DOK2

DOK2
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2D9W, 2DLW
Identifiers
Aliases	DOK2 , p56DOK, p56dok-2, docking protein 2
External IDs	OMIM: 604997 MGI: 1332623 HomoloGene: 2957 GeneCards: DOK2
Gene location (Human)
Chr.	Chromosome 8 (human)
End	21,913,690 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	70,778,495 bp
RNA expression pattern
	Top expressed in
	monocyte; ; blood; ; spleen; ; lymph node; ; appendix; ; upper lobe of left lung; ; lower lobe of lung; ; right lung; ; synovial membrane; ; bone marrow;
	Top expressed in
	thymus; ; blood; ; spleen; ; morula; ; lymph node; ; lip; ; bone marrow; ; spermatid; ; yolk sac; ; subcutaneous adipose tissue;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	protein binding ; transmembrane receptor protein tyrosine kinase adaptor activity ;
Cellular component	cytosol ;
Biological process	cell surface receptor signaling pathway ; Ras protein signal transduction ; leukocyte migration ; signal transduction ; transmembrane receptor protein tyrosine kinase signaling pathway ; axon guidance ;
	Sources:Amigo / QuickGO
Orthologs
	9046
	13449
	ENSG00000147443
	ENSMUSG00000022102
	O60496
	O70469
	NM_003974 ; NM_201349 ; NM_001317800 ; NM_001401272
	NM_010071
	NP_001304729 ; NP_003965 ; NP_958728
	NP_034201 ; NP_001388209 ; NP_001388210
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 14, 2022

Docking protein 2 is a protein that in humans is encoded by the DOK2 gene.^[5]^[6]^[7]

Function

The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells.^[7]

Interactions

DOK2 has been shown to interact with INPP5D ^[8] and TEK tyrosine kinase.^[9]^[10]

Related Research Articles

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.

<span class="mw-page-title-main">Philadelphia chromosome</span> Medical condition

The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.

Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus.

Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene.

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

Cbl is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.

RAS p21 protein activator 1 or RasGAP, also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:

Docking protein 1 is a protein that in humans is encoded by the DOK1 gene.

Angiopoietin-1 receptor also known as CD202B is a protein that in humans is encoded by the TEK gene. Also known as TIE2, it is an angiopoietin receptor.

Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1(SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the INPP5D gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies.

Ribosomal protein S6 kinase alpha-5 is an enzyme that in humans is encoded by the RPS6KA5 gene. This kinase, together with RPS6KA4, are thought to mediate the phosphorylation of histone H3, linked to the expression of immediate early genes.

Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene.

Activated CDC42 kinase 1, also known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene. TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor (IR). ACK1 also interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.

Proto-oncogene tyrosine-protein kinase FER is an enzyme that in humans is encoded by the FER gene.

Ras and Rab interactor 1 is a protein that in humans is encoded by the RIN1 gene.

Docking protein 5 is a protein that in humans is encoded by the DOK5 gene.

Docking protein 3 is a protein that in humans is encoded by the DOK3 gene.

A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.

A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. The proteins are activated by adding a phosphate group to the protein (phosphorylation), a step that TKIs inhibit. TKIs are typically used as anticancer drugs. For example, they have substantially improved outcomes in chronic myelogenous leukemia. They have also been used to treat other diseases, such as idiopathic pulmonary fibrosis.

Tyrosine phosphorylation is the addition of a phosphate (PO₄³⁻) group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyrosine phosphorylation is a key step in signal transduction and the regulation of enzymatic activity.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000147443 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022102 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Di Cristofano A, Carpino N, Dunant N, Friedland G, Kobayashi R, Strife A, Wisniewski D, Clarkson B, Pandolfi PP, Resh MD (March 1998). "Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins". J Biol Chem. 273 (9): 4827–30. doi: 10.1074/jbc.273.9.4827 . PMID 9478921.
↑ Garcia A, Prabhakar S, Hughan S, Anderson TW, Brock CJ, Pearce AC, Dwek RA, Watson SP, Hebestreit HF, Zitzmann N (March 2004). "Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins". Blood. 103 (6): 2088–95. doi: 10.1182/blood-2003-07-2392 . PMID 14645010.
1 2 "Entrez Gene: DOK2 docking protein 2, 56kDa".
↑ Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cell. Signal. 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. PMID 10822173.
↑ Jones N, Dumont DJ (1998). "The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R". Oncogene. 17 (9): 1097–108. doi: 10.1038/sj.onc.1202115 . PMID 9764820.
↑ Master Z, Jones N, Tran J, Jones J, Kerbel RS, Dumont DJ (2001). "Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak". EMBO J. 20 (21): 5919–28. doi:10.1093/emboj/20.21.5919. PMC 125712 . PMID 11689432.

Jiang H, Harris MB, Rothman P (2000). "IL-4/IL-13 signaling beyond JAK/STAT". J. Allergy Clin. Immunol. 105 (6 Pt 1): 1063–70. doi:10.1067/mai.2000.107604. PMID 10856136.
Jones N, Dumont DJ (1998). "The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R". Oncogene. 17 (9): 1097–108. doi: 10.1038/sj.onc.1202115 . PMID 9764820.
Jones N, Dumont DJ (2000). "Recruitment of Dok-R to the EGF receptor through its PTB domain is required for attenuation of Erk MAP kinase activation". Curr. Biol. 9 (18): 1057–60. doi: 10.1016/S0960-9822(99)80458-8 . PMID 10508618. S2CID 18831513.
Némorin JG, Duplay P (2000). "Evidence that Llck-mediated phosphorylation of p56dok and p62dok may play a role in CD2 signaling". J. Biol. Chem. 275 (19): 14590–7. doi: 10.1074/jbc.275.19.14590 . PMID 10799545.
Dunant NM, Wisniewski D, Strife A, et al. (2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cell. Signal. 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. PMID 10822173.
Némorin JG, Laporte P, Bérubé G, Duplay P (2001). "p62dok negatively regulates CD2 signaling in Jurkat cells". J. Immunol. 166 (7): 4408–15. doi: 10.4049/jimmunol.166.7.4408 . PMID 11254695.
Grimm J, Sachs M, Britsch S, et al. (2001). "Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation" (PDF). J. Cell Biol. 154 (2): 345–54. doi:10.1083/jcb.200102032. PMC 2150770 . PMID 11470823.
Master Z, Jones N, Tran J, et al. (2001). "Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak". EMBO J. 20 (21): 5919–28. doi:10.1093/emboj/20.21.5919. PMC 125712 . PMID 11689432.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC 139241 . PMID 12477932.
Salomon AR, Ficarro SB, Brill LM, et al. (2003). "Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry". Proc. Natl. Acad. Sci. U.S.A. 100 (2): 443–8. Bibcode:2003PNAS..100..443S. doi: 10.1073/pnas.2436191100 . PMC 141014 . PMID 12522270.
Jones N, Chen SH, Sturk C, et al. (2003). "A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function". Mol. Cell. Biol. 23 (8): 2658–68. doi:10.1128/MCB.23.8.2658-2668.2003. PMC 152553 . PMID 12665569.
Master Z, Tran J, Bishnoi A, et al. (2003). "Dok-R binds c-Abl and regulates Abl kinase activity and mediates cytoskeletal reorganization". J. Biol. Chem. 278 (32): 30170–9. doi: 10.1074/jbc.M301339200 . PMID 12777393.
Gérard A, Favre C, Garçon F, et al. (2004). "Functional interaction of RasGAP-binding proteins Dok-1 and Dok-2 with the Tec protein tyrosine kinase". Oncogene. 23 (8): 1594–8. doi: 10.1038/sj.onc.1207283 . PMID 14647425.
Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928 . PMID 15489334.
Rush J, Moritz A, Lee KA, et al. (2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nat. Biotechnol. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455. S2CID 7200157.
Van Slyke P, Coll ML, Master Z, et al. (2005). "Dok-R mediates attenuation of epidermal growth factor-dependent mitogen-activated protein kinase and Akt activation through processive recruitment of c-Src and Csk". Mol. Cell. Biol. 25 (9): 3831–41. doi:10.1128/MCB.25.9.3831-3841.2005. PMC 1084282 . PMID 15831486.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000147443 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022102 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9478921-5] Di Cristofano A, Carpino N, Dunant N, Friedland G, Kobayashi R, Strife A, Wisniewski D, Clarkson B, Pandolfi PP, Resh MD (March 1998). "Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins". J Biol Chem. 273 (9): 4827–30. doi: 10.1074/jbc.273.9.4827 . PMID 9478921.

[pmid14645010-6] Garcia A, Prabhakar S, Hughan S, Anderson TW, Brock CJ, Pearce AC, Dwek RA, Watson SP, Hebestreit HF, Zitzmann N (March 2004). "Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins". Blood. 103 (6): 2088–95. doi: 10.1182/blood-2003-07-2392 . PMID 14645010.

[entrez-7] 1 2 "Entrez Gene: DOK2 docking protein 2, 56kDa".

[pmid10822173-8] Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells". Cell. Signal. 12 (5): 317–26. doi:10.1016/S0898-6568(00)00073-5. PMID 10822173.

[pmid9764820-9] Jones N, Dumont DJ (1998). "The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R". Oncogene. 17 (9): 1097–108. doi: 10.1038/sj.onc.1202115 . PMID 9764820.

[pmid11689432-10] Master Z, Jones N, Tran J, Jones J, Kerbel RS, Dumont DJ (2001). "Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak". EMBO J. 20 (21): 5919–28. doi:10.1093/emboj/20.21.5919. PMC 125712 . PMID 11689432.

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DOK2

Contents

Function

Interactions

Related Research Articles

References

Further reading