Reviewed, UniProtKB/Swiss-Prot P00167 (CYB5_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytochrome b5

Gene names

Name:	CYB5A
Synonyms:	CYB5

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	134 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	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	Defects in CYB5A are the cause of type IV hereditary methemoglobinemia [MIM:250790].
Sequence similarities	Belongs to the cytochrome b5 family. Contains 1 cytochrome b5 heme-binding domain.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Cytoplasm Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Ligand	Heme Iron Metal-binding
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial outer membrane Inferred from Experiment. Source: Reactome
Molecular function	aldo-keto reductase activity Inferred from Experiment. Source: Reactome cytochrome-c oxidase activity Ref.4 Traceable author statement. Source: ProtInc heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Chain

2 – 134

133

Cytochrome b5

PRO_0000166010

Regions

Transmembrane

109 – 131

23

Potential

Domain

9 – 85

77

Cytochrome b5 heme-binding

Sites

Metal binding

44

1

Iron (heme axial ligand)

Metal binding

68

1

Iron (heme axial ligand)

Amino acid modifications

Modified residue

2

1

N-acetylalanine

Modified residue

19

1

N6-acetyllysine By similarity

Natural variations

Alternative sequence

98

1

T → P in isoform 2.

VSP_001240

Alternative sequence

99 – 134

36

Missing in isoform 2.

VSP_001241

Experimental info

Sequence conflict

2 – 4

3

Missing AA sequence Ref.6

Sequence conflict

4

1

Q → E AA sequence Ref.9

Sequence conflict

15 – 18

4

EEIQ → QEIE AA sequence Ref.6

Sequence conflict

15 – 18

4

EEIQ → QEIE AA sequence Ref.7

Sequence conflict

15 – 18

4

EEIQ → QEIE AA sequence Ref.8

Sequence conflict

22

1

Missing AA sequence Ref.8

Sequence conflict

62

1

N → D AA sequence Ref.6

Sequence conflict

62

1

N → D AA sequence Ref.7

Sequence conflict

62

1

N → D AA sequence Ref.8

Sequence conflict

89 – 91

3

RPK → KPR AA sequence Ref.5

Sequence conflict

89 – 91

3

RPK → KPR AA sequence Ref.6

Sequence conflict

89 – 91

3

RPK → KPR AA sequence Ref.7

Sequence conflict

89 – 91

3

RPK → KPR AA sequence Ref.8

Sequence conflict

122

1

A → V AA sequence Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

134

Helix Strand Turn

Details...

Beta strand

3 – 5

3

Helix

14 – 17

4

Helix

18 – 20

3

Beta strand

25 – 36

12

Turn

38 – 43

6

Helix

49 – 52

4

Beta strand

55 – 58

4

Helix

61 – 65

5

Helix

70 – 75

6

Helix

76 – 78

3

Beta strand

80 – 84

5

Turn

86 – 88

3

Turn

91 – 93

3

Beta strand

96 – 100

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Liver) (Membrane-bound) [UniParc]. Last modified January 23, 2007. Version 2. Checksum: B6AD2AB747555048	FASTA	134	15,330
	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
	Isoform 2 (Erythrocyte) (Cytoplasmic). Checksum: 62D9B54C7BCDF9F3	FASTA	98	11,268
	10 20 30 40 50 60 MAEQSDEAVK YYTLEEIQKH NHSKSTWLIL HHKVYDLTKF LEEHPGGEEV LREQAGGDAT 70 80 90 ENFEDVGHST DAREMSKTFI IGELHPDDRP KLNKPPEP

References

	« Hide 'large scale' referencesShow '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: 3178851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"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: 7733981] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[4]	"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: 1712589] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-98. Tissue: Erythrocyte.
[5]	"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: 4030743] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-98. Tissue: Erythrocyte.
[6]	"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: 4993957] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-91.
[7]	"Cytochrome b5 from a normal human liver. Isolation and the partial amino acid sequence." Ozols J. J. Biol. Chem. 247:2242-2245(1972) [PubMed: 5062820] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-91.
[8]	"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: 4770377] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-91.
[9]	"Structure of cytochrome b5 and its topology in the microsomal membrane." Ozols J. Biochim. Biophys. Acta 997:121-130(1989) [PubMed: 2752049] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-36 AND 84-134.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M22865 mRNA. Translation: AAA35729.1.
L39945 , L39792, L39941, L39942, L39943, L39944 Genomic DNA. Translation: AAA63169.1. Sequence problems.
BC015182 mRNA. Translation: AAH15182.1.
M60174 mRNA. Translation: AAA52165.1.

IPI

IPI00182933.
IPI00397860.

PIR

CBHU5. A28936.
CBHU5E. JN0075.

RefSeq

NP_001905.1.
NP_683725.1.

UniGene

Hs.465413

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I96	NMR	-	A	1-108	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P00167. 1 interaction.

PTM databases

PhosphoSite

P00167.

Proteomic databases

PRIDE

P00167.

Genome annotation databases

Ensembl

ENSG00000166347. Homo sapiens. [Contig view]

GeneID

1528.

KEGG

hsa:1528.

UCSC

uc002llh.1. human.
uc002lli.1. human.

Organism-specific databases

GeneCards

GC18M070072.

H-InvDB

HIX0014522.

HGNC

HGNC:2570. CYB5A.

HPA

CAB006333.

MIM

250790. gene+phenotype.

Orphanet

621. Hereditary methemoglobinemia.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P00167.

HOVERGEN

P00167.

OMA

P00167. QKHNHSK.

Enzyme and pathway databases

Reactome

REACT_11193. Metabolism of vitamins and cofactors.

Gene expression databases

ArrayExpress

P00167.

Bgee

P00167.

CleanEx

HS_CYB5A.

GermOnline

ENSG00000166347. Homo sapiens.

Family and domain databases

InterPro

IPR001199. Cyt_B5.
IPR018506. Cyt_B5_heme-BS.
[Graphical view]

Gene3D

G3DSA:3.10.120.10. Cyt_B5. 1 hit.

Pfam

PF00173. Cyt-b5. 1 hit.
[Graphical view]

PRINTS

PR00363. CYTOCHROMEB5.

ProDom

PD000612. Cyt_B5. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB01028. Methoxyflurane.

NextBio

6325.

SOURCE

Search...

Entry information

Entry name

CYB5_HUMAN

Accession

Primary (citable) accession number: P00167

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	July 7, 2009
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)