ID HINT3_HUMAN Reviewed; 182 AA.
AC Q9NQE9; B3KQ91; Q8N0Y9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 27-MAR-2024, entry version 158.
DE RecName: Full=Adenosine 5'-monophosphoramidase HINT3 {ECO:0000305|PubMed:17870088};
DE EC=3.9.1.- {ECO:0000269|PubMed:17870088};
DE AltName: Full=Histidine triad nucleotide-binding protein 3;
DE Short=HINT-3;
GN Name=HINT3;
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], AND VARIANT ALA-36.
RA Huang C.-H.;
RT "Human HINT-4 is a novel member of the histidine triad protein family with
RT differential polyadenylation.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Cheng J.L., Liu B.L., Chou T.F., Drontle D., Wagner C.R.;
RT "HINT-3-2, a novel member of HIT family, and Hint3-1 with phosphoramidase
RT activity.";
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-36.
RC TISSUE=Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [7]
RP GENE FAMILY.
RX PubMed=12119013; DOI=10.1021/bi025942q;
RA Brenner C.;
RT "Hint, Fhit, and GalT: function, structure, evolution, and mechanism of
RT three branches of the histidine triad superfamily of nucleotide hydrolases
RT and transferases.";
RL Biochemistry 41:9003-9014(2002).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT
RP ALA-36, ACTIVE SITE, MUTAGENESIS OF HIS-145, CATALYTIC ACTIVITY, AND
RP SUBUNIT.
RX PubMed=17870088; DOI=10.1016/j.jmb.2007.08.023;
RA Chou T.-F., Cheng J., Tikh I.B., Wagner C.R.;
RT "Evidence that human histidine triad nucleotide binding protein 3 (Hint3)
RT is a distinct branch of the histidine triad (HIT) superfamily.";
RL J. Mol. Biol. 373:978-989(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Exhibits adenosine 5'-monophosphoramidase activity,
CC hydrolyzing purine nucleotide phosphoramidates with a single phosphate
CC group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP
CC and NH2 (PubMed:17870088). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-
CC alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase
CC (PubMed:17870088). Hydrolyzes 3-indolepropionic acyl-adenylate and
CC fluorogenic purine nucleoside tryptamine phosphoramidates in vitro
CC (PubMed:17870088). {ECO:0000269|PubMed:17870088}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine 5'-phosphoramidate + H2O = AMP + NH4(+);
CC Xref=Rhea:RHEA:67916, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57890, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:17870088};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 uM for indolepropinoic acyl-adenylate
CC {ECO:0000269|PubMed:17870088};
CC KM=22 uM for tryptamine adenine phosphoramidate monoester
CC {ECO:0000269|PubMed:17870088};
CC KM=29 uM for tryptamine guanine phosphoramidate monoester
CC {ECO:0000269|PubMed:17870088};
CC KM=32 uM for tryptamine hypoxanthine phosphoramidate monoester
CC {ECO:0000269|PubMed:17870088};
CC KM=121 uM for tryptamine uracil phosphoramidate monoester
CC {ECO:0000269|PubMed:17870088};
CC KM=181 uM for tryptamine cytosine phosphoramidate monoester
CC {ECO:0000269|PubMed:17870088};
CC Note=HINT3 prefers purine over pyrimidine-based substrates.;
CC -!- SUBUNIT: Forms dimers to octamers and even larger oligomer
CC (PubMed:17870088). Interacts with CALM1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9CPS6, ECO:0000269|PubMed:17870088}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17870088}. Nucleus
CC {ECO:0000269|PubMed:17870088}. Note=Localized as aggregates in the
CC cytoplasm and the nucleus.
CC -!- SIMILARITY: Belongs to the HINT family. {ECO:0000305}.
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DR EMBL; AY035387; AAK71347.1; -; mRNA.
DR EMBL; AY035388; AAK71348.1; -; mRNA.
DR EMBL; AY486460; AAR89533.1; -; mRNA.
DR EMBL; AY486461; AAR89534.1; -; mRNA.
DR EMBL; AK057688; BAG51953.1; -; mRNA.
DR EMBL; AL035689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48129.1; -; Genomic_DNA.
DR EMBL; BC015732; AAH15732.1; -; mRNA.
DR CCDS; CCDS5133.1; -.
DR RefSeq; NP_612638.3; NM_138571.4.
DR AlphaFoldDB; Q9NQE9; -.
DR SMR; Q9NQE9; -.
DR BioGRID; 126420; 30.
DR IntAct; Q9NQE9; 6.
DR STRING; 9606.ENSP00000229633; -.
DR GlyGen; Q9NQE9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NQE9; -.
DR PhosphoSitePlus; Q9NQE9; -.
DR SwissPalm; Q9NQE9; -.
DR BioMuta; HINT3; -.
DR DMDM; 74752900; -.
DR EPD; Q9NQE9; -.
DR jPOST; Q9NQE9; -.
DR MassIVE; Q9NQE9; -.
DR MaxQB; Q9NQE9; -.
DR PaxDb; 9606-ENSP00000229633; -.
DR PeptideAtlas; Q9NQE9; -.
DR ProteomicsDB; 82145; -.
DR Pumba; Q9NQE9; -.
DR Antibodypedia; 32730; 98 antibodies from 18 providers.
DR DNASU; 135114; -.
DR Ensembl; ENST00000229633.7; ENSP00000229633.5; ENSG00000111911.7.
DR GeneID; 135114; -.
DR KEGG; hsa:135114; -.
DR MANE-Select; ENST00000229633.7; ENSP00000229633.5; NM_138571.5; NP_612638.3.
DR UCSC; uc003qal.5; human.
DR AGR; HGNC:18468; -.
DR CTD; 135114; -.
DR DisGeNET; 135114; -.
DR GeneCards; HINT3; -.
DR HGNC; HGNC:18468; HINT3.
DR HPA; ENSG00000111911; Tissue enhanced (skeletal).
DR MIM; 609998; gene.
DR neXtProt; NX_Q9NQE9; -.
DR OpenTargets; ENSG00000111911; -.
DR PharmGKB; PA29288; -.
DR VEuPathDB; HostDB:ENSG00000111911; -.
DR eggNOG; KOG4359; Eukaryota.
DR GeneTree; ENSGT00510000047616; -.
DR HOGENOM; CLU_056776_4_2_1; -.
DR InParanoid; Q9NQE9; -.
DR OMA; FCKIVNN; -.
DR OrthoDB; 2782915at2759; -.
DR PhylomeDB; Q9NQE9; -.
DR TreeFam; TF353069; -.
DR PathwayCommons; Q9NQE9; -.
DR SABIO-RK; Q9NQE9; -.
DR SignaLink; Q9NQE9; -.
DR BioGRID-ORCS; 135114; 15 hits in 1165 CRISPR screens.
DR ChiTaRS; HINT3; human.
DR GenomeRNAi; 135114; -.
DR Pharos; Q9NQE9; Tdark.
DR PRO; PR:Q9NQE9; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9NQE9; Protein.
DR Bgee; ENSG00000111911; Expressed in endothelial cell and 190 other cell types or tissues.
DR Genevisible; Q9NQE9; HS.
DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB.
DR GO; GO:0005634; C:nucleus; IMP:UniProtKB.
DR GO; GO:0043530; F:adenosine 5'-monophosphoramidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR CDD; cd01278; aprataxin_related; 1.
DR Gene3D; 3.30.428.10; HIT-like; 1.
DR InterPro; IPR011146; HIT-like.
DR InterPro; IPR036265; HIT-like_sf.
DR PANTHER; PTHR12486:SF5; ADENOSINE 5'-MONOPHOSPHORAMIDASE HINT3; 1.
DR PANTHER; PTHR12486; APRATAXIN-RELATED; 1.
DR Pfam; PF11969; DcpS_C; 1.
DR SUPFAM; SSF54197; HIT-like; 1.
DR PROSITE; PS51084; HIT_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Hydrolase; Nucleotide-binding; Nucleus;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..182
FT /note="Adenosine 5'-monophosphoramidase HINT3"
FT /id="PRO_0000324327"
FT DOMAIN 49..160
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT REGION 1..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 143..147
FT /note="Histidine triad motif"
FT ACT_SITE 145
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000269|PubMed:17870088"
FT BINDING 76..77
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT BINDING 145..147
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT VARIANT 36
FT /note="G -> A (2.5-fold increase in affinity for
FT indolepropinoic acyl-adenylate and cytosine; 2-fold
FT decrease in hypoxanthine affinity; nearly no change in
FT affinity for adenine, guanine and uracil; dbSNP:rs2295005)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17870088, ECO:0000269|Ref.1"
FT /id="VAR_039734"
FT MUTAGEN 145
FT /note="H->A: Abolishes adenosine 5'-monophosphoramidase
FT activity."
FT /evidence="ECO:0000269|PubMed:17870088"
SQ SEQUENCE 182 AA; 20361 MW; B5E7EA8A07068251 CRC64;
MAEEQVNRSA GLAPDCEASA TAETTVSSVG TCEAAGKSPE PKDYDSTCVF CRIAGRQDPG
TELLHCENED LICFKDIKPA ATHHYLVVPK KHIGNCRTLR KDQVELVENM VTVGKTILER
NNFTDFTNVR MGFHMPPFCS ISHLHLHVLA PVDQLGFLSK LVYRVNSYWF ITADHLIEKL
RT
//
