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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei290 – 2901ATP
Active sitei381 – 3811Proton acceptor

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi268 – 2769ATP

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

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi3 – 31G → C: Slight palmitoylation, cytoplasmic and caveolar localization; in isoform 1;. 2 Publications
Mutagenesisi3 – 31G → S: Abolishes palmitoylation and localization at the cell membrane. 2 Publications
Mutagenesisi23 – 231G → A: Myristoylation and palmitoylation are abolished, leading to entirely cytoplasmic localization; in isoform 2. 1 Publication
Mutagenesisi24 – 241C → S: Palmitoylation is abolished, some cytoplasmic and no calveolar localization; in isoform 2. 1 Publication
Mutagenesisi290 – 2901K → E: Loss of kinase activity. 1 Publication
Mutagenesisi305 – 3051E → A: Loss of kinase activity. 1 Publication
Mutagenesisi381 – 3811D → E: Loss of kinase activity. 1 Publication
Mutagenesisi411 – 4111Y → A: Reduced catalytic activity and higher affinity for target peptides. 1 Publication
Mutagenesisi522 – 5221Y → F: Constitutively activated kinase, leading to cellular transformation. 2 Publications

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA29216.

Chemistry

ChEMBLiCHEMBL2363074.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2032.

Polymorphism and mutation databases

BioMutaiHCK.
DMDMi20141296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved
Chaini2 – 526525Tyrosine-protein kinase HCKPRO_0000024433Add
BLAST
Isoform 2 (identifier: P08631-2)
Initiator methionineiRemoved

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei36 – 361PhosphothreonineCombined sources
Modified residuei51 – 511Phosphotyrosine; by autocatalysis1 Publication
Modified residuei202 – 2021PhosphothreonineCombined sources
Modified residuei209 – 2091PhosphotyrosineBy similarity
Modified residuei411 – 4111Phosphotyrosine; by autocatalysis2 Publications
Modified residuei462 – 4621PhosphoserineCombined sources
Modified residuei522 – 5221Phosphotyrosine5 Publications
Isoform 2 (identifier: P08631-2)
Lipidationi2 – 21N-myristoyl glycine

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.
PhosphoSiteiP08631.
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 interactions.
DIPiDIP-1051N.
IntActiP08631. 72 interactions.
MINTiMINT-135300.
STRINGi9606.ENSP00000365012.

Chemistry

BindingDBiP08631.

Structurei

Secondary structure

1
526
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi81 – 877Combined sources
Beta strandi93 – 964Combined sources
Beta strandi104 – 1096Combined sources
Beta strandi114 – 1196Combined sources
Turni120 – 1223Combined sources
Beta strandi125 – 1295Combined sources
Helixi130 – 1323Combined sources
Beta strandi133 – 1353Combined sources
Helixi136 – 1383Combined sources
Helixi139 – 1413Combined sources
Beta strandi145 – 1484Combined sources
Helixi151 – 1599Combined sources
Beta strandi168 – 1725Combined sources
Beta strandi174 – 1763Combined sources
Beta strandi180 – 1889Combined sources
Turni189 – 1913Combined sources
Beta strandi192 – 20211Combined sources
Beta strandi204 – 2063Combined sources
Beta strandi208 – 2114Combined sources
Beta strandi214 – 2185Combined sources
Helixi219 – 22810Combined sources
Beta strandi233 – 2353Combined sources
Turni252 – 2554Combined sources
Helixi259 – 2613Combined sources
Beta strandi262 – 2698Combined sources
Beta strandi272 – 28110Combined sources
Turni282 – 2843Combined sources
Beta strandi285 – 2928Combined sources
Beta strandi294 – 2974Combined sources
Helixi299 – 30911Combined sources
Beta strandi320 – 3245Combined sources
Beta strandi326 – 3283Combined sources
Beta strandi330 – 3334Combined sources
Helixi341 – 3466Combined sources
Helixi348 – 3514Combined sources
Helixi355 – 37420Combined sources
Helixi384 – 3863Combined sources
Beta strandi387 – 3893Combined sources
Beta strandi395 – 3973Combined sources
Helixi402 – 4054Combined sources
Helixi409 – 4124Combined sources
Beta strandi416 – 4194Combined sources
Helixi421 – 4233Combined sources
Helixi426 – 4316Combined sources
Helixi436 – 45116Combined sources
Turni452 – 4543Combined sources
Beta strandi457 – 4604Combined sources
Helixi463 – 47210Combined sources
Beta strandi480 – 4823Combined sources
Helixi484 – 49310Combined sources
Helixi498 – 5003Combined sources
Helixi504 – 5129Combined sources
Beta strandi514 – 5185Combined sources
Beta strandi521 – 5233Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 49-526.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08631.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini78 – 13861SH3PROSITE-ProRule annotationAdd
BLAST
Domaini144 – 24198SH2PROSITE-ProRule annotationAdd
BLAST
Domaini262 – 515254Protein kinasePROSITE-ProRule annotationAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 241C → S in AAA52643 (PubMed:3496523).Curated
Sequence conflicti69 – 691N → D in BAF82585 (PubMed:14702039).Curated
Sequence conflicti144 – 1441W → R in BAB15482 (PubMed:14702039).Curated
Sequence conflicti168 – 1681F → Y in BAF82585 (PubMed:14702039).Curated
Sequence conflicti378 – 3781I → T in AAI13855 (PubMed:15489334).Curated
Sequence conflicti488 – 4881N → S in BAF82585 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 441A → T.1 Publication
Corresponds to variant rs56029200 [ dbSNP | Ensembl ].
VAR_041707
Natural varianti105 – 1051M → L.2 Publications
Corresponds to variant rs55722810 [ dbSNP | Ensembl ].
VAR_041708
Natural varianti399 – 3991D → G in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication
VAR_041709
Natural varianti502 – 5021P → Q.
Corresponds to variant rs17093828 [ dbSNP | Ensembl ].
VAR_033836

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2121Missing in isoform 2 and isoform 3. 3 PublicationsVSP_018858Add
BLAST
Alternative sequencei76 – 761Missing in isoform 3 and isoform 4. 2 PublicationsVSP_041926

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
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. Positions 49-526.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109305. 61 interactions.
DIPiDIP-1051N.
IntActiP08631. 72 interactions.
MINTiMINT-135300.
STRINGi9606.ENSP00000365012.

Chemistry

BindingDBiP08631.
ChEMBLiCHEMBL2363074.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2032.

PTM databases

iPTMnetiP08631.
PhosphoSiteiP08631.
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.
GeneCardsiHCK.
HGNCiHGNC:4840. HCK.
HPAiCAB005195.
MIMi142370. gene.
neXtProtiNX_P08631.
PharmGKBiPA29216.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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: September 7, 2016
This is version 217 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.