Hmdb loader
Identification
HMDB Protein ID HMDBP09213
Secondary Accession Numbers
  • 14995
Name Transmembrane prolyl 4-hydroxylase
Synonyms
  1. HIF-PH4
  2. HIF-prolyl hydroxylase 4
  3. HPH-4
  4. Hypoxia-inducible factor prolyl hydroxylase 4
  5. P4H-TM
Gene Name P4HTM
Protein Type Enzyme
Biological Properties
General Function Involved in calcium ion binding
Specific 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.
Pathways Not Available
Reactions
An HIF alpha chain L-proline + Oxoglutaric acid + Oxygen → An HIF alpha chain trans-4-hydroxy-L-proline + Succinic acid + CO(2) details
GO Classification
Cellular Component
endoplasmic reticulum membrane
integral to membrane
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
l-ascorbic acid binding
iron ion binding
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
vitamin binding
oxidoreductase activity
calcium ion binding
Molecular Function
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
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
L-ascorbic acid binding
iron ion binding
calcium ion binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Single-pass type II membrane protein
Gene Properties
Chromosome Location 3
Locus 3p21.3
SNPs P4HTM
Gene Sequence
>1509 bp
ATGGCGGCAGCGGCGGTGACAGGCCAGCGGCCTGAGACCGCGGCGGCCGAGGAGGCCTCG
AGGCCGCAGTGGGCGCCGCCAGACCACTGCCAGGCTCAGGCGGCGGCCGGGCTGGGCGAC
GGCGAGGACGCACCGGTGCGTCCGCTGTGCAAGCCCCGCGGCATCTGCTCGCGCGCCTAC
TTCCTGGTGCTGATGGTGTTCGTGCACCTGTACCTGGGTAACGTGCTGGCGCTGCTGCTC
TTCGTGCACTACAGCAACGGCGACGAAAGCAGCGATCCCGGGCCCCAACACCGTGCCCAG
GGCCCCGGGCCCGAGCCCACCTTAGGTCCCCTCACCCGGCTGGAGGGCATCAAGGTGGGG
CACGAGCGTAAGGTCCAGCTGGTCACCGACAGGGATCACTTCATCCGAACCCTCAGCCTC
AAGCCGCTGCTCTTCGAAATCCCCGGCTTCCTGACTGATGAAGAGTGTCGGCTCATCATC
CATCTGGCGCAGATGAAGGGGTTACAGCGCAGCCAGATCCTGCCTACTGAAGAGTATGAA
GAGGCAATGAGCACTATGCAGGTCAGCCAGCTGGACCTCTTCCGGCTGCTGGACCAGAAC
CGTGATGGGCACCTTCAGCTCCGTGAGGTTCTGGCCCAGACTCGCCTGGGAAATGGATGG
TGGATGACTCCAGAGAGCATTCAGGAGATGTACGCCGCGATCAAGGCTGACCCTGATGGT
GACGGAGTGCTGAGTCTGCAGGAGTTCTCCAACATGGACCTTCGGGACTTCCACAAGTAC
ATGAGGAGCCACAAGGCAGAGTCCAGTGAGCTGGTGCGGAACAGCCACCATACCTGGCTC
TACCAGGGTGAGGGTGCCCACCACATCATGCGTGCCATCCGCCAGAGGGTGCTGCGCCTC
ACTCGCCTGTCGCCTGAGATCGTGGAGCTCAGCGAGCCGCTGCAGGTTGTTCGATATGGT
GAGGGGGGCCACTACCATGCCCACGTGGACAGTGGGCCTGTGTACCCAGAGACCATCTGC
TCCCATACCAAGCTGGTAGCCAACGAGTCTGTACCCTTCGAGACCTCCTGCCGCTACATG
ACAGTGCTGTTTTATTTGAACAACGTCACTGGTGGGGGCGAGACTGTTTTCCCTGTAGCA
GATAACAGAACCTACGATGAAATGAGTCTGATTCAGGATGACGTGGACCTCCGTGACACA
CGGAGGCACTGTGACAAGGGAAACCTGCGTGTCAAGCCCCAACAGGGCACAGCAGTCTTC
TGGTACAACTACCTGCCTGATGGGCAAGGTTGGGTGGGTGACGTAGACGACTACTCGCTG
CACGGGGGCTGCCTGGTCACGCGCGGCACCAAGTGGATTGCCAACAACTGGATTAATGTG
GACCCCAGCCGAGCGCGGCAAGCGCTGTTCCAACAGGAGATGGCCCGCCTTGCCCGAGAA
GGGGGCACCGACTCACAGCCCGAGTGGGCTCTGGACCGGGCCTACCGCGATGCGCGCGTG
GAACTCTGA
Protein Properties
Number of Residues 502
Molecular Weight 63111.98
Theoretical pI 6.102
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Transmembrane prolyl 4-hydroxylase
MAAAAVTGQRPETAAAEEASRPQWAPPDHCQAQAAAGLGDGEDAPVRPLCKPRGICSRAY
FLVLMVFVHLYLGNVLALLLFVHYSNGDESSDPGPQHRAQGPGPEPTLGPLTRLEGIKVG
HERKVQLVTDRDHFIRTLSLKPLLFEIPGFLTDEECRLIIHLAQMKGLQRSQILPTEEYE
EAMSTMQVSQLDLFRLLDQNRDGHLQLREVLAQTRLGNGWWMTPESIQEMYAAIKADPDG
DGVLSLQEFSNMDLRDFHKYMRSHKAESSELVRNSHHTWLYQGEGAHHIMRAIRQRVLRL
TRLSPEIVELSEPLQVVRYGEGGHYHAHVDSGPVYPETICSHTKLVANESVPFETSCRYM
TVLFYLNNVTGGGETVFPVADNRTYDEMSLIQDDVDLRDTRRHCDKGNLRVKPQQGTAVF
WYNYLPDGQGWVGDVDDYSLHGGCLVTRGTKWIANNWINVDPSRARQALFQQEMARLARE
GGTDSQPEWALDRAYRDARVEL
GenBank ID Protein 29570771
UniProtKB/Swiss-Prot ID Q9NXG6
UniProtKB/Swiss-Prot Entry Name P4HTM_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_177939.2
GeneCard ID P4HTM
GenAtlas ID P4HTM
HGNC ID HGNC:28858
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  4. Oehme F, Ellinghaus P, Kolkhof P, Smith TJ, Ramakrishnan S, Hutter J, Schramm M, Flamme I: Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors. Biochem Biophys Res Commun. 2002 Aug 16;296(2):343-9. [PubMed:12163023 ]
  5. Koivunen P, Tiainen P, Hyvarinen J, Williams KE, Sormunen R, Klaus SJ, Kivirikko KI, Myllyharju J: An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha. J Biol Chem. 2007 Oct 19;282(42):30544-52. Epub 2007 Aug 27. [PubMed:17726031 ]