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
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei99Purine nucleotide phosphoramidate1
Active sitei112Tele-AMP-histidine intermediate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi43 – 44Purine nucleotide phosphoramidate2
Nucleotide bindingi105 – 107Purine nucleotide phosphoramidate3
Nucleotide bindingi112 – 114Purine nucleotide phosphoramidate3

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

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Transcription, Transcription regulation
LigandNucleotide-binding

Enzyme and pathway databases

SABIO-RKiP49773

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

EuPathDBiHostDB:ENSG00000169567.11
HGNCiHGNC:4912 HINT1
MIMi601314 gene
neXtProtiNX_P49773

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Neuromyotonia and axonal neuropathy, autosomal recessive (NMAN)2 Publications
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_06921237R → P in NMAN; negligible protein expression due to post-translational degradation. 1 PublicationCorresponds to variant dbSNP:rs149782619EnsemblClinVar.1
Natural variantiVAR_06921351H → R in NMAN; no mutant protein is detected due to post-translational degradation. 1 PublicationCorresponds to variant dbSNP:rs397514491EnsemblClinVar.1
Natural variantiVAR_06921484C → R in NMAN; negligible protein expression due to post-translational degradation. 1 PublicationCorresponds to variant dbSNP:rs397514489EnsemblClinVar.1
Natural variantiVAR_06921589G → V in NMAN. 1 PublicationCorresponds to variant dbSNP:rs397514490EnsemblClinVar.1
Natural variantiVAR_06921693G → D in NMAN. 1 PublicationCorresponds to variant dbSNP:rs397514493EnsemblClinVar.1
Natural variantiVAR_069217112H → N in NMAN; the enzyme has no residual activity although the mutant protein is expressed at normal levels. 2 PublicationsCorresponds to variant dbSNP:rs373849532EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi97V → D or E: Loss of dimerization. Strongly reduced enzyme activity. 1 Publication1
Mutagenesisi105G → A: Reduces enzyme activity. 1 Publication1
Mutagenesisi107S → A: Reduces enzyme activity. 1 Publication1
Mutagenesisi114H → A: Nearly abolishes enzyme activity. 1 Publication1
Mutagenesisi123W → A: Nearly abolishes enzyme activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Neuropathy

Organism-specific databases

DisGeNETi3094
MalaCardsiHINT1
MIMi137200 phenotype
OpenTargetsiENSG00000169567
Orphaneti324442 Autosomal recessive axonal neuropathy with neuromyotonia
PharmGKBiPA29286

Chemistry databases

ChEMBLiCHEMBL5878
DrugBankiDB02162 5'-O-(N-Ethyl-Sulfamoyl)Adenosine
DB03349 8-Bromo-Adenosine-5'-Monophosphate
DB00131 Adenosine monophosphate
DB02183 Adenosine-5'-Ditungstate
DB01972 Guanosine-5'-Monophosphate

Polymorphism and mutation databases

DMDMi1708543

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001097812 – 126Histidine triad nucleotide-binding protein 1Add BLAST125

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei21N6-acetyllysineCombined sources1
Modified residuei30N6-acetyllysineCombined sources1
Modified residuei45PhosphoserineBy similarity1
Modified residuei72PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49773
MaxQBiP49773
PaxDbiP49773
PeptideAtlasiP49773
PRIDEiP49773
TopDownProteomicsiP49773

2D gel databases

OGPiP49773
UCD-2DPAGEiP49773

PTM databases

iPTMnetiP49773
PhosphoSitePlusiP49773
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

Binary interactionsi

WithEntry#Exp.IntActNotes
CPSF7Q8N684-34EBI-1054330,EBI-11523759

GO - Molecular functioni

  • protein kinase C binding Source: ProtInc

Protein-protein interaction databases

BioGridi109341, 83 interactors
IntActiP49773, 12 interactors
MINTiP49773
STRINGi9606.ENSP00000304229

Chemistry databases

BindingDBiP49773

Structurei

Secondary structure

1126
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi18 – 23Combined sources6
Beta strandi31 – 34Combined sources4
Beta strandi36 – 42Combined sources7
Beta strandi47 – 58Combined sources12
Helixi63 – 65Combined sources3
Helixi68 – 70Combined sources3
Helixi71 – 87Combined sources17
Beta strandi94 – 97Combined sources4
Helixi101 – 104Combined sources4
Beta strandi108 – 110Combined sources3
Beta strandi113 – 119Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5ED3X-ray1.31A/B1-126[»]
5ED6X-ray1.52A/B1-126[»]
5EMTX-ray1.50A/B1-126[»]
5I2EX-ray1.60A/B1-126[»]
5I2FX-ray1.25A/B1-126[»]
5IPBX-ray1.55A/B1-126[»]
5IPCX-ray1.30A/B1-126[»]
5IPDX-ray1.75A/B1-126[»]
5IPEX-ray1.45A/B1-126[»]
5KLYX-ray1.30A/B1-126[»]
5KLZX-ray1.50A/B1-126[»]
5KM0X-ray1.53A/B/C/D1-126[»]
5KM1X-ray1.65A/B1-126[»]
5KM2X-ray1.25A/B1-126[»]
5KM3X-ray1.20A/B1-126[»]
5KM4X-ray1.40A/B1-126[»]
5KM6X-ray1.60A1-126[»]
5KMAX-ray1.55A/B1-126[»]
5KMBX-ray1.60A/B1-126[»]
5KMCX-ray1.35A/B1-126[»]
5O8GX-ray1.50A/B1-126[»]
5O8IX-ray1.27A/B1-126[»]
5WA8X-ray1.30A/B1-126[»]
5WA9X-ray1.15A/B1-126[»]
6B42X-ray1.13A1-126[»]
ProteinModelPortaliP49773
SMRiP49773
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49773

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 126HITPROSITE-ProRule annotationAdd BLAST109

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi110 – 114Histidine triad motif5

Sequence similaritiesi

Belongs to the HINT family.Curated

Phylogenomic databases

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

Family and domain databases

Gene3Di3.30.428.10, 1 hit
InterProiView protein in InterPro
IPR019808 Histidine_triad_CS
IPR001310 Histidine_triad_HIT
IPR011146 HIT-like
IPR036265 HIT-like_sf
PANTHERiPTHR23089 PTHR23089, 1 hit
PfamiView protein in Pfam
PF01230 HIT, 1 hit
PRINTSiPR00332 HISTRIAD
SUPFAMiSSF54197 SSF54197, 1 hit
PROSITEiView protein in PROSITE
PS00892 HIT_1, 1 hit
PS51084 HIT_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti25K → E in BAB15500 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06921237R → P in NMAN; negligible protein expression due to post-translational degradation. 1 PublicationCorresponds to variant dbSNP:rs149782619EnsemblClinVar.1
Natural variantiVAR_06921351H → R in NMAN; no mutant protein is detected due to post-translational degradation. 1 PublicationCorresponds to variant dbSNP:rs397514491EnsemblClinVar.1
Natural variantiVAR_06921484C → R in NMAN; negligible protein expression due to post-translational degradation. 1 PublicationCorresponds to variant dbSNP:rs397514489EnsemblClinVar.1
Natural variantiVAR_06921589G → V in NMAN. 1 PublicationCorresponds to variant dbSNP:rs397514490EnsemblClinVar.1
Natural variantiVAR_06921693G → D in NMAN. 1 PublicationCorresponds to variant dbSNP:rs397514493EnsemblClinVar.1
Natural variantiVAR_069217112H → N in NMAN; the enzyme has no residual activity although the mutant protein is expressed at normal levels. 2 PublicationsCorresponds to variant dbSNP:rs373849532EnsemblClinVar.1

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

Similar proteinsi

Entry informationi

Entry nameiHINT1_HUMAN
AccessioniPrimary (citable) accession number: P49773
Secondary accession number(s): Q9H5W8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 182 of the entry and version 2 of the sequence. See 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

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

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health