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P00387 (NB5R3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 191. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NADH-cytochrome b5 reductase 3

Short name=B5R
Short name=Cytochrome b5 reductase
EC=1.6.2.2
Alternative name(s):
Diaphorase-1
Gene names
Name:CYB5R3
Synonyms:DIA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length301 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Cellular componentCytoplasm
Endoplasmic reticulum
Membrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityAlternative promoter usage
Alternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandFAD
Flavoprotein
NAD
   Molecular functionOxidoreductase
   PTMAcetylation
Lipoprotein
Myristate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processL-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

small molecule metabolic process

Traceable author statement. Source: Reactome

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Traceable author statement PubMed 9207238. Source: ProtInc

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

membrane

Traceable author statement PubMed 9207238. Source: ProtInc

mitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial outer membrane

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay PubMed 20833797. Source: UniProt

   Molecular_functionADP binding

Inferred from electronic annotation. Source: Ensembl

AMP binding

Inferred from electronic annotation. Source: Ensembl

FAD binding

Inferred from direct assay PubMed 20861021. Source: UniProtKB

NAD binding

Inferred from electronic annotation. Source: Ensembl

cytochrome-b5 reductase activity, acting on NAD(P)H

Traceable author statement. Source: Reactome

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: Ensembl

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:
     2-23: Missing.
Isoform 3 (identifier: P00387-3)

The sequence of this isoform differs from the canonical sequence as follows:
     2-7: GAQLST → MNRSLLVGCMQSKDIWGREESICERLKQDGLDVERAESWE
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 301300NADH-cytochrome b5 reductase 3 membrane-bound form
PRO_0000019392
Chain27 – 301275NADH-cytochrome b5 reductase 3 soluble form
PRO_0000019394

Regions

Domain40 – 152113FAD-binding FR-type
Nucleotide binding132 – 14716FAD By similarity
Nucleotide binding171 – 20636FAD By similarity

Amino acid modifications

Modified residue421N6-acetyllysine Ref.19
Modified residue431Phosphotyrosine Ref.18
Modified residue1201N6-acetyllysine By similarity
Lipidation21N-myristoyl glycine Ref.13

Natural variations

Alternative sequence2 – 2322Missing in isoform 2.
VSP_010200
Alternative sequence2 – 76GAQLST → MNRSLLVGCMQSKDIWGREE SICERLKQDGLDVERAESWE in isoform 3.
VSP_042827
Natural variant581R → Q in METHB-CYB5R3; type 1; 62% of activity. Ref.4 Ref.23 Ref.31
VAR_004619
Natural variant661S → P. Ref.1 Ref.4 Ref.11
Corresponds to variant rs1130706 [ dbSNP | Ensembl ].
VAR_018419
Natural variant731L → P in METHB-CYB5R3; type 1. Ref.4 Ref.28
VAR_010750
Natural variant1061V → M in METHB-CYB5R3; type 1; 77% of activity. Ref.24
Corresponds to variant rs121965009 [ dbSNP | Ensembl ].
VAR_004620
Natural variant1171T → S. Ref.5 Ref.27
Corresponds to variant rs1800457 [ dbSNP | Ensembl ].
VAR_010751
Natural variant1281S → P in METHB-CYB5R3; type 2; Hiroshima. Ref.22
VAR_004621
Natural variant1491L → P in METHB-CYB5R3. Ref.23
VAR_004622
Natural variant1791A → V in METHB-CYB5R3; type 1. Ref.29
Corresponds to variant rs201232518 [ dbSNP | Ensembl ].
VAR_010752
Natural variant2041C → R in METHB-CYB5R3; type 2. Ref.26
VAR_010753
Natural variant2041C → Y in METHB-CYB5R3; type 1. Ref.4 Ref.30
VAR_010754
Natural variant2561Missing in METHB-CYB5R3; type 1; retains approximately 38% of residual diaphorase activity. Ref.32 Ref.33
VAR_037315
Natural variant2731Missing in METHB-CYB5R3; type 2. Ref.26
VAR_010755
Natural variant2921G → D in METHB-CYB5R3; type 1; retains approximately 58% of residual diaphorase activity. Ref.32 Ref.33
VAR_037316
Natural variant2991Missing in METHB-CYB5R3; type2; almost complete loss of activity. Ref.25
VAR_004623

Experimental info

Sequence conflict28 – 325QRSTP → RWPRA in AAA52307. Ref.11
Sequence conflict291R → G in AAA59900. Ref.1
Sequence conflict311T → K in CAA09006. Ref.4
Sequence conflict311T → K in CAA09007. Ref.4
Sequence conflict311T → K in CAA09008. Ref.4
Sequence conflict34 – 352IT → LA in AAA52307. Ref.11
Sequence conflict187 – 1882ML → IV in CAA09006. Ref.4
Sequence conflict187 – 1882ML → IV in CAA09007. Ref.4
Sequence conflict191 – 1922IR → MS in CAA09006. Ref.4
Sequence conflict191 – 1922IR → MS in CAA09007. Ref.4
Sequence conflict1921R → G in AAA52306. Ref.11
Sequence conflict233 – 2342FK → CN in CAA09006. Ref.4
Sequence conflict233 – 2342FK → CN in CAA09007. Ref.4
Sequence conflict2801I → N in AAL87744. Ref.3

Secondary structure

.................................................. 301
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (M) [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: FDCDCDC4EC3570B4

FASTA30134,235
        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 

« Hide

Isoform 2 (S) [UniParc].

Checksum: 033CBEBCDB564606
Show »

FASTA27931,760
Isoform 3 [UniParc].

Checksum: 34EB129AA0EC65DB
Show »

FASTA33538,358

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M28713 expand/collapse EMBL AC list , 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.
PIRRDHUB5. JS0468.
RefSeqNP_000389.1. NM_000398.6.
NP_001123291.1. NM_001129819.2.
NP_001165131.1. NM_001171660.1.
NP_015565.1. NM_007326.4.
UniGeneHs.561064.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M91model-A1-301[»]
1UMKX-ray1.75A27-301[»]
ProteinModelPortalP00387.
SMRP00387. Positions 31-301.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108071. 8 interactions.
DIPDIP-50463N.
IntActP00387. 2 interactions.
MINTMINT-5003981.

Chemistry

ChEMBLCHEMBL2146.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP00387.

Polymorphism databases

DMDM127846.

2D gel databases

REPRODUCTION-2DPAGEIPI00446235.

Proteomic databases

PaxDbP00387.
PRIDEP00387.

Protocols and materials databases

DNASU1727.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000352397; ENSP00000338461; ENSG00000100243. [P00387-1]
ENST00000361740; ENSP00000354468; ENSG00000100243. [P00387-3]
ENST00000396303; ENSP00000379597; ENSG00000100243. [P00387-2]
ENST00000402438; ENSP00000385679; ENSG00000100243. [P00387-2]
ENST00000407332; ENSP00000384457; ENSG00000100243. [P00387-2]
ENST00000407623; ENSP00000384834; ENSG00000100243. [P00387-2]
GeneID1727.
KEGGhsa:1727.
UCSCuc003bcx.3. human. [P00387-1]
uc011aps.2. human. [P00387-3]

Organism-specific databases

CTD1727.
GeneCardsGC22M043014.
HGNCHGNC:2873. CYB5R3.
HPAHPA001566.
MIM250800. phenotype.
613213. gene.
neXtProtNX_P00387.
Orphanet139373. Recessive hereditary methemoglobinemia type 1.
139380. Recessive hereditary methemoglobinemia type 2.
PharmGKBPA27331.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0543.
HOGENOMHOG000175005.
HOVERGENHBG052580.
InParanoidP00387.
KOK00326.
OMAPPPMINA.
OrthoDBEOG7CZK69.
PhylomeDBP00387.
TreeFamTF314333.

Enzyme and pathway databases

BioCycMetaCyc:HS02015-MONOMER.
BRENDA1.6.2.2. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP00387.

Gene expression databases

ArrayExpressP00387.
BgeeP00387.
CleanExHS_CYB5R3.
GenevestigatorP00387.

Family and domain databases

InterProIPR017927. 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]
PfamPF00970. FAD_binding_6. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00406. CYTB5RDTASE.
PR00371. FPNCR.
SUPFAMSSF63380. SSF63380. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00387.
GeneWikiCYB5R3.
GenomeRNAi1727.
NextBio6983.
PROP00387.
SOURCESearch...

Entry information

Entry nameNB5R3_HUMAN
AccessionPrimary (citable) accession number: P00387
Secondary accession number(s): B1AHF2 expand/collapse secondary AC list , 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: April 16, 2014
This is version 191 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM