NB5R3_HUMAN
ID NB5R3_HUMAN Reviewed; 301 AA.
AC P00387; B1AHF2; B7Z7L3; O75675; Q8TDL8; Q8WTS8; Q9UEN4; Q9UEN5; Q9UL55;
AC Q9UL56;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 259.
DE RecName: Full=NADH-cytochrome b5 reductase 3 {ECO:0000305};
DE Short=B5R;
DE Short=Cytochrome b5 reductase;
DE EC=1.6.2.2 {ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:2019583, ECO:0000269|PubMed:8119939};
DE AltName: Full=Diaphorase-1;
DE Contains:
DE RecName: Full=NADH-cytochrome b5 reductase 3 membrane-bound form;
DE Contains:
DE RecName: Full=NADH-cytochrome b5 reductase 3 soluble form;
GN Name=CYB5R3 {ECO:0000312|HGNC:HGNC:2873}; Synonyms=DIA1;
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 [GENOMIC DNA], AND VARIANT PRO-66.
RC TISSUE=Placenta;
RX PubMed=2479590; DOI=10.1016/0378-1119(89)90299-0;
RA Tomatsu S., Kobayashi Y., Fukumaki Y., Yubisui T., Orii T., Sakaki Y.;
RT "The organization and the complete nucleotide sequence of the human NADH-
RT cytochrome b5 reductase gene.";
RL Gene 80:353-361(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Voice M.W.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Yoon B., Chung H., Ko E., Lee D.;
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-66, AND VARIANTS HM
RP GLN-58; PRO-73 AND TYR-204.
RC TISSUE=Leukocyte;
RA Lan F.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-117.
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-301 (ISOFORM 1), AND VARIANT PRO-66.
RC TISSUE=Liver;
RX PubMed=3035541; DOI=10.1073/pnas.84.11.3609;
RA Yubisui T., Naitoh Y., Zenno S., Tamura M., Takeshita M., Sakaki Y.;
RT "Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5
RT reductase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:3609-3613(1987).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 101-250 (ISOFORM 1).
RA Diss J.K.J., Fraser S.P., Coombes R.C., Djamgoz M.B.A.;
RT "Upregulation of voltage-gated Na+ channel expression and metastatic
RT potential in human breast cancer: correlative studies on cell lines and
RT biopsy tissues.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP PROTEIN SEQUENCE OF 2-25, AND MYRISTOYLATION AT GLY-2.
RX PubMed=2498303; DOI=10.1093/oxfordjournals.jbchem.a122659;
RA Murakami K., Yubisui T., Takeshita M., Miyata T.;
RT "The NH2-terminal structures of human and rat liver microsomal NADH-
RT cytochrome b5 reductases.";
RL J. Biochem. 105:312-317(1989).
RN [14]
RP PROTEIN SEQUENCE OF 27-301.
RC TISSUE=Erythrocyte;
RX PubMed=3700359; DOI=10.1093/oxfordjournals.jbchem.a135495;
RA Yubisui T., Miyata T., Iwanaga S., Tamura M., Takeshita M.;
RT "Complete amino acid sequence of NADH-cytochrome b5 reductase purified from
RT human erythrocytes.";
RL J. Biochem. 99:407-422(1986).
RN [15]
RP PROTEIN SEQUENCE OF 27-301.
RC TISSUE=Erythrocyte;
RX PubMed=6389526; DOI=10.1093/oxfordjournals.jbchem.a134871;
RA Yubisui T., Miyata T., Iwanaga S., Tamura M., Yoshida S., Takeshita M.,
RA Nakajima H.;
RT "Amino acid sequence of NADH-cytochrome b5 reductase of human
RT erythrocytes.";
RL J. Biochem. 96:579-582(1984).
RN [16]
RP ALTERNATIVE PROMOTER USAGE.
RX PubMed=9639531;
RA Bulbarelli A., Valentini A., De Silvestris M., Cappellini M.D., Borgese N.;
RT "An erythroid-specific transcript generates the soluble form of NADH-
RT cytochrome b5 reductase in humans.";
RL Blood 92:310-319(1998).
RN [17]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF
RP CYS-204; CYS-274; CYS-284 AND CYS-298.
RX PubMed=2019583; DOI=10.1016/s0021-9258(20)89479-4;
RA Shirabe K., Yubisui T., Nishino T., Takeshita M.;
RT "Role of cysteine residues in human NADH-cytochrome b5 reductase studied by
RT site-directed mutagenesis. Cys-273 and Cys-283 are located close to the
RT NADH-binding site but are not catalytically essential.";
RL J. Biol. Chem. 266:7531-7536(1991).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-43, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25255805; DOI=10.1038/ncomms5919;
RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT "Global profiling of co- and post-translationally N-myristoylated proteomes
RT in human cells.";
RL Nat. Commun. 5:4919-4919(2014).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-301.
RX PubMed=15502298; DOI=10.1107/s0907444904020645;
RA Bando S., Takano T., Yubisui T., Shirabe K., Takeshita M., Nakagawa A.;
RT "Structure of human erythrocyte NADH-cytochrome b5 reductase.";
RL Acta Crystallogr. D 60:1929-1934(2004).
RN [25]
RP VARIANT METHB-CYB5R3 PRO-128, MUTAGENESIS OF SER-128, CHARACTERIZATION OF
RP VARIANT METHB-CYB5R3 PRO-128, CATALYTIC ACTIVITY, COFACTOR, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=1898726; DOI=10.1016/s0021-9258(18)52402-9;
RA Yubisui T., Shirabe K., Takeshita M., Kobayashi Y., Fukumaki Y., Sakaki Y.,
RA Takano T.;
RT "Structural role of serine 127 in the NADH-binding site of human NADH-
RT cytochrome b5 reductase.";
RL J. Biol. Chem. 266:66-70(1991).
RN [26]
RP VARIANTS METHB-CYB5R3 GLN-58 AND PRO-149.
RX PubMed=1707593;
RA Katsube T., Sakamoto N., Kobayashi Y., Seki R., Hirano M., Tanishima K.,
RA Tomoda A., Takazakura E., Yubisui T., Takeshita M., Sakaki Y., Fukumaki Y.;
RT "Exonic point mutations in NADH-cytochrome B5 reductase genes of
RT homozygotes for hereditary methemoglobinemia, types I and III: putative
RT mechanisms of tissue-dependent enzyme deficiency.";
RL Am. J. Hum. Genet. 48:799-808(1991).
RN [27]
RP VARIANT METHB-CYB5R3 MET-106.
RX PubMed=1400360; DOI=10.1016/s0021-9258(19)88718-5;
RA Shirabe K., Yubisui T., Borgese N., Tang C.-Y., Hultquist D.E.,
RA Takeshita M.;
RT "Enzymatic instability of NADH-cytochrome b5 reductase as a cause of
RT hereditary methemoglobinemia type I (red cell type).";
RL J. Biol. Chem. 267:20416-20421(1992).
RN [28]
RP VARIANT METHB-CYB5R3 PHE-299 DEL, CHARACTERIZATION OF VARIANT METHB-CYB5R3
RP PHE-299 DEL, MUTAGENESIS OF 299-PHE--PHE-301; PHE-299 AND PHE-301,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX PubMed=8119939; DOI=10.1016/s0021-9258(17)37554-3;
RA Shirabe K., Fujimoto Y., Yubisui T., Takeshita M.;
RT "An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene
RT results in hereditary methemoglobinemia type II (generalized type). A
RT functional implication for the role of the COOH-terminal region of the
RT enzyme.";
RL J. Biol. Chem. 269:5952-5957(1994).
RN [29]
RP VARIANTS METHB-CYB5R3 ARG-204 AND MET-273 DEL.
RX PubMed=7718898;
RA Vieira L.M., Kaplan J.-C., Kahn A., Leroux A.;
RT "Four new mutations in the NADH-cytochrome b5 reductase gene from patients
RT with recessive congenital methemoglobinemia type II.";
RL Blood 85:2254-2262(1995).
RN [30]
RP VARIANT SER-117.
RX PubMed=9048929; DOI=10.1007/s004390050347;
RA Jenkins M.M., Prchal J.T.;
RT "A high-frequency polymorphism of NADH-cytochrome b5 reductase in African-
RT Americans.";
RL Hum. Genet. 99:248-250(1997).
RN [31]
RP VARIANT METHB-CYB5R3 PRO-73.
RX PubMed=9695975; DOI=10.1046/j.1365-2141.1998.00782.x;
RA Wu Y.-S., Huang C.-H., Wan Y., Huang Q.-J., Zhu Z.-Y.;
RT "Identification of a novel point mutation (Leu72-to-Pro) in the NADH-
RT cytochrome b5 reductase gene of a patient with hereditary
RT methaemoglobinaemia type I.";
RL Br. J. Haematol. 102:575-577(1998).
RN [32]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 76-83 AND 171-187, AND VARIANT
RP METHB-CYB5R3 VAL-179.
RX PubMed=9886302; DOI=10.1046/j.1365-2141.1998.01123.x;
RA Higasa K., Manabe J.I., Yubisui T., Sumimoto H., Pung-Amritt P.,
RA Tanphaichitr V.S., Fukumaki Y.;
RT "Molecular basis of hereditary methaemoglobinaemia, types I and II: two
RT novel mutations in the NADH-cytochrome b5 reductase gene.";
RL Br. J. Haematol. 103:922-930(1998).
RN [33]
RP VARIANT METHB-CYB5R3 TYR-204, CHARACTERIZATION VARIANT METHB-CYB5R3
RP TYR-204, AND CATALYTIC ACTIVITY.
RX PubMed=10807796;
RA Wang Y., Wu Y.-S., Zheng P.-Z., Yang W.-X., Fang G.-A., Tang Y.-C., Xie F.,
RA Lan F.-H., Zhu Z.-Y.;
RT "A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese
RT patient with recessive congenital methemoglobinemia.";
RL Blood 95:3250-3255(2000).
RN [34]
RP VARIANT METHB-CYB5R3 GLN-58.
RX PubMed=15622768;
RA Huang C.-H., Xie Y., Wang Y., Wu Y.-S.;
RT "Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5
RT reductase in Chinese hereditary methemoglobinemia.";
RL Zhonghua Xue Ye Xue Za Zhi 18:200-203(1997).
RN [35]
RP VARIANTS METHB-CYB5R3 GLU-256 DEL AND ASP-292.
RX PubMed=12393396; DOI=10.1182/blood-2002-05-1405;
RA Percy M.J., Gillespie M.J.S., Savage G., Hughes A.E., McMullin M.F.,
RA Lappin T.R.J.;
RT "Familial idiopathic methemoglobinemia revisited: original cases reveal 2
RT novel mutations in NADH-cytochrome b5 reductase.";
RL Blood 100:3447-3449(2002).
RN [36]
RP CHARACTERIZATION OF VARIANTS METHB-CYB5R3 GLU-256 DEL AND ASP-292,
RP CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=15953014; DOI=10.1111/j.1365-2141.2005.05526.x;
RA Percy M.J., Crowley L.J., Davis C.A., McMullin M.F., Savage G., Hughes J.,
RA McMahon C., Quinn R.J.M., Smith O., Barber M.J., Lappin T.R.J.;
RT "Recessive congenital methaemoglobinaemia: functional characterization of
RT the novel D239G mutation in the NADH-binding lobe of cytochrome b5
RT reductase.";
RL Br. J. Haematol. 129:847-853(2005).
CC -!- FUNCTION: Transfers two electrons from NADH to two molecules of
CC cytochrome b5 through an enzyme-bound FAD. Electrons from the reduced
CC cytochrome b5 are then transferred to various electron acceptors,
CC thereby participating in methemoglobin reduction in red blood cells and
CC in the desaturation and elongation of fatty acids, cholesterol
CC biosynthesis and cytochrome P-450-mediated drug metabolism other
CC tissues. {ECO:0000305|PubMed:8119939}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +
CC H(+) + NAD(+); Xref=Rhea:RHEA:46680, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.2.2;
CC Evidence={ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:15953014,
CC ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:2019583,
CC ECO:0000269|PubMed:8119939};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46681;
CC Evidence={ECO:0000305|PubMed:10807796, ECO:0000305|PubMed:15953014,
CC ECO:0000305|PubMed:1898726, ECO:0000305|PubMed:2019583,
CC ECO:0000305|PubMed:8119939};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1898726};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.5 uM for NADH {ECO:0000269|PubMed:1898726,
CC ECO:0000269|PubMed:8119939};
CC KM=6.6 uM for 2 Fe(III)-[cytochrome b5] {ECO:0000269|PubMed:1898726,
CC ECO:0000269|PubMed:8119939};
CC KM=8.6 uM for 2 Fe(III)-[cytochrome b5] {ECO:0000269|PubMed:2019583};
CC Note=kcat is 896 sec(-1). {ECO:0000269|PubMed:15953014,
CC ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:8119939};
CC -!- SUBUNIT: Component of a complex composed of cytochrome b5, NADH-
CC cytochrome b5 reductase (CYB5R3) and MTARC2 (By similarity). Interacts
CC with MTLN; the interaction is required to maintain cellular lipid
CC composition and leads to stimulation of mitochondrial respiratory
CC complex I activity (By similarity). {ECO:0000250|UniProtKB:P83686,
CC ECO:0000250|UniProtKB:Q9DCN2}.
CC -!- INTERACTION:
CC P00387; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-1046040, EBI-10225815;
CC P00387; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-1046040, EBI-11522760;
CC P00387; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-1046040, EBI-11957045;
CC P00387; Q9BVK2: ALG8; NbExp=3; IntAct=EBI-1046040, EBI-3921603;
CC P00387; Q13520: AQP6; NbExp=3; IntAct=EBI-1046040, EBI-13059134;
CC P00387; P07306: ASGR1; NbExp=3; IntAct=EBI-1046040, EBI-1172335;
CC P00387; Q12982: BNIP2; NbExp=3; IntAct=EBI-1046040, EBI-752094;
CC P00387; O14735: CDIPT; NbExp=3; IntAct=EBI-1046040, EBI-358858;
CC P00387; Q9HA82: CERS4; NbExp=3; IntAct=EBI-1046040, EBI-2622997;
CC P00387; O95406: CNIH1; NbExp=3; IntAct=EBI-1046040, EBI-12172273;
CC P00387; Q4VAQ0: COL8A2; NbExp=3; IntAct=EBI-1046040, EBI-10241815;
CC P00387; Q8N6G5: CSGALNACT2; NbExp=3; IntAct=EBI-1046040, EBI-10267100;
CC P00387; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-1046040, EBI-18535450;
CC P00387; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-1046040, EBI-18938272;
CC P00387; Q92520: FAM3C; NbExp=3; IntAct=EBI-1046040, EBI-2876774;
CC P00387; Q96IV6: FAXDC2; NbExp=3; IntAct=EBI-1046040, EBI-12142299;
CC P00387; Q9BWH2: FUNDC2; NbExp=3; IntAct=EBI-1046040, EBI-714482;
CC P00387; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-1046040, EBI-12175685;
CC P00387; P01350: GAST; NbExp=3; IntAct=EBI-1046040, EBI-3436637;
CC P00387; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-1046040, EBI-13345167;
CC P00387; Q14416: GRM2; NbExp=3; IntAct=EBI-1046040, EBI-10232876;
CC P00387; P69905: HBA2; NbExp=2; IntAct=EBI-1046040, EBI-714680;
CC P00387; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-1046040, EBI-18053395;
CC P00387; Q13571: LAPTM5; NbExp=3; IntAct=EBI-1046040, EBI-2865663;
CC P00387; O75427: LRCH4; NbExp=3; IntAct=EBI-1046040, EBI-718707;
CC P00387; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-1046040, EBI-2858252;
CC P00387; Q92982: NINJ1; NbExp=3; IntAct=EBI-1046040, EBI-2802124;
CC P00387; Q8IXM6: NRM; NbExp=3; IntAct=EBI-1046040, EBI-10262547;
CC P00387; P42857: NSG1; NbExp=3; IntAct=EBI-1046040, EBI-6380741;
CC P00387; Q969Y0: NXPE3; NbExp=3; IntAct=EBI-1046040, EBI-17973370;
CC P00387; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-1046040, EBI-11075081;
CC P00387; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-1046040, EBI-8652812;
CC P00387; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-1046040, EBI-7545592;
CC P00387; Q14973: SLC10A1; NbExp=3; IntAct=EBI-1046040, EBI-3923031;
CC P00387; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-1046040, EBI-18159983;
CC P00387; Q8WWT9: SLC13A3; NbExp=3; IntAct=EBI-1046040, EBI-12938720;
CC P00387; Q96G79: SLC35A4; NbExp=3; IntAct=EBI-1046040, EBI-12363689;
CC P00387; Q8TB61: SLC35B2; NbExp=3; IntAct=EBI-1046040, EBI-1054782;
CC P00387; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-1046040, EBI-10314552;
CC P00387; P27105: STOM; NbExp=3; IntAct=EBI-1046040, EBI-1211440;
CC P00387; Q12893: TMEM115; NbExp=3; IntAct=EBI-1046040, EBI-8633987;
CC P00387; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-1046040, EBI-8638294;
CC P00387; Q9P0S9: TMEM14C; NbExp=3; IntAct=EBI-1046040, EBI-2339195;
CC P00387; Q5SNT2-2: TMEM201; NbExp=3; IntAct=EBI-1046040, EBI-11994282;
CC P00387; Q9NW97: TMEM51; NbExp=3; IntAct=EBI-1046040, EBI-726044;
CC P00387; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-1046040, EBI-2852148;
CC P00387; Q9BSE2: TMEM79; NbExp=3; IntAct=EBI-1046040, EBI-8649725;
CC P00387; P01375: TNF; NbExp=3; IntAct=EBI-1046040, EBI-359977;
CC P00387; O14798: TNFRSF10C; NbExp=3; IntAct=EBI-1046040, EBI-717441;
CC P00387; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-1046040, EBI-2819725;
CC P00387; P23763-3: VAMP1; NbExp=3; IntAct=EBI-1046040, EBI-12097582;
CC P00387; O75379: VAMP4; NbExp=3; IntAct=EBI-1046040, EBI-744953;
CC P00387; O95183: VAMP5; NbExp=3; IntAct=EBI-1046040, EBI-10191195;
CC P00387; Q96GC9: VMP1; NbExp=3; IntAct=EBI-1046040, EBI-2800296;
CC P00387; Q14508: WFDC2; NbExp=3; IntAct=EBI-1046040, EBI-723529;
CC P00387; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-1046040, EBI-12837904;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum membrane;
CC Lipid-anchor; Cytoplasmic side. Mitochondrion outer membrane; Lipid-
CC anchor; Cytoplasmic side.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Note=Produces the soluble
CC form found in erythrocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=M;
CC IsoId=P00387-1; Sequence=Displayed;
CC Name=2; Synonyms=S;
CC IsoId=P00387-2; Sequence=VSP_010200;
CC Name=3;
CC IsoId=P00387-3; Sequence=VSP_042827;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed at late stages of erythroid
CC maturation.
CC -!- POLYMORPHISM: Ser-117 seems to only be found in persons of African
CC origin. The allele frequency is 0.23 in African Americans. It was not
CC found in Caucasians, Asians, Indo-Aryans, or Arabs. There seems to be
CC no effect on the enzyme activity. {ECO:0000269|PubMed:9048929}.
CC -!- DISEASE: Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800]:
CC A form of methemoglobinemia, a hematologic disease characterized by the
CC presence of excessive amounts of methemoglobin in blood cells,
CC resulting in decreased oxygen carrying capacity of the blood, cyanosis
CC and hypoxia. There are two types of methemoglobinemia CYB5R3-related.
CC In type 1, the defect affects the soluble form of the enzyme, is
CC restricted to red blood cells, and causes well-tolerated
CC methemoglobinemia. In type 2, the defect affects both the soluble and
CC microsomal forms of the enzyme and is thus generalized, affecting red
CC cells, leukocytes and all body tissues. Type 2 methemoglobinemia is
CC associated with mental deficiency and other neurologic symptoms.
CC {ECO:0000269|PubMed:10807796, ECO:0000269|PubMed:12393396,
CC ECO:0000269|PubMed:1400360, ECO:0000269|PubMed:15622768,
CC ECO:0000269|PubMed:15953014, ECO:0000269|PubMed:1707593,
CC ECO:0000269|PubMed:1898726, ECO:0000269|PubMed:7718898,
CC ECO:0000269|PubMed:8119939, ECO:0000269|PubMed:9695975,
CC ECO:0000269|PubMed:9886302}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dia1/";
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DR EMBL; M28713; AAA59900.1; -; Genomic_DNA.
DR EMBL; M28705; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; M28706; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; M28707; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; M28708; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; M28709; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; M28710; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; M28711; AAA59900.1; JOINED; Genomic_DNA.
DR EMBL; Y09501; CAA70696.1; -; mRNA.
DR EMBL; AF361370; AAL87744.1; -; mRNA.
DR EMBL; AJ010116; CAA09006.1; -; mRNA.
DR EMBL; AJ010117; CAA09007.1; -; mRNA.
DR EMBL; AJ010118; CAA09008.1; -; mRNA.
DR EMBL; AY341030; AAP88936.1; -; Genomic_DNA.
DR EMBL; BT009821; AAP88823.1; -; mRNA.
DR EMBL; CR456435; CAG30321.1; -; mRNA.
DR EMBL; AF061830; AAF06818.1; -; Genomic_DNA.
DR EMBL; AF061831; AAF06819.1; -; Genomic_DNA.
DR EMBL; AK302204; BAH13649.1; -; mRNA.
DR EMBL; Z93241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004821; AAH04821.1; -; mRNA.
DR EMBL; AJ310899; CAC84523.1; -; mRNA.
DR EMBL; AJ310900; CAC84524.1; -; mRNA.
DR EMBL; M16461; AAA52306.1; -; mRNA.
DR EMBL; M16462; AAA52307.1; -; mRNA.
DR CCDS; CCDS14040.1; -. [P00387-2]
DR CCDS; CCDS33658.1; -. [P00387-1]
DR CCDS; CCDS54535.1; -. [P00387-3]
DR PIR; JS0468; RDHUB5.
DR RefSeq; NP_000389.1; NM_000398.6. [P00387-1]
DR RefSeq; NP_001123291.1; NM_001129819.2. [P00387-2]
DR RefSeq; NP_001165131.1; NM_001171660.1. [P00387-3]
DR RefSeq; NP_001165132.1; NM_001171661.1. [P00387-2]
DR RefSeq; NP_015565.1; NM_007326.4. [P00387-2]
DR PDB; 1UMK; X-ray; 1.75 A; A=27-301.
DR PDBsum; 1UMK; -.
DR AlphaFoldDB; P00387; -.
DR SMR; P00387; -.
DR BioGRID; 108071; 292.
DR DIP; DIP-50463N; -.
DR IntAct; P00387; 109.
DR MINT; P00387; -.
DR STRING; 9606.ENSP00000354468; -.
DR ChEMBL; CHEMBL2146; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB03147; Flavin adenine dinucleotide.
DR DrugBank; DB00157; NADH.
DR GlyGen; P00387; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P00387; -.
DR MetOSite; P00387; -.
DR PhosphoSitePlus; P00387; -.
DR SwissPalm; P00387; -.
DR BioMuta; CYB5R3; -.
DR DMDM; 127846; -.
DR REPRODUCTION-2DPAGE; IPI00446235; -.
DR CPTAC; CPTAC-55; -.
DR CPTAC; CPTAC-56; -.
DR EPD; P00387; -.
DR jPOST; P00387; -.
DR MassIVE; P00387; -.
DR MaxQB; P00387; -.
DR PaxDb; P00387; -.
DR PeptideAtlas; P00387; -.
DR PRIDE; P00387; -.
DR ProteomicsDB; 51238; -. [P00387-1]
DR ProteomicsDB; 51239; -. [P00387-2]
DR ProteomicsDB; 51240; -. [P00387-3]
DR TopDownProteomics; P00387-1; -. [P00387-1]
DR TopDownProteomics; P00387-2; -. [P00387-2]
DR Antibodypedia; 219; 442 antibodies from 36 providers.
DR DNASU; 1727; -.
DR Ensembl; ENST00000352397.10; ENSP00000338461.6; ENSG00000100243.22. [P00387-1]
DR Ensembl; ENST00000402438.6; ENSP00000385679.1; ENSG00000100243.22. [P00387-2]
DR Ensembl; ENST00000407623.8; ENSP00000384834.3; ENSG00000100243.22. [P00387-2]
DR Ensembl; ENST00000687198.1; ENSP00000508492.1; ENSG00000100243.22. [P00387-2]
DR Ensembl; ENST00000688117.1; ENSP00000509015.1; ENSG00000100243.22. [P00387-3]
DR Ensembl; ENST00000692152.1; ENSP00000509317.1; ENSG00000100243.22. [P00387-2]
DR GeneID; 1727; -.
DR KEGG; hsa:1727; -.
DR MANE-Select; ENST00000352397.10; ENSP00000338461.6; NM_000398.7; NP_000389.1.
DR UCSC; uc003bcx.4; human. [P00387-1]
DR CTD; 1727; -.
DR DisGeNET; 1727; -.
DR GeneCards; CYB5R3; -.
DR HGNC; HGNC:2873; CYB5R3.
DR HPA; ENSG00000100243; Low tissue specificity.
DR MalaCards; CYB5R3; -.
DR MIM; 250800; phenotype.
DR MIM; 613213; gene.
DR neXtProt; NX_P00387; -.
DR OpenTargets; ENSG00000100243; -.
DR Orphanet; 621; Hereditary methemoglobinemia.
DR PharmGKB; PA27331; -.
DR VEuPathDB; HostDB:ENSG00000100243; -.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00940000153962; -.
DR HOGENOM; CLU_003827_9_2_1; -.
DR InParanoid; P00387; -.
DR OMA; HAKERCF; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; P00387; -.
DR TreeFam; TF314333; -.
DR BioCyc; MetaCyc:HS02015-MON; -.
DR BRENDA; 1.6.2.2; 2681.
DR PathwayCommons; P00387; -.
DR Reactome; R-HSA-196836; Vitamin C (ascorbate) metabolism.
DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SABIO-RK; P00387; -.
DR SignaLink; P00387; -.
DR BioGRID-ORCS; 1727; 18 hits in 1080 CRISPR screens.
DR ChiTaRS; CYB5R3; human.
DR EvolutionaryTrace; P00387; -.
DR GeneWiki; CYB5R3; -.
DR GenomeRNAi; 1727; -.
DR Pharos; P00387; Tbio.
DR PRO; PR:P00387; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P00387; protein.
DR Bgee; ENSG00000100243; Expressed in descending thoracic aorta and 210 other tissues.
DR ExpressionAtlas; P00387; baseline and differential.
DR Genevisible; P00387; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005833; C:hemoglobin complex; TAS:ProtInc.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB.
DR GO; GO:1903958; C:nitric-oxide synthase complex; IDA:FlyBase.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IMP:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:FlyBase.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR001834; CBR-like.
DR InterPro; IPR008333; Cbr1-like_FAD-bd_dom.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR19370; PTHR19370; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR PRINTS; PR00371; FPNCR.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage;
KW Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism;
KW Cytoplasm; Direct protein sequencing; Disease variant;
KW Endoplasmic reticulum; FAD; Flavoprotein; Lipid biosynthesis;
KW Lipid metabolism; Lipoprotein; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Myristate; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:25255805"
FT CHAIN 2..301
FT /note="NADH-cytochrome b5 reductase 3 membrane-bound form"
FT /id="PRO_0000019392"
FT CHAIN 27..301
FT /note="NADH-cytochrome b5 reductase 3 soluble form"
FT /id="PRO_0000019394"
FT DOMAIN 40..152
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 132..147
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 171..206
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT MOD_RES 42
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 43
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 120
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN2"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:2498303,
FT ECO:0000269|PubMed:25255805"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_010200"
FT VAR_SEQ 1..7
FT /note="MGAQLST -> MNRSLLVGCMQSKDIWGREESICERLKQDGLDVERAESWE
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042827"
FT VARIANT 58
FT /note="R -> Q (in METHB-CYB5R3; type 1; 62% of activity;
FT dbSNP:rs121965007)"
FT /evidence="ECO:0000269|PubMed:15622768,
FT ECO:0000269|PubMed:1707593, ECO:0000269|Ref.4"
FT /id="VAR_004619"
FT VARIANT 66
FT /note="S -> P (in dbSNP:rs1130706)"
FT /evidence="ECO:0000269|PubMed:2479590,
FT ECO:0000269|PubMed:3035541, ECO:0000269|Ref.4"
FT /id="VAR_018419"
FT VARIANT 73
FT /note="L -> P (in METHB-CYB5R3; type 1; dbSNP:rs121965013)"
FT /evidence="ECO:0000269|PubMed:9695975, ECO:0000269|Ref.4"
FT /id="VAR_010750"
FT VARIANT 106
FT /note="V -> M (in METHB-CYB5R3; type 1; 77% of activity;
FT dbSNP:rs121965009)"
FT /evidence="ECO:0000269|PubMed:1400360"
FT /id="VAR_004620"
FT VARIANT 117
FT /note="T -> S (in dbSNP:rs1800457)"
FT /evidence="ECO:0000269|PubMed:9048929, ECO:0000269|Ref.5"
FT /id="VAR_010751"
FT VARIANT 128
FT /note="S -> P (in METHB-CYB5R3; type 2; Hiroshima;
FT decreased NADH-cytochrome b5 reductase actitiy; highly
FT increased Km for NADH and decreased Kcat;
FT dbSNP:rs121965006)"
FT /evidence="ECO:0000269|PubMed:1898726"
FT /id="VAR_004621"
FT VARIANT 149
FT /note="L -> P (in METHB-CYB5R3; dbSNP:rs121965008)"
FT /evidence="ECO:0000269|PubMed:1707593"
FT /id="VAR_004622"
FT VARIANT 179
FT /note="A -> V (in METHB-CYB5R3; type 1; dbSNP:rs201232518)"
FT /evidence="ECO:0000269|PubMed:9886302"
FT /id="VAR_010752"
FT VARIANT 204
FT /note="C -> R (in METHB-CYB5R3; type 2; dbSNP:rs121965011)"
FT /evidence="ECO:0000269|PubMed:7718898"
FT /id="VAR_010753"
FT VARIANT 204
FT /note="C -> Y (in METHB-CYB5R3; type 1; reduced protein
FT stability; no effect on NADH-cytochrome b5 reductase
FT activity; dbSNP:rs121965015)"
FT /evidence="ECO:0000269|PubMed:10807796, ECO:0000269|Ref.4"
FT /id="VAR_010754"
FT VARIANT 256
FT /note="Missing (in METHB-CYB5R3; type 1; retains
FT approximately 38% of residual diaphorase activity;
FT dbSNP:rs121965017)"
FT /evidence="ECO:0000269|PubMed:12393396,
FT ECO:0000269|PubMed:15953014"
FT /id="VAR_037315"
FT VARIANT 273
FT /note="Missing (in METHB-CYB5R3; type 2;
FT dbSNP:rs794728012)"
FT /evidence="ECO:0000269|PubMed:7718898"
FT /id="VAR_010755"
FT VARIANT 292
FT /note="G -> D (in METHB-CYB5R3; type 1; retains
FT approximately 58% of residual diaphorase activity;
FT dbSNP:rs121965016)"
FT /evidence="ECO:0000269|PubMed:12393396,
FT ECO:0000269|PubMed:15953014"
FT /id="VAR_037316"
FT VARIANT 299
FT /note="Missing (in METHB-CYB5R3; type2; almost complete
FT loss of activity; dbSNP:rs121965012)"
FT /evidence="ECO:0000269|PubMed:8119939"
FT /id="VAR_004623"
FT MUTAGEN 128
FT /note="S->A: Decreased NADH-cytochrome b5 reductase
FT actitiy, highly increases Km for NADH and decreases Kcat."
FT /evidence="ECO:0000269|PubMed:1898726"
FT MUTAGEN 204
FT /note="C->S: No effect on NADH-cytochrome b5 reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:2019583"
FT MUTAGEN 274
FT /note="C->A: Loss of 30% of NADH-cytochrome b5 reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:2019583"
FT MUTAGEN 274
FT /note="C->A: Loss of 80% of NADH-cytochrome b5 reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:2019583"
FT MUTAGEN 274
FT /note="C->S: No effect on NADH-cytochrome b5 reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:2019583"
FT MUTAGEN 284
FT /note="C->S: No effect on NADH-cytochrome b5 reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:2019583"
FT MUTAGEN 298
FT /note="C->S: No effect on NADH-cytochrome b5 reductase
FT activity."
FT /evidence="ECO:0000269|PubMed:2019583"
FT MUTAGEN 299..301
FT /note="FVF->LVL: No effect on protein stability and NADH-
FT cytochrome b5 reductase activity."
FT /evidence="ECO:0000269|PubMed:8119939"
FT MUTAGEN 299
FT /note="F->A: Decreases protein stability and slightly
FT decreases NADH-cytochrome b5 reductase activity."
FT /evidence="ECO:0000269|PubMed:8119939"
FT MUTAGEN 299
FT /note="F->L: No effect on protein stability and NADH-
FT cytochrome b5 reductase activity."
FT /evidence="ECO:0000269|PubMed:8119939"
FT MUTAGEN 301
FT /note="F->A: Decreases protein stability and slightly
FT decreases NADH-cytochrome b5 reductase activity."
FT /evidence="ECO:0000269|PubMed:8119939"
FT MUTAGEN 301
FT /note="F->L: No effect on protein stability and NADH-
FT cytochrome b5 reductase activity."
FT /evidence="ECO:0000269|PubMed:8119939"
FT CONFLICT 28..32
FT /note="QRSTP -> RWPRA (in Ref. 11; AAA52307)"
FT /evidence="ECO:0000305"
FT CONFLICT 29
FT /note="R -> G (in Ref. 1; AAA59900)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="T -> K (in Ref. 4; CAA09006/CAA09007/CAA09008)"
FT /evidence="ECO:0000305"
FT CONFLICT 34..35
FT /note="IT -> LA (in Ref. 11; AAA52307)"
FT /evidence="ECO:0000305"
FT CONFLICT 187..188
FT /note="ML -> IV (in Ref. 4; CAA09006/CAA09007)"
FT /evidence="ECO:0000305"
FT CONFLICT 191..192
FT /note="IR -> MS (in Ref. 4; CAA09006/CAA09007)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="R -> G (in Ref. 11; AAA52306)"
FT /evidence="ECO:0000305"
FT CONFLICT 233..234
FT /note="FK -> CN (in Ref. 4; CAA09006/CAA09007)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="I -> N (in Ref. 3; AAL87744)"
FT /evidence="ECO:0000305"
FT STRAND 43..52
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 54..63
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 78..85
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 126..133
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 168..171
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 173..180
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 184..195
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 203..212
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:1UMK"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 233..241
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 255..261
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 265..267
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 270..275
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 277..282
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 285..291
FT /evidence="ECO:0007829|PDB:1UMK"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:1UMK"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:1UMK"
SQ SEQUENCE 301 AA; 34235 MW; FDCDCDC4EC3570B4 CRC64;
MGAQLSTLGH MVLFPVWFLY SLLMKLFQRS TPAITLESPD IKYPLRLIDR EIISHDTRRF
RFALPSPQHI LGLPVGQHIY LSARIDGNLV VRPYTPISSD DDKGFVDLVI KVYFKDTHPK
FPAGGKMSQY LESMQIGDTI EFRGPSGLLV YQGKGKFAIR PDKKSNPIIR TVKSVGMIAG
GTGITPMLQV IRAIMKDPDD HTVCHLLFAN QTEKDILLRP ELEELRNKHS ARFKLWYTLD
RAPEAWDYGQ GFVNEEMIRD HLPPPEEEPL VLMCGPPPMI QYACLPNLDH VGHPTERCFV
F
