STEA4_HUMAN
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 03-AUG-2022, entry version 141.
DE RecName: Full=Metalloreductase STEAP4;
DE EC=1.16.1.9 {ECO:0000269|PubMed:30337524};
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 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:18430367, PubMed:18381574).
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 a Fe(II)-siderophore + H(+) + NADP(+) = 2 a Fe(III)-
CC siderophore + NADPH; Xref=Rhea:RHEA:28795, Rhea:RHEA-COMP:11342,
CC Rhea:RHEA-COMP:11344, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:29034, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.16.1.9;
CC Evidence={ECO:0000269|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; Xref=ChEBI:CHEBI:30413;
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};
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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 SMR; Q687X5; -.
DR BioGRID; 122810; 10.
DR IntAct; Q687X5; 2.
DR STRING; 9606.ENSP00000369419; -.
DR TCDB; 5.B.6.1.3; the transmembrane epithelial antigen protein-3 ferric reductase (steap) family.
DR GlyGen; Q687X5; 1 site.
DR iPTMnet; Q687X5; -.
DR PhosphoSitePlus; Q687X5; -.
DR BioMuta; STEAP4; -.
DR DMDM; 74748242; -.
DR EPD; Q687X5; -.
DR jPOST; Q687X5; -.
DR MassIVE; Q687X5; -.
DR MaxQB; Q687X5; -.
DR PaxDb; Q687X5; -.
DR PeptideAtlas; Q687X5; -.
DR PRIDE; Q687X5; -.
DR ProteomicsDB; 65993; -. [Q687X5-1]
DR ProteomicsDB; 65994; -. [Q687X5-2]
DR Antibodypedia; 29814; 296 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 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; 638341at2759; -.
DR PhylomeDB; Q687X5; -.
DR TreeFam; TF332031; -.
DR PathwayCommons; Q687X5; -.
DR SignaLink; Q687X5; -.
DR BioGRID-ORCS; 79689; 9 hits in 1065 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 tissues.
DR ExpressionAtlas; Q687X5; baseline and differential.
DR Genevisible; Q687X5; HS.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of 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 InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR028939; P5C_Rdtase_cat_N.
DR Pfam; PF03807; F420_oxidored; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR SUPFAM; SSF51735; SSF51735; 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; Reference proteome; Transmembrane;
KW 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 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"
FT /ligand_id="ChEBI:CHEBI:30413"
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 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"
FT /ligand_id="ChEBI:CHEBI:30413"
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
