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PHPT1 phosphohistidine phosphatase 1 [ Homo sapiens (human) ]

Gene ID: 29085, updated on 19-Aug-2025
Official Symbol
PHPT1provided by HGNC
Official Full Name
phosphohistidine phosphatase 1provided by HGNC
Primary source
HGNC:HGNC:30033
See related
Ensembl:ENSG00000054148 MIM:610167; AllianceGenome:HGNC:30033
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PHP; PHP14; CGI-202; HSPC141; HEL-S-132P
Summary
This gene encodes an enzyme that catalyzes the reversible dephosphorylation of histidine residues in proteins. It may be involved in the dephosphorylation of G-beta and ATP citrate lyase and in negatively regulating CD4 T lymphocytes by dephosphorylation and inhibition of KCa3.1 channels. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
Expression
Ubiquitous expression in heart (RPKM 26.6), prostate (RPKM 24.5) and 25 other tissues See more
Orthologs
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See PHPT1 in Genome Data Viewer
Location:
9q34.3
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (136849409..136851024)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (149083591..149085206)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (139743861..139745476)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene RAB, member RAS oncogene family like 6 Neighboring gene microRNA 4292 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139732768-139733649 Neighboring gene Sharpr-MPRA regulatory region 5679 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr9:139736293-139737174 and GRCh37_chr9:139737175-139738055 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139738056-139738936 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20549 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20550 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20551 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20552 Neighboring gene apical junction component 1 homolog Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20553 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29329 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20554 Neighboring gene MAM domain containing 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:139752096-139752733 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20555 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20556 Neighboring gene endothelial differentiation related factor 1

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Influence of protein histidine phosphatase overexpression and down-regulation on human umbilical-vein endothelial cell viability. Seeger A, et al. Cell Biol Int, 2012 Mar 1. PMID 21967643
  2. Clinical significance of PHPT1 protein expression in lung cancer. Xu AJ, et al. Chin Med J (Engl), 2010 Nov. PMID 21163124
  3. A salt bridge of the C-terminal carboxyl group regulates PHPT1 substrate affinity and catalytic activity. Zavala E, et al. Protein Sci, 2024 Jun. PMID 38747379, Free PMC Article
  4. PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway. Xu A, et al. J Mol Med (Berl), 2018 Feb. PMID 29098317
  5. A splice variant of the human phosphohistidine phosphatase 1 (PHPT1) is degraded by the proteasome. Inturi R, et al. Int J Biochem Cell Biol, 2014 Dec. PMID 25450458

See all (72) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A salt bridge of the C-terminal carboxyl group regulates PHPT1 substrate affinity and catalytic activity.
    Title: A salt bridge of the C-terminal carboxyl group regulates PHPT1 substrate affinity and catalytic activity.
  2. FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer.
    Title: FBXO32 targets PHPT1 for ubiquitination to regulate the growth of EGFR mutant lung cancer.
  3. Our study reveals the important role of PHP14 in regulating hepatic stellate cell migration in liver fibrosis
    Title: PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway.
  4. In the process of assay optimization, we discovered that PHPT1 is sensitive to a reducing environment and inhibited by transition-metal ions, with one apparent Cu(II) binding site with IC50 value of 500 +/- 20 muM and two apparent Zn(II) binding sites with IC50 values of 25 +/- 1 and 490 +/- 20 muM
    Title: Facile, Fluorogenic Assay for Protein Histidine Phosphatase Activity.
  5. High PHPT1 expression is associated with cancer.
    Title: Influence of Confounding Factors on Radiation Dose Estimation Using In Vivo Validated Transcriptional Biomarkers.
  6. H2O2 exposure induces selective oxidation of hPHPT1 at Met95, a residue within the substrate binding region. Molecular dynamics simulations suggest that if Met95 oxidation alters hPHPT1 activity, then it will do so by altering the stability of an intermediate state. Mass spectrometry showed that H2O2-induced oxidation does not impact hPHPT1 function negatively.
    Title: Structural and activity characterization of human PHPT1 after oxidative modification.
  7. PHPT1 was expressed in the epithelium of proximal tubuli and nuclei of clear-cell renal cell carcinoma tissue samples.
    Title: Nuclear expression and clinical significance of phosphohistidine phosphatase 1 in clear-cell renal cell carcinoma.
  8. PHPT1 can dephosphorylate phospholysine in chemically phosphorylated histone H1 and polylysine
    Title: Phosphohistidine phosphatase 1 (PHPT1) also dephosphorylates phospholysine of chemically phosphorylated histone H1 and polylysine.
  9. The specific degradation of the PHPT1 splice variant indicates that the quality control and the self-guarding of the cellular system works at two levels, first at the RNA level and proteasome level.
    Title: A splice variant of the human phosphohistidine phosphatase 1 (PHPT1) is degraded by the proteasome.
  10. the histidine phosphatase, protein histidine phosphatase 1, inhibits NDPK-B-activated TRPV5 in inside/out patch experiments.
    Title: Regulation of the epithelial Ca²⁺ channel TRPV5 by reversible histidine phosphorylation mediated by NDPK-B and PHPT1.
Submit: New GeneRIF Correction See all GeneRIFs (20)

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Potential readthrough

Included gene: MAMDC4

Homology

Clone Names

  • bA216L13.10, DKFZp564M173, 1700008C22Rik, RP11-216L13.10

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables actin filament binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium channel inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables enzyme inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables hydrolase activity IEA
Inferred from Electronic Annotation
more info
  
enables phosphoprotein phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein histidine phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein histidine phosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein histidine phosphatase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein histidine phosphatase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables transmembrane transporter binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in actin cytoskeleton organization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in actin cytoskeleton organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in lamellipodium organization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of T cell receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of cell motility IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of cell motility IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cell motility IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of insulin secretion involved in cellular response to glucose stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular exosome HDA PubMed 
located_in leading edge of lamellipodium IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
Preferred Names
14 kDa phosphohistidine phosphatase
Names
epididymis secretory sperm binding protein Li 132P
protein histidine phosphatase
protein janus-A homolog
sex-regulated protein janus-a
NP_001129333.1
NP_001274271.1
NP_001274272.1
NP_054891.2

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001135861.3 → NP_001129333.1  14 kDa phosphohistidine phosphatase isoform 2

    Status: VALIDATED

    Source sequence(s)
    AL355987
    Consensus CDS
    CCDS48060.1
    UniProtKB/Swiss-Prot
    Q9NRX4
    Related
    ENSP00000360724.1, ENST00000371661.5
    Conserved Domains (1) summary
    pfam05005
    Location:9 → 95
    Ocnus; Janus/Ocnus family (Ocnus)

  2. NM_001287342.2 → NP_001274271.1  14 kDa phosphohistidine phosphatase isoform 4

    Status: VALIDATED

    Source sequence(s)
    AL355987
    UniProtKB/TrEMBL
    Q6FIE5
    Conserved Domains (1) summary
    pfam05005
    Location:6 → 119
    Ocnus; Janus/Ocnus family (Ocnus)

  3. NM_001287343.2 → NP_001274272.1  14 kDa phosphohistidine phosphatase isoform 5

    Status: VALIDATED

    Source sequence(s)
    AL355987
    Related
    ENST00000462205.5
    Conserved Domains (1) summary
    pfam05005
    Location:6 → 96
    Ocnus; Janus/Ocnus family (Ocnus)

  4. NM_014172.6 → NP_054891.2  14 kDa phosphohistidine phosphatase isoform 3

    See identical proteins and their annotated locations for NP_054891.2

    Status: VALIDATED

    Source sequence(s)
    AL355987
    Consensus CDS
    CCDS7009.1
    UniProtKB/Swiss-Prot
    B1AMX0, B1AMX1, Q9H0Y3, Q9NRX4
    UniProtKB/TrEMBL
    Q6FIE5, V9HWC4
    Related
    ENSP00000247665.10, ENST00000247665.12
    Conserved Domains (1) summary
    pfam05005
    Location:9 → 114
    Ocnus; Janus/Ocnus family (Ocnus)

RNA

  1. NR_109807.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AL355987

  2. NR_109808.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AL355987

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    136849409..136851024
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    149083591..149085206
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001135860.1: Suppressed sequence

    Description
    NM_001135860.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NRX4.1 GenPept UniProtKB/Swiss-Prot:Q9NRX4

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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