Free for academic non-profit institutions. Other users need a Commercial license

Aliases for P4HTM Gene

Aliases for P4HTM Gene

  • Prolyl 4-Hydroxylase, Transmembrane 2 3 5
  • Prolyl 4-Hydroxylase, Transmembrane (Endoplasmic Reticulum) 2 3
  • Hypoxia-Inducible Factor Prolyl Hydroxylase 4 3 4
  • Prolyl Hydroxlase Domain-Containing 4 2 3
  • HIF-Prolyl Hydroxylase 4 3 4
  • HIF-PH4 3 4
  • P4H-TM 3 4
  • HPH-4 3 4
  • PH4 3 4
  • Hypoxia-Inducible Factor Prolyl 4-Hydroxylase 3
  • Hypoxia Inducible Factor Prolyl 4 Hydroxylase 2
  • Transmembrane Prolyl 4-Hydroxylase 3
  • P4H With Transmembrane Domain 3
  • Proline 4-Hydroxylase 3
  • EC 1.14.11.- 4
  • HIFPH4 3
  • EGLN4 3
  • PH-4 3
  • PHD4 3

External Ids for P4HTM Gene

Previous GeneCards Identifiers for P4HTM Gene

  • GC03P049004
  • GC03P049027
  • GC03P048991
  • GC03P048996
  • GC03P049009
  • GC03P049048
  • GC03P049058
  • GC03P049069
  • GC03P049077
  • GC03P049086

Summaries for P4HTM Gene

Entrez Gene Summary for P4HTM Gene

  • 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]

GeneCards Summary for P4HTM Gene

P4HTM (Prolyl 4-Hydroxylase, Transmembrane) is a Protein Coding gene. Diseases associated with P4HTM include Hypoxia. Gene Ontology (GO) annotations related to this gene include calcium ion binding and iron ion binding.

UniProtKB/Swiss-Prot for P4HTM Gene

  • Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at Pro-402 and Pro-564. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.

Additional gene information for P4HTM Gene

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for P4HTM Gene

Genomics for P4HTM Gene

GeneHancer (GH) Regulatory Elements for P4HTM Gene

Promoters and enhancers for P4HTM Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03J048988 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 650.7 +1.3 1333 3 HDGF SMAD1 SIN3A ZNF2 IRF4 YY1 ZNF143 FOS JUNB REST P4HTM ENSG00000223343 ENSG00000285416
GH03J048987 Enhancer 0.9 Ensembl ENCODE 650.7 -1.1 -1099 0.4 CTCF IRF2 MXI1 SAP130 RB1 ARID4B CEBPG RAD21 TEAD3 SCRT2 P4HTM LOC105377079 ENSG00000223343 GMPPB
GH03J049016 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 40.2 +31.2 31161 6.8 CLOCK ZFP64 FEZF1 IRF4 YY1 E2F8 ZNF143 SP3 NFYC ZFP41 DALRD3 GC03M049024 NDUFAF3 MIR425 MIR191 WDR6 ENSG00000235236 NICN1 FCF1P2 QRICH1
GH03J049338 Promoter/Enhancer 2.7 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 10.4 +357.0 356950 14.7 MLX ZFP64 DMAP1 IRF4 YY1 SLC30A9 ZNF143 SP3 NFYC ZC3H11A USP4 AMT QRICH1 RBM6 RBM5 IP6K2 ATRIP USP19 WDR6 BSN-AS1
GH03J048085 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 10.4 -901.2 -901199 5.3 CLOCK FEZF1 DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF416 ZNF143 ZNF263 MAP4 ATRIP DHX30 ZNF589 SETD2 ENSG00000235236 PTPN23 BOLA2P2 SCAP TMEM89
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around P4HTM on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the P4HTM gene promoter:
  • POU2F1
  • POU2F1a
  • AML1a
  • c-Myb
  • NF-1
  • Msx-1
  • HEN1
  • STAT5A
  • Evi-1

Genomic Locations for P4HTM Gene

Genomic Locations for P4HTM Gene
chr3:48,989,100-49,007,154
(GRCh38/hg38)
Size:
18,055 bases
Orientation:
Plus strand
chr3:49,027,319-49,044,587
(GRCh37/hg19)
Size:
17,269 bases
Orientation:
Plus strand

Genomic View for P4HTM Gene

Genes around P4HTM on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
P4HTM Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for P4HTM Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for P4HTM Gene

Proteins for P4HTM Gene

  • Protein details for P4HTM Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NXG6-P4HTM_HUMAN
    Recommended name:
    Transmembrane prolyl 4-hydroxylase
    Protein Accession:
    Q9NXG6
    Secondary Accessions:
    • Q6PAG6
    • Q8TCJ9
    • Q8WV55
    • Q96F22
    • Q9BW77

    Protein attributes for P4HTM Gene

    Size:
    502 amino acids
    Molecular mass:
    56661 Da
    Cofactor:
    Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
    Cofactor:
    Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
    Quaternary structure:
    • Homodimer.
    SequenceCaution:
    • Sequence=AAH60321.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; Sequence=BAA91045.1; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAD28518.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};

    Alternative splice isoforms for P4HTM Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for P4HTM Gene

Post-translational modifications for P4HTM Gene

Other Protein References for P4HTM Gene

No data available for DME Specific Peptides for P4HTM Gene

Domains & Families for P4HTM Gene

Gene Families for P4HTM Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for P4HTM Gene

Suggested Antigen Peptide Sequences for P4HTM Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with P4HTM: view

No data available for UniProtKB/Swiss-Prot for P4HTM Gene

Function for P4HTM Gene

Molecular function for P4HTM Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at Pro-402 and Pro-564. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
UniProtKB/Swiss-Prot CatalyticActivity:
An HIF alpha chain L-proline + 2-oxoglutarate + O(2) = An HIF alpha chain trans-4-hydroxy-L-proline + succinate + CO(2).
UniProtKB/Swiss-Prot Induction:
By hypoxia in many cultured cell lines.

Enzyme Numbers (IUBMB) for P4HTM Gene

Phenotypes From GWAS Catalog for P4HTM Gene

Gene Ontology (GO) - Molecular Function for P4HTM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005506 iron ion binding IEA --
GO:0005509 calcium ion binding IEA --
GO:0016491 oxidoreductase activity IEA --
GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen IEA --
GO:0016706 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors IDA 22955912
genes like me logo Genes that share ontologies with P4HTM: view
genes like me logo Genes that share phenotypes with P4HTM: view

Animal Models for P4HTM Gene

MGI Knock Outs for P4HTM:

Animal Model Products

  • Taconic Biosciences Mouse Models for P4HTM

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for P4HTM

No data available for Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for P4HTM Gene

Localization for P4HTM Gene

Subcellular locations from UniProtKB/Swiss-Prot for P4HTM Gene

Endoplasmic reticulum membrane; Single-pass type II membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for P4HTM gene
Compartment Confidence
endoplasmic reticulum 4
plasma membrane 3
cytosol 3
lysosome 2
extracellular 1
mitochondrion 1
nucleus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (1)
  • Vesicles (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for P4HTM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with P4HTM: view

Pathways & Interactions for P4HTM Gene

SuperPathways for P4HTM Gene

No Data Available

Gene Ontology (GO) - Biological Process for P4HTM Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0045646 regulation of erythrocyte differentiation IEA --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with P4HTM: view

No data available for Pathways by source and SIGNOR curated interactions for P4HTM Gene

Drugs & Compounds for P4HTM Gene

(9) Drugs for P4HTM Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Vitamin C Approved Nutra Target 581,581
hydroxyproline Approved, Experimental Pharma 0
Oxygen Approved, Vet_approved Pharma 0
L-Proline Approved Nutra 0
Succinic acid Approved Nutra Full agonist, Agonist 0

(2) Additional Compounds for P4HTM Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with P4HTM: view

Transcripts for P4HTM Gene

mRNA/cDNA for P4HTM Gene

Unigene Clusters for P4HTM Gene

Prolyl 4-hydroxylase, transmembrane (endoplasmic reticulum):
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for P4HTM

Alternative Splicing Database (ASD) splice patterns (SP) for P4HTM Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b
SP1: - - -
SP2: - - -
SP3: - - -
SP4: -
SP5:
SP6:

Relevant External Links for P4HTM Gene

GeneLoc Exon Structure for
P4HTM
ECgene alternative splicing isoforms for
P4HTM

Expression for P4HTM Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for P4HTM Gene

Protein differential expression in normal tissues from HIPED for P4HTM Gene

This gene is overexpressed in Testis (37.8) and Retina (10.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for P4HTM Gene



Protein tissue co-expression partners for P4HTM Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of P4HTM Gene:

P4HTM

SOURCE GeneReport for Unigene cluster for P4HTM Gene:

Hs.654944

mRNA Expression by UniProt/SwissProt for P4HTM Gene:

Q9NXG6-P4HTM_HUMAN
Tissue specificity: Widely expressed with highest levels in adult pancreas, heart, skeletal muscle, brain, placenta, kidney and adrenal gland. Expressed at lower levels in epiphyseal cartilage and in fibroblasts.

Evidence on tissue expression from TISSUES for P4HTM Gene

  • Nervous system(4.9)
  • Lung(4.6)
  • Intestine(4.4)
genes like me logo Genes that share expression patterns with P4HTM: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for P4HTM Gene

Orthologs for P4HTM Gene

This gene was present in the common ancestor of chordates.

Orthologs for P4HTM Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia P4HTM 34 33
  • 99.67 (n)
OneToOne
dog
(Canis familiaris)
Mammalia P4HTM 34 33
  • 91.75 (n)
OneToOne
cow
(Bos Taurus)
Mammalia P4HTM 34 33
  • 90.49 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia P4htm 33
  • 86.52 (n)
mouse
(Mus musculus)
Mammalia P4htm 16 34 33
  • 86.32 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia P4HTM 34
  • 74 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia P4HTM 34
  • 67 (a)
OneToOne
chicken
(Gallus gallus)
Aves P4HTM 34 33
  • 75.87 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia P4HTM 34
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia p4htm 33
  • 67.23 (n)
zebrafish
(Danio rerio)
Actinopterygii LOC799930 33
  • 60.43 (n)
P4HTM 34
  • 51 (a)
OneToOne
Species where no ortholog for P4HTM was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for P4HTM Gene

ENSEMBL:
Gene Tree for P4HTM (if available)
TreeFam:
Gene Tree for P4HTM (if available)
Aminode:
Evolutionary constrained regions (ECRs) for P4HTM: view image

Paralogs for P4HTM Gene

No data available for Paralogs for P4HTM Gene

Variants for P4HTM Gene

Sequence variations from dbSNP and Humsavar for P4HTM Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1000043222 -- 49,002,863(+) C/G intron_variant
rs1000294746 -- 48,994,909(+) C/T intron_variant
rs1000318609 -- 48,995,884(+) C/T intron_variant
rs1000603771 -- 49,001,074(+) T/G intron_variant
rs1000791676 -- 49,000,187(+) T/C intron_variant

Structural Variations from Database of Genomic Variants (DGV) for P4HTM Gene

Variant ID Type Subtype PubMed ID
nsv954487 CNV deletion 24416366
nsv954488 CNV deletion 24416366

Variation tolerance for P4HTM Gene

Residual Variation Intolerance Score: 28.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.30; 25.79% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for P4HTM Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
P4HTM

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for P4HTM Gene

Disorders for P4HTM Gene

MalaCards: The human disease database

(1) MalaCards diseases for P4HTM Gene - From: GeneCards

Disorder Aliases PubMed IDs
hypoxia
- elite association - COSMIC cancer census association via MalaCards
Search P4HTM in MalaCards View complete list of genes associated with diseases

Additional Disease Information for P4HTM

genes like me logo Genes that share disorders with P4HTM: view

No data available for UniProtKB/Swiss-Prot and Genatlas for P4HTM Gene

Publications for P4HTM Gene

  1. Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors. (PMID: 12163023) Oehme F … Flamme I (Biochemical and biophysical research communications 2002) 2 3 4 22 58
  2. An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha. (PMID: 17726031) Koivunen P … Myllyharju J (The Journal of biological chemistry 2007) 2 3 4 58
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58
  5. Sestrin2 inhibits hypoxia-inducible factor-1α accumulation via AMPK-mediated prolyl hydroxylase regulation. (PMID: 27840318) Seo K … Shin SM (Free radical biology & medicine 2016) 3 58

Products for P4HTM Gene

Sources for P4HTM Gene

Content
Loading form....