Ecto-ADP-ribosyltransferase 4 (ART4)

The protein contains 314 amino acids for an estimated molecular weight of 35878 Da.

 

No function (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 68%
Model score: 46
MODL_I-TASSER-3.0

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VariantDescription
Hy1 and Hy2
Jo(a)
dbSNP:rs28362799
dbSNP:rs28362800
Do(b), Hy1 and Hy2
Hy1

No binding partner found

The reference OMIM entry for this protein is 110600

Adp-ribosyltransferase 4; art4
Dok1

CLONING

Mono-ADP-ribosylation is a posttranslational protein modification that involves the transfer of the ADP-ribose moiety from NAD+ to a specific amino acid in the target protein. This modification helps regulate cellular metabolism in prokaryotes and is the mechanism by which some bacterial toxins function. The rodent T-cell alloantigen Rt6 has structural homology to prokaryotic ADP-ribosylation proteins and possesses mono-ADP-ribosyltransferase enzyme activity. By searching an EST database with the deduced protein sequences of ART1 (601625) and ART2P (see ART1), both of which are homologous to Rt6, Koch-Nolte et al. (1997) identified human cDNAs encoding ART3 (603086) and ART4. They isolated the corresponding genes from P1 and PAC1 genomic clones by PCR using EST-derived primers. Southern blot analysis demonstrated that human ART4 is a single-copy gene which has homologs in other primates and in mouse. Northern blot analysis detected prominent ART4 transcripts of 1.4, 2.4, and 5.5 kb only in spleen, or T-cell, RNA. The predicted ART3 and ART4 proteins contain structural motifs similar to those in ADP-ribosylating toxins, as well as hydrophobic N-terminal and C-terminal signal peptides characteristic of glycosylphosphatidylinositol (GPI)-anchored cell membrane proteins; unlike ART3, ART4 does not contain a repeated motif at the C terminus. Koch-Nolte et al. (1997) reported that ART1 is the closest known family member of ART4, with 39% amino acid sequence identity. Gubin et al. (2000) provided the first molecular description of the Dombrock (Do) blood group system (616060). A candidate gene, ART4, which they called DOK1, was identified by in silico analyses of approximately 5,000 ESTs from terminally differentiating human erythroid cells. Transfection experiments demonstrated specific binding of anti-Dombrock and confirmed GPI membrane attachment. DOK1 expression was developmentally regulated during erythroid differentiation and occurred at highest levels in fetal liver. Homology studies suggested that DOK1 is a member of the ADP-ribosyltransferase ectoenzyme gene family. Lucien et al. (2002) noted that the ART4 gene encodes a predicted 314-amino acid polypeptide containing an arginine-glycine-aspartic acid (RGD) motif, present in the DO*B allele product only, that is commonly involved in cell-cell interactions involving integrin binding and the GPI anchor motif. They stated that although the identity of DO to ART4 had been established, enzymatic activity had not been demonstrated in any cell type, including erythroid cells.

GENE STRUCTURE

A comparison of the genomic and cDNA sequences of ART4 by Koch-Nolte et al. (1997) revealed a conserved exon/intron structure, with an unusually large exon encoding the mature protein. The ART4 gene contains 3 exons spanning 14 kb (Gubin et al., 2000).

MAPPING

By PCR screening of human/rodent somatic cell hybrids and by in situ hybridization, Koch-Nolte et al. (1997) mapped the ART4 gene to 12p13.1-p12.2. Gross (2014) mapped the ART4 gene to chromosome 12p12.3 based on an alignment of the ART4 sequence (GenBank GENBANK AF290204) with the genomic sequence (GRCh38).

MOLECULAR GENETICS

Genotypic comparisons performed by Gubin et al. (2000) suggested that Do(a) versus Do(b) antigenicity of the Do blood group system results from a single amino acid substitution within an encoded RGD motif of ART4 (110600.0001). The antithetical Dombrock antigens Do(a)/Do(b) a ... More on the omim web site

The reference OMIM entry for this protein is 616060

Blood group, dombrock system; do
Dombrock blood group system

A number sign (#) is used with this entry because the Dombrock (DO) blood group system is based on variation in the gene encoding ADP-ribosyltransferase-4 (ART4; 110600) on chromosome 12p12.3.

DESCRIPTION

The DO blood group was discovered with serologic tests of blood and named after the original DO(a) serum donor in 1965. Nearly a decade passed before the discovery of the antithetical antigen, DO(b). The DO(a) and DO(b) antigens reside on a glycosylphosphatidylinositol (GPI)-anchored red blood cell (RBC) membrane glycoprotein, ART4, that also carries 3 high-incidence antigens, Gregory (Gy(a)), Holley (Hy), and Joseph (Jo(a)). The DO blood group is not associated with hemolytic disease of the newborn, but severe hemolytic transfusion reactions due to the presence of anti-DO antibodies have been reported among adults (summary by Gubin et al. (2000) and Lucien et al. (2002)).

MAPPING

Lewis et al. (1983) reported evidence of linkage of DO and PGD (172200) on chromosome 1, but data presented by Mohr et al. (1985) appeared to negate this assignment of DO. In a linkage study of 832 families from the Copenhagen region, Eiberg and Mohr (1996) found a strong indication of tight linkage of DO with 2 flanking DNA polymorphisms, D12S358 and D12S364. They thus assigned the DO locus to 12p13.2-p12.1. Gubin et al. (2000) determined that the DO blood group system results from variation in the ART4 gene, which Gross (2014) mapped the chromosome 12p12.3.

MOLECULAR GENETICS

Genotypic comparisons performed by Gubin et al. (2000) suggested that DO(a) versus DO(b) antigenicity of the DO blood group system results from a single amino acid substitution within an encoded RGD motif of ART4 (110600.0001). The antithetical Dombrock antigens DO(a)/Oo(b) also carry 3 high-incidence antigens: Gy(a), Hy, and Jo(a) (Lucien et al., 2002). The Hy polymorphisms derive from a DO*B background. The rare Dombrock-null phenotype, in which the RBCs lack all 5 antigens, may arise from a single nucleotide mutation in the acceptor splice site of intron 1, causing skipping of exon 2 (110600.0002) (Rios et al., 2001) or from the absence of GPI-anchored proteins on RBCs from patients with paroxysmal nocturnal hemoglobinemia (PNH; 300818). In all cases, negative and null phenotypes can develop anti-Dombrock antibodies that may cause severe hemolytic transfusion reactions (Halverson et al., 1994; Strupp et al., 1998). Rios et al. (2002) studied 2 probands in whom RBCs with the Dombrock-null phenotype lacked all antigens in the Dombrock blood group system. Sequence analysis of DNA from 1 proband with the Dombrock-null phenotype revealed a T-to-C mutation (110600.0004) with outsplicing of exon 2. The second proband was homozygous for a 442C-T mutation (110600.0005) in exon 2. Lucien et al. (2002) identified an 8-bp deletion (110600.0003) in the ART4 gene in a woman with the DO-null phenotype. Telen (1996) reviewed erythrocyte blood group antigens that represent polymorphisms of functionally important molecules.

POPULATION GENETICS

About 64% of northern Europeans are DO(a+) (Swanson et al., 1965). ... More on the omim web site

Subscribe to this protein entry history

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 616060 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 110600 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 616060 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 110600 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 616060 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 110600 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 616060 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 110600 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Sept. 22, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Aug. 20, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Jan. 21, 2019: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

July 2, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

July 2, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 110600 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 616060 was added.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for ART4

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 110600 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed