Gene Symbol: ART4
Description: ADP-ribosyltransferase 4 (Dombrock blood group)
Alias: ARTC4, CD297, DOK1, ecto-ADP-ribosyltransferase 4, ADP-ribosyltransferase 4 (DO blood group), ADP-ribosyltransferase C2 and C3 toxin-like 4, Dombrock blood group carrier molecule, NAD(+)--protein-arginine ADP-ribosyltransferase 4, NAD(P)(+)--arginine ADP-ribosyltransferase 4, mono-ADP-ribosyltransferase 4
Species: human
Products:     ART4

Top Publications

  1. Wawrzycka D, Sadlak J, Maciaszczyk Dziubinska E, Wysocki R. Rsp5-dependent endocytosis and degradation of the arsenite transporter Acr3 requires its N-terminal acidic tail as an endocytic sorting signal and arrestin-related ubiquitin-ligase adaptors. Biochim Biophys Acta Biomembr. 2019;1861:916-925 pubmed publisher
    ..The turnover of Acr3 also depends on two arrestin-related proteins, Art3/Aly2 and Art4/Rod1, that enable recruitment of Rsp5 to its targets...
  2. Mercier P, Bachvarova M, Plante M, Gregoire J, Renaud M, Ghani K, et al. Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011;5:438-53 pubmed publisher
    ..Among the genes identified, one of particular interest was DOK1, or downstream of tyrosine kinase 1, previously recognized as a candidate tumor suppressor gene (TSG) for leukemia ..
  3. Zhang L, Li R, Hu K, Dai Y, Pang Y, Jiao Y, et al. Prognostic role of DOK family adapters in acute myeloid leukemia. Cancer Gene Ther. 2018;: pubmed publisher
    ..A total of 155 AML patients with DOK family (DOK1-7) expression data from The Cancer Genome Atlas database were enrolled in the study...
  4. Mukherjee M, Chow S, Yusoff P, Seetharaman J, Ng C, Sinniah S, et al. Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin. EMBO J. 2012;31:1308-19 pubmed publisher
    ..phosphorylated tyrosines and flanking acidic amino acids of Src substrates, such as E-cadherin, cortactin and DOK1. NMR and mutational analysis identified the Hakai residues required for target binding within the binding pocket, ..
  5. Jiang X, Huang L, Xing D. Photoactivation of Dok1/ERK/PPARγ signaling axis inhibits excessive lipolysis in insulin-resistant adipocytes. Cell Signal. 2015;27:1265-75 pubmed publisher
    ..that LPLI suppresses excessive lipolysis of insulin-resistant adipocytes by activating tyrosine kinases-1(Dok1)/ERK/PPARγ pathway...
  6. O Donnell A, McCartney R, Chandrashekarappa D, Zhang B, Thorner J, Schmidt M. 2-Deoxyglucose impairs Saccharomyces cerevisiae growth by stimulating Snf1-regulated and α-arrestin-mediated trafficking of hexose transporters 1 and 3. Mol Cell Biol. 2015;35:939-55 pubmed publisher
    ..2DG-stimulated trafficking of Hxt1 and Hxt3 requires Rod1/Art4 and Rog3/Art7, two members of the α-arrestin trafficking adaptor family...
  7. Chatterjee D, D Souza A, Zhang Y, Bin W, Tan S, Bhattacharjya S. Interaction Analyses of 14-3-3ζ, Dok1, and Phosphorylated Integrin β Cytoplasmic Tails Reveal a Bi-molecular Switch in Integrin Regulation. J Mol Biol. 2018;430:4419-4430 pubmed publisher
    ..In this study, we examined the binding interactions between 14-3-3ζ, Dok1, and phosphorylated integrin β2 and β3 CTs...
  8. Park S, Beaven M. Mechanism of upregulation of the inhibitory regulator, src-like adaptor protein (SLAP), by glucocorticoids in mast cells. Mol Immunol. 2009;46:492-7 pubmed publisher upregulation of inhibitory regulators such as Src-like adaptor protein1 (SLAP), downstream of tyrosine kinase1 (Dok1), and dual specificity protein phospahatase1 (DUSP1)...
  9. Stiffel V, Amoui M, Sheng M, Mohan S, Lau K. EphA4 receptor is a novel negative regulator of osteoclast activity. J Bone Miner Res. 2014;29:804-19 pubmed publisher
    ..the tyr-747 residue, which led to increased binding of the stimulatory talin and reduced binding of the inhibitory Dok1 to β3 -integrin. This in turn activated Vav3 and the bone resorption activity of osteoclasts...

More Information


  1. Arcones I, Sacristan C, Roncero C. Maintaining protein homeostasis: early and late endosomal dual recycling for the maintenance of intracellular pools of the plasma membrane protein Chs3. Mol Biol Cell. 2016;27:4021-4032 pubmed
    ..Moreover, the N-terminal ubiquitination of Chs3 at the plasma membrane by Rsp5/Art4 distinctly labels the protein and regulates its retromer-mediated recycling by enabling Chs3 to be recognized by ..
  2. Chatterjee D, Zhiping L, Tan S, Bhattacharjya S. Interaction Analyses of the Integrin ?2 Cytoplasmic Tail with the F3 FERM Domain of Talin and 14-3-3? Reveal a Ternary Complex with Phosphorylated Tail. J Mol Biol. 2016;428:4129-4142 pubmed publisher
    ..cytosolic tails (?-CTs) of integrins interact with a number of cytosolic proteins including talin, Dok1, and 14-3-3?...
  3. Tian X, Ye M, Cao Y, Wang C. Losartan Improves Palmitate-Induced Insulin Resistance in 3T3-L1 Adipocytes Through Upregulation of Src Phosphorylation. Exp Clin Endocrinol Diabetes. 2017;125:136-140 pubmed publisher
    ..glucose uptake, along with increased Src phosphorylation as well as reduced expression of docking protein 1(DOK1) in palmitate-treated 3T3-L1 adipocytes...
  4. Llopis Torregrosa V, Ferri Blázquez A, Adam Artigues A, Deffontaines E, Van Heusden G, Yenush L. Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 ?-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein. J Biol Chem. 2016;291:14973-85 pubmed publisher
    ..Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 ..
  5. Ding X, Wang W, Wang M, Wu J, Yao F. DOK1/PPARgamma pathway mediates anti-tumor ability of all-trans retinoic acid in breast cancer MCF-7 cells. Biochem Biophys Res Commun. 2017;487:189-193 pubmed publisher
    ..MCF-7 cell proliferation and promoted its apoptosis, along with an enhanced expression of docking protein 1 (DOK1). ATRA's effects on cell proliferation and apoptosis were prevented by DOK1 knockdown...
  6. De Simone M, Spagnuolo L, Lorè N, Cigana C, De Fino I, Broman K, et al. Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice. BMC Genomics. 2016;17:351 pubmed publisher
    ..aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment ..
  7. Alvaro C, Aindow A, Thorner J. Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-regulates Mating Pheromone Response in Saccharomyces cerevisiae. Genetics. 2016;203:299-317 pubmed publisher
    ..agonist-stimulated internalization of Ste2 requires its association with an adaptor protein, the α-arrestin Rod1/Art4, which recruits the HECT-domain ubiquitin ligase Rsp5, allowing for ubiquitinylation of the C-terminal tail of the ..
  8. Guittard G, Pontarotti P, Granjeaud S, Rodrigues M, Abi Rached L, Nunes J. Evolutionary and expression analyses reveal a pattern of ancient duplications and functional specializations in the diversification of the Downstream of Kinase (DOK) genes. Dev Comp Immunol. 2018;84:193-198 pubmed publisher
    ..Using phylogenetics and intron/exon structure data, we show here that the seven human DOK genes (DOK1 to DOK7) form three highly divergent groups that emerged before the protostome-deuterostome split: DOK1/2/3, DOK4/5/..
  9. Goel R, Paczkowska M, Reimand J, Napper S, Lukong K. Phosphoproteomics Analysis Identifies Novel Candidate Substrates of the Nonreceptor Tyrosine Kinase, Src-related Kinase Lacking C-terminal Regulatory Tyrosine and N-terminal Myristoylation Sites (SRMS). Mol Cell Proteomics. 2018;17:925-947 pubmed publisher
    ..b>DOK1, a previously characterized SRMS substrate, was also identified in our analyses...
  10. Friedrich T, Söhn M, Gutting T, Janssen K, Behrens H, Rocken C, et al. Subcellular compartmentalization of docking protein-1 contributes to progression in colorectal cancer. EBioMedicine. 2016;8:159-172 pubmed publisher
    Full-length (FL) docking protein-1 (DOK1) is an adapter protein which inhibits growth factor and immune response pathways in normal tissues, but is frequently lost in human cancers...
  11. Coppin E, De Grandis M, Pandolfi P, Arcangeli M, Aurrand Lions M, Nunes J. Dok1 and Dok2 Proteins Regulate Cell Cycle in Hematopoietic Stem and Progenitor Cells. J Immunol. 2016;196:4110-21 pubmed publisher
    b>Dok1 and Dok2 proteins play a crucial role in myeloid cell proliferation as demonstrated by Dok1 and Dok2 gene inactivation, which induces a myeloproliferative disease in aging mice...
  12. Sarin N, Engel F, Rothweiler F, Cinatl J, Michaelis M, Frötschl R, et al. Key Players of Cisplatin Resistance: Towards a Systems Pharmacology Approach. Int J Mol Sci. 2018;19: pubmed publisher
    ..with available gene annotations and without a previously defined hypothesis HRas, MAPK14 (p38), CCL2, DOK1 and PTK2B were identified as genes possibly relevant for cisplatin resistance...
  13. Ohsugi T, Wakamiya M, Morikawa S, Fujita M. Expression of DOK1, 2, and 3 genes in HTLV-1-infected T cells. Acta Virol. 2016;60:211-3 pubmed
    ..In this study, we examined the expression of the downstream of tyrosine kinase (DOK) family members DOK1, DOK2 and DOK3, recently reported to be tumor suppressors, in HTLV-1-transformed T cells (MT-2 and HUT-102) and TL-..
  14. Yu L, Fang F, Lu S, Li X, Yang Y, Wang Z. lncRNA-HIT promotes cell proliferation of non-small cell lung cancer by association with E2F1. Cancer Gene Ther. 2017;24:221-226 pubmed publisher
    ..showed that lncRNA-HIT interacted with E2F1 to regulate its target genes, such as Survivin, FOXM1, SKP2, NELL2 and DOK1. Collectively, our findings indicated that lncRNA-HIT affected the proliferation of NSCLC cells at least in part ..
  15. Chen C, Bartenhagen C, Gombert M, Okpanyi V, Binder V, Röttgers S, et al. Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients. Leuk Res. 2015;39:990-1001 pubmed publisher
    ..Eleven novel translocations involved the genes ART4, C12orf60, MACROD2, TBL1XR1, LRRN4, KIAA1467, and ELMO1/MIR1200...
  16. Fichou Y, Mariez M, Le Marechal C, Ferec C. The experience of extended blood group genotyping by next-generation sequencing (NGS): investigation of patients with sickle-cell disease. Vox Sang. 2016;111:418-424 pubmed publisher
    ..Unreferenced alleles in the ACHE and ART4 genes, respectively, involved in the Yt and Dombrock blood groups, were identified, then contributing to extend the ..
  17. Ho H, MacGurn J, Emr S. Deubiquitinating enzymes Ubp2 and Ubp15 regulate endocytosis by limiting ubiquitination and degradation of ARTs. Mol Biol Cell. 2017;28:1271-1283 pubmed publisher
    ..Specifically, we show that loss of both Ubp2 and Ubp15 results in a defect in Hxt6 endocytosis associated with Art4 instability...
  18. Ly N, Cyert M. Calcineurin, the Ca2+-dependent phosphatase, regulates Rga2, a Cdc42 GTPase-activating protein, to modulate pheromone signaling. Mol Biol Cell. 2017;28:576-586 pubmed publisher
    ..Calcineurin regulates Dig2 and Rod1/Art4 to inhibit mating-induced gene expression and activate receptor internalization, respectively...
  19. Gupta S, Chit J, Feng C, Bhunia A, Tan S, Bhattacharjya S. An Alternative Phosphorylation Switch in Integrin β2 (CD18) Tail for Dok1 Binding. Sci Rep. 2015;5:11630 pubmed publisher
    ..A large number of proteins interact with the cytoplasmic tails of integrins. Dok1 is a negative regulator of integrin activation and it binds to the phosphorylated membrane proximal NxxY motif in a ..
  20. Araujo O, Rosa A, Fernandes A, Niel C, Villela Nogueira C, Pannain V, et al. RASSF1A and DOK1 Promoter Methylation Levels in Hepatocellular Carcinoma, Cirrhotic and Non-Cirrhotic Liver, and Correlation with Liver Cancer in Brazilian Patients. PLoS ONE. 2016;11:e0153796 pubmed publisher
    ..The aim of this study was to determine whether aberrant methylation of RASSF1A and DOK1 gene promoters is associated with the progression of liver disease in Brazilian patients...
  21. Rios M, Storry J, Hue Roye K, Chung A, Reid M. Two new molecular bases for the Dombrock null phenotype. Br J Haematol. 2002;117:765-7 pubmed
    ..The molecular bases described in these two probands provide an explanation for the lack of Do glycoprotein on their RBCs. ..
  22. Wu G, Jin S, Deng Z, Zhao T. Polymerase chain reaction with sequence-specific primers-based genotyping of the human Dombrock blood group DO1 and DO2 alleles and the DO gene frequencies in Chinese blood donors. Vox Sang. 2001;81:49-51 pubmed
  23. Gubin A, Njoroge J, Wojda U, Pack S, Rios M, Reid M, et al. Identification of the dombrock blood group glycoprotein as a polymorphic member of the ADP-ribosyltransferase gene family. Blood. 2000;96:2621-7 pubmed
    ..Genotypic comparisons suggest Do(a) versus Do(b) antigenicity results from a single amino acid substitution within an encoded arginine-glycine-aspartic acid (RGD) motif of the molecule. ..
  24. Hashmi G, Shariff T, Seul M, Vissavajjhala P, Hue Roye K, Charles Pierre D, et al. A flexible array format for large-scale, rapid blood group DNA typing. Transfusion. 2005;45:680-8 pubmed
    ..It has been shown that microarray technology can be used to type DNA and detect new alleles in donor cohorts. ..
  25. Friedrich M, Grahnert A, Hauschildt S. Analysis of the 3' UTR of the ART3 and ART4 gene by 3' inverse RACE-PCR. DNA Seq. 2005;16:53-7 pubmed
    ..method to analyze the 3' UTR of human mono-ADP-ribosyltransferase (ART) 3 mRNA in testis and heart muscle and of ART4 mRNA in HEL cells...
  26. Mauthe J, Coghlan G, Zelinski T. Confirmation of the assignment of the Dombrock blood group locus (DO) to chromosome 12p: narrowing the boundaries to 12p12.3-p13.2. Vox Sang. 2000;79:53-6 pubmed
    ..16 at peak recombination fraction (theta) = 0.08 and 7.69 at theta = 0.08, respectively. We have confirmed the assignment of the Dombrock blood group locus to chromosome 12p and have refined its regional localization to 12p12.3-p13.2. ..
  27. Chapel Fernandes S, Callebaut I, Halverson G, Reid M, Bailly P, Chiaroni J. Dombrock genotyping in a native Congolese cohort reveals two novel alleles. Transfusion. 2009;49:1661-71 pubmed publisher
    ..Expression studies highlighted the impact of changes on Do protein expression. These findings suggest that allelic diversity is greater than expected and that expression level of DO alleles should be taken into account in transfusion ..
  28. Durousseau de Coulgeans C, Chiaroni J, Bailly P, Chapel Fernandes S. Sequencing of the ART4 gene in sub-Saharan cohorts reveals ethnic differences and two new DO alleles: DO*B-Ile5Thr and DO*B-Trp266Arg. Transfusion. 2015;55:2376-83 pubmed publisher
    ..populations especially between nonpygmoids and pygmoids, differences are expected during investigation of the DO/ART4 gene...
  29. Choi E, Lee J, Kim M, Song S, Yoo N, Lee S. Intratumoral Heterogeneity of Somatic Mutations for NRIP1, DOK1, ULK1, ULK2, DLGAP3, PARD3 and PRKCI in Colon Cancers. Pathol Oncol Res. 2018;24:827-832 pubmed publisher
    Both NRIP1 and DOK1 genes are considered candidate tumor suppressor genes (TSGs)...
  30. He P, Xu Z, Zhou J, Li X, Zhang W, Wu D, et al. Methylation-associated DOK1 and DOK2 down-regulation: potential biomarkers for predicting adverse prognosis in acute myeloid leukemia. J Cell Physiol. 2017;: pubmed publisher
    DOK-1 and DOK-2 (DOK1/2) are closely related members of downstream of tyrosine kinase (DOK) family genes, which are found to be frequently rearranged in several hematopoietic cancers...
  31. Onodera T, Tsuneyama H, Ogasawara K, Isa K, Satake M, Tadokoro K, et al. A novel DO null allele with a c.268C>T (p.Gln90Stop) mutation in Japanese. Vox Sang. 2015;109:191-3 pubmed publisher
    ..Do(a) /Do(b) polymorphism is associated with c.793A>G (p.Asn265Asp) in exon 2 of the DO (ART4) gene, and the corresponding alleles are named DO*01 and DO*02...
  32. Grodecka M, Wasniowska K, Halverson G, Yazdanbakhsh K, Reid M, Lisowska E. The production, serologic evaluation, and epitope mapping of ten murine monoclonal Dombrock antibodies. Immunohematology. 2012;28:124-9 pubmed
    ..The dependence of some epitopes on antigen glycosylation is also a possibility. ..
  33. Di Cristofaro J, Silvy M, Chiaroni J, Bailly P. Single PCR multiplex SNaPshot reaction for detection of eleven blood group nucleotide polymorphisms: optimization, validation, and one year of routine clinical use. J Mol Diagn. 2010;12:453-60 pubmed publisher
    ..The findings show that this assay can provide a low-cost and fast genotyping tool well adapted to local ethnically mixed populations. ..
  34. Polin H, Danzer M, Proll J, Hofer K, Heilinger U, Zopf A, et al. Introduction of a real-time-based blood-group genotyping approach. Vox Sang. 2008;95:125-30 pubmed publisher
    ..The advantages of this real-time polymerase chain reaction method are its automation potential, the flexibility regarding hardware and the rapid cycling time. ..
  35. Grahnert A, Friedrich M, Engeland K, Hauschildt S. Analysis of mono-ADP-ribosyltransferase 4 gene expression in human monocytes: splicing pattern and potential regulatory elements. Biochim Biophys Acta. 2005;1730:173-86 pubmed
    ..b>ART4 could be detected on HEL cells and erythrocytes by FACS analysis while it was absent from activated monocytes, ..
  36. Reid M. The Dombrock blood group system: a review. Transfusion. 2003;43:107-14 pubmed
  37. Glowacki G, Braren R, Firner K, Nissen M, Kühl M, Reche P, et al. The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse. Protein Sci. 2002;11:1657-70 pubmed
    ..This suggests that the two enzyme families that catalyze reversible mono-ADP-ribosylation either were lost from the genomes of these nonchordata eucaryotes or were subject to horizontal gene transfer between kingdoms. ..
  38. Rios M, Hue Roye K, Øyen R, Miller J, Reid M. Insights into the Holley- and Joseph- phenotypes. Transfusion. 2002;42:52-8 pubmed
    ..The 898 C>G mutation, within the sequence motif for glycosylphosphatidylinositol linkage, may cause reduced efficiency of anchoring the protein to the RBC membrane, thereby weakening the expression of Gy(a) and Do(b). ..
  39. Eiberg H, Mohr J. Dombrock blood group (DO): assignment to chromosome 12p. Hum Genet. 1996;98:518-21 pubmed
    ..66; at theta M = 0.001, theta F = 0.031) and D12S364 (z = 8.53; at theta M = 0.068, theta F = 0.031). DO is assigned to the region 12p13.2-12p12.1 by physically localised markers. ..
  40. Tippett P. Genetics of the Dombrock blood group system. J Med Genet. 1967;4:7-11 pubmed
  41. Lomas Francis C, Reid M. The Dombrock blood group system: a review. Immunohematology. 2010;26:71-8 pubmed
    ..The gene (DO, ART4) encoding the Do glycoprotein, located on the short arm of chromosome 12, has been cloned and sequenced, allowing ..
  42. Koch Nolte F, Haag F, Braren R, Kuhl M, Hoovers J, Balasubramanian S, et al. Two novel human members of an emerging mammalian gene family related to mono-ADP-ribosylating bacterial toxins. Genomics. 1997;39:370-6 pubmed the public database and cloned the two novel human genes from which these are derived (designated ART3 and ART4)...