Transmembrane prolyl 4-hydroxylase

Details

Name
Transmembrane prolyl 4-hydroxylase
Synonyms
  • 1.14.11.-
  • HIF-PH4
  • HIF-prolyl hydroxylase 4
  • HPH-4
  • Hypoxia-inducible factor prolyl hydroxylase 4
  • P4H-TM
  • PH4
Gene Name
P4HTM
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004363|Transmembrane prolyl 4-hydroxylase
MAAAAVTGQRPETAAAEEASRPQWAPPDHCQAQAAAGLGDGEDAPVRPLCKPRGICSRAY
FLVLMVFVHLYLGNVLALLLFVHYSNGDESSDPGPQHRAQGPGPEPTLGPLTRLEGIKVG
HERKVQLVTDRDHFIRTLSLKPLLFEIPGFLTDEECRLIIHLAQMKGLQRSQILPTEEYE
EAMSTMQVSQLDLFRLLDQNRDGHLQLREVLAQTRLGNGWWMTPESIQEMYAAIKADPDG
DGVLSLQEFSNMDLRDFHKYMRSHKAESSELVRNSHHTWLYQGEGAHHIMRAIRQRVLRL
TRLSPEIVELSEPLQVVRYGEGGHYHAHVDSGPVYPETICSHTKLVANESVPFETSCRYM
TVLFYLNNVTGGGETVFPVADNRTYDEMSLIQDDVDLRDTRRHCDKGNLRVKPQQGTAVF
WYNYLPDGQGWVGDVDDYSLHGGCLVTRGTKWIANNWINVDPSRARQALFQQEMARLARE
GGTDSQPEWALDRAYRDARVEL
Number of residues
502
Molecular Weight
56660.535
Theoretical pI
5.99
GO Classification
Functions
iron ion binding / L-ascorbic acid binding / 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
Processes
regulation of erythrocyte differentiation
Components
endoplasmic reticulum membrane / integral component of membrane
General Function
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
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.
Pfam Domain Function
Transmembrane Regions
61-81
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0011604|Transmembrane prolyl 4-hydroxylase (P4HTM)
ATGGCGGCAGCGGCGGTGACAGGCCAGCGGCCTGAGACCGCGGCGGCCGAGGAGGCCTCG
AGGCCGCAGTGGGCGCCGCCAGACCACTGCCAGGCTCAGGCGGCGGCCGGGCTGGGCGAC
GGCGAGGACGCACCGGTGCGTCCGCTGTGCAAGCCCCGCGGCATCTGCTCGCGCGCCTAC
TTCCTGGTGCTGATGGTGTTCGTGCACCTGTACCTGGGTAACGTGCTGGCGCTGCTGCTC
TTCGTGCACTACAGCAACGGCGACGAAAGCAGCGATCCCGGGCCCCAACACCGTGCCCAG
GGCCCCGGGCCCGAGCCCACCTTAGGTCCCCTCACCCGGCTGGAGGGCATCAAGGTGGGG
CACGAGCGTAAGGTCCAGCTGGTCACCGACAGGGATCACTTCATCCGAACCCTCAGCCTC
AAGCCGCTGCTCTTCGAAATCCCCGGCTTCCTGACTGATGAAGAGTGTCGGCTCATCATC
CATCTGGCGCAGATGAAGGGGTTACAGCGCAGCCAGATCCTGCCTACTGAAGAGTATGAA
GAGGCAATGAGCACTATGCAGGTCAGCCAGCTGGACCTCTTCCGGCTGCTGGACCAGAAC
CGTGATGGGCACCTTCAGCTCCGTGAGGTTCTGGCCCAGACTCGCCTGGGAAATGGATGG
TGGATGACTCCAGAGAGCATTCAGGAGATGTACGCCGCGATCAAGGCTGACCCTGATGGT
GACGGAGTGCTGAGTCTGCAGGAGTTCTCCAACATGGACCTTCGGGACTTCCACAAGTAC
ATGAGGAGCCACAAGGCAGAGTCCAGTGAGCTGGTGCGGAACAGCCACCATACCTGGCTC
TACCAGGGTGAGGGTGCCCACCACATCATGCGTGCCATCCGCCAGAGGGTGCTGCGCCTC
ACTCGCCTGTCGCCTGAGATCGTGGAGCTCAGCGAGCCGCTGCAGGTTGTTCGATATGGT
GAGGGGGGCCACTACCATGCCCACGTGGACAGTGGGCCTGTGTACCCAGAGACCATCTGC
TCCCATACCAAGCTGGTAGCCAACGAGTCTGTACCCTTCGAGACCTCCTGCCGGCAAGTA
TCTCCCAACTGGGGGCTGCCTTCAATCCTCAGACCAGGAACACCCATGACACAGGCACAG
CCCTGCACTGTGGGCGTGCCCCTTGGCATGGGGCCAGGAGATCACTGGGTTATCCCGGTA
AGCCCCTGGGAGCATCCACAACTGGGGACCTGCTCAGTGCCCCCCCTGCCTTACAGCTAC
ATGACAGTGCTGTTTTATTTGAACAACGTCACTGGTGGGGGCGAGACTGTTTTCCCTGTA
GCAGATAACAGAACCTACGATGAAATGAGTCTGATTCAGGATGACGTGGACCTCCGTGAC
ACACGGAGGCACTGTGACAAGGGAAACCTGCGTGTCAAGCCCCAACAGGGCACAGCAGTC
TTCTGGTACAACTACCTGCCTGATGGGCAAGGTTGGGTGGGTGACGTAGACGACTACTCG
CTGCACGGGGGCTGCCTGGTCACGCGCGGCACCAAGTGGATTGCCAACAACTGGATTAAT
GTGGACCCCAGCCGAGCGCGGCAAGCGCTGTTCCAACAGGAGATGGCCCGCCTTGCCCGA
GAAGGGGGCACCGACTCACAGCCCGAGTGGGCTCTGGACCGGGCCTACCGCGATGCGCGC
GTGGAACTCTGA
Chromosome Location
3
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDQ9NXG6
UniProtKB Entry NameP4HTM_HUMAN
GenBank Protein ID28566186
GenBank Gene IDAY198406
HGNC IDHGNC:28858
General References
  1. 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]
  2. 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]
  3. 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]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
  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]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00126Ascorbic acidapproved, nutraceuticalunknownDetails