ID NAR4_HUMAN Reviewed; 314 AA. AC Q93070; Q9BZ50; Q9BZ51; Q9HB06; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2024, sequence version 3. DT 27-MAR-2024, entry version 182. DE RecName: Full=Ecto-ADP-ribosyltransferase 4; DE EC=2.4.2.31; DE AltName: Full=ADP-ribosyltransferase C2 and C3 toxin-like 4; DE Short=ARTC4; DE AltName: Full=Dombrock blood group carrier molecule; DE AltName: Full=Mono(ADP-ribosyl)transferase 4; DE AltName: Full=NAD(P)(+)--arginine ADP-ribosyltransferase 4; DE AltName: CD_antigen=CD297; DE Flags: Precursor; GN Name=ART4; Synonyms=DO, DOK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM, AND VARIANT ASN-265. RX PubMed=11001920; RA Gubin A.N., Njoroge J.M., Wojda U., Pack S.D., Rios M., Reid M.E., RA Miller J.L.; RT "Identification of the Dombrock blood group glycoprotein as a polymorphic RT member of the ADP-ribosyltransferase gene family."; RL Blood 96:2621-2627(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], POLYMORPHISM, AND VARIANTS VAL-108; RP ILE-117; ASN-265 AND VAL-300. RX PubMed=11896313; DOI=10.1046/j.1537-2995.2002.00004.x; RA Rios M., Hue-Roye K., Oyen R., Miller J., Reid M.E.; RT "Insights into the Holley- and Joseph- phenotypes."; RL Transfusion 42:52-58(2002). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-108; ILE-117; GLU-135; RP MET-189 AND VAL-300. RG SeattleSNPs variation discovery resource; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-265. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 48-314. RX PubMed=9119374; DOI=10.1006/geno.1996.4520; RA Koch-Nolte F., Haag F., Braren R., Kuehl M., Hoovers J., RA Balasubramanian S., Bazan J.F., Thiele H.-G.; RT "Two novel human members of an emerging mammalian gene family related to RT mono-ADP-ribosylating bacterial toxins."; RL Genomics 39:370-376(1997). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 49-284, POLYMORPHISM, AND VARIANT RP ASN-265. RX PubMed=11520417; DOI=10.1046/j.1423-0410.2001.00052.x; RA Wu G.-G., Jin S.-Z., Deng Z.-H., Zhao T.-M.; RT "Polymerase chain reaction with sequence-specific primers-based genotyping RT of the human Dombrock blood group DO1 and DO2 alleles and the DO gene RT frequencies in Chinese blood donors."; RL Vox Sang. 81:49-51(2001). RN [8] RP NOMENCLATURE. RX PubMed=20106667; DOI=10.1016/j.tibs.2009.12.003; RA Hottiger M.O., Hassa P.O., Luscher B., Schuler H., Koch-Nolte F.; RT "Toward a unified nomenclature for mammalian ADP-ribosyltransferases."; RL Trends Biochem. Sci. 35:208-219(2010). CC -!- CATALYTIC ACTIVITY: CC Reaction=L-arginyl-[protein] + NAD(+) = H(+) + N(omega)-(ADP-D- CC ribosyl)-L-arginyl-[protein] + nicotinamide; Xref=Rhea:RHEA:19149, CC Rhea:RHEA-COMP:10532, Rhea:RHEA-COMP:15087, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17154, ChEBI:CHEBI:29965, ChEBI:CHEBI:57540, CC ChEBI:CHEBI:142554; EC=2.4.2.31; CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. CC -!- TISSUE SPECIFICITY: Expressed in spleen and T-cells. CC -!- POLYMORPHISM: Variations in the ART4 gene are the basis of the Dombrock CC blood group system (Do). ART4 carries two antithetical antigens (Do(a) CC and Do(b)) and 3 high-incidence antigens, Gregory (Gy(a)), Holley (Hy), CC and Joseph (Jo(a)). Do(a) and Do(b) differ by a single variation at CC position 265, with Asn-265 corresponding to Do(a) and Asp-265 (shown in CC this entry) to Do(b). {ECO:0000269|PubMed:11520417, CC ECO:0000269|PubMed:11896313}. CC -!- SIMILARITY: Belongs to the Arg-specific ADP-ribosyltransferase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation CC database; CC URL="https://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=dombrock"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/do/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF290204; AAG17845.1; -; mRNA. DR EMBL; AF382213; AAM21462.1; -; Genomic_DNA. DR EMBL; AF382211; AAM21462.1; JOINED; Genomic_DNA. DR EMBL; AF382212; AAM21462.1; JOINED; Genomic_DNA. DR EMBL; AF382216; AAM21464.1; -; Genomic_DNA. DR EMBL; AF382214; AAM21464.1; JOINED; Genomic_DNA. DR EMBL; AF382215; AAM21464.1; JOINED; Genomic_DNA. DR EMBL; AF382219; AAM21465.1; -; Genomic_DNA. DR EMBL; AF382217; AAM21465.1; JOINED; Genomic_DNA. DR EMBL; AF382218; AAM21465.1; JOINED; Genomic_DNA. DR EMBL; AF382222; AAM21466.1; -; Genomic_DNA. DR EMBL; AF382220; AAM21466.1; JOINED; Genomic_DNA. DR EMBL; AF382221; AAM21466.1; JOINED; Genomic_DNA. DR EMBL; AF382225; AAM21467.1; -; Genomic_DNA. DR EMBL; AF382223; AAM21467.1; JOINED; Genomic_DNA. DR EMBL; AF382224; AAM21467.1; JOINED; Genomic_DNA. DR EMBL; AY899803; AAW65375.1; -; Genomic_DNA. DR EMBL; AC007655; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC074727; AAH74727.1; -; mRNA. DR EMBL; X95826; CAA65095.1; -; Genomic_DNA. DR EMBL; AF340233; AAK11274.1; -; Genomic_DNA. DR EMBL; AF340234; AAK11275.1; -; Genomic_DNA. DR CCDS; CCDS8668.1; -. DR RefSeq; NP_066549.2; NM_021071.2. DR AlphaFoldDB; Q93070; -. DR SMR; Q93070; -. DR BioGRID; 106913; 24. DR IntAct; Q93070; 1. DR STRING; 9606.ENSP00000228936; -. DR GlyConnect; 1934; 17 N-Linked glycans (3 sites). DR GlyCosmos; Q93070; 5 sites, 17 glycans. DR GlyGen; Q93070; 6 sites, 17 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q93070; -. DR PhosphoSitePlus; Q93070; -. DR BioMuta; ART4; -. DR DMDM; 22261809; -. DR jPOST; Q93070; -. DR MassIVE; Q93070; -. DR PaxDb; 9606-ENSP00000228936; -. DR PeptideAtlas; Q93070; -. DR ProteomicsDB; 75698; -. DR Antibodypedia; 23686; 173 antibodies from 22 providers. DR DNASU; 420; -. DR Ensembl; ENST00000228936.6; ENSP00000228936.4; ENSG00000111339.12. DR GeneID; 420; -. DR KEGG; hsa:420; -. DR MANE-Select; ENST00000228936.6; ENSP00000228936.4; NM_021071.4; NP_066549.2. DR UCSC; uc001rcl.2; human. DR AGR; HGNC:726; -. DR CTD; 420; -. DR DisGeNET; 420; -. DR GeneCards; ART4; -. DR HGNC; HGNC:726; ART4. DR HPA; ENSG00000111339; Tissue enhanced (liver, lymphoid tissue). DR MalaCards; ART4; -. DR MIM; 110600; gene. DR MIM; 616060; phenotype. DR neXtProt; NX_Q93070; -. DR OpenTargets; ENSG00000111339; -. DR PharmGKB; PA142672580; -. DR VEuPathDB; HostDB:ENSG00000111339; -. DR eggNOG; ENOG502SKQR; Eukaryota. DR GeneTree; ENSGT01030000234601; -. DR InParanoid; Q93070; -. DR OrthoDB; 2897283at2759; -. DR PhylomeDB; Q93070; -. DR TreeFam; TF335356; -. DR PathwayCommons; Q93070; -. DR Reactome; R-HSA-163125; Post-translational modification: synthesis of GPI-anchored proteins. DR SignaLink; Q93070; -. DR BioGRID-ORCS; 420; 10 hits in 1140 CRISPR screens. DR ChiTaRS; ART4; human. DR GeneWiki; ART4; -. DR GenomeRNAi; 420; -. DR Pharos; Q93070; Tbio. DR PRO; PR:Q93070; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q93070; Protein. DR Bgee; ENSG00000111339; Expressed in liver and 111 other cell types or tissues. DR ExpressionAtlas; Q93070; baseline and differential. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0098552; C:side of membrane; IEA:UniProtKB-KW. DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IBA:GO_Central. DR GO; GO:0106274; F:NAD+-protein-arginine ADP-ribosyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW. DR GO; GO:0006525; P:arginine metabolic process; NAS:UniProtKB. DR InterPro; IPR000768; ART. DR PANTHER; PTHR10339; ADP-RIBOSYLTRANSFERASE; 1. DR PANTHER; PTHR10339:SF1; ECTO-ADP-RIBOSYLTRANSFERASE 4; 1. DR Pfam; PF01129; ART; 1. DR PRINTS; PR00970; RIBTRNSFRASE. DR SUPFAM; SSF56399; ADP-ribosylation; 1. DR PROSITE; PS01291; ART; 1. DR PROSITE; PS51996; TR_MART; 1. DR Genevisible; Q93070; HS. PE 2: Evidence at transcript level; KW Blood group antigen; Cell membrane; Disulfide bond; Glycoprotein; KW Glycosyltransferase; GPI-anchor; Lipoprotein; Membrane; NAD; NADP; KW Nucleotidyltransferase; Reference proteome; Signal; Transferase. FT SIGNAL 1..46 FT /evidence="ECO:0000255" FT CHAIN 47..285 FT /note="Ecto-ADP-ribosyltransferase 4" FT /id="PRO_0000019329" FT PROPEP 286..314 FT /note="Removed in mature form" FT /evidence="ECO:0000255" FT /id="PRO_0000019330" FT DOMAIN 91..276 FT /note="TR mART core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01340" FT BINDING 126 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 206 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 240 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT LIPID 285 FT /note="GPI-anchor amidated alanine" FT /evidence="ECO:0000255" FT CARBOHYD 114 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 178 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 222 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 257 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 274 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 69..280 FT /evidence="ECO:0000250" FT DISULFID 182..231 FT /evidence="ECO:0000250" FT VARIANT 108 FT /note="G -> V (in Dombrock blood group antigens Hy1 and FT Hy2; dbSNP:rs28362797)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_013707" FT VARIANT 117 FT /note="T -> I (in Dombrock blood group antigen Jo(a); FT dbSNP:rs28362798)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_013708" FT VARIANT 135 FT /note="D -> E (in dbSNP:rs28362799)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022266" FT VARIANT 189 FT /note="T -> M (in dbSNP:rs28362800)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_022267" FT VARIANT 265 FT /note="D -> N (in Dombrock blood group antigen Do(a); FT dbSNP:rs11276)" FT /evidence="ECO:0000269|PubMed:11001920, FT ECO:0000269|PubMed:11520417, ECO:0000269|PubMed:11896313, FT ECO:0000269|PubMed:15489334" FT /id="VAR_013709" FT VARIANT 300 FT /note="L -> V (in Dombrock blood group antigen Hy1; FT dbSNP:rs3088190)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_013710" FT CONFLICT 48 FT /note="E -> Q (in Ref. 6; CAA65095)" FT /evidence="ECO:0000305" FT CONFLICT 116 FT /note="T -> S (in Ref. 6; CAA65095)" FT /evidence="ECO:0000305" SQ SEQUENCE 314 AA; 35879 MW; 1744A8E4B7FD158F CRC64; MGPLINRCKK ILLPTTVPPA TMRIWLLGGL LPFLLLLSGL QRPTEGSEVA IKIDFDFAPG SFDDQYQGCS KQVMEKLTQG DYFTKDIEAQ KNYFRMWQKA HLAWLNQGKV LPQNMTTTHA VAILFYTLNS NVHSDFTRAM ASVARTPQQY ERSFHFKYLH YYLTSAIQLL RKDSIMENGT LCYEVHYRTK DVHFNAYTGA TIRFGQFLST SLLKEEAQEF GNQTLFTIFT CLGAPVQYFS LKKEVLIPPY ELFKVINMSY HPRGDWLQLR STGNLSTYNC QLLKASSKKC IPDPIAIASL SFLTSVIIFS KSRV //