P4HTM_HUMAN
ID P4HTM_HUMAN Reviewed; 502 AA.
AC Q9NXG6; Q6PAG6; Q8TCJ9; Q8WV55; Q96F22; Q9BW77;
DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Transmembrane prolyl 4-hydroxylase;
DE Short=P4H-TM;
DE EC=1.14.11.29 {ECO:0000269|PubMed:17726031};
DE AltName: Full=Hypoxia-inducible factor prolyl hydroxylase 4;
DE Short=HIF-PH4;
DE Short=HIF-prolyl hydroxylase 4;
DE Short=HPH-4;
GN Name=P4HTM; Synonyms=PH4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=12163023; DOI=10.1016/s0006-291x(02)00862-8;
RA Oehme F., Ellinghaus P., Kolkhof P., Smith T.J., Ramakrishnan S.,
RA Huetter J., Schramm M., Flamme I.;
RT "Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates
RT activity of hypoxia-inducible transcription factors.";
RL Biochem. Biophys. Res. Commun. 296:343-349(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 166-502 (ISOFORM 1).
RC TISSUE=Duodenum, Hippocampus, and Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-502 (ISOFORM 2).
RC TISSUE=Colon mucosa;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, TOPOLOGY, AND GLYCOSYLATION.
RX PubMed=17726031; DOI=10.1074/jbc.m704988200;
RA Koivunen P., Tiainen P., Hyvaerinen J., Williams K.E., Sormunen R.,
RA Klaus S.J., Kivirikko K.I., Myllyharju J.;
RT "An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by
RT hypoxia and acts on hypoxia-inducible factor alpha.";
RL J. Biol. Chem. 282:30544-30552(2007).
RN [6]
RP INVOLVEMENT IN HIDEA, AND VARIANTS HIDEA PRO-161 AND 471-GLN--LEU-502 DEL.
RX PubMed=30940925; DOI=10.1038/s41436-019-0503-4;
RA Rahikkala E., Myllykoski M., Hinttala R., Vieira P., Nayebzadeh N.,
RA Weiss S., Plomp A.S., Bittner R.E., Kurki M.I., Kuismin O., Lewis A.M.,
RA Vaeisaenen M.L., Kokkonen H., Westermann J., Bernert G., Tuominen H.,
RA Palotie A., Aaltonen L., Yang Y., Potocki L., Moilanen J.,
RA van Koningsbruggen S., Wang X., Schmidt W.M., Koivunen P., Uusimaa J.;
RT "Biallelic loss-of-function P4HTM gene variants cause hypotonia,
RT hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye
RT abnormalities (HIDEA syndrome).";
RL Genet. Med. 21:2355-2363(2019).
CC -!- FUNCTION: Catalyzes the post-translational formation of 4-
CC hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins.
CC Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a
CC cellular oxygen sensor and, under normoxic conditions, may target HIF
CC through the hydroxylation for proteasomal degradation via the von
CC Hippel-Lindau ubiquitination complex. {ECO:0000269|PubMed:17726031}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-prolyl-[hypoxia-inducible factor alpha
CC subunit] + O2 = CO2 + succinate + trans-4-hydroxy-L-prolyl-[hypoxia-
CC inducible factor alpha subunit]; Xref=Rhea:RHEA:48400, Rhea:RHEA-
CC COMP:12093, Rhea:RHEA-COMP:12094, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:50342, ChEBI:CHEBI:61965; EC=1.14.11.29;
CC Evidence={ECO:0000269|PubMed:17726031};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000250};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17726031}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12163023, ECO:0000269|PubMed:17726031}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:12163023,
CC ECO:0000269|PubMed:17726031}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NXG6-1; Sequence=Displayed;
CC Name=2; Synonyms=b;
CC IsoId=Q9NXG6-2; Sequence=VSP_007574;
CC Name=3;
CC IsoId=Q9NXG6-3; Sequence=VSP_007573;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in adult
CC pancreas, heart, skeletal muscle, brain, placenta, kidney and adrenal
CC gland. Expressed at lower levels in epiphyseal cartilage and in
CC fibroblasts. {ECO:0000269|PubMed:12163023,
CC ECO:0000269|PubMed:17726031}.
CC -!- INDUCTION: By hypoxia in many cultured cell lines.
CC {ECO:0000269|PubMed:17726031}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:17726031}.
CC -!- DISEASE: Hypotonia, hyperventilation, impaired intellectual
CC development, dysautonomia, epilepsy, and eye abnormalities (HIDEA)
CC [MIM:618493]: An autosomal recessive neurodevelopmental disorder
CC characterized by global developmental delay, poor or absent speech,
CC hypotonia, variable ocular movement and visual abnormalities, and
CC respiratory difficulties. Disease onset is in infancy and death due to
CC respiratory insufficiency may occur. {ECO:0000269|PubMed:30940925}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH60321.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=BAA91045.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAD28518.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; AY198406; AAO43431.1; -; mRNA.
DR EMBL; AL713728; CAD28518.2; ALT_SEQ; mRNA.
DR EMBL; BC000580; AAH00580.1; -; mRNA.
DR EMBL; BC011710; AAH11710.3; -; mRNA.
DR EMBL; BC047566; AAH47566.1; -; mRNA.
DR EMBL; BC060321; AAH60321.1; ALT_SEQ; mRNA.
DR EMBL; AK000269; BAA91045.1; ALT_INIT; mRNA.
DR CCDS; CCDS2781.2; -. [Q9NXG6-3]
DR CCDS; CCDS43089.1; -. [Q9NXG6-1]
DR RefSeq; NP_808807.2; NM_177938.2. [Q9NXG6-3]
DR RefSeq; NP_808808.1; NM_177939.2. [Q9NXG6-1]
DR PDB; 6TP5; X-ray; 2.25 A; A/B=88-502.
DR PDBsum; 6TP5; -.
DR AlphaFoldDB; Q9NXG6; -.
DR SMR; Q9NXG6; -.
DR BioGRID; 120100; 131.
DR IntAct; Q9NXG6; 4.
DR MINT; Q9NXG6; -.
DR BindingDB; Q9NXG6; -.
DR ChEMBL; CHEMBL3047; -.
DR DrugBank; DB00126; Ascorbic acid.
DR GlyGen; Q9NXG6; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NXG6; -.
DR MetOSite; Q9NXG6; -.
DR PhosphoSitePlus; Q9NXG6; -.
DR BioMuta; P4HTM; -.
DR DMDM; 32129516; -.
DR EPD; Q9NXG6; -.
DR jPOST; Q9NXG6; -.
DR MassIVE; Q9NXG6; -.
DR MaxQB; Q9NXG6; -.
DR PaxDb; Q9NXG6; -.
DR PeptideAtlas; Q9NXG6; -.
DR PRIDE; Q9NXG6; -.
DR ProteomicsDB; 83095; -. [Q9NXG6-1]
DR ProteomicsDB; 83096; -. [Q9NXG6-2]
DR ProteomicsDB; 83097; -. [Q9NXG6-3]
DR Antibodypedia; 2007; 245 antibodies from 22 providers.
DR DNASU; 54681; -.
DR Ensembl; ENST00000343546.8; ENSP00000341422.4; ENSG00000178467.18. [Q9NXG6-3]
DR Ensembl; ENST00000383729.9; ENSP00000373235.4; ENSG00000178467.18. [Q9NXG6-1]
DR GeneID; 54681; -.
DR KEGG; hsa:54681; -.
DR MANE-Select; ENST00000383729.9; ENSP00000373235.4; NM_177939.3; NP_808808.1.
DR UCSC; uc003cvg.4; human. [Q9NXG6-1]
DR CTD; 54681; -.
DR DisGeNET; 54681; -.
DR GeneCards; P4HTM; -.
DR HGNC; HGNC:28858; P4HTM.
DR HPA; ENSG00000178467; Low tissue specificity.
DR MalaCards; P4HTM; -.
DR MIM; 614584; gene.
DR MIM; 618493; phenotype.
DR neXtProt; NX_Q9NXG6; -.
DR OpenTargets; ENSG00000178467; -.
DR PharmGKB; PA164724295; -.
DR VEuPathDB; HostDB:ENSG00000178467; -.
DR eggNOG; KOG1591; Eukaryota.
DR GeneTree; ENSGT00390000014570; -.
DR HOGENOM; CLU_035319_0_0_1; -.
DR InParanoid; Q9NXG6; -.
DR OMA; PLPYSYM; -.
DR OrthoDB; 1438683at2759; -.
DR PhylomeDB; Q9NXG6; -.
DR TreeFam; TF332923; -.
DR PathwayCommons; Q9NXG6; -.
DR SignaLink; Q9NXG6; -.
DR BioGRID-ORCS; 54681; 9 hits in 1069 CRISPR screens.
DR ChiTaRS; P4HTM; human.
DR GenomeRNAi; 54681; -.
DR Pharos; Q9NXG6; Tchem.
DR PRO; PR:Q9NXG6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NXG6; protein.
DR Bgee; ENSG00000178467; Expressed in right uterine tube and 189 other tissues.
DR ExpressionAtlas; Q9NXG6; baseline and differential.
DR Genevisible; Q9NXG6; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0004656; F:procollagen-proline 4-dioxygenase activity; IBA:GO_Central.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IBA:GO_Central.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; IEA:Ensembl.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR InterPro; IPR045054; P4HA-like.
DR InterPro; IPR006620; Pro_4_hyd_alph.
DR InterPro; IPR044862; Pro_4_hyd_alph_FE2OG_OXY.
DR PANTHER; PTHR10869; PTHR10869; 1.
DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00702; P4Hc; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Dioxygenase; Disease variant;
KW Endoplasmic reticulum; Epilepsy; Glycoprotein; Intellectual disability;
KW Iron; Membrane; Metal-binding; Oxidoreductase; Reference proteome; Repeat;
KW Signal-anchor; Transmembrane; Transmembrane helix; Vitamin C.
FT CHAIN 1..502
FT /note="Transmembrane prolyl 4-hydroxylase"
FT /id="PRO_0000206668"
FT TOPO_DOM 1..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..502
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 185..220
FT /note="EF-hand 1"
FT DOMAIN 224..259
FT /note="EF-hand 2"
FT DOMAIN 310..460
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 204
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 241
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10142"
FT BINDING 328
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 330
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 374
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 451
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 358
FT /note="R -> RQVSPNWGLPSILRPGTPMTQAQPCTVGVPLGMGPGDHWVIPVSPWE
FT HPQLGTCSVPPLPYS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007573"
FT VAR_SEQ 359..502
FT /note="YMTVLFYLNNVTGGGETVFPVADNRTYDEMSLIQDDVDLRDTRRHCDKGNLR
FT VKPQQGTAVFWYNYLPDGQGWVGDVDDYSLHGGCLVTRGTKWIANNWINVDPSRARQAL
FT FQQEMARLAREGGTDSQPEWALDRAYRDARVEL -> QVSPNWGLPSILRPGTPMTQAQ
FT PCTVGVPLGMGPGDHWVIPVSDALTSPHKLFTQWLERGGYWSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_007574"
FT VARIANT 161
FT /note="H -> P (in HIDEA; dbSNP:rs1576606484)"
FT /evidence="ECO:0000269|PubMed:30940925"
FT /id="VAR_082950"
FT VARIANT 471..502
FT /note="Missing (in HIDEA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30940925"
FT /id="VAR_082951"
FT CONFLICT 213
FT /note="Q -> K (in Ref. 3; AAH47566)"
FT /evidence="ECO:0000305"
FT CONFLICT 240
FT /note="G -> A (in Ref. 1; AAO43431)"
FT /evidence="ECO:0000305"
FT STRAND 122..125
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:6TP5"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 144..147
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 153..166
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 169..172
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 190..197
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 207..211
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 224..233
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 246..250
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 254..263
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 288..301
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 305..309
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 324..328
FT /evidence="ECO:0007829|PDB:6TP5"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 358..365
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:6TP5"
FT TURN 378..381
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 387..390
FT /evidence="ECO:0007829|PDB:6TP5"
FT TURN 400..402
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 407..411
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 418..426
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 428..435
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 437..439
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 441..443
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:6TP5"
FT STRAND 451..459
FT /evidence="ECO:0007829|PDB:6TP5"
FT HELIX 464..480
FT /evidence="ECO:0007829|PDB:6TP5"
SQ SEQUENCE 502 AA; 56661 MW; A2DAE4ACF4A2E18C CRC64;
MAAAAVTGQR PETAAAEEAS RPQWAPPDHC QAQAAAGLGD GEDAPVRPLC KPRGICSRAY
FLVLMVFVHL YLGNVLALLL FVHYSNGDES SDPGPQHRAQ GPGPEPTLGP LTRLEGIKVG
HERKVQLVTD RDHFIRTLSL KPLLFEIPGF LTDEECRLII HLAQMKGLQR SQILPTEEYE
EAMSTMQVSQ LDLFRLLDQN RDGHLQLREV LAQTRLGNGW WMTPESIQEM YAAIKADPDG
DGVLSLQEFS NMDLRDFHKY MRSHKAESSE LVRNSHHTWL YQGEGAHHIM RAIRQRVLRL
TRLSPEIVEL SEPLQVVRYG EGGHYHAHVD SGPVYPETIC SHTKLVANES VPFETSCRYM
TVLFYLNNVT GGGETVFPVA DNRTYDEMSL IQDDVDLRDT RRHCDKGNLR VKPQQGTAVF
WYNYLPDGQG WVGDVDDYSL HGGCLVTRGT KWIANNWINV DPSRARQALF QQEMARLARE
GGTDSQPEWA LDRAYRDARV EL
