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Protein

Histidine triad nucleotide-binding protein 1

Gene

HINT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolyzes purine nucleotide phosphoramidates with a single phosphate group, 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, as well as Met-AMP, His-AMP and Asp-AMP, 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. In addition, functions 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.7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei99 – 991Purine nucleotide phosphoramidate
Active sitei112 – 1121Tele-AMP-histidine intermediate1 Publication

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

  • hydrolase activity Source: UniProtKB
  • nucleotide binding Source: UniProtKB-KW
  • protein kinase C binding Source: ProtInc

GO - Biological processi

  • intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
  • positive regulation of calcium-mediated signaling Source: Ensembl
  • purine ribonucleotide catabolic process Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • signal transduction Source: ProtInc
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

Nucleotide-binding

Enzyme and pathway databases

SABIO-RKP49773.

Names & Taxonomyi

Protein namesi
Recommended name:
Histidine triad nucleotide-binding protein 1 (EC:3.-.-.-)
Alternative name(s):
Adenosine 5'-monophosphoramidase
Protein kinase C inhibitor 1
Protein kinase C-interacting protein 1
Short name:
PKCI-1
Gene namesi
Name:HINT1
Synonyms:HINT, PKCI1, PRKCNH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:4912. HINT1.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Interaction with CDK7 leads to a more nuclear localization.

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytoskeleton Source: ProtInc
  • extracellular exosome Source: UniProtKB
  • histone deacetylase complex Source: UniProtKB
  • nucleus Source: HPA
  • plasma membrane Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Neuromyotonia and axonal neuropathy, autosomal recessive (NMAN)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 and distal hereditary motor neuropathy. Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves.
See also OMIM:137200
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti37 – 371R → P in NMAN; negligible protein expression due to post-translational degradation. 1 Publication
Corresponds to variant rs149782619 [ dbSNP | Ensembl ].
VAR_069212
Natural varianti51 – 511H → R in NMAN; no mutant protein is detected due to post-translational degradation. 1 Publication
Corresponds to variant rs397514491 [ dbSNP | Ensembl ].
VAR_069213
Natural varianti84 – 841C → R in NMAN; negligible protein expression due to post-translational degradation. 1 Publication
Corresponds to variant rs397514489 [ dbSNP | Ensembl ].
VAR_069214
Natural varianti89 – 891G → V in NMAN. 1 Publication
Corresponds to variant rs397514490 [ dbSNP | Ensembl ].
VAR_069215
Natural varianti93 – 931G → D in NMAN. 1 Publication
Corresponds to variant rs397514493 [ dbSNP | Ensembl ].
VAR_069216
Natural varianti112 – 1121H → N in NMAN; the enzyme has no residual activity although the mutant protein is expressed at normal levels. 2 Publications
Corresponds to variant rs373849532 [ dbSNP | Ensembl ].
VAR_069217

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi97 – 971V → D or E: Loss of dimerization. Strongly reduced enzyme activity. 1 Publication
Mutagenesisi105 – 1051G → A: Reduces enzyme activity. 1 Publication
Mutagenesisi107 – 1071S → A: Reduces enzyme activity. 1 Publication
Mutagenesisi114 – 1141H → A: Nearly abolishes enzyme activity. 1 Publication
Mutagenesisi123 – 1231W → A: Nearly abolishes enzyme activity. 1 Publication

Keywords - Diseasei

Disease mutation, Neuropathy

Organism-specific databases

MalaCardsiHINT1.
MIMi137200. phenotype.
Orphaneti324442. Autosomal recessive axonal neuropathy with neuromyotonia.
PharmGKBiPA29286.

Chemistry

ChEMBLiCHEMBL5878.
DrugBankiDB00131. Adenosine monophosphate.

Polymorphism and mutation databases

DMDMi1708543.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources1 Publication
Chaini2 – 126125Histidine triad nucleotide-binding protein 1PRO_0000109781Add
BLAST

Amino acid modifications

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49773.
MaxQBiP49773.
PaxDbiP49773.
PeptideAtlasiP49773.
PRIDEiP49773.
TopDownProteomicsiP49773.

2D gel databases

OGPiP49773.
UCD-2DPAGEP49773.

PTM databases

iPTMnetiP49773.
PhosphoSiteiP49773.
SwissPalmiP49773.

Expressioni

Tissue specificityi

Widely expressed.

Gene expression databases

BgeeiENSG00000169567.
CleanExiHS_HINT1.
ExpressionAtlasiP49773. baseline and differential.
GenevisibleiP49773. HS.

Organism-specific databases

HPAiHPA044577.

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.9 Publications

GO - Molecular functioni

  • protein kinase C binding Source: ProtInc

Protein-protein interaction databases

BioGridi109341. 74 interactions.
IntActiP49773. 10 interactions.
MINTiMINT-5001048.
STRINGi9606.ENSP00000304229.

Chemistry

BindingDBiP49773.

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 – 1007Combined 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
1AV5X-ray2.00A/B2-126[»]
1KPAX-ray2.00A/B2-126[»]
1KPBX-ray2.00A/B2-126[»]
1KPCX-ray2.20A/B/C/D2-126[»]
1KPEX-ray1.80A/B2-126[»]
1KPFX-ray1.50A2-126[»]
3TW2X-ray1.38A/B1-126[»]
4EQEX-ray1.52A/B1-126[»]
4EQGX-ray1.52A/B1-126[»]
4EQHX-ray1.67A/B1-126[»]
4ZKLX-ray2.34A/B/C/D1-126[»]
4ZKVX-ray1.92A/B/C/D1-126[»]
5I2EX-ray1.60A/B1-126[»]
5I2FX-ray1.25A/B1-126[»]
ProteinModelPortaliP49773.
SMRiP49773. Positions 11-126.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49773.

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.
InParanoidiP49773.
KOiK02503.
OMAiYRLITNN.
OrthoDBiEOG091G1001.
PhylomeDBiP49773.
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.

P49773-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MADEIAKAQV ARPGGDTIFG KIIRKEIPAK IIFEDDRCLA FHDISPQAPT
60 70 80 90 100
HFLVIPKKHI SQISVAEDDD ESLLGHLMIV GKKCAADLGL NKGYRMVVNE
110 120
GSDGGQSVYH VHLHVLGGRQ MHWPPG
Length:126
Mass (Da):13,802
Last modified:January 23, 2007 - v2
Checksum:i6C2B0119370384AA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251K → E in BAB15500 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti37 – 371R → P in NMAN; negligible protein expression due to post-translational degradation. 1 Publication
Corresponds to variant rs149782619 [ dbSNP | Ensembl ].
VAR_069212
Natural varianti51 – 511H → R in NMAN; no mutant protein is detected due to post-translational degradation. 1 Publication
Corresponds to variant rs397514491 [ dbSNP | Ensembl ].
VAR_069213
Natural varianti84 – 841C → R in NMAN; negligible protein expression due to post-translational degradation. 1 Publication
Corresponds to variant rs397514489 [ dbSNP | Ensembl ].
VAR_069214
Natural varianti89 – 891G → V in NMAN. 1 Publication
Corresponds to variant rs397514490 [ dbSNP | Ensembl ].
VAR_069215
Natural varianti93 – 931G → D in NMAN. 1 Publication
Corresponds to variant rs397514493 [ dbSNP | Ensembl ].
VAR_069216
Natural varianti112 – 1121H → N in NMAN; the enzyme has no residual activity although the mutant protein is expressed at normal levels. 2 Publications
Corresponds to variant rs373849532 [ dbSNP | Ensembl ].
VAR_069217

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U27143 mRNA. Translation: AAA82926.1.
U51004 mRNA. Translation: AAC71077.1.
AK026557 mRNA. Translation: BAB15500.1.
CR457048 mRNA. Translation: CAG33329.1.
BC001287 mRNA. Translation: AAH01287.1.
BC007090 mRNA. Translation: AAH07090.1.
CCDSiCCDS4147.1.
PIRiS72501.
RefSeqiNP_005331.1. NM_005340.6.
UniGeneiHs.483305.

Genome annotation databases

EnsembliENST00000304043; ENSP00000304229; ENSG00000169567.
GeneIDi3094.
KEGGihsa:3094.
UCSCiuc003kve.5. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U27143 mRNA. Translation: AAA82926.1.
U51004 mRNA. Translation: AAC71077.1.
AK026557 mRNA. Translation: BAB15500.1.
CR457048 mRNA. Translation: CAG33329.1.
BC001287 mRNA. Translation: AAH01287.1.
BC007090 mRNA. Translation: AAH07090.1.
CCDSiCCDS4147.1.
PIRiS72501.
RefSeqiNP_005331.1. NM_005340.6.
UniGeneiHs.483305.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AV5X-ray2.00A/B2-126[»]
1KPAX-ray2.00A/B2-126[»]
1KPBX-ray2.00A/B2-126[»]
1KPCX-ray2.20A/B/C/D2-126[»]
1KPEX-ray1.80A/B2-126[»]
1KPFX-ray1.50A2-126[»]
3TW2X-ray1.38A/B1-126[»]
4EQEX-ray1.52A/B1-126[»]
4EQGX-ray1.52A/B1-126[»]
4EQHX-ray1.67A/B1-126[»]
4ZKLX-ray2.34A/B/C/D1-126[»]
4ZKVX-ray1.92A/B/C/D1-126[»]
5I2EX-ray1.60A/B1-126[»]
5I2FX-ray1.25A/B1-126[»]
ProteinModelPortaliP49773.
SMRiP49773. Positions 11-126.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109341. 74 interactions.
IntActiP49773. 10 interactions.
MINTiMINT-5001048.
STRINGi9606.ENSP00000304229.

Chemistry

BindingDBiP49773.
ChEMBLiCHEMBL5878.
DrugBankiDB00131. Adenosine monophosphate.

PTM databases

iPTMnetiP49773.
PhosphoSiteiP49773.
SwissPalmiP49773.

Polymorphism and mutation databases

DMDMi1708543.

2D gel databases

OGPiP49773.
UCD-2DPAGEP49773.

Proteomic databases

EPDiP49773.
MaxQBiP49773.
PaxDbiP49773.
PeptideAtlasiP49773.
PRIDEiP49773.
TopDownProteomicsiP49773.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000304043; ENSP00000304229; ENSG00000169567.
GeneIDi3094.
KEGGihsa:3094.
UCSCiuc003kve.5. human.

Organism-specific databases

CTDi3094.
GeneCardsiHINT1.
HGNCiHGNC:4912. HINT1.
HPAiHPA044577.
MalaCardsiHINT1.
MIMi137200. phenotype.
601314. gene.
neXtProtiNX_P49773.
Orphaneti324442. Autosomal recessive axonal neuropathy with neuromyotonia.
PharmGKBiPA29286.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3275. Eukaryota.
COG0537. LUCA.
GeneTreeiENSGT00510000046448.
HOGENOMiHOG000061064.
HOVERGENiHBG051906.
InParanoidiP49773.
KOiK02503.
OMAiYRLITNN.
OrthoDBiEOG091G1001.
PhylomeDBiP49773.
TreeFamiTF314862.

Enzyme and pathway databases

SABIO-RKP49773.

Miscellaneous databases

ChiTaRSiHINT1. human.
EvolutionaryTraceiP49773.
GeneWikiiHINT1.
GenomeRNAii3094.
PROiP49773.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169567.
CleanExiHS_HINT1.
ExpressionAtlasiP49773. baseline and differential.
GenevisibleiP49773. HS.

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...

Entry informationi

Entry nameiHINT1_HUMAN
AccessioniPrimary (citable) accession number: P49773
Secondary accession number(s): Q9H5W8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: September 7, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.