ADAL_HUMAN
ID ADAL_HUMAN Reviewed; 355 AA.
AC Q6DHV7; A6NHZ3; B4DQM8;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Adenosine deaminase-like protein;
DE EC=3.5.4.- {ECO:0000269|PubMed:21755941, ECO:0000269|PubMed:29884623};
DE AltName: Full=Adenosine deaminase-like protein isoform 1 {ECO:0000303|PubMed:21755941};
DE AltName: Full=N6-mAMP deaminase {ECO:0000303|PubMed:29884623};
DE Short=HsMAPDA {ECO:0000303|PubMed:29884623};
DE AltName: Full=N6-methyl-AMP aminohydrolase {ECO:0000303|PubMed:21755941};
GN Name=ADAL; Synonyms=ADAL1 {ECO:0000303|PubMed:21755941};
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 [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 92-355 (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=21755941; DOI=10.1021/jm200650j;
RA Murakami E., Bao H., Mosley R.T., Du J., Sofia M.J., Furman P.A.;
RT "Adenosine deaminase-like protein 1 (ADAL1): characterization and substrate
RT specificity in the hydrolysis of N(6)- or O(6)-substituted purine or 2-
RT aminopurine nucleoside monophosphates.";
RL J. Med. Chem. 54:5902-5914(2011).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=29884623; DOI=10.1105/tpc.18.00236;
RA Chen M., Urs M.J., Sanchez-Gonzalez I., Olayioye M.A., Herde M.,
RA Witte C.P.;
RT "m6A RNA degradation products are catabolized by an evolutionarily
RT conserved N6-methyl-AMP deaminase in plant and mammalian cells.";
RL Plant Cell 30:1511-1522(2018).
CC -!- FUNCTION: Catalyzes the hydrolysis of the free cytosolic methylated
CC adenosine nucleotide N(6)-methyl-AMP (N6-mAMP) to produce inositol
CC monophosphate (IMP) and methylamine (PubMed:21755941, PubMed:29884623).
CC Is required for the catabolism of cytosolic N6-mAMP, which is derived
CC from the degradation of mRNA containing N6-methylated adenine (m6A)
CC (PubMed:21755941, PubMed:29884623). Catalyzes the removal of different
CC alkyl groups not only from N6-substituted purine or 2-aminopurine
CC nucleoside monophosphates but also from O6-substituted compounds in
CC vitro (PubMed:21755941). {ECO:0000269|PubMed:21755941,
CC ECO:0000269|PubMed:29884623}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O + N(6)-methyl-AMP = IMP + methylamine;
CC Xref=Rhea:RHEA:16001, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58053, ChEBI:CHEBI:59338, ChEBI:CHEBI:144842;
CC Evidence={ECO:0000269|PubMed:21755941, ECO:0000269|PubMed:29884623};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16002;
CC Evidence={ECO:0000269|PubMed:21755941, ECO:0000269|PubMed:29884623};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:21755941, ECO:0000269|PubMed:29884623};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000305|PubMed:21755941};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.5 uM for N(6)-methyl-AMP {ECO:0000269|PubMed:21755941};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:21755941}.
CC -!- INTERACTION:
CC Q6DHV7-2; P55212: CASP6; NbExp=3; IntAct=EBI-18899653, EBI-718729;
CC Q6DHV7-2; P06307: CCK; NbExp=3; IntAct=EBI-18899653, EBI-6624398;
CC Q6DHV7-2; P41091: EIF2S3; NbExp=3; IntAct=EBI-18899653, EBI-1054228;
CC Q6DHV7-2; O75460-2: ERN1; NbExp=3; IntAct=EBI-18899653, EBI-25852368;
CC Q6DHV7-2; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-18899653, EBI-10226858;
CC Q6DHV7-2; P30519: HMOX2; NbExp=3; IntAct=EBI-18899653, EBI-712096;
CC Q6DHV7-2; P54652: HSPA2; NbExp=3; IntAct=EBI-18899653, EBI-356991;
CC Q6DHV7-2; P13473-2: LAMP2; NbExp=3; IntAct=EBI-18899653, EBI-21591415;
CC Q6DHV7-2; Q14696: MESD; NbExp=3; IntAct=EBI-18899653, EBI-6165891;
CC Q6DHV7-2; P16284: PECAM1; NbExp=3; IntAct=EBI-18899653, EBI-716404;
CC Q6DHV7-2; P05771-2: PRKCB; NbExp=3; IntAct=EBI-18899653, EBI-5774511;
CC Q6DHV7-2; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-18899653, EBI-5280197;
CC Q6DHV7-2; P62826: RAN; NbExp=3; IntAct=EBI-18899653, EBI-286642;
CC Q6DHV7-2; P49591: SARS1; NbExp=3; IntAct=EBI-18899653, EBI-1053431;
CC Q6DHV7-2; P31948: STIP1; NbExp=3; IntAct=EBI-18899653, EBI-1054052;
CC Q6DHV7-2; P61086: UBE2K; NbExp=3; IntAct=EBI-18899653, EBI-473850;
CC Q6DHV7-2; P08670: VIM; NbExp=3; IntAct=EBI-18899653, EBI-353844;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6DHV7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6DHV7-2; Sequence=VSP_024821;
CC Name=3;
CC IsoId=Q6DHV7-3; Sequence=VSP_042782;
CC -!- SIMILARITY: Belongs to the metallo-dependent hydrolases superfamily.
CC Adenosine and AMP deaminases family. {ECO:0000305}.
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DR EMBL; AK126583; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK298870; BAG60990.1; -; mRNA.
DR EMBL; AC009852; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC018924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075857; AAH75857.1; -; mRNA.
DR CCDS; CCDS32214.1; -. [Q6DHV7-2]
DR CCDS; CCDS53936.1; -. [Q6DHV7-3]
DR CCDS; CCDS81868.1; -. [Q6DHV7-1]
DR RefSeq; NP_001012987.1; NM_001012969.3. [Q6DHV7-2]
DR RefSeq; NP_001152752.1; NM_001159280.2. [Q6DHV7-3]
DR RefSeq; NP_001311293.1; NM_001324364.1. [Q6DHV7-2]
DR RefSeq; NP_001311294.1; NM_001324365.1. [Q6DHV7-2]
DR RefSeq; NP_001311295.1; NM_001324366.1. [Q6DHV7-1]
DR RefSeq; NP_001311297.1; NM_001324368.1. [Q6DHV7-2]
DR RefSeq; XP_011519593.1; XM_011521291.2. [Q6DHV7-1]
DR RefSeq; XP_016877453.1; XM_017021964.1. [Q6DHV7-1]
DR RefSeq; XP_016877454.1; XM_017021965.1. [Q6DHV7-1]
DR RefSeq; XP_016877455.1; XM_017021966.1. [Q6DHV7-1]
DR AlphaFoldDB; Q6DHV7; -.
DR SMR; Q6DHV7; -.
DR BioGRID; 127803; 6.
DR IntAct; Q6DHV7; 17.
DR STRING; 9606.ENSP00000398744; -.
DR ChEMBL; CHEMBL1795150; -.
DR iPTMnet; Q6DHV7; -.
DR PhosphoSitePlus; Q6DHV7; -.
DR BioMuta; ADAL; -.
DR DMDM; 146286026; -.
DR EPD; Q6DHV7; -.
DR jPOST; Q6DHV7; -.
DR MassIVE; Q6DHV7; -.
DR MaxQB; Q6DHV7; -.
DR PeptideAtlas; Q6DHV7; -.
DR PRIDE; Q6DHV7; -.
DR ProteomicsDB; 66225; -. [Q6DHV7-1]
DR ProteomicsDB; 66226; -. [Q6DHV7-2]
DR ProteomicsDB; 66227; -. [Q6DHV7-3]
DR Antibodypedia; 23863; 92 antibodies from 16 providers.
DR DNASU; 161823; -.
DR Ensembl; ENST00000389651.8; ENSP00000374302.4; ENSG00000168803.16. [Q6DHV7-2]
DR Ensembl; ENST00000422466.6; ENSP00000398744.3; ENSG00000168803.16. [Q6DHV7-3]
DR Ensembl; ENST00000428046.7; ENSP00000413074.3; ENSG00000168803.16. [Q6DHV7-3]
DR Ensembl; ENST00000562188.7; ENSP00000456242.1; ENSG00000168803.16. [Q6DHV7-1]
DR Ensembl; ENST00000610420.4; ENSP00000478575.1; ENSG00000168803.16. [Q6DHV7-2]
DR GeneID; 161823; -.
DR KEGG; hsa:161823; -.
DR MANE-Select; ENST00000562188.7; ENSP00000456242.1; NM_001324366.2; NP_001311295.1.
DR UCSC; uc001zrh.5; human. [Q6DHV7-1]
DR CTD; 161823; -.
DR GeneCards; ADAL; -.
DR HGNC; HGNC:31853; ADAL.
DR HPA; ENSG00000168803; Low tissue specificity.
DR MIM; 619346; gene.
DR neXtProt; NX_Q6DHV7; -.
DR OpenTargets; ENSG00000168803; -.
DR PharmGKB; PA142672643; -.
DR VEuPathDB; HostDB:ENSG00000168803; -.
DR eggNOG; KOG1097; Eukaryota.
DR GeneTree; ENSGT00950000183113; -.
DR HOGENOM; CLU_039228_6_0_1; -.
DR InParanoid; Q6DHV7; -.
DR OMA; RPQFKPY; -.
DR PhylomeDB; Q6DHV7; -.
DR TreeFam; TF314270; -.
DR BioCyc; MetaCyc:ENSG00000168803-MON; -.
DR PathwayCommons; Q6DHV7; -.
DR Reactome; R-HSA-2161541; Abacavir metabolism.
DR Reactome; R-HSA-74217; Purine salvage.
DR SignaLink; Q6DHV7; -.
DR BioGRID-ORCS; 161823; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; ADAL; human.
DR GenomeRNAi; 161823; -.
DR Pharos; Q6DHV7; Tbio.
DR PRO; PR:Q6DHV7; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q6DHV7; protein.
DR Bgee; ENSG00000168803; Expressed in left ventricle myocardium and 146 other tissues.
DR ExpressionAtlas; Q6DHV7; baseline and differential.
DR Genevisible; Q6DHV7; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004000; F:adenosine deaminase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0062154; F:N6-mAMP deaminase activity; IEA:RHEA.
DR GO; GO:0006154; P:adenosine catabolic process; IBA:GO_Central.
DR GO; GO:0046103; P:inosine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009117; P:nucleotide metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR001365; A_deaminase_dom.
DR InterPro; IPR006330; Ado/ade_deaminase.
DR InterPro; IPR032466; Metal_Hydrolase.
DR PANTHER; PTHR11409; PTHR11409; 1.
DR Pfam; PF00962; A_deaminase; 1.
DR SUPFAM; SSF51556; SSF51556; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Metal-binding; Nucleotide metabolism;
KW Reference proteome; Zinc.
FT CHAIN 1..355
FT /note="Adenosine deaminase-like protein"
FT /id="PRO_0000285090"
FT ACT_SITE 211
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P03958"
FT BINDING 24
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 26
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 28
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 74
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 106..109
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 148
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 181
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 211
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 293
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT BINDING 294
FT /ligand="N(6)-methyl-AMP"
FT /ligand_id="ChEBI:CHEBI:144842"
FT /evidence="ECO:0000250|UniProtKB:Q8LPL7"
FT SITE 232
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:P03958"
FT VAR_SEQ 185..211
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042782"
FT VAR_SEQ 258..355
FT /note="ELCLTSNVKSQTVPSYDQHHFGFWYSIAHPSVICTDDKGVFATHLSQEYQLA
FT AETFNLTQSQVWDLSYESINYIFASDSTRSELRKKWNHLKPRVLHI -> GKAWSFRSS
FT R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024821"
FT CONFLICT 119
FT /note="K -> E (in Ref. 1; AK126583)"
FT /evidence="ECO:0000305"
FT CONFLICT 139
FT /note="I -> T (in Ref. 1; AK126583)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 355 AA; 40264 MW; 02810E9BC5F56CD5 CRC64;
MIEAEEQQPC KTDFYSELPK VELHAHLNGS ISSHTMKKLI AQKPDLKIHD QMTVIDKGKK
RTLEECFQMF QTIHQLTSSP EDILMVTKDV IKEFADDGVK YLELRSTPRR ENATGMTKKT
YVESILEGIK QSKQENLDID VRYLIAVDRR GGPLVAKETV KLAEEFFLST EGTVLGLDLS
GDPTVGQAKD FLEPLLEAKK AGLKLALHLS EIPNQKKETQ ILLDLLPDRI GHGTFLNSGE
GGSLDLVDFV RQHRIPLELC LTSNVKSQTV PSYDQHHFGF WYSIAHPSVI CTDDKGVFAT
HLSQEYQLAA ETFNLTQSQV WDLSYESINY IFASDSTRSE LRKKWNHLKP RVLHI
