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P00167 (CYB5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome b5
Alternative name(s):
Microsomal cytochrome b5 type A
Short name=MCB5
Gene names
Name:CYB5A
Synonyms:CYB5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length134 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytochrome b5 is a membrane bound hemoprotein which function as an electron carrier for several membrane bound oxygenases.

Subcellular location

Isoform 1: Endoplasmic reticulum membrane; Single-pass membrane protein; Cytoplasmic side. Microsome membrane; Single-pass membrane protein; Cytoplasmic side.

Isoform 2: Cytoplasm.

Involvement in disease

Methemoglobinemia CYB5A-related (METHB-CYB5A) [MIM:250790]: 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

Sequence similarities

Belongs to the cytochrome b5 family.

Contains 1 cytochrome b5 heme-binding domain.

Sequence caution

The sequence AAA63169.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processElectron transport
Transport
   Cellular componentCytoplasm
Endoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandHeme
Iron
Metal-binding
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processL-ascorbic acid metabolic process

Traceable author statement. Source: Reactome

hydrogen ion transmembrane transport

Traceable author statement Ref.2. Source: GOC

response to cadmium ion

Inferred from electronic annotation. Source: Ensembl

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_componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 22375059. Source: MGI

mitochondrial outer membrane

Traceable author statement. Source: Reactome

   Molecular_functionaldo-keto reductase (NADP) activity

Traceable author statement. Source: Reactome

cytochrome-c oxidase activity

Traceable author statement Ref.2. Source: ProtInc

enzyme binding

Inferred from physical interaction PubMed 15680923. Source: BHF-UCL

heme binding

Inferred from electronic annotation. Source: InterPro

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P00167-1)

Also known as: Liver; Membrane-bound;

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: P00167-2)

Also known as: Erythrocyte; Cytoplasmic;

The sequence of this isoform differs from the canonical sequence as follows:
     98-98: T → P
     99-134: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Isoform 3 (identifier: P00167-3)

The sequence of this isoform differs from the canonical sequence as follows:
     86-95: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Chain2 – 134133Cytochrome b5
PRO_0000166010

Regions

Transmembrane109 – 13123Helical; Potential
Domain9 – 8577Cytochrome b5 heme-binding

Sites

Metal binding441Iron (heme axial ligand)
Metal binding681Iron (heme axial ligand)

Amino acid modifications

Modified residue21N-acetylalanine Ref.13
Modified residue101N6-acetyllysine By similarity
Modified residue191N6-acetyllysine By similarity

Natural variations

Alternative sequence86 – 9510Missing in isoform 3.
VSP_045367
Alternative sequence981T → P in isoform 2.
VSP_001240
Alternative sequence99 – 13436Missing in isoform 2.
VSP_001241

Experimental info

Sequence conflict2 – 43Missing AA sequence Ref.10
Sequence conflict41Q → E AA sequence Ref.13
Sequence conflict15 – 184EEIQ → QEIE AA sequence Ref.10
Sequence conflict15 – 184EEIQ → QEIE AA sequence Ref.11
Sequence conflict15 – 184EEIQ → QEIE AA sequence Ref.12
Sequence conflict221Missing AA sequence Ref.12
Sequence conflict521R → W in CA771478. Ref.4
Sequence conflict621N → D AA sequence Ref.10
Sequence conflict621N → D AA sequence Ref.11
Sequence conflict621N → D AA sequence Ref.12
Sequence conflict89 – 913RPK → KPR AA sequence Ref.9
Sequence conflict89 – 913RPK → KPR AA sequence Ref.10
Sequence conflict89 – 913RPK → KPR AA sequence Ref.11
Sequence conflict89 – 913RPK → KPR AA sequence Ref.12
Sequence conflict1221A → V AA sequence Ref.13

Secondary structure

........................... 134
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Liver) (Membrane-bound) [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: B6AD2AB747555048

FASTA13415,330
        10         20         30         40         50         60 
MAEQSDEAVK YYTLEEIQKH NHSKSTWLIL HHKVYDLTKF LEEHPGGEEV LREQAGGDAT 

        70         80         90        100        110        120 
ENFEDVGHST DAREMSKTFI IGELHPDDRP KLNKPPETLI TTIDSSSSWW TNWVIPAISA 

       130 
VAVALMYRLY MAED 

« Hide

Isoform 2 (Erythrocyte) (Cytoplasmic) [UniParc].

Checksum: 62D9B54C7BCDF9F3
Show »

FASTA9811,268
Isoform 3 [UniParc].

Checksum: AC952456B4827706
Show »

FASTA12414,169

References

« Hide 'large scale' references
[1]"The complete nucleotide sequence of human liver cytochrome b5 mRNA."
Yoo M., Steggles A.W.
Biochem. Biophys. Res. Commun. 156:576-580(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[2]"The human liver and reticulocyte cytochrome b5 mRNAs are products from a single gene."
Giordano S.J., Steggles A.W.
Biochem. Biophys. Res. Commun. 178:38-44(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Erythrocyte.
[3]"The isolation and characterization of the human cytochrome b5 gene."
Li X.R., Giordano S.J., Yoo M., Steggles A.W.
Biochem. Biophys. Res. Commun. 209:894-900(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Endocrine pancreas consortium."
Melton D., Brown J., Kenty G., Permutt A., Lee C., Kaestner K., Lemishka I., Scearce M., Brestelli J., Gradwohl G., Clifton S., Hillier L., Marra M., Pape D., Wylie T., Martin J., Blistain A., Schmitt A. expand/collapse author list , Theising B., Ritter E., Ronko I., Bennett J., Cardenas M., Gibbons M., McCann R., Cole R., Tsagareishvili R., Williams T., Jackson Y., Bowers Y.
Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Pancreas.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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: Uterus.
[9]"Amino acid sequences of cytochrome b5 from human, porcine, and bovine erythrocytes and comparison with liver microsomal cytochrome b5."
Abe K., Kimura S., Kizawa R., Anan F.K., Sugita Y.
J. Biochem. 97:1659-1668(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-98.
Tissue: Erythrocyte.
[10]"Amino acid sequences of tryptic peptides of cytochromes b5 from microsomes of human, monkey, porcine, and chicken liver."
Nobrega F.G., Ozols J.
J. Biol. Chem. 246:1706-1717(1971) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-91.
[11]"Cytochrome b5 from a normal human liver. Isolation and the partial amino acid sequence."
Ozols J.
J. Biol. Chem. 247:2242-2245(1972) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-91.
[12]"Structural studies of cytochrome b5. 3. Sequential studies on human liver cytochrome b5."
Rashid M.A., Hagihara B., Kobayashi M., Tani S., Tsugita A.
J. Biochem. 74:985-1002(1973) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-91.
[13]"Structure of cytochrome b5 and its topology in the microsomal membrane."
Ozols J.
Biochim. Biophys. Acta 997:121-130(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-36 AND 84-134, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2.
[14]"A splicing mutation in the cytochrome b5 gene from a patient with congenital methemoglobinemia and pseudohermaphrodism."
Giordano S.J., Kaftory A., Steggles A.W.
Hum. Genet. 93:568-570(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN METHB-CYB5A.
[15]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M22865 mRNA. Translation: AAA35729.1.
M60174 mRNA. Translation: AAA52165.1.
L39945 expand/collapse EMBL AC list , L39792, L39941, L39942, L39943, L39944 Genomic DNA. Translation: AAA63169.1. Sequence problems.
CA771478 mRNA. No translation available.
CR456990 mRNA. Translation: CAG33271.1.
AC090398 Genomic DNA. No translation available.
CH471117 Genomic DNA. Translation: EAW66544.1.
BC015182 mRNA. Translation: AAH15182.1.
CCDSCCDS12004.1. [P00167-1]
CCDS12005.1. [P00167-2]
CCDS54188.1. [P00167-3]
PIRCBHU5. A28936.
CBHU5E. JN0075.
RefSeqNP_001177736.1. NM_001190807.2. [P00167-3]
NP_001905.1. NM_001914.3. [P00167-2]
NP_683725.1. NM_148923.3. [P00167-1]
UniGeneHs.465413.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2I96NMR-A1-108[»]
ProteinModelPortalP00167.
SMRP00167. Positions 1-108.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107908. 14 interactions.
IntActP00167. 4 interactions.
MINTMINT-3003425.
STRING9606.ENSP00000341625.

Chemistry

ChEMBLCHEMBL6170.
DrugBankDB01028. Methoxyflurane.

PTM databases

PhosphoSiteP00167.

Polymorphism databases

DMDM117809.

Proteomic databases

MaxQBP00167.
PaxDbP00167.
PRIDEP00167.

Protocols and materials databases

DNASU1528.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000340533; ENSP00000341625; ENSG00000166347. [P00167-1]
ENST00000397914; ENSP00000381011; ENSG00000166347. [P00167-3]
ENST00000494131; ENSP00000436461; ENSG00000166347. [P00167-2]
GeneID1528.
KEGGhsa:1528.
UCSCuc002llh.3. human. [P00167-2]
uc002lli.3. human. [P00167-1]

Organism-specific databases

CTD1528.
GeneCardsGC18M071920.
HGNCHGNC:2570. CYB5A.
HPACAB006333.
MIM250790. phenotype.
613218. gene.
neXtProtNX_P00167.
Orphanet90796. 46,XY disorder of sex development due to isolated 17, 20 lyase deficiency.
PharmGKBPA27068.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5274.
HOGENOMHOG000039853.
HOVERGENHBG002653.
InParanoidP00167.
OMAMAEQSDK.
PhylomeDBP00167.
TreeFamTF314537.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000166347-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

ArrayExpressP00167.
BgeeP00167.
CleanExHS_CYB5A.
GenevestigatorP00167.

Family and domain databases

Gene3D3.10.120.10. 1 hit.
InterProIPR001199. Cyt_B5-like_heme/steroid-bd.
IPR018506. Cyt_B5_heme-BS.
[Graphical view]
PfamPF00173. Cyt-b5. 1 hit.
[Graphical view]
PRINTSPR00363. CYTOCHROMEB5.
SUPFAMSSF55856. SSF55856. 1 hit.
PROSITEPS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYB5A. human.
EvolutionaryTraceP00167.
GeneWikiCytochrome_b5,_type_A.
GenomeRNAi1528.
NextBio6325.
PROP00167.
SOURCESearch...

Entry information

Entry nameCYB5_HUMAN
AccessionPrimary (citable) accession number: P00167
Secondary accession number(s): A8MV91, F8WEU4, Q6IB14
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 163 of the entry and version 2 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 chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM