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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

  1. ATP binding Source: UniProtKB-KW
  2. non-membrane spanning protein tyrosine kinase activity Source: GO_Central
  3. protein tyrosine kinase activity Source: UniProtKB
  4. receptor binding Source: GO_Central

GO - Biological processi

  1. cell adhesion Source: UniProtKB
  2. cell differentiation Source: GO_Central
  3. cellular response to peptide hormone stimulus Source: GO_Central
  4. cytokine-mediated signaling pathway Source: UniProtKB
  5. Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  6. inflammatory response Source: UniProtKB-KW
  7. innate immune response Source: GO_Central
  8. innate immune response-activating signal transduction Source: UniProtKB
  9. integrin-mediated signaling pathway Source: UniProtKB
  10. interferon-gamma-mediated signaling pathway Source: UniProtKB
  11. leukocyte degranulation Source: UniProtKB
  12. leukocyte migration involved in immune response Source: UniProtKB
  13. lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  14. mesoderm development Source: ProtInc
  15. negative regulation of apoptotic process Source: UniProtKB
  16. peptidyl-tyrosine autophosphorylation Source: GO_Central
  17. peptidyl-tyrosine phosphorylation Source: UniProtKB
  18. positive regulation of actin cytoskeleton reorganization Source: UniProtKB
  19. positive regulation of actin filament polymerization Source: UniProtKB
  20. positive regulation of cell proliferation Source: UniProtKB
  21. protein autophosphorylation Source: UniProtKB
  22. protein phosphorylation Source: ProtInc
  23. regulation of cell shape Source: UniProtKB
  24. regulation of defense response to virus by virus Source: Reactome
  25. regulation of inflammatory response Source: UniProtKB
  26. regulation of phagocytosis Source: UniProtKB
  27. regulation of podosome assembly Source: UniProtKB
  28. regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  29. respiratory burst after phagocytosis Source: UniProtKB
  30. transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
  31. viral process Source: Reactome
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.
ReactomeiREACT_11068. Nef and signal transduction.
REACT_160274. FCGR activation.
REACT_23787. Regulation of signaling by CBL.
SignaLinkiP08631.

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
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:4840. HCK.

Subcellular locationi

Isoform 1 :
  1. Lysosome
  2. Membrane; Lipid-anchor
  3. Cell projectionpodosome membrane; Lipid-anchor
  4. Cytoplasmcytosol

  5. Note: Associated with specialized secretory lysosomes called azurophil granules. At least half of this isoform is found in the cytoplasm, some of this fraction is myristoylated.
Isoform 2 :
  1. Cell membrane 1 Publication; Lipid-anchor 1 Publication
  2. Membranecaveola 1 Publication; Lipid-anchor 1 Publication
  3. Cell junctionfocal adhesion 1 Publication
  4. Cytoplasmcytoskeleton 1 Publication
  5. Golgi apparatus 1 Publication
  6. Cytoplasmic vesicle 1 Publication
  7. Lysosome 1 Publication
  8. Nucleus 1 Publication

  9. 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

  1. caveola Source: UniProtKB
  2. cell projection Source: UniProtKB-KW
  3. cytoskeleton Source: UniProtKB-SubCell
  4. cytosol Source: Reactome
  5. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
  6. focal adhesion Source: UniProtKB
  7. Golgi apparatus Source: UniProtKB-SubCell
  8. lysosome Source: UniProtKB
  9. nucleus Source: UniProtKB-SubCell
  10. 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

DrugBankiDB06616. Bosutinib.

Polymorphism and mutation databases

BioMutaiHCK.
DMDMi20141296.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed
Chaini2 – 526525Tyrosine-protein kinase HCKPRO_0000024433Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycine1 Publication
Modified residuei36 – 361Phosphothreonine1 Publication
Modified residuei51 – 511Phosphotyrosine; by autocatalysis1 Publication
Modified residuei202 – 2021Phosphothreonine1 Publication
Modified residuei209 – 2091PhosphotyrosineBy similarity
Modified residuei411 – 4111Phosphotyrosine; by autocatalysis2 Publications
Modified residuei462 – 4621Phosphoserine1 Publication
Modified residuei522 – 5221Phosphotyrosine5 Publications

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.
PRIDEiP08631.

PTM databases

PhosphoSiteiP08631.

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

BgeeiP08631.
ExpressionAtlasiP08631. baseline and differential.
GenevestigatoriP08631.

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 C2orf44.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
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
PAK2Q131772EBI-346340,EBI-1045887
PDCD6IPQ8WUM44EBI-346340,EBI-310624
PIK3CBP423382EBI-346340,EBI-2609540
PLCG1P191742EBI-346340,EBI-79387
SOS1Q078894EBI-346340,EBI-297487
vifP125043EBI-346340,EBI-779991From a different organism.
WASP427689EBI-346340,EBI-346375
WIPF1O435163EBI-346340,EBI-346356

Protein-protein interaction databases

BioGridi109305. 51 interactions.
DIPiDIP-1051N.
IntActiP08631. 65 interactions.
MINTiMINT-135300.

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

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP08631.
KOiK08893.
OrthoDBiEOG7GTT2V.
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: Initiator Met-1 is removed. Contains a N-myristoyl glycine at position 2. 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 AAA52643.1 differs from that shown. Reason: Frameshift at position 20. Curated
The sequence BAF82585.1 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]
GeneIDi3055.
KEGGihsa:3055.
UCSCiuc002wxh.3. human. [P08631-1]
uc002wxi.3. human. [P08631-3]

Polymorphism and mutation databases

BioMutaiHCK.

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. 51 interactions.
DIPiDIP-1051N.
IntActiP08631. 65 interactions.
MINTiMINT-135300.

Chemistry

BindingDBiP08631.
ChEMBLiCHEMBL3234.
DrugBankiDB06616. Bosutinib.
GuidetoPHARMACOLOGYi2032.

PTM databases

PhosphoSiteiP08631.

Polymorphism and mutation databases

BioMutaiHCK.
DMDMi20141296.

Proteomic databases

MaxQBiP08631.
PaxDbiP08631.
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]
GeneIDi3055.
KEGGihsa:3055.
UCSCiuc002wxh.3. human. [P08631-1]
uc002wxi.3. human. [P08631-3]

Organism-specific databases

CTDi3055.
GeneCardsiGC20P030652.
HGNCiHGNC:4840. HCK.
HPAiCAB005195.
MIMi142370. gene.
neXtProtiNX_P08631.
PharmGKBiPA29216.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118938.
HOGENOMiHOG000233858.
HOVERGENiHBG008761.
InParanoidiP08631.
KOiK08893.
OrthoDBiEOG7GTT2V.
PhylomeDBiP08631.

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiREACT_11068. Nef and signal transduction.
REACT_160274. FCGR activation.
REACT_23787. Regulation of signaling by CBL.
SignaLinkiP08631.

Miscellaneous databases

ChiTaRSiHCK. human.
EvolutionaryTraceiP08631.
GeneWikiiHCK.
GenomeRNAii3055.
NextBioi12093.
PROiP08631.
SOURCEiSearch...

Gene expression databases

BgeeiP08631.
ExpressionAtlasiP08631. baseline and differential.
GenevestigatoriP08631.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of a human gene (HCK) that encodes a protein-tyrosine kinase and is expressed in hemopoietic cells."
    Quintrell N., Lebo R., Varmus H., Bishop J.M., Pettenati M.J., le Beau M.M., Diaz M.O., Rowley J.D.
    Mol. Cell. Biol. 7:2267-2275(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Novel protein-tyrosine kinase gene (hck) preferentially expressed in cells of hematopoietic origin."
    Ziegler S.F., Marth J.D., Lewis D.B., Perlmutter R.M.
    Mol. Cell. Biol. 7:2276-2285(1987) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), VARIANT LEU-105.
    Tissue: Corpus callosum and Ileal mucosa.
  4. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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] (ISOFORMS 1 AND 3).
    Tissue: B-cell and Lymph.
  7. "Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization."
    Lock P., Ralph S., Stanley E., Boulet I., Ramsay R., Dunn A.R.
    Mol. Cell. Biol. 11:4363-4370(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-21 (ISOFORM 1), ALTERNATIVE INITIATION.
    Tissue: Bone marrow.
  8. "The genomic locus of the human hemopoietic-specific cell protein tyrosine kinase (PTK)-encoding gene (HCK) confirms conservation of exon-intron structure among human PTKs of the src family."
    Hradetzky D., Strebhardt K., Ruesamen-Waigmann H.
    Gene 113:275-280(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 178-526.
    Tissue: Spleen.
  9. "Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells."
    Ghazizadeh S., Bolen J.B., Fleit H.B.
    J. Biol. Chem. 269:8878-8884(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FCGR2A, CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF FCGR2A.
  10. "Physical and functional association of the high affinity immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and Lyn."
    Wang A.V., Scholl P.R., Geha R.S.
    J. Exp. Med. 180:1165-1170(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FCGR1A, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, PHOSPHORYLATION.
  11. "The Fc gamma RI receptor signals through the activation of hck and MAP kinase."
    Durden D.L., Kim H.M., Calore B., Liu Y.
    J. Immunol. 154:4039-4047(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN FCGR1A SIGNALING, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, ENZYME REGULATION.
  12. "Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and association with caveolae."
    Robbins S.M., Quintrell N.A., Bishop J.M.
    Mol. Cell. Biol. 15:3507-3515(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, ALTERNATIVE INITIATION, MYRISTOYLATION AT GLY-2, PALMITOYLATION, MUTAGENESIS OF GLY-3; GLY-23 AND CYS-24.
  13. "Signal transduction of interleukin-6 involves tyrosine phosphorylation of multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck, and Lyn in multiple myeloma cell lines."
    Hallek M., Neumann C., Schaffer M., Danhauser-Riedl S., von Bubnoff N., de Vos G., Druker B.J., Yasukawa K., Griffin J.D., Emmerich B.
    Exp. Hematol. 25:1367-1377(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION, INTERACTION WITH IL6ST.
  14. "Hck is activated by opsonized zymosan and A23187 in distinct subcellular fractions of human granulocytes."
    Welch H., Maridonneau-Parini I.
    J. Biol. Chem. 272:102-109(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
  15. "SH3-mediated Hck tyrosine kinase activation and fibroblast transformation by the Nef protein of HIV-1."
    Briggs S.D., Sharkey M., Stevenson M., Smithgall T.E.
    J. Biol. Chem. 272:17899-17902(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, INTERACTION WITH HIV-1 NEF.
  16. "The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr."
    Warmuth M., Bergmann M., Priess A., Hauslmann K., Emmerich B., Hallek M.
    J. Biol. Chem. 272:33260-33270(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF BCR, INTERACTION WITH BCR-ABL.
  17. "The proto-oncogene p120(Cbl) is a downstream substrate of the Hck protein-tyrosine kinase."
    Howlett C.J., Bisson S.A., Resek M.E., Tigley A.W., Robbins S.M.
    Biochem. Biophys. Res. Commun. 257:129-138(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CBL PHOSPHORYLATION; CELL PROLIFERATION AND REGULATION OF CELL SHAPE, CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, MUTAGENESIS OF TYR-522, INTERACTION WITH CBL.
  18. "IL-2 signaling in human monocytes involves the phosphorylation and activation of p59hck."
    Bosco M.C., Curiel R.E., Zea A.H., Malabarba M.G., Ortaldo J.R., Espinoza-Delgado I.
    J. Immunol. 164:4575-4585(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN IL2 SIGNALING, CATALYTIC ACTIVITY, INDUCTION, ENZYME REGULATION, PHOSPHORYLATION.
  19. "Reciprocal regulation of Hck activity by phosphorylation of Tyr(527) and Tyr(416). Effect of introducing a high affinity intramolecular SH2 ligand."
    Porter M., Schindler T., Kuriyan J., Miller W.T.
    J. Biol. Chem. 275:2721-2726(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-411 AND TYR-522, IDENTIFICATION BY MASS SPECTROMETRY, ENZYME REGULATION, MUTAGENESIS OF GLU-305 AND TYR-411.
  20. "Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI."
    Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E., Xu L., Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.
    Nat. Immunol. 1:227-233(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN IL8-MEDIATED DEGRANULATION, ENZYME REGULATION, INTERACTION WITH ARRB1 AND ARRB2.
  21. "The tyrosine kinase Hck is an inhibitor of HIV-1 replication counteracted by the viral vif protein."
    Hassaine G., Courcoul M., Bessou G., Barthalay Y., Picard C., Olive D., Collette Y., Vigne R., Decroly E.
    J. Biol. Chem. 276:16885-16893(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HIV-1 VIF.
  22. "The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK."
    Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D.
    J. Biol. Chem. 276:42389-42400(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
  23. "The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells."
    Klejman A., Schreiner S.J., Nieborowska-Skorska M., Slupianek A., Wilson M., Smithgall T.E., Skorski T.
    EMBO J. 21:5766-5774(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS EFFECTOR OF THE BCR-ABL FUSION PROTEIN IN PHOSPHORYLATION OF STAT5B, INTERACTION WITH STAT5B AND THE BCR-ABL FUSION PROTEIN, PHOSPHORYLATION.
  24. "Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases."
    Poghosyan Z., Robbins S.M., Houslay M.D., Webster A., Murphy G., Edwards D.R.
    J. Biol. Chem. 277:4999-5007(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ADAM15, FUNCTION IN PHOSPHORYLATION OF ADAM15.
  25. "p59Hck isoform induces F-actin reorganization to form protrusions of the plasma membrane in a Cdc42- and Rac-dependent manner."
    Carreno S., Caron E., Cougoule C., Emorine L.J., Maridonneau-Parini I.
    J. Biol. Chem. 277:21007-21016(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REORGANIZATION OF THE ACTIN CYTOSKELETON; FORMATION OF CELL PROTRUSIONS AND PHAGOCYTOSIS (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORM 2), MUTAGENESIS OF GLY-3.
  26. "Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediated cellular transformation."
    Howlett C.J., Robbins S.M.
    Oncogene 21:1707-1716(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL PROLIFERATION, UBIQUITINATION, PHOSPHORYLATION AT TYR-51; TYR-411 AND TYR-522, SUBCELLULAR LOCATION, INTERACTION WITH CBL (ISOFORM 2), MUTAGENESIS OF LYS-290 AND TYR-522.
  27. "Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells."
    Podar K., Mostoslavsky G., Sattler M., Tai Y.T., Hayashi T., Catley L.P., Hideshima T., Mulligan R.C., Chauhan D., Anderson K.C.
    J. Biol. Chem. 279:21658-21665(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN IL6 SIGNALING CASCADE AND IN PHOSPHORYLATION OF GAB1 AND GAB2.
  28. "Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src-family kinase Hck."
    Yokoyama N., deBakker C.D., Zappacosta F., Huddleston M.J., Annan R.S., Ravichandran K.S., Miller W.T.
    Biochemistry 44:8841-8849(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF ELMO1, INTERACTION WITH ELMO1.
  29. "Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes."
    Cougoule C., Carreno S., Castandet J., Labrousse A., Astarie-Dequeker C., Poincloux R., Le Cabec V., Maridonneau-Parini I.
    Traffic 6:682-694(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-381.
  30. "HIV-1 Nef selectively activates Src family kinases Hck, Lyn, and c-Src through direct SH3 domain interaction."
    Trible R.P., Emert-Sedlak L., Smithgall T.E.
    J. Biol. Chem. 281:27029-27038(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HIV-1 NEF, ENZYME REGULATION.
  31. "Regulation of p73 by Hck through kinase-dependent and independent mechanisms."
    Paliwal P., Radha V., Swarup G.
    BMC Mol. Biol. 8:45-45(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION AND INHIBITION OF TP73 ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH TP73 AND YAP1.
  32. "Inhibition of IL-6-dependent growth of myeloma cells by an acidic peptide repressing the gp130-mediated activation of Src family kinases."
    Hausherr A., Tavares R., Schaffer M., Obermeier A., Miksch C., Mitina O., Ellwart J., Hallek M., Krause G.
    Oncogene 26:4987-4998(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH IL6ST.
  33. "Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
    Voss M., Lettau M., Janssen O.
    BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FASLG.
  34. "The oncogenic activity of the Src family kinase Hck requires the cooperative action of the plasma membrane- and lysosome-associated isoforms."
    Poincloux R., Al Saati T., Maridonneau-Parini I., Le Cabec V.
    Eur. J. Cancer 45:321-327(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REORGANIZATION OF ACTIN CYTOSKELETON AND CELL PROLIFERATION, ROLE IN DISEASE.
  35. "Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins."
    Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.
    J. Cell. Biochem. 108:877-885(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ADAM15.
  36. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND SER-462, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  37. "c-Abl and Src-family kinases cross-talk in regulation of myeloid cell migration."
    Baruzzi A., Iacobucci I., Soverini S., Lowell C.A., Martinelli G., Berton G.
    FEBS Lett. 584:15-21(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ABL1-MEDIATED CELL MIGRATION, IDENTIFICATION IN A COMPLEX WITH ITGB1 AND WITH ABL1.
  38. "Expression of a Src family kinase in chronic myelogenous leukemia cells induces resistance to imatinib in a kinase-dependent manner."
    Pene-Dumitrescu T., Smithgall T.E.
    J. Biol. Chem. 285:21446-21457(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN DISEASE, FUNCTION IN PHOSPHORYLATION OF THE BCR-ABL FUSION PROTEIN.
  39. "Hematopoietic cell kinase (Hck) isoforms and phagocyte duties - from signaling and actin reorganization to migration and phagocytosis."
    Guiet R., Poincloux R., Castandet J., Marois L., Labrousse A., Le Cabec V., Maridonneau-Parini I.
    Eur. J. Cell Biol. 87:527-542(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON ROLE IN PHAGOCYTOSIS AND SUBSTRATES.
  40. "Protein tyrosine kinases in neutrophil activation and recruitment."
    Zarbock A., Ley K.
    Arch. Biochem. Biophys. 510:112-119(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE IN NEUTROPHIL FUNCTION, SIGNALING.
  41. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  42. "Molecular characterization of WDCP, a novel fusion partner for the anaplastic lymphoma tyrosine kinase ALK."
    Yokoyama N., Miller W.T.
    Biomed. Rep. 3:9-13(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH C2ORF44.
  43. "Sequential assignment and secondary structure determination for the Src homology 2 domain of hematopoietic cellular kinase."
    Zhang W., Smithgall T.E., Gmeiner W.H.
    FEBS Lett. 406:131-135(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 140-245.
  44. "Crystal structure of the Src family tyrosine kinase Hck."
    Sicheri F., Moarefi I., Kuriyan J.
    Nature 385:602-609(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 78-526 IN COMPLEX WITH CALCIUM, PHOSPHORYLATION AT TYR-522.
  45. "RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef."
    Arold S., O'Brien R., Franken P., Strub M.-P., Hoh F., Dumas C., Ladbury J.E.
    Biochemistry 37:14683-14691(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 81-137.
  46. "Solution structure of the human Hck SH3 domain and identification of its ligand binding site."
    Horita D.A., Baldisseri D.M., Zhang W., Altieri A.S., Smithgall T.E., Gmeiner W.H., Byrd R.A.
    J. Mol. Biol. 278:253-265(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 72-143.
  47. "Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor."
    Schindler T., Sicheri F., Pico A., Gazit A., Levitzki A., Kuriyan J.
    Mol. Cell 3:639-648(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 81-522 IN COMPLEX WITH THE PYRAZOLO PYRIMIDINE-TYPE INHIBITOR PP1, PHOSPHORYLATION AT TYR-522.
  48. "Discovery of A-770041, a src-family selective orally active lck inhibitor that prevents organ allograft rejection."
    Burchat A., Borhani D.W., Calderwood D.J., Hirst G.C., Li B., Stachlewitz R.F.
    Bioorg. Med. Chem. Lett. 16:118-122(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 81-522 IN COMPLEXES WITH INHIBITORS A-420983; A-641359 AND A-770041, ENZYME REGULATION, PHOSPHORYLATION AT TYR-522.
  49. "The development of 2-benzimidazole substituted pyrimidine based inhibitors of lymphocyte specific kinase (Lck)."
    Sabat M., VanRens J.C., Laufersweiler M.J., Brugel T.A., Maier J., Golebiowski A., De B., Easwaran V., Hsieh L.C., Walter R.L., Mekel M.J., Evdokimov A., Janusz M.J.
    Bioorg. Med. Chem. Lett. 16:5973-5977(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 247-513 IN COMPLEX WITH INHIBITOR PG-1009247.
  50. "Solution structure of a Hck SH3 domain ligand complex reveals novel interaction modes."
    Schmidt H., Hoffmann S., Tran T., Stoldt M., Stangler T., Wiesehan K., Willbold D.
    J. Mol. Biol. 365:1517-1532(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 61-140 IN COMPLEX WITH PROLINE-RICH SYNTHETIC PEPTIDE.
  51. "Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism."
    Alvarado J.J., Betts L., Moroco J.A., Smithgall T.E., Yeh J.I.
    J. Biol. Chem. 285:35455-35461(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 72-256, ENZYME REGULATION, CATALYTIC ACTIVITY.
  52. "Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef."
    Breuer S., Schievink S.I., Schulte A., Blankenfeldt W., Fackler O.T., Geyer M.
    PLoS ONE 6:E20033-E20033(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.45 ANGSTROMS) OF 79-138 IN COMPLEX WITH HIV-1 NEF, INTERACTION WITH HIV-1 NEF.
  53. "Conformation of the dileucine-based sorting motif in HIV-1 Nef revealed by intermolecular domain assembly."
    Horenkamp F.A., Breuer S., Schulte A., Lulf S., Weyand M., Saksela K., Geyer M.
    Traffic 12:867-877(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 79-138 IN COMPLEX WITH HIV-1 NEF, INTERACTION WITH HIV-1 NEF.
  54. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-44; LEU-105 AND GLY-399.

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: April 29, 2015
This is version 202 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

External Data

Dasty 3

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 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.