LOCUS       NM_177939               1771 bp    mRNA    linear   PRI 17-MAR-2024
DEFINITION  Homo sapiens prolyl 4-hydroxylase, transmembrane (P4HTM),
            transcript variant 1, mRNA.
ACCESSION   NM_177939 XM_001133929 XM_001133930
VERSION     NM_177939.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1771)
  AUTHORS   Gulcu Ustun,N.S.
  TITLE     A pathogenic P4HTM gene variant in two brothers with autism
            spectrum disorder
  JOURNAL   Psychiatr Genet 34 (2), 68-69 (2024)
   PUBMED   38441145
  REMARK    GeneRIF: A pathogenic P4HTM gene variant in two brothers with
            autism spectrum disorder.
REFERENCE   2  (bases 1 to 1771)
  AUTHORS   Saeed,S., Ning,L., Badreddine,A., Mirza,M.U., Boissel,M.,
            Khanam,R., Manzoor,J., Janjua,Q.M., Khan,W.I., Toussaint,B.,
            Vaillant,E., Amanzougarene,S., Derhourhi,M., Trant,J.F.,
            Siegert,A.M., Lam,B.Y.H., Yeo,G.S.H., Chabraoui,L., Touzani,A.,
            Kulkarni,A., Farooqi,I.S., Bonnefond,A., Arslan,M. and Froguel,P.
  TITLE     Biallelic Mutations in P4HTM Cause Syndromic Obesity
  JOURNAL   Diabetes 72 (9), 1228-1234 (2023)
   PUBMED   37083980
  REMARK    GeneRIF: Biallelic Mutations in P4HTM Cause Syndromic Obesity.
REFERENCE   3  (bases 1 to 1771)
  AUTHORS   Myllykoski,M., Sutinen,A., Koski,M.K., Kallio,J.P., Raasakka,A.,
            Myllyharju,J., Wierenga,R.K. and Koivunen,P.
  TITLE     Structure of transmembrane prolyl 4-hydroxylase reveals unique
            organization of EF and dioxygenase domains
  JOURNAL   J Biol Chem 296, 100197 (2021)
   PUBMED   33334883
  REMARK    GeneRIF: Structure of transmembrane prolyl 4-hydroxylase reveals
            unique organization of EF and dioxygenase domains.
REFERENCE   4  (bases 1 to 1771)
  AUTHORS   Maddirevula,S., Ben-Omran,T., AlMureikhi,M., Eyaid,W., Arabi,H.,
            Alkuraya,H., Alfaifi,A., Alfalah,A.H., Alsaif,H.S., Abdulwahab,F.,
            Alfadhel,M. and Alkuraya,F.S.
  TITLE     Further delineation of HIDEA syndrome
  JOURNAL   Am J Med Genet A 182 (12), 2999-3006 (2020)
   PUBMED   32965080
  REMARK    GeneRIF: Further delineation of HIDEA syndrome.
REFERENCE   5  (bases 1 to 1771)
  AUTHORS   Seo,K., Seo,S., Ki,S.H. and Shin,S.M.
  TITLE     Sestrin2 inhibits hypoxia-inducible factor-1alpha accumulation via
            AMPK-mediated prolyl hydroxylase regulation
  JOURNAL   Free Radic Biol Med 101, 511-523 (2016)
   PUBMED   27840318
  REMARK    GeneRIF: 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.
REFERENCE   6  (bases 1 to 1771)
  AUTHORS   Koivunen,P., Tiainen,P., Hyvarinen,J., Williams,K.E., Sormunen,R.,
            Klaus,S.J., Kivirikko,K.I. and Myllyharju,J.
  TITLE     An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is
            induced by hypoxia and acts on hypoxia-inducible factor alpha
  JOURNAL   J Biol Chem 282 (42), 30544-30552 (2007)
   PUBMED   17726031
REFERENCE   7  (bases 1 to 1771)
  AUTHORS   Hirota,K. and Semenza,G.L.
  TITLE     Regulation of hypoxia-inducible factor 1 by prolyl and asparaginyl
            hydroxylases
  JOURNAL   Biochem Biophys Res Commun 338 (1), 610-616 (2005)
   PUBMED   16154531
  REMARK    GeneRIF: This review summarizes recent progress in elucidating the
            molecular mechanisms of hypoxia-inducible factor (HIF)-1
            activation, focusing on the role of oxygen-dependent asparaginyl
            hydroxylase in hypoxia signal transduction.
            Review article
REFERENCE   8  (bases 1 to 1771)
  AUTHORS   Pekkala,M., Hieta,R., Bergmann,U., Kivirikko,K.I., Wierenga,R.K.
            and Myllyharju,J.
  TITLE     The peptide-substrate-binding domain of collagen prolyl
            4-hydroxylases is a tetratricopeptide repeat domain with functional
            aromatic residues
  JOURNAL   J Biol Chem 279 (50), 52255-52261 (2004)
   PUBMED   15456751
  REMARK    GeneRIF: crystal structure of the peptide-substrate-binding domain
REFERENCE   9  (bases 1 to 1771)
  AUTHORS   Hirsila,M., Koivunen,P., Gunzler,V., Kivirikko,K.I. and
            Myllyharju,J.
  TITLE     Characterization of the human prolyl 4-hydroxylases that modify the
            hypoxia-inducible factor
  JOURNAL   J Biol Chem 278 (33), 30772-30780 (2003)
   PUBMED   12788921
  REMARK    GeneRIF: the longest and shortest isoenzymes have major transcripts
            encoding inactive polypeptides, which suggest novel regulation by
            alternative splicing.
REFERENCE   10 (bases 1 to 1771)
  AUTHORS   Oehme,F., Ellinghaus,P., Kolkhof,P., Smith,T.J., Ramakrishnan,S.,
            Hutter,J., Schramm,M. and Flamme,I.
  TITLE     Overexpression of PH-4, a novel putative proline 4-hydroxylase,
            modulates activity of hypoxia-inducible transcription factors
  JOURNAL   Biochem Biophys Res Commun 296 (2), 343-349 (2002)
   PUBMED   12163023
  REMARK    GeneRIF: 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.
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC047566.1, BC011710.2,
            BC000580.1, AW072069.1 and AC137630.9.
            
            On Nov 23, 2018 this sequence version replaced NM_177939.2.
            
            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].
            
            Transcript Variant: This variant (1) represents the shortest
            transcript.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660805.80976.1,
                                           SRR3476690.955576.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000383729.9/ ENSP00000373235.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-652               BC047566.1         335-986
            653-1089            BC011710.2         642-1078
            1090-1448           BC047566.1         2154-2512
            1449-1733           BC000580.1         940-1224
            1734-1767           AW072069.1         12-45               c
            1768-1771           AC137630.9         55619-55622
FEATURES             Location/Qualifiers
     source          1..1771
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3p21.31"
     gene            1..1771
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /note="prolyl 4-hydroxylase, transmembrane"
                     /db_xref="GeneID:54681"
                     /db_xref="HGNC:HGNC:28858"
                     /db_xref="MIM:614584"
     exon            1..370
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     CDS             17..1525
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /EC_number="1.14.11.29"
                     /note="isoform a is encoded by transcript variant 1; P4H
                     with transmembrane domain; Prolyl hydroxlase
                     domain-containing 4; hypoxia-inducible factor prolyl
                     4-hydroxylase; proline 4-hydroxylase; transmembrane prolyl
                     4-hydroxylase; HPH-4; HIF-PH4; HIF-prolyl hydroxylase 4;
                     hypoxia-inducible factor prolyl hydroxylase 4; prolyl
                     4-hydroxylase, transmembrane (endoplasmic reticulum)"
                     /codon_start=1
                     /product="transmembrane prolyl 4-hydroxylase isoform a"
                     /protein_id="NP_808808.1"
                     /db_xref="CCDS:CCDS43089.1"
                     /db_xref="GeneID:54681"
                     /db_xref="HGNC:HGNC:28858"
                     /db_xref="MIM:614584"
                     /translation="MAAAAVTGQRPETAAAEEASRPQWAPPDHCQAQAAAGLGDGEDA
                     PVRPLCKPRGICSRAYFLVLMVFVHLYLGNVLALLLFVHYSNGDESSDPGPQHRAQGP
                     GPEPTLGPLTRLEGIKVGHERKVQLVTDRDHFIRTLSLKPLLFEIPGFLTDEECRLII
                     HLAQMKGLQRSQILPTEEYEEAMSTMQVSQLDLFRLLDQNRDGHLQLREVLAQTRLGN
                     GWWMTPESIQEMYAAIKADPDGDGVLSLQEFSNMDLRDFHKYMRSHKAESSELVRNSH
                     HTWLYQGEGAHHIMRAIRQRVLRLTRLSPEIVELSEPLQVVRYGEGGHYHAHVDSGPV
                     YPETICSHTKLVANESVPFETSCRYMTVLFYLNNVTGGGETVFPVADNRTYDEMSLIQ
                     DDVDLRDTRRHCDKGNLRVKPQQGTAVFWYNYLPDGQGWVGDVDDYSLHGGCLVTRGT
                     KWIANNWINVDPSRARQALFQQEMARLAREGGTDSQPEWALDRAYRDARVEL"
     exon            371..452
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            453..643
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            644..740
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            741..903
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            904..1089
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1090..1180
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1181..1304
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     exon            1305..1771
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1712..1717
                     /regulatory_class="polyA_signal_sequence"
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /note="hexamer: AATAAA"
     polyA_site      1733
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
                     /note="major polyA site"
     polyA_site      1771
                     /gene="P4HTM"
                     /gene_synonym="EGLN4; HIDEA; HIFPH4; P4H-TM; PH-4; PH4;
                     PHD4"
ORIGIN      
        1 gcgcgacctg ggtgccatgg cggcagcggc ggtgacaggc cagcggcctg agaccgcggc
       61 ggccgaggag gcctcgaggc cgcagtgggc gccgccagac cactgccagg ctcaggcggc
      121 ggccgggctg ggcgacggcg aggacgcacc ggtgcgtccg ctgtgcaagc cccgcggcat
      181 ctgctcgcgc gcctacttcc tggtgctgat ggtgttcgtg cacctgtacc tgggtaacgt
      241 gctggcgctg ctgctcttcg tgcactacag caacggcgac gaaagcagcg atcccgggcc
      301 ccaacaccgt gcccagggcc ccgggcccga gcccacctta ggtcccctca cccggctgga
      361 gggcatcaag gtggggcacg agcgtaaggt ccagctggtc accgacaggg atcacttcat
      421 ccgaaccctc agcctcaagc cgctgctctt cgaaatcccc ggcttcctga ctgatgaaga
      481 gtgtcggctc atcatccatc tggcgcagat gaaggggtta cagcgcagcc agatcctgcc
      541 tactgaagag tatgaagagg caatgagcac tatgcaggtc agccagctgg acctcttccg
      601 gctgctggac cagaaccgtg atgggcacct tcagctccgt gaggttctgg cccagactcg
      661 cctgggaaat ggatggtgga tgactccaga gagcattcag gagatgtacg ccgcgatcaa
      721 ggctgaccct gatggtgacg gagtgctgag tctgcaggag ttctccaaca tggaccttcg
      781 ggacttccac aagtacatga ggagccacaa ggcagagtcc agtgagctgg tgcggaacag
      841 ccaccatacc tggctctacc agggtgaggg tgcccaccac atcatgcgtg ccatccgcca
      901 gagggtgctg cgcctcactc gcctgtcgcc tgagatcgtg gagctcagcg agccgctgca
      961 ggttgttcga tatggtgagg ggggccacta ccatgcccac gtggacagtg ggcctgtgta
     1021 cccagagacc atctgctccc ataccaagct ggtagccaac gagtctgtac ccttcgagac
     1081 ctcctgccgc tacatgacag tgctgtttta tttgaacaac gtcactggtg ggggcgagac
     1141 tgttttccct gtagcagata acagaaccta cgatgaaatg agtctgattc aggatgacgt
     1201 ggacctccgt gacacacgga ggcactgtga caagggaaac ctgcgtgtca agccccaaca
     1261 gggcacagca gtcttctggt acaactacct gcctgatggg caaggttggg tgggtgacgt
     1321 agacgactac tcgctgcacg ggggctgcct ggtcacgcgc ggcaccaagt ggattgccaa
     1381 caactggatt aatgtggacc ccagccgagc gcggcaagcg ctgttccaac aggagatggc
     1441 ccgccttgcc cgagaagggg gcaccgactc acagcccgag tgggctctgg accgggccta
     1501 ccgcgatgcg cgcgtggaac tctgagggaa gagttagccc cggttcccag ccgcgggtcg
     1561 ccagttgccc aagatcaggg gtccggctgt ccttctgtcc tgctgcagac taaaggtctg
     1621 gccaatgtct tgccccaccc cgccagccgc gatacggcgc agttcctata ttcatgttat
     1681 ttattgtgta ctgactccat ctgccccgtc aaataaaaaa ccacaaggtt cgagccgccg
     1741 ggcccgacaa actccgggtc ggcgaaacag a
//
