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P4HTM prolyl 4-hydroxylase, transmembrane [ Homo sapiens (human) ]

Gene ID: 54681, updated on 17-Mar-2024

Summary

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Official Symbol
P4HTMprovided by HGNC
Official Full Name
prolyl 4-hydroxylase, transmembraneprovided by HGNC
Primary source
HGNC:HGNC:28858
See related
Ensembl:ENSG00000178467 MIM:614584; AllianceGenome:HGNC:28858
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PH4; PH-4; PHD4; EGLN4; HIDEA; HIFPH4; P4H-TM
Summary
The product of this gene belongs to the family of prolyl 4-hydroxylases. This protein is a prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia. It plays a role in adaptation to hypoxia and may be related to cellular oxygen sensing. Alternatively spliced variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in brain (RPKM 16.9), adrenal (RPKM 14.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
3p21.31; 3p21.3
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (48989908..49007153)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (49017960..49035193)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (49027341..49044586)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene hESC enhancers GRCh37_chr3:48955152-48955902 and GRCh37_chr3:48955903-48956654 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:48956655-48957405 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:48959089-48959589 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:48961592-48962092 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:48962093-48962593 Neighboring gene ARIH2 opposite strand lncRNA Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19846 Neighboring gene ariadne RBR E3 ubiquitin protein ligase 2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19847 Neighboring gene MPRA-validated peak4646 silencer Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:49000975-49001622 Neighboring gene uncharacterized LOC124909376 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:49026394-49026957 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:49026958-49027520 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14344 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:49028085-49028646 Neighboring gene uncharacterized LOC124906235 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49043602-49044590 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14345 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14346 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:49051026-49051863 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19849 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:49054789-49055560 Neighboring gene WD repeat domain 6 Neighboring gene DALR anticodon binding domain containing 3 Neighboring gene microRNA 425

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains. Myllykoski M, et al. J Biol Chem, 2021 Jan-Jun. PMID 33334883, Free PMC Article
  2. Further delineation of HIDEA syndrome. Maddirevula S, et al. Am J Med Genet A, 2020 Dec. PMID 32965080
  3. The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration. Fan L, et al. Biomed Res Int, 2014. PMID 24895555, Free PMC Article
  4. Human prolyl hydroxylase expression in uterine leiomyoma during the menstrual cycle. Iwahashi M, et al. Reprod Biol Endocrinol, 2012 Dec 17. PMID 23241241, Free PMC Article
  5. The peptide-substrate-binding domain of collagen prolyl 4-hydroxylases is a tetratricopeptide repeat domain with functional aromatic residues. Pekkala M, et al. J Biol Chem, 2004 Dec 10. PMID 15456751

See all (26) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. A pathogenic P4HTM gene variant in two brothers with autism spectrum disorder.
    Title: A pathogenic P4HTM gene variant in two brothers with autism spectrum disorder.
  2. Biallelic Mutations in P4HTM Cause Syndromic Obesity.
    Title: Biallelic Mutations in P4HTM Cause Syndromic Obesity.
  3. Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains.
    Title: Structure of transmembrane prolyl 4-hydroxylase reveals unique organization of EF and dioxygenase domains.
  4. Further delineation of HIDEA syndrome.
    Title: Further delineation of HIDEA syndrome.
  5. The results suggest that SESN2 increases degradation of HIF-1A via AMPK-PHD regulation that contributes to inhibition of in vitro and in vivo tumorigenesis.
    Title: Sestrin2 inhibits hypoxia-inducible factor-1α accumulation via AMPK-mediated prolyl hydroxylase regulation.
  6. This review will expand our knowledge of biology of HIFs, PHDs, PHD inhibitors, and bone regeneration, and it may also aid the design of novel therapies for accelerating bone repair and regeneration or inhibiting bone tumours. [review]
    Title: The hypoxia-inducible factor pathway, prolyl hydroxylase domain protein inhibitors, and their roles in bone repair and regeneration.
  7. Results suggest that increased expression of prolyl hydroxylase (PH) might play an role in the physiology of uterine leiomyoma during the menstrual cycle.
    Title: Human prolyl hydroxylase expression in uterine leiomyoma during the menstrual cycle.
  8. crystal structure of the peptide-substrate-binding domain
    Title: The peptide-substrate-binding domain of collagen prolyl 4-hydroxylases is a tetratricopeptide repeat domain with functional aromatic residues.
  9. the longest and shortest isoenzymes have major transcripts encoding inactive polypeptides, which suggest novel regulation by alternative splicing.
    Title: Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor.
  10. Data suggest that PH-4 is a novel hypoxia-inducible factor-prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia.
    Title: Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors.
Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Nef nef The yeast two-hybrid screen and the coimmunoprecipitation analysis identify the HIV-1 Nef interacting human protein prolyl 4-hydroxylase (PH4) in cells PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 2-oxoglutarate-dependent dioxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables L-ascorbic acid binding IEA
Inferred from Electronic Annotation
more info
  
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables hypoxia-inducible factor-proline dioxygenase activity IEA
Inferred from Electronic Annotation
more info
  
enables iron ion binding IEA
Inferred from Electronic Annotation
more info
  
enables procollagen-proline 4-dioxygenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in peptidyl-proline hydroxylation to 4-hydroxy-L-proline IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of erythrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
transmembrane prolyl 4-hydroxylase
Names
HIF-PH4
HIF-prolyl hydroxylase 4
HPH-4
P4H with transmembrane domain
Prolyl hydroxlase domain-containing 4
hypoxia-inducible factor prolyl 4-hydroxylase
hypoxia-inducible factor prolyl hydroxylase 4
proline 4-hydroxylase
prolyl 4-hydroxylase, transmembrane (endoplasmic reticulum)
NP_808807.2
NP_808808.1
XP_047304323.1
XP_047304324.1
XP_054202924.1
XP_054202925.1

NCBI Reference Sequences (RefSeq)

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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_177938.2 → NP_808807.2  transmembrane prolyl 4-hydroxylase isoform c

    See identical proteins and their annotated locations for NP_808807.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains two additional segments in the coding region, compared to variant 1. The resulting isoform (c) is longer, compared to isoform a.
    Source sequence(s)
    AW072069, BC000580, BC011710, BC047566
    Consensus CDS
    CCDS2781.2
    UniProtKB/Swiss-Prot
    Q9NXG6
    Related
    ENSP00000341422.4, ENST00000343546.8
    Conserved Domains (3) summary
    smart00702
    Location:246 → 519
    P4Hc; Prolyl 4-hydroxylase alpha subunit homologues
    cd00051
    Location:194 → 252
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam13499
    Location:192 → 252
    EF-hand_7; EF-hand domain pair

  2. NM_177939.3 → NP_808808.1  transmembrane prolyl 4-hydroxylase isoform a

    See identical proteins and their annotated locations for NP_808808.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shortest transcript.
    Source sequence(s)
    AC137630, AW072069, BC000580, BC011710, BC047566
    Consensus CDS
    CCDS43089.1
    UniProtKB/Swiss-Prot
    Q6PAG6, Q8TCJ9, Q8WV55, Q96F22, Q9BW77, Q9NXG6
    Related
    ENSP00000373235.4, ENST00000383729.9
    Conserved Domains (3) summary
    smart00702
    Location:246 → 458
    P4Hc; Prolyl 4-hydroxylase alpha subunit homologues
    cd00051
    Location:194 → 252
    EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...
    pfam13499
    Location:192 → 252
    EF-hand_7; EF-hand domain pair

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    48989908..49007153
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047448367.1 → XP_047304323.1  transmembrane prolyl 4-hydroxylase isoform X1

  2. XM_047448368.1 → XP_047304324.1  transmembrane prolyl 4-hydroxylase isoform X2

RNA

  1. XR_007095696.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    49017960..49035193
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054346949.1 → XP_054202924.1  transmembrane prolyl 4-hydroxylase isoform X1

  2. XM_054346950.1 → XP_054202925.1  transmembrane prolyl 4-hydroxylase isoform X2

RNA

  1. XR_008486738.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_017732.3: Suppressed sequence

    Description
    NM_017732.3: 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
Q9NXG6.2 GenPept UniProtKB/Swiss-Prot:Q9NXG6

Gene LinkOut

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