HINT1_RABIT
ID HINT1_RABIT Reviewed; 126 AA.
AC P80912;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Adenosine 5'-monophosphoramidase HINT1 {ECO:0000305|PubMed:11805111};
DE EC=3.9.1.- {ECO:0000250|UniProtKB:P49773};
DE AltName: Full=Desumoylating isopeptidase HINT1 {ECO:0000250|UniProtKB:P49773};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:P49773};
DE AltName: Full=Histidine triad nucleotide-binding protein 1;
DE AltName: Full=P13.7;
GN Name=HINT1; Synonyms=HINT;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=9291120; DOI=10.1042/bj3260471;
RA Gilmour J., Liang N., Lowenstein J.M.;
RT "Isolation, cloning and characterization of a low-molecular-mass purine
RT nucleoside- and nucleotide-binding protein.";
RL Biochem. J. 326:471-477(1997).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11805111; DOI=10.1074/jbc.m111480200;
RA Bieganowski P., Garrison P.N., Hodawadekar S.C., Faye G., Barnes L.D.,
RA Brenner C.;
RT "Adenosine monophosphoramidase activity of Hint and Hnt1 supports function
RT of Kin28, Ccl1, and Tfb3.";
RL J. Biol. Chem. 277:10852-10860(2002).
RN [3]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=15703176; DOI=10.1074/jbc.m500434200;
RA Chou T.F., Bieganowski P., Shilinski K., Cheng J., Brenner C., Wagner C.R.;
RT "31P NMR and genetic analysis establish hinT as the only Escherchia coli
RT purine nucleoside phosphoramidase and as essential for growth under high
RT salt conditions.";
RL J. Biol. Chem. 280:15356-15361(2005).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 12-126 IN COMPLEXES WITH
RP 8-BROMO-ADENOSINE-5'-MONOPHOSPHATE AND GUANOSINE-5'-MONOPHOSPHATE.
RX PubMed=9164465; DOI=10.1038/nsb0397-231;
RA Brenner C., Garrison P., Gilmour J., Peisach D., Ringe D., Petsko G.A.,
RA Lowenstein J.M.;
RT "Crystal structures of HINT demonstrate that histidine triad proteins are
RT GalT-related nucleotide-binding proteins.";
RL Nat. Struct. Biol. 4:231-238(1997).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-125 IN COMPLEX WITH
RP 5'-O-(N-ETHYL-SULFAMOYL)ADENOSINE, AND SUBUNIT.
RX PubMed=14982931; DOI=10.1074/jbc.m314271200;
RA Krakowiak A., Pace H.C., Blackburn G.M., Adams M., Mekhalfia A.,
RA Kaczmarek R., Baraniak J., Stec W.J., Brenner C.;
RT "Biochemical, crystallographic, and mutagenic characterization of hint, the
RT AMP-lysine hydrolase, with novel substrates and inhibitors.";
RL J. Biol. Chem. 279:18711-18716(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.08 ANGSTROMS) IN COMPLEX WITH ADENOSINE
RP 5'-O-PHOSPHOROTHIOATE, FUNCTION, SUBUNIT, AND MUTAGENESIS OF CYS-38;
RP CYS-84; SER-107 AND HIS-114.
RX PubMed=20940308; DOI=10.1074/jbc.m110.162065;
RA Ozga M., Dolot R., Janicka M., Kaczmarek R., Krakowiak A.;
RT "Histidine triad nucleotide-binding protein 1 (HINT-1) phosphoramidase
RT transforms nucleoside 5'-O-phosphorothioates to nucleoside 5'-O-
RT phosphates.";
RL J. Biol. Chem. 285:40809-40818(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) IN COMPLEX WITH ADENOSINE, AND
RP SUBUNIT.
RX PubMed=21697598; DOI=10.1107/s0907444911015605;
RA Dolot R., Ozga M., Krakowiak A., Nawrot B.;
RT "High-resolution X-ray structure of the rabbit histidine triad nucleotide-
RT binding protein 1 (rHINT1)-adenosine complex at 1.10 A resolution.";
RL Acta Crystallogr. D 67:601-607(2011).
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:11805111, PubMed:15703176). Hydrolyzes adenosine
CC 5'monophosphomorpholidate (AMP-morpholidate) and guanosine
CC 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176).
CC Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl
CC ester)) generated by lysine tRNA ligase (PubMed:20940308). Hydrolyzes
CC Met-AMP, His-AMP, Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl
CC lysine methyl ester)) and AMP-N-alanine methyl ester (By similarity).
CC Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-
CC phosphorothioate to the corresponding nucleoside 5'-O-phosphates with
CC concomitant release of hydrogen sulfide (PubMed:20940308). In addition,
CC functions as scaffolding protein that modulates transcriptional
CC activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed
CC with MITF and CTNNB1 (By similarity). Modulates p53/TP53 levels and
CC p53/TP53-mediated apoptosis. Modulates proteasomal degradation of
CC target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-
CC protein ligase complex (By similarity). Also exhibits SUMO-specific
CC isopeptidase activity, deconjugating SUMO1 from RANGAP1 and RGS17 (By
CC similarity). {ECO:0000250|UniProtKB:P49773,
CC ECO:0000250|UniProtKB:P70349, ECO:0000269|PubMed:11805111,
CC ECO:0000269|PubMed:15703176, ECO:0000269|PubMed:20940308}.
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:0000250|UniProtKB:P49773};
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with CDK7 (By
CC similarity). Interacts with RUVBL1 and RUVBL2 and is associated with
CC the LEF1/TCF1-CTNNB1 complex and with a KAT5 histone acetyltransferase
CC complex (By similarity). Identified in a complex with MITF and CTNNB1
CC (By similarity). Interacts with CDC34 and RBX1, and is part of a SCF
CC (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By
CC similarity). Interacts with SUMO1, SUMO2 and RGS17 (By similarity).
CC Interacts with the Ten-1 ICD form of TENM1 (By similarity). Interacts
CC with CALM1; interaction increases in the presence of calcium ions (By
CC similarity). {ECO:0000250|UniProtKB:P49773,
CC ECO:0000250|UniProtKB:P70349}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49773}. Nucleus
CC {ECO:0000250|UniProtKB:P49773}.
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- SIMILARITY: Belongs to the HINT family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a protein kinase C inhibitor and
CC to bind zinc in solution. Both seem to be incorrect. {ECO:0000305}.
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DR EMBL; Y11175; CAA72061.1; -; mRNA.
DR RefSeq; NP_001076092.1; NM_001082623.1.
DR PDB; 1RZY; X-ray; 1.80 A; A=2-126.
DR PDB; 3O1C; X-ray; 1.08 A; A=1-126.
DR PDB; 3O1X; X-ray; 1.08 A; A=1-126.
DR PDB; 3O1Z; X-ray; 1.30 A; A=1-126.
DR PDB; 3QGZ; X-ray; 1.10 A; A=1-126.
DR PDB; 3RHN; X-ray; 2.10 A; A=12-126.
DR PDB; 4RHN; X-ray; 1.90 A; A=12-126.
DR PDB; 5RHN; X-ray; 2.31 A; A=12-126.
DR PDB; 6RHN; X-ray; 2.15 A; A=12-126.
DR PDBsum; 1RZY; -.
DR PDBsum; 3O1C; -.
DR PDBsum; 3O1X; -.
DR PDBsum; 3O1Z; -.
DR PDBsum; 3QGZ; -.
DR PDBsum; 3RHN; -.
DR PDBsum; 4RHN; -.
DR PDBsum; 5RHN; -.
DR PDBsum; 6RHN; -.
DR AlphaFoldDB; P80912; -.
DR SMR; P80912; -.
DR STRING; 9986.ENSOCUP00000005709; -.
DR ChEMBL; CHEMBL3232701; -.
DR Ensembl; ENSOCUT00000006605; ENSOCUP00000005709; ENSOCUG00000006607.
DR GeneID; 100009302; -.
DR KEGG; ocu:100009302; -.
DR CTD; 3094; -.
DR eggNOG; KOG3275; Eukaryota.
DR GeneTree; ENSGT00940000154451; -.
DR HOGENOM; CLU_056776_8_1_1; -.
DR InParanoid; P80912; -.
DR OMA; YHLHAHL; -.
DR OrthoDB; 1190598at2759; -.
DR TreeFam; TF314862; -.
DR EvolutionaryTrace; P80912; -.
DR Proteomes; UP000001811; Chromosome 3.
DR Bgee; ENSOCUG00000006607; Expressed in kidney and 18 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043530; F:adenosine 5'-monophosphoramidase activity; IEA:RHEA.
DR GO; GO:0016929; F:deSUMOylase activity; ISS:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; ISS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0016926; P:protein desumoylation; ISS:UniProtKB.
DR GO; GO:0009154; P:purine ribonucleotide catabolic process; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:UniProtKB.
DR Gene3D; 3.30.428.10; -; 1.
DR InterPro; IPR019808; Histidine_triad_CS.
DR InterPro; IPR001310; Histidine_triad_HIT.
DR InterPro; IPR011146; HIT-like.
DR InterPro; IPR036265; HIT-like_sf.
DR PANTHER; PTHR23089; PTHR23089; 1.
DR Pfam; PF01230; HIT; 1.
DR PRINTS; PR00332; HISTRIAD.
DR SUPFAM; SSF54197; SSF54197; 1.
DR PROSITE; PS00892; HIT_1; 1.
DR PROSITE; PS51084; HIT_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Cytoplasm; Hydrolase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Protease; Reference proteome;
KW Thiol protease; Transcription; Transcription regulation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P62958"
FT CHAIN 2..126
FT /note="Adenosine 5'-monophosphoramidase HINT1"
FT /id="PRO_0000109783"
FT DOMAIN 18..126
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT MOTIF 110..114
FT /note="Histidine triad motif"
FT ACT_SITE 112
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT BINDING 43..44
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT BINDING 99
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT BINDING 105..107
FT /ligand="AMP"
FT /ligand_id="ChEBI:CHEBI:456215"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT BINDING 112..114
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:0000250|UniProtKB:P62958"
FT MOD_RES 21
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT MOD_RES 30
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49773"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70349"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P70349"
FT MUTAGEN 38
FT /note="C->A: No effect on its ability to convert adenosine
FT 5'-O-phosphorothioate into 5'-O-monophosphate."
FT /evidence="ECO:0000269|PubMed:20940308"
FT MUTAGEN 84
FT /note="C->A: No effect on its ability to convert adenosine
FT 5'-O-phosphorothioate into 5'-O-monophosphate."
FT /evidence="ECO:0000269|PubMed:20940308"
FT MUTAGEN 107
FT /note="S->A: No effect on its ability to convert adenosine
FT 5'-O-phosphorothioate into 5'-O-monophosphate."
FT /evidence="ECO:0000269|PubMed:20940308"
FT MUTAGEN 114
FT /note="H->D: Nearly abolishes its ability to convert
FT adenosine 5'-O-phosphorothioate into 5'-O-monophosphate."
FT /evidence="ECO:0000269|PubMed:20940308"
FT HELIX 18..23
FT /evidence="ECO:0007829|PDB:3O1C"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:3O1C"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:3O1C"
FT STRAND 47..58
FT /evidence="ECO:0007829|PDB:3O1C"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:3O1C"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:3O1C"
FT HELIX 71..87
FT /evidence="ECO:0007829|PDB:3O1C"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:3O1C"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:3O1C"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:3O1C"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:3O1C"
SQ SEQUENCE 126 AA; 13693 MW; 7322271D00F2E099 CRC64;
MADEIAKAQV ARPGGDTIFG KIIRKEIPAK IIFEDDQCLA FHDISPQAPT HFLVIPKKHI
SQISAAEDAD ESLLGHLMIV GKKCAADLGL KKGYRMVVNE GSDGGQSVYH VHLHVLGGRQ
MNWPPG
