P00387 (NB5R3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADH-cytochrome b5 reductase 3
Short name=B5R
Short name=Cytochrome b5 reductase
EC=1.6.2.2

Alternative name(s):
Diaphorase-1

Cleaved into the following 2 chains:

1. NADH-cytochrome b5 reductase 3 membrane-bound form
2. NADH-cytochrome b5 reductase 3 soluble form

Gene names

Name:	CYB5R3
Synonyms:	DIA1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	301 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Desaturation and elongation of fatty acids, cholesterol biosynthesis, drug metabolism, and, in erythrocyte, methemoglobin reduction.
Catalytic activity	NADH + 2 ferricytochrome b5 = NAD+ + H+ + 2 ferrocytochrome b5.
Cofactor	FAD.
Subunit structure	Component of a complex composed of cytochrome b5, NADH-cytochrome b5 reductase (CYB5R3) and MOSC2 By similarity.
Subcellular location	Isoform 1: Endoplasmic reticulum membrane; Lipid-anchor; Cytoplasmic side. Mitochondrion outer membrane; Lipid-anchor; Cytoplasmic side. Isoform 2: Cytoplasm. Note: Produces the soluble form found in erythrocytes.
Tissue specificity	Isoform 2 is expressed at late stages of erythroid maturation.
Polymorphism	Ser-117 seems to only be found in persons of African origin. The allele frequency is 0.23 in African Americans. It was not found in Caucasians, Asians, Indo-Aryans, or Arabs. There seems to be no effect on the enzyme activity.
Involvement in disease	Methemoglobinemia CYB5R3-related (METHB-CYB5R3) [MIM:250800]: A form of methemoglobinemia, a hematologic disease characterized by the presence of excessive amounts of methemoglobin in blood cells, resulting in decreased oxygen carrying capacity of the blood, cyanosis and hypoxia. There are two types of methemoglobinemia CYB5R3-related. In type 1, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type 2, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes and all body tissues. Type 2 methemoglobinemia is associated with mental deficiency and other neurologic symptoms. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33
Sequence similarities	Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family. Contains 1 FAD-binding FR-type domain.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Alternative promoter usage Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	FAD Flavoprotein NAD
Molecular function	Oxidoreductase
PTM	Acetylation Lipoprotein Myristate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	L-ascorbic acid metabolic process Traceable author statement. Source: Reactome blood circulation Traceable author statement Ref.24. Source: ProtInc cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from direct assay. Source: HPA endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell hemoglobin complex Traceable author statement Ref.24. Source: ProtInc lipid particle Inferred from direct assay PubMed 14741744. Source: UniProtKB mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial outer membrane Traceable author statement. Source: Reactome
Molecular_function	ADP binding Inferred from electronic annotation. Source: Compara AMP binding Inferred from electronic annotation. Source: Compara FAD binding Inferred from direct assay PubMed 20861021. Source: UniProtKB NAD binding Inferred from electronic annotation. Source: Compara cytochrome-b5 reductase activity, acting on NAD(P)H Traceable author statement. Source: Reactome flavin adenine dinucleotide binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform 1 (identifier: P00387-1)

Also known as: M;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P00387-2)

Also known as: S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Isoform 3 (identifier: P00387-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-7: MGAQLST → MNRSLLVGCMQSKDIWGREESICERLKQDGLDVERAESWE

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 301

300

NADH-cytochrome b5 reductase 3 membrane-bound form

PRO_0000019392

Chain

27 – 301

275

NADH-cytochrome b5 reductase 3 soluble form

PRO_0000019394

Regions

Domain

40 – 152

113

FAD-binding FR-type

Nucleotide binding

132 – 147

16

FAD By similarity

Nucleotide binding

171 – 206

36

FAD By similarity

Amino acid modifications

Modified residue

42

1

N6-acetyllysine Ref.19

Modified residue

43

1

Phosphotyrosine Ref.18

Modified residue

120

1

N6-acetyllysine By similarity

Modified residue

130

1

Phosphotyrosine By similarity

Lipidation

2

1

N-myristoyl glycine Ref.13

Natural variations

Alternative sequence

1 – 23

23

Missing in isoform 2.

VSP_010200

Alternative sequence

1 – 7

7

MGAQLST → MNRSLLVGCMQSKDIWGREE SICERLKQDGLDVERAESWE in isoform 3.

VSP_042827

Natural variant

58

1

R → Q in METHB-CYB5R3; type 1; 62% of activity. Ref.4 Ref.23 Ref.31

VAR_004619

Natural variant

66

1

S → P. Ref.1 Ref.4 Ref.11
Corresponds to variant rs1130706 [ dbSNP | Ensembl ].

VAR_018419

Natural variant

73

1

L → P in METHB-CYB5R3; type 1. Ref.4 Ref.28

VAR_010750

Natural variant

106

1

V → M in METHB-CYB5R3; type 1; 77% of activity. Ref.24

VAR_004620

Natural variant

117

1

T → S. Ref.5 Ref.27
Corresponds to variant rs1800457 [ dbSNP | Ensembl ].

VAR_010751

Natural variant

128

1

S → P in METHB-CYB5R3; type 2; Hiroshima. Ref.22

VAR_004621

Natural variant

149

1

L → P in METHB-CYB5R3. Ref.23

VAR_004622

Natural variant

179

1

A → V in METHB-CYB5R3; type 1. Ref.29

VAR_010752

Natural variant

204

1

C → R in METHB-CYB5R3; type 2. Ref.26

VAR_010753

Natural variant

204

1

C → Y in METHB-CYB5R3; type 1. Ref.4 Ref.30

VAR_010754

Natural variant

256

1

Missing in METHB-CYB5R3; type 1; retains approximately 38% of residual diaphorase activity. Ref.32 Ref.33

VAR_037315

Natural variant

273

1

Missing in METHB-CYB5R3; type 2. Ref.26

VAR_010755

Natural variant

292

1

G → D in METHB-CYB5R3; type 1; retains approximately 58% of residual diaphorase activity. Ref.32 Ref.33

VAR_037316

Natural variant

299

1

Missing in METHB-CYB5R3; type2; almost complete loss of activity. Ref.25

VAR_004623

Experimental info

Sequence conflict

28 – 32

5

QRSTP → RWPRA in AAA52307. Ref.11

Sequence conflict

29

1

R → G in AAA59900. Ref.1

Sequence conflict

31

1

T → K in CAA09006. Ref.4

Sequence conflict

31

1

T → K in CAA09007. Ref.4

Sequence conflict

31

1

T → K in CAA09008. Ref.4

Sequence conflict

34 – 35

2

IT → LA in AAA52307. Ref.11

Sequence conflict

187 – 188

2

ML → IV in CAA09006. Ref.4

Sequence conflict

187 – 188

2

ML → IV in CAA09007. Ref.4

Sequence conflict

191 – 192

2

IR → MS in CAA09006. Ref.4

Sequence conflict

191 – 192

2

IR → MS in CAA09007. Ref.4

Sequence conflict

192

1

R → G in AAA52306. Ref.11

Sequence conflict

233 – 234

2

FK → CN in CAA09006. Ref.4

Sequence conflict

233 – 234

2

FK → CN in CAA09007. Ref.4

Sequence conflict

280

1

I → N in AAL87744. Ref.3

Secondary structure

1

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301

Helix Strand Turn

Details...

Beta strand

43 – 52

10

Beta strand

54 – 63

10

Beta strand

78 – 85

8

Beta strand

88 – 94

7

Beta strand

104 – 111

8

Beta strand

115 – 118

4

Helix

126 – 133

8

Beta strand

139 – 146

8

Beta strand

148 – 153

6

Beta strand

156 – 159

4

Beta strand

168 – 171

4

Beta strand

173 – 180

8

Helix

181 – 183

3

Helix

184 – 195

12

Beta strand

203 – 212

10

Helix

213 – 215

3

Helix

219 – 228

10

Turn

230 – 232

3

Beta strand

233 – 241

9

Beta strand

247 – 252

6

Helix

255 – 261

7

Helix

265 – 267

3

Beta strand

270 – 275

6

Helix

277 – 282

6

Helix

285 – 291

7

Helix

295 – 297

3

Beta strand

298 – 300

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (M) [UniParc]. Last modified January 23, 2007. Version 3. Checksum: FDCDCDC4EC3570B4	FASTA	301	34,235
	10 20 30 40 50 60 MGAQLSTLGH MVLFPVWFLY SLLMKLFQRS TPAITLESPD IKYPLRLIDR EIISHDTRRF 70 80 90 100 110 120 RFALPSPQHI LGLPVGQHIY LSARIDGNLV VRPYTPISSD DDKGFVDLVI KVYFKDTHPK 130 140 150 160 170 180 FPAGGKMSQY LESMQIGDTI EFRGPSGLLV YQGKGKFAIR PDKKSNPIIR TVKSVGMIAG 190 200 210 220 230 240 GTGITPMLQV IRAIMKDPDD HTVCHLLFAN QTEKDILLRP ELEELRNKHS ARFKLWYTLD 250 260 270 280 290 300 RAPEAWDYGQ GFVNEEMIRD HLPPPEEEPL VLMCGPPPMI QYACLPNLDH VGHPTERCFV F
	Isoform 2 (S) [UniParc]. Checksum: 229597F14FA6582E	FASTA	278	31,629
	10 20 30 40 50 60 MKLFQRSTPA ITLESPDIKY PLRLIDREII SHDTRRFRFA LPSPQHILGL PVGQHIYLSA 70 80 90 100 110 120 RIDGNLVVRP YTPISSDDDK GFVDLVIKVY FKDTHPKFPA GGKMSQYLES MQIGDTIEFR 130 140 150 160 170 180 GPSGLLVYQG KGKFAIRPDK KSNPIIRTVK SVGMIAGGTG ITPMLQVIRA IMKDPDDHTV 190 200 210 220 230 240 CHLLFANQTE KDILLRPELE ELRNKHSARF KLWYTLDRAP EAWDYGQGFV NEEMIRDHLP 250 260 270 PPEEEPLVLM CGPPPMIQYA CLPNLDHVGH PTERCFVF
	Isoform 3 [UniParc]. Checksum: 91CCE3D9A18621E8	FASTA	334	38,226
	10 20 30 40 50 60 MNRSLLVGCM QSKDIWGREE SICERLKQDG LDVERAESWE LGHMVLFPVW FLYSLLMKLF 70 80 90 100 110 120 QRSTPAITLE SPDIKYPLRL IDREIISHDT RRFRFALPSP QHILGLPVGQ HIYLSARIDG 130 140 150 160 170 180 NLVVRPYTPI SSDDDKGFVD LVIKVYFKDT HPKFPAGGKM SQYLESMQIG DTIEFRGPSG 190 200 210 220 230 240 LLVYQGKGKF AIRPDKKSNP IIRTVKSVGM IAGGTGITPM LQVIRAIMKD PDDHTVCHLL 250 260 270 280 290 300 FANQTEKDIL LRPELEELRN KHSARFKLWY TLDRAPEAWD YGQGFVNEEM IRDHLPPPEE 310 320 330 EPLVLMCGPP PMIQYACLPN LDHVGHPTER CFVF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene." Tomatsu S., Kobayashi Y., Fukumaki Y., Yubisui T., Orii T., Sakaki Y. Gene 80:353-361(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-66. Tissue: Placenta.
[2]	Voice M.W. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	Yoon B., Chung H., Ko E., Lee D. Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	Lan F. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PRO-66, VARIANTS HM GLN-58; PRO-73 AND TYR-204. Tissue: Leukocyte.
[5]	NIEHS SNPs program Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-117.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[7]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Testis.
[9]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[11]	"Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase." Yubisui T., Naitoh Y., Zenno S., Tamura M., Takeshita M., Sakaki Y. Proc. Natl. Acad. Sci. U.S.A. 84:3609-3613(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 8-301 (ISOFORM 1), VARIANT PRO-66. Tissue: Liver.
[12]	"Upregulation of voltage-gated Na+ channel expression and metastatic potential in human breast cancer: correlative studies on cell lines and biopsy tissues." Diss J.K.J., Fraser S.P., Coombes R.C., Djamgoz M.B.A. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-250 (ISOFORM 1).
[13]	"The NH2-terminal structures of human and rat liver microsomal NADH-cytochrome b5 reductases." Murakami K., Yubisui T., Takeshita M., Miyata T. J. Biochem. 105:312-317(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-25, MYRISTOYLATION AT GLY-2.
[14]	"Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes." Yubisui T., Miyata T., Iwanaga S., Tamura M., Takeshita M. J. Biochem. 99:407-422(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-301. Tissue: Erythrocyte.
[15]	"Amino acid sequence of NADH-cytochrome b5 reductase of human erythrocytes." Yubisui T., Miyata T., Iwanaga S., Tamura M., Yoshida S., Takeshita M., Nakajima H. J. Biochem. 96:579-582(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-301. Tissue: Erythrocyte.
[16]	"An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5 reductase in humans." Bulbarelli A., Valentini A., De Silvestris M., Cappellini M.D., Borgese N. Blood 92:310-319(1998) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE PROMOTER USAGE.
[17]	"Role of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Cys-273 and Cys-283 are located close to the NADH-binding site but are not catalytically essential." Shirabe K., Yubisui T., Nishino T., Takeshita M. J. Biol. Chem. 266:7531-7536(1991) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYSTEINE RESIDUES.
[18]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-43, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42, MASS SPECTROMETRY.
[20]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"Structure of human erythrocyte NADH-cytochrome b5 reductase." Bando S., Takano T., Yubisui T., Shirabe K., Takeshita M., Nakagawa A. Acta Crystallogr. D 60:1929-1934(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 31-301.
[22]	"Structural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase." Yubisui T., Shirabe K., Takeshita M., Kobayashi Y., Fukumaki Y., Sakaki Y., Takano T. J. Biol. Chem. 266:66-70(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT METHB-CYB5R3 PRO-128.
[23]	"Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency." Katsube T., Sakamoto N., Kobayashi Y., Seki R., Hirano M., Tanishima K., Tomoda A., Takazakura E., Yubisui T., Takeshita M., Sakaki Y., Fukumaki Y. Am. J. Hum. Genet. 48:799-808(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS METHB-CYB5R3 GLN-58 AND PRO-149.
[24]	"Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type)." Shirabe K., Yubisui T., Borgese N., Tang C.-Y., Hultquist D.E., Takeshita M. J. Biol. Chem. 267:20416-20421(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT METHB-CYB5R3 MET-106.
[25]	"An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene results in hereditary methemoglobinemia type II (generalized type). A functional implication for the role of the COOH-terminal region of the enzyme." Shirabe K., Fujimoto Y., Yubisui T., Takeshita M. J. Biol. Chem. 269:5952-5957(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT METHB-CYB5R3 PHE-299 DEL.
[26]	"Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II." Vieira L.M., Kaplan J.-C., Kahn A., Leroux A. Blood 85:2254-2262(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS METHB-CYB5R3 ARG-204 AND MET-273 DEL.
[27]	"A high-frequency polymorphism of NADH-cytochrome b5 reductase in African-Americans." Jenkins M.M., Prchal J.T. Hum. Genet. 99:248-250(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-117.
[28]	"Identification of a novel point mutation (Leu72-to-Pro) in the NADH-cytochrome b5 reductase gene of a patient with hereditary methaemoglobinaemia type I." Wu Y.-S., Huang C.-H., Wan Y., Huang Q.-J., Zhu Z.-Y. Br. J. Haematol. 102:575-577(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT METHB-CYB5R3 PRO-73.
[29]	"Molecular basis of hereditary methaemoglobinaemia, types I and II: two novel mutations in the NADH-cytochrome b5 reductase gene." Higasa K., Manabe J.I., Yubisui T., Sumimoto H., Pung-Amritt P., Tanphaichitr V.S., Fukumaki Y. Br. J. Haematol. 103:922-930(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 76-83 AND 171-187, VARIANT METHB-CYB5R3 VAL-179.
[30]	"A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia." Wang Y., Wu Y.-S., Zheng P.-Z., Yang W.-X., Fang G.-A., Tang Y.-C., Xie F., Lan F.-H., Zhu Z.-Y. Blood 95:3250-3255(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT METHB-CYB5R3 TYR-204.
[31]	"Arginine-glutamine replacement at residue 57 of NADH-cytochrome b5 reductase in Chinese hereditary methemoglobinemia." Huang C.-H., Xie Y., Wang Y., Wu Y.-S. Zhonghua Xue Ye Xue Za Zhi 18:200-203(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT METHB-CYB5R3 GLN-58.
[32]	"Familial idiopathic methemoglobinemia revisited: original cases reveal 2 novel mutations in NADH-cytochrome b5 reductase." Percy M.J., Gillespie M.J.S., Savage G., Hughes A.E., McMullin M.F., Lappin T.R.J. Blood 100:3447-3449(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS METHB-CYB5R3 GLU-256 DEL AND ASP-292.
[33]	"Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase." Percy M.J., Crowley L.J., Davis C.A., McMullin M.F., Savage G., Hughes J., McMahon C., Quinn R.J.M., Smith O., Barber M.J., Lappin T.R.J. Br. J. Haematol. 129:847-853(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS METHB-CYB5R3 GLU-256 DEL AND ASP-292.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M28713 , M28705, M28706, M28707, M28708, M28709, M28710, M28711 Genomic DNA. Translation: AAA59900.1.
Y09501 mRNA. Translation: CAA70696.1.
AF361370 mRNA. Translation: AAL87744.1.
AJ010116 mRNA. Translation: CAA09006.1.
AJ010117 mRNA. Translation: CAA09007.1.
AJ010118 mRNA. Translation: CAA09008.1.
AY341030 Genomic DNA. Translation: AAP88936.1.
BT009821 mRNA. Translation: AAP88823.1.
CR456435 mRNA. Translation: CAG30321.1.
AF061830 Genomic DNA. Translation: AAF06818.1.
AF061831 Genomic DNA. Translation: AAF06819.1.
AK302204 mRNA. Translation: BAH13649.1.
Z93241 Genomic DNA. Translation: CAB42843.1.
Z93241 Genomic DNA. Translation: CAQ08414.1.
BC004821 mRNA. Translation: AAH04821.1.
AJ310899 mRNA. Translation: CAC84523.1.
AJ310900 mRNA. Translation: CAC84524.1.
M16461 mRNA. Translation: AAA52306.1.
M16462 mRNA. Translation: AAA52307.1.

IPI

IPI00328415.
IPI00446235.
IPI00954806.

PIR

RDHUB5. JS0468.

RefSeq

NP_000389.1. NM_000398.6.
NP_001123291.1. NM_001129819.2.
NP_001165131.1. NM_001171660.1.
NP_001165132.1. NM_001171661.1.
NP_015565.1. NM_007326.4.

UniGene

Hs.561064.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1M91	model	-	A	1-301	[»]
1UMK	X-ray	1.75	A	27-301	[»]

ProteinModelPortal

P00387.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-50463N.

IntAct

P00387. 2 interactions.

PTM databases

PhosphoSite

P00387.

Polymorphism databases

DMDM

127846.

2D gel databases

REPRODUCTION-2DPAGE

IPI00446235.

Proteomic databases

PaxDb

P00387.

PRIDE

P00387.

Protocols and materials databases

DNASU

1727.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000352397; ENSP00000338461; ENSG00000100243.
ENST00000361740; ENSP00000354468; ENSG00000100243.
ENST00000396303; ENSP00000379597; ENSG00000100243.
ENST00000402438; ENSP00000385679; ENSG00000100243.
ENST00000407332; ENSP00000384457; ENSG00000100243.
ENST00000407623; ENSP00000384834; ENSG00000100243.

GeneID

1727.

KEGG

hsa:1727.

UCSC

uc003bcx.3. human.

Organism-specific databases

CTD

1727.

GeneCards

GC22M043014.

HGNC

HGNC:2873. CYB5R3.

HPA

HPA001566.

MIM

250800. phenotype.
613213. gene.

neXtProt

NX_P00387.

Orphanet

139373. Recessive hereditary methemoglobinemia type 1.
139380. Recessive hereditary methemoglobinemia type 2.

PharmGKB

PA27331.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0543.

HOGENOM

HOG000175005.

HOVERGEN

HBG052580.

InParanoid

P00387.

KO

K00326.

OMA

ISHDTRK.

OrthoDB

EOG418BNW.

PhylomeDB

P00387.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02015-MONOMER.

BRENDA

1.6.2.2. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P00387.

Gene expression databases

ArrayExpress

P00387.

Bgee

P00387.

CleanEx

HS_CYB5R3.

Genevestigator

P00387.

GermOnline

ENSG00000100243. Homo sapiens.

Family and domain databases

InterPro

IPR017927. Fd_Rdtase_FAD-bd.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR001834. NADH-Cyt_B5_reductase.
IPR008333. OxRdtase_FAD-bd_dom.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]

Pfam

PF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]

PRINTS

PR00406. CYTB5RDTASE.
PR00371. FPNCR.

SUPFAM

SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.

PROSITE

PS51384. FAD_FR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2146.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P00387.

GenomeRNAi

1727.

NextBio

6983.

SOURCE

Search...

Entry information

Entry name

NB5R3_HUMAN

Accession

Primary (citable) accession number: P00387
Secondary accession number(s): B1AHF2 , B7Z7L3, O75675, Q8TDL8, Q8WTS8, Q9UEN4, Q9UEN5, Q9UL55, Q9UL56

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 180 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.