Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Histidine triad nucleotide-binding protein 1

Gene

HINT1

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions as enzyme, and as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1. Modulates p53/TP53 levels and p53/TP53-mediated apoptosis. Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By similarity). Hydrolyzes purine nucleotide phosphoramidates, including adenosine 5'monophosphoramidate (AMP-NH2), adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester. Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide.By similarity3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei99 – 991Purine nucleotide phosphoramidate
Active sitei112 – 1121Tele-AMP-histidine intermediateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi43 – 442Purine nucleotide phosphoramidate
Nucleotide bindingi105 – 1073Purine nucleotide phosphoramidate
Nucleotide bindingi112 – 1143Purine nucleotide phosphoramidate

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Histidine triad nucleotide-binding protein 1 (EC:3.-.-.-)
Alternative name(s):
Adenosine 5'-monophosphoramidase
P13.7
Gene namesi
Name:HINT1
Synonyms:HINT
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Chromosome 3

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi38 – 381C → A: No effect. 1 Publication
Mutagenesisi84 – 841C → A: No effect. 1 Publication
Mutagenesisi107 – 1071S → A: No effect. 1 Publication
Mutagenesisi114 – 1141H → D: Nearly abolishes enzyme activity. 1 Publication

Chemistry

ChEMBLiCHEMBL3232701.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy similarity
Chaini2 – 126125Histidine triad nucleotide-binding protein 1PRO_0000109783Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei21 – 211N6-acetyllysineBy similarity
Modified residuei30 – 301N6-acetyllysineBy similarity
Modified residuei45 – 451PhosphoserineBy similarity
Modified residuei72 – 721PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Expressioni

Tissue specificityi

Widely expressed.

Interactioni

Subunit structurei

Homodimer. Interacts with CDK7. Interacts with RUVBL1 and RUVBL2 and is associated with the LEF1/TCF1-CTNNB1 complex and with a KAT5 histone acetyltransferase complex. Identified in a complex with MITF and CTNNB1. Interacts with CDC34 and RBX1, and is part of a SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By similarity).By similarity

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000005709.

Structurei

Secondary structure

1
126
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi18 – 236Combined sources
Beta strandi31 – 344Combined sources
Beta strandi36 – 427Combined sources
Beta strandi47 – 5812Combined sources
Helixi63 – 653Combined sources
Helixi68 – 703Combined sources
Helixi71 – 8717Combined sources
Beta strandi94 – 974Combined sources
Helixi101 – 1044Combined sources
Beta strandi108 – 1103Combined sources
Beta strandi113 – 1197Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RZYX-ray1.80A2-126[»]
3O1CX-ray1.08A1-126[»]
3O1XX-ray1.08A1-126[»]
3O1ZX-ray1.30A1-126[»]
3QGZX-ray1.10A1-126[»]
3RHNX-ray2.10A12-126[»]
4RHNX-ray1.90A12-126[»]
5RHNX-ray2.31A12-126[»]
6RHNX-ray2.15A12-126[»]
ProteinModelPortaliP80912.
SMRiP80912. Positions 12-126.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP80912.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini18 – 126109HITPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi110 – 1145Histidine triad motif

Sequence similaritiesi

Belongs to the HINT family.Curated
Contains 1 HIT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3275. Eukaryota.
COG0537. LUCA.
GeneTreeiENSGT00510000046448.
HOGENOMiHOG000061064.
HOVERGENiHBG051906.
InParanoidiP80912.
KOiK02503.
OMAiCNPYPDG.
OrthoDBiEOG75QR5T.
TreeFamiTF314862.

Family and domain databases

Gene3Di3.30.428.10. 1 hit.
InterProiIPR019808. Histidine_triad_CS.
IPR001310. Histidine_triad_HIT.
IPR011146. HIT-like.
[Graphical view]
PANTHERiPTHR23089. PTHR23089. 1 hit.
PfamiPF01230. HIT. 1 hit.
[Graphical view]
PRINTSiPR00332. HISTRIAD.
SUPFAMiSSF54197. SSF54197. 1 hit.
PROSITEiPS00892. HIT_1. 1 hit.
PS51084. HIT_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P80912-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADEIAKAQV ARPGGDTIFG KIIRKEIPAK IIFEDDQCLA FHDISPQAPT
60 70 80 90 100
HFLVIPKKHI SQISAAEDAD ESLLGHLMIV GKKCAADLGL KKGYRMVVNE
110 120
GSDGGQSVYH VHLHVLGGRQ MNWPPG
Length:126
Mass (Da):13,693
Last modified:January 23, 2007 - v2
Checksum:i7322271D00F2E099
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11175 mRNA. Translation: CAA72061.1.
RefSeqiNP_001076092.1. NM_001082623.1.
UniGeneiOcu.3078.

Genome annotation databases

EnsembliENSOCUT00000006605; ENSOCUP00000005709; ENSOCUG00000006607.
GeneIDi100009302.
KEGGiocu:100009302.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11175 mRNA. Translation: CAA72061.1.
RefSeqiNP_001076092.1. NM_001082623.1.
UniGeneiOcu.3078.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RZYX-ray1.80A2-126[»]
3O1CX-ray1.08A1-126[»]
3O1XX-ray1.08A1-126[»]
3O1ZX-ray1.30A1-126[»]
3QGZX-ray1.10A1-126[»]
3RHNX-ray2.10A12-126[»]
4RHNX-ray1.90A12-126[»]
5RHNX-ray2.31A12-126[»]
6RHNX-ray2.15A12-126[»]
ProteinModelPortaliP80912.
SMRiP80912. Positions 12-126.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000005709.

Chemistry

ChEMBLiCHEMBL3232701.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSOCUT00000006605; ENSOCUP00000005709; ENSOCUG00000006607.
GeneIDi100009302.
KEGGiocu:100009302.

Organism-specific databases

CTDi3094.

Phylogenomic databases

eggNOGiKOG3275. Eukaryota.
COG0537. LUCA.
GeneTreeiENSGT00510000046448.
HOGENOMiHOG000061064.
HOVERGENiHBG051906.
InParanoidiP80912.
KOiK02503.
OMAiCNPYPDG.
OrthoDBiEOG75QR5T.
TreeFamiTF314862.

Miscellaneous databases

EvolutionaryTraceiP80912.

Family and domain databases

Gene3Di3.30.428.10. 1 hit.
InterProiIPR019808. Histidine_triad_CS.
IPR001310. Histidine_triad_HIT.
IPR011146. HIT-like.
[Graphical view]
PANTHERiPTHR23089. PTHR23089. 1 hit.
PfamiPF01230. HIT. 1 hit.
[Graphical view]
PRINTSiPR00332. HISTRIAD.
SUPFAMiSSF54197. SSF54197. 1 hit.
PROSITEiPS00892. HIT_1. 1 hit.
PS51084. HIT_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Isolation, cloning and characterization of a low-molecular-mass purine nucleoside- and nucleotide-binding protein."
    Gilmour J., Liang N., Lowenstein J.M.
    Biochem. J. 326:471-477(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  2. "Adenosine monophosphoramidase activity of Hint and Hnt1 supports function of Kin28, Ccl1, and Tfb3."
    Bieganowski P., Garrison P.N., Hodawadekar S.C., Faye G., Barnes L.D., Brenner C.
    J. Biol. Chem. 277:10852-10860(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  3. "31P NMR and genetic analysis establish hinT as the only Escherchia coli purine nucleoside phosphoramidase and as essential for growth under high salt conditions."
    Chou T.F., Bieganowski P., Shilinski K., Cheng J., Brenner C., Wagner C.R.
    J. Biol. Chem. 280:15356-15361(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION.
  4. "Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins."
    Brenner C., Garrison P., Gilmour J., Peisach D., Ringe D., Petsko G.A., Lowenstein J.M.
    Nat. Struct. Biol. 4:231-238(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 12-126 IN COMPLEXES WITH 8-BROMO-ADENOSINE-5'-MONOPHOSPHATE AND GUANOSINE-5'-MONOPHOSPHATE.
  5. "Biochemical, crystallographic, and mutagenic characterization of hint, the AMP-lysine hydrolase, with novel substrates and inhibitors."
    Krakowiak A., Pace H.C., Blackburn G.M., Adams M., Mekhalfia A., Kaczmarek R., Baraniak J., Stec W.J., Brenner C.
    J. Biol. Chem. 279:18711-18716(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-125 IN COMPLEX WITH 5'-O-(N-ETHYL-SULFAMOYL)ADENOSINE, SUBUNIT.
  6. "Histidine triad nucleotide-binding protein 1 (HINT-1) phosphoramidase transforms nucleoside 5'-O-phosphorothioates to nucleoside 5'-O-phosphates."
    Ozga M., Dolot R., Janicka M., Kaczmarek R., Krakowiak A.
    J. Biol. Chem. 285:40809-40818(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.08 ANGSTROMS) IN COMPLEX WITH ADENOSINE 5'-O-PHOSPHOROTHIOATE, FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-38; CYS-84; SER-107 AND HIS-114.
  7. "High-resolution X-ray structure of the rabbit histidine triad nucleotide-binding protein 1 (rHINT1)-adenosine complex at 1.10 A resolution."
    Dolot R., Ozga M., Krakowiak A., Nawrot B.
    Acta Crystallogr. D 67:601-607(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) IN COMPLEX WITH ADENOSINE, SUBUNIT.

Entry informationi

Entry nameiHINT1_RABIT
AccessioniPrimary (citable) accession number: P80912
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: November 11, 2015
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Was originally thought to be a protein kinase C inhibitor and to bind zinc in solution. Both seem to be incorrect.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.