-256[»]
3RBBX-ray2.35B/D79-138[»]
3REAX-ray2.00B/D79-138[»]
3REBX-ray3.45B/D79-138[»]
3VRYX-ray2.48A/B81-526[»]
3VRZX-ray2.22A/B81-526[»]
3VS0X-ray2.93A/B81-526[»]
3VS1X-ray2.46A/B81-526[»]
3VS2X-ray2.61A/B81-526[»]
3VS3X-ray2.17A/B81-526[»]
3VS4X-ray2.75A/B81-526[»]
3VS5X-ray2.85A/B81-526[»]
3VS6X-ray2.37A/B81-526[»]
3VS7X-ray3.00A/B81-526[»]
4HCKNMR-A72-143[»]
4LUDX-ray2.85A/B81-526[»]
4LUEX-ray3.04A/B81-526[»]
4ORZX-ray2.00A77-138[»]
4U5WX-ray1.86B/D72-242[»]
5HCKNMR-A72-143[»]
ProteinModelPortaliP08631.
SMRiP08631.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109305. 61 interactors.
DIPiDIP-1051N.
IntActiP08631. 87 interactors.
MINTiMINT-135300.
STRINGi9606.ENSP00000365012.

Chemistry databases

BindingDBiP08631.
ChEMBLiCHEMBL3234.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2032.

PTM databases

iPTMnetiP08631.
PhosphoSitePlusiP08631.
SwissPalmiP08631.

Polymorphism and mutation databases

BioMutaiHCK.
DMDMi20141296.

Proteomic databases

MaxQBiP08631.
PaxDbiP08631.
PeptideAtlasiP08631.
PRIDEiP08631.

Protocols and materials databases

DNASUi3055.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000518730; ENSP00000427757; ENSG00000101336. [P08631-3]
ENST00000520553; ENSP00000429848; ENSG00000101336. [P08631-2]
ENST00000538448; ENSP00000441169; ENSG00000101336. [P08631-2]
ENST00000629881; ENSP00000486627; ENSG00000101336. [P08631-2]
GeneIDi3055.
KEGGihsa:3055.
UCSCiuc002wxi.4. human. [P08631-1]

Organism-specific databases

CTDi3055.
DisGeNETi3055.
GeneCardsiHCK.
HGNCiHGNC:4840. HCK.
HPAiCAB005195.
MIMi142370. gene.
neXtProtiNX_P08631.
OpenTargetsiENSG00000101336.
PharmGKBiPA29216.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0197. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP08631.
KOiK08893.
PhylomeDBiP08631.

Enzyme and pathway databases

BioCyciZFISH:HS02246-MONOMER.
BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-164944. Nef and signal transduction.
R-HSA-2029481. FCGR activation.
R-HSA-912631. Regulation of signaling by CBL.
SignaLinkiP08631.
SIGNORiP08631.

Miscellaneous databases

ChiTaRSiHCK. human.
EvolutionaryTraceiP08631.
GeneWikiiHCK.
GenomeRNAii3055.
PROiP08631.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101336.
ExpressionAtlasiP08631. baseline and differential.
GenevisibleiP08631. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P08631
Secondary accession number(s): A8K1I1
, B4DQB6, E1P5M2, Q29RX1, Q2VPE2, Q504R5, Q5T7K1, Q5T7K2, Q96CC0, Q9H5Y5, Q9NUA4, Q9UMJ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 220 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.