ID STEA4_HUMAN Reviewed; 459 AA. AC Q687X5; Q658Q9; Q687X4; Q8WWB0; Q9H5R1; DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 1. DT 02-OCT-2024, entry version 153. DE RecName: Full=Metalloreductase STEAP4; DE EC=1.16.1.-; DE AltName: Full=Six-transmembrane epithelial antigen of prostate 4; DE AltName: Full=SixTransMembrane protein of prostate 2; DE AltName: Full=Tumor necrosis factor, alpha-induced protein 9; GN Name=STEAP4; Synonyms=STAMP2 {ECO:0000303|PubMed:15897894}, TNFAIP9; 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, INDUCTION, RP AND TISSUE SPECIFICITY. RC TISSUE=Prostatic carcinoma; RX PubMed=15897894; DOI=10.1038/sj.onc.1208677; RA Korkmaz C.G., Korkmaz K.S., Kurys P., Elbi C., Wang L., Klokk T.I., RA Hammarstrom C., Troen G., Svindland A., Hager G.L., Saatcioglu F.; RT "Molecular cloning and characterization of STAMP2, an androgen-regulated RT six transmembrane protein that is overexpressed in prostate cancer."; RL Oncogene 24:4934-4945(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-75. RC TISSUE=Lung; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=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 325-459. RC TISSUE=Stomach; 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 [5] RP TISSUE SPECIFICITY. RX PubMed=16227996; DOI=10.1038/ng1658; RA Ohgami R.S., Campagna D.R., Greer E.L., Antiochos B., McDonald A., Chen J., RA Sharp J.J., Fujiwara Y., Barker J.E., Fleming M.D.; RT "Identification of a ferrireductase required for efficient transferrin- RT dependent iron uptake in erythroid cells."; RL Nat. Genet. 37:1264-1269(2005). RN [6] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INDUCTION BY TNF. RX PubMed=18430367; DOI=10.1111/j.1745-7254.2008.00793.x; RA Zhang C.M., Chi X., Wang B., Zhang M., Ni Y.H., Chen R.H., Li X.N., RA Guo X.R.; RT "Downregulation of STEAP4, a highly-expressed TNF-alpha-inducible gene in RT adipose tissue, is associated with obesity in humans."; RL Acta Pharmacol. Sin. 29:587-592(2008). RN [7] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=18381574; DOI=10.1210/jc.2008-0206; RA Arner P., Stenson B.M., Dungner E., Naeslund E., Hoffstedt J., Ryden M., RA Dahlman I.; RT "Expression of six transmembrane protein of prostate 2 in human adipose RT tissue associates with adiposity and insulin resistance."; RL J. Clin. Endocrinol. Metab. 93:2249-2254(2008). RN [8] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=19660107; DOI=10.1186/ar2779; RA Inoue A., Matsumoto I., Tanaka Y., Iwanami K., Kanamori A., Ochiai N., RA Goto D., Ito S., Sumida T.; RT "Tumor necrosis factor alpha-induced adipose-related protein expression in RT experimental arthritis and in rheumatoid arthritis."; RL Arthritis Res. Ther. 11:R118-R118(2009). RN [9] RP INDUCTION BY IL1B, AND TISSUE SPECIFICITY. RX PubMed=19289123; DOI=10.1016/j.febslet.2009.03.015; RA Kralisch S., Sommer G., Weise S., Lipfert J., Lossner U., Kamprad M., RA Schrock K., Bluher M., Stumvoll M., Fasshauer M.; RT "Interleukin-1beta is a positive regulator of TIARP/STAMP2 gene and protein RT expression in adipocytes in vitro."; RL FEBS Lett. 583:1196-1200(2009). RN [10] RP FUNCTION, INTERACTION WITH PTK2/FAK1, AND SUBCELLULAR LOCATION. RX PubMed=19787193; DOI=10.3892/ijmm_00000270; RA Tamura T., Chiba J.; RT "STEAP4 regulates focal adhesion kinase activation and CpG motifs within RT STEAP4 promoter region are frequently methylated in DU145, human androgen- RT independent prostate cancer cells."; RL Int. J. Mol. Med. 24:599-604(2009). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [12] {ECO:0007744|PDB:6HCY, ECO:0007744|PDB:6HD1} RP STRUCTURE BY ELECTRON MICROSCOPY (3.10 ANGSTROMS) IN COMPLEX WITH FAD; RP NADP; HEME AND IRON, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, TOPOLOGY, GLYCOSYLATION AT ASN-323, RP AND MUTAGENESIS OF SER-138. RX PubMed=30337524; DOI=10.1038/s41467-018-06817-7; RA Oosterheert W., van Bezouwen L.S., Rodenburg R.N.P., Granneman J., RA Forster F., Mattevi A., Gros P.; RT "Cryo-EM structures of human STEAP4 reveal mechanism of iron(III) RT reduction."; RL Nat. Commun. 9:4337-4337(2018). CC -!- FUNCTION: Integral membrane protein that functions as a NADPH-dependent CC ferric-chelate reductase, using NADPH from one side of the membrane to CC reduce a Fe(3+) chelate that is bound on the other side of the CC membrane. Mediates sequential transmembrane electron transfer from CC NADPH to FAD and onto heme, and finally to the Fe(3+) chelate CC (PubMed:30337524). Can also reduce Cu(2+) to Cu(1+) (By similarity). CC Plays a role in systemic metabolic homeostasis, integrating CC inflammatory and metabolic responses (By similarity). Associated with CC obesity and insulin-resistance (PubMed:18381574, PubMed:18430367). CC Involved in inflammatory arthritis, through the regulation of CC inflammatory cytokines (PubMed:19660107). Inhibits anchorage- CC independent cell proliferation (PubMed:19787193). CC {ECO:0000250|UniProtKB:Q923B6, ECO:0000269|PubMed:18381574, CC ECO:0000269|PubMed:18430367, ECO:0000269|PubMed:19660107, CC ECO:0000269|PubMed:19787193, ECO:0000269|PubMed:30337524}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Fe(2+) + H(+) + NADP(+) = 2 Fe(3+) + NADPH; CC Xref=Rhea:RHEA:71767, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, CC ChEBI:CHEBI:29034, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000269|PubMed:30337524}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71769; CC Evidence={ECO:0000305|PubMed:30337524}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Cu(+) + H(+) + NADP(+) = 2 Cu(2+) + NADPH; CC Xref=Rhea:RHEA:71771, ChEBI:CHEBI:15378, ChEBI:CHEBI:29036, CC ChEBI:CHEBI:49552, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; CC Evidence={ECO:0000250|UniProtKB:Q4V8K1}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:71773; CC Evidence={ECO:0000305|PubMed:30337524}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000269|PubMed:30337524}; CC Note=Can also utilize FMN (PubMed:30337524). Can also utilize CC riboflavin. {ECO:0000250|UniProtKB:Q4V8K1, CC ECO:0000269|PubMed:30337524}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; CC Evidence={ECO:0000269|PubMed:30337524}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=13.7 uM for Fe(3+)-NTA {ECO:0000269|PubMed:30337524}; CC KM=4.2 uM for NADPH {ECO:0000269|PubMed:30337524}; CC -!- SUBUNIT: Homotrimer (PubMed:30337524). Interacts with PTK2/FAK1; the CC interaction may regulate PTK2 phosphorylation. CC {ECO:0000269|PubMed:19787193, ECO:0000269|PubMed:30337524}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15897894, CC ECO:0000269|PubMed:18430367}; Multi-pass membrane protein CC {ECO:0000269|PubMed:30337524}. Golgi apparatus membrane CC {ECO:0000269|PubMed:15897894}; Multi-pass membrane protein CC {ECO:0000269|PubMed:30337524}. Early endosome membrane CC {ECO:0000269|PubMed:15897894}; Multi-pass membrane protein CC {ECO:0000269|PubMed:30337524}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q687X5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q687X5-2; Sequence=VSP_024833; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in adipose tissue. CC Expressed in placenta, lung, heart and prostate. Detected at lower CC levels in liver, skeletal muscle, pancreas, testis and small intestine. CC Highly expressed in joints of patients with rheumatoid arthritis and CC localized with CD68 cells, a marker for macrophages. CC {ECO:0000269|PubMed:15897894, ECO:0000269|PubMed:16227996, CC ECO:0000269|PubMed:18381574, ECO:0000269|PubMed:18430367, CC ECO:0000269|PubMed:19289123, ECO:0000269|PubMed:19660107}. CC -!- INDUCTION: By TNF and IL1B/interleukin-1 beta in adipose tissue. Up- CC regulated by androgens, including testosterone and dihydrotestosterone CC (DHT). {ECO:0000269|PubMed:15897894, ECO:0000269|PubMed:18430367, CC ECO:0000269|PubMed:19289123}. CC -!- SIMILARITY: Belongs to the STEAP family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ04064.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB15559.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=CAH56271.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF423422; AAQ04063.1; -; mRNA. DR EMBL; AF423423; AAQ04064.1; ALT_FRAME; mRNA. DR EMBL; AK026806; BAB15559.1; ALT_FRAME; mRNA. DR EMBL; BC020600; AAH20600.1; -; mRNA. DR EMBL; AL833044; CAH56271.1; ALT_INIT; mRNA. DR CCDS; CCDS43611.1; -. [Q687X5-1] DR CCDS; CCDS56494.1; -. [Q687X5-2] DR RefSeq; NP_001192244.1; NM_001205315.1. [Q687X5-1] DR RefSeq; NP_001192245.1; NM_001205316.1. [Q687X5-2] DR RefSeq; NP_078912.2; NM_024636.3. [Q687X5-1] DR PDB; 6HCY; EM; 3.10 A; A/B/C=1-459. DR PDB; 6HD1; EM; 3.80 A; A/B/C=1-459. DR PDBsum; 6HCY; -. DR PDBsum; 6HD1; -. DR AlphaFoldDB; Q687X5; -. DR EMDB; EMD-0199; -. DR EMDB; EMD-0200; -. DR SMR; Q687X5; -. DR BioGRID; 122810; 11. DR IntAct; Q687X5; 6. DR STRING; 9606.ENSP00000369419; -. DR TCDB; 5.B.6.1.3; the transmembrane epithelial antigen protein-3 ferric reductase (steap) family. DR GlyCosmos; Q687X5; 1 site, No reported glycans. DR GlyGen; Q687X5; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q687X5; -. DR PhosphoSitePlus; Q687X5; -. DR SwissPalm; Q687X5; -. DR BioMuta; STEAP4; -. DR DMDM; 74748242; -. DR jPOST; Q687X5; -. DR MassIVE; Q687X5; -. DR PaxDb; 9606-ENSP00000369419; -. DR PeptideAtlas; Q687X5; -. DR ProteomicsDB; 65993; -. [Q687X5-1] DR ProteomicsDB; 65994; -. [Q687X5-2] DR Antibodypedia; 29814; 318 antibodies from 36 providers. DR DNASU; 79689; -. DR Ensembl; ENST00000301959.9; ENSP00000305545.5; ENSG00000127954.13. [Q687X5-2] DR Ensembl; ENST00000380079.9; ENSP00000369419.4; ENSG00000127954.13. [Q687X5-1] DR GeneID; 79689; -. DR KEGG; hsa:79689; -. DR MANE-Select; ENST00000380079.9; ENSP00000369419.4; NM_024636.4; NP_078912.2. DR UCSC; uc003ujs.4; human. [Q687X5-1] DR AGR; HGNC:21923; -. DR CTD; 79689; -. DR DisGeNET; 79689; -. DR GeneCards; STEAP4; -. DR HGNC; HGNC:21923; STEAP4. DR HPA; ENSG00000127954; Tissue enhanced (adipose). DR MIM; 611098; gene. DR neXtProt; NX_Q687X5; -. DR OpenTargets; ENSG00000127954; -. DR PharmGKB; PA134874572; -. DR VEuPathDB; HostDB:ENSG00000127954; -. DR eggNOG; ENOG502R746; Eukaryota. DR GeneTree; ENSGT00390000008042; -. DR HOGENOM; CLU_034618_1_1_1; -. DR InParanoid; Q687X5; -. DR OMA; GWERNPK; -. DR OrthoDB; 5361at2759; -. DR PhylomeDB; Q687X5; -. DR TreeFam; TF332031; -. DR PathwayCommons; Q687X5; -. DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling. DR SignaLink; Q687X5; -. DR BioGRID-ORCS; 79689; 11 hits in 1145 CRISPR screens. DR ChiTaRS; STEAP4; human. DR GenomeRNAi; 79689; -. DR Pharos; Q687X5; Tbio. DR PRO; PR:Q687X5; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q687X5; protein. DR Bgee; ENSG00000127954; Expressed in pericardium and 171 other cell types or tissues. DR ExpressionAtlas; Q687X5; baseline and differential. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IBA:GO_Central. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0008823; F:cupric reductase activity; IBA:GO_Central. DR GO; GO:0009055; F:electron transfer activity; IDA:UniProtKB. DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB. DR GO; GO:0052851; F:ferric-chelate reductase (NADPH) activity; IDA:UniProtKB. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0015677; P:copper ion import; IBA:GO_Central. DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB. DR GO; GO:0033212; P:iron import into cell; IEA:Ensembl. DR GO; GO:0070207; P:protein homotrimerization; IDA:UniProtKB. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR013130; Fe3_Rdtase_TM_dom. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR028939; P5C_Rdtase_cat_N. DR InterPro; IPR051267; STEAP_metalloreductase. DR PANTHER; PTHR14239; DUDULIN-RELATED; 1. DR PANTHER; PTHR14239:SF5; METALLOREDUCTASE STEAP4; 1. DR Pfam; PF03807; F420_oxidored; 1. DR Pfam; PF01794; Ferric_reduct; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Copper; KW Electron transport; Endosome; FAD; Flavoprotein; Glycoprotein; KW Golgi apparatus; Heme; Ion transport; Iron; Iron transport; Membrane; KW Metal-binding; NADP; Oxidoreductase; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..459 FT /note="Metalloreductase STEAP4" FT /id="PRO_0000285174" FT TRANSMEM 202..224 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30337524" FT TRANSMEM 236..256 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30337524" FT TRANSMEM 293..313 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30337524" FT TRANSMEM 342..362 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30337524" FT TRANSMEM 381..401 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30337524" FT TRANSMEM 419..439 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:30337524" FT DOMAIN 247..395 FT /note="Ferric oxidoreductase" FT /evidence="ECO:0000255" FT BINDING 27..30 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 49..50 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 67 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 81..85 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 106 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 139 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:Q4V8K1" FT BINDING 140 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 148 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 171 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:Q4V8K1" FT BINDING 217 FT /ligand="Fe(3+)" FT /ligand_id="ChEBI:CHEBI:29034" FT /evidence="ECO:0000250|UniProtKB:Q658P3" FT BINDING 269 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 290 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 304 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 307 FT /ligand="Fe(3+)" FT /ligand_id="ChEBI:CHEBI:29034" FT /evidence="ECO:0000250|UniProtKB:Q658P3" FT BINDING 366 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 383 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT BINDING 397 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000269|PubMed:30337524, FT ECO:0007744|PDB:6HCY" FT CARBOHYD 323 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:30337524, ECO:0007744|PDB:6HCY" FT VAR_SEQ 153..328 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024833" FT VARIANT 75 FT /note="G -> D (in dbSNP:rs1981529)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_031976" FT VARIANT 122 FT /note="A -> T (in dbSNP:rs34741656)" FT /id="VAR_031977" FT MUTAGEN 138 FT /note="S->Q: Strongly reduced enzyme activity. No effect on FT trimerization and on heme binding." FT /evidence="ECO:0000269|PubMed:30337524" FT STRAND 21..25 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 29..39 FT /evidence="ECO:0007829|PDB:6HCY" FT TURN 40..42 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 44..48 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 67..70 FT /evidence="ECO:0007829|PDB:6HCY" FT TURN 71..73 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 75..79 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 87..92 FT /evidence="ECO:0007829|PDB:6HCY" FT TURN 93..95 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 100..103 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 112..115 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 117..124 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 128..132 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 134..137 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 139..144 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 152..158 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 160..172 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 176..179 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 183..185 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 186..191 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 201..222 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 225..228 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:6HCY" FT TURN 239..242 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 243..256 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 261..272 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 275..277 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 283..287 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 290..308 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 311..313 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 315..330 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 339..365 FT /evidence="ECO:0007829|PDB:6HCY" FT TURN 368..370 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 371..374 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 376..383 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 385..403 FT /evidence="ECO:0007829|PDB:6HCY" FT TURN 404..407 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 413..415 FT /evidence="ECO:0007829|PDB:6HCY" FT STRAND 419..422 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 425..438 FT /evidence="ECO:0007829|PDB:6HCY" FT HELIX 440..449 FT /evidence="ECO:0007829|PDB:6HCY" SQ SEQUENCE 459 AA; 51981 MW; FA3BF0F2B1001FE5 CRC64; MEKTCIDALP LTMNSSEKQE TVCIFGTGDF GRSLGLKMLQ CGYSVVFGSR NPQKTTLLPS GAEVLSYSEA AKKSGIIIIA IHREHYDFLT ELTEVLNGKI LVDISNNLKI NQYPESNAEY LAHLVPGAHV VKAFNTISAW ALQSGALDAS RQVFVCGNDS KAKQRVMDIV RNLGLTPMDQ GSLMAAKEIE KYPLQLFPMW RFPFYLSAVL CVFLFFYCVI RDVIYPYVYE KKDNTFRMAI SIPNRIFPIT ALTLLALVYL PGVIAAILQL YRGTKYRRFP DWLDHWMLCR KQLGLVALGF AFLHVLYTLV IPIRYYVRWR LGNLTVTQAI LKKENPFSTS SAWLSDSYVA LGILGFFLFV LLGITSLPSV SNAVNWREFR FVQSKLGYLT LILCTAHTLV YGGKRFLSPS NLRWYLPAAY VLGLIIPCTV LVIKFVLIMP CVDNTLTRIR QGWERNSKH //