ID   CYB5_BOVIN              Reviewed;         134 AA.
AC   P00171; Q27947; Q28837; Q32PH5;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   04-NOV-2026, entry version 206.
DE   RecName: Full=Cytochrome b5;
GN   Name=CYB5A; Synonyms=CYB5;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2915932; DOI=10.1093/nar/17.2.799;
RA   Cristiano R.J., Steggles A.W.;
RT   "The complete nucleotide sequence of bovine liver cytochrome b5 mRNA.";
RL   Nucleic Acids Res. 17:799-799(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Liver;
RX   PubMed=8406485; DOI=10.1006/geno.1993.1331;
RA   Cristiano R.J., Giordano S.J., Steggles A.W.;
RT   "The isolation and characterization of the bovine cytochrome b5 gene, and a
RT   transcribed pseudogene.";
RL   Genomics 17:348-354(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal liver;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PROTEIN SEQUENCE OF 2-98, AND ACETYLATION AT ALA-2.
RC   TISSUE=Erythrocyte;
RX   PubMed=4030743; DOI=10.1093/oxfordjournals.jbchem.a135224;
RA   Abe K., Kimura S., Kizawa R., Anan F.K., Sugita Y.;
RT   "Amino acid sequences of cytochrome b5 from human, porcine, and bovine
RT   erythrocytes and comparison with liver microsomal cytochrome b5.";
RL   J. Biochem. 97:1659-1668(1985).
RN   [5]
RP   PROTEIN SEQUENCE OF 2-11 AND 131-134.
RX   PubMed=4810060; DOI=10.1021/bi00700a005;
RA   Ozols J.;
RT   "Cytochrome b5 from microsomal membranes of equine, bovine, and porcine
RT   livers. Isolation and properties of preparations containing the membranous
RT   segment.";
RL   Biochemistry 13:426-434(1974).
RN   [6]
RP   PROTEIN SEQUENCE OF 2-6 AND 15-18, AND ACETYLATION AT ALA-2.
RX   PubMed=2752049; DOI=10.1016/0167-4838(89)90143-x;
RA   Ozols J.;
RT   "Structure of cytochrome b5 and its topology in the microsomal membrane.";
RL   Biochim. Biophys. Acta 997:121-130(1989).
RN   [7]
RP   PROTEIN SEQUENCE OF 6-98.
RX   PubMed=5391285; DOI=10.1016/s0021-9258(18)63450-7;
RA   Ozols J., Strittmatter P.;
RT   "Correction of the amino acid sequence of calf liver microsomal cytochrome
RT   b5.";
RL   J. Biol. Chem. 244:6617-6618(1969).
RN   [8]
RP   PROTEIN SEQUENCE OF 6-96.
RX   PubMed=5272324; DOI=10.1073/pnas.67.1.442;
RA   Tsugita A., Kobayashi M., Tani S., Kyo S., Rashid M.A., Yoshida Y.,
RA   Kajihara T., Hagihara B.;
RT   "Comparative study of the primary structures of cytochrome b5 from four
RT   species.";
RL   Proc. Natl. Acad. Sci. U.S.A. 67:442-447(1970).
RN   [9]
RP   PROTEIN SEQUENCE OF 92-134.
RX   PubMed=670203; DOI=10.1016/s0021-9258(17)30380-0;
RA   Fleming P.J., Dailey H.A., Corcoran D., Strittmatter P.;
RT   "The primary structure of the nonpolar segment of bovine cytochrome b5.";
RL   J. Biol. Chem. 253:5369-5372(1978).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY OF OXIDIZED FORM.
RA   Mathews F.S., Argos P., Levine M.;
RT   "The structure of cytochrome b-5 at 2.0-A resolution.";
RL   Cold Spring Harb. Symp. Quant. Biol. 37:387-395(1971).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY OF REDUCED FORM.
RX   PubMed=1167544; DOI=10.1016/s0021-9258(19)41959-5;
RA   Argos P., Mathews F.S.;
RT   "The structure of ferrocytochrome b5 at 2.8-A resolution.";
RL   J. Biol. Chem. 250:747-751(1975).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY.
RX   PubMed=15299727; DOI=10.1107/s0907444995007827;
RA   Durley R.C.E., Mathews F.S.;
RT   "Refinement and structural analysis of bovine cytochrome b5 at 1.5-A
RT   resolution.";
RL   Acta Crystallogr. D 52:65-76(1996).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY, AND MUTAGENESIS.
RX   PubMed=10842340;
RX   DOI=10.1002/(sici)1097-0134(20000801)40:2<249::aid-prot70>3.0.co;2-h;
RA   Wu J., Gan J.-H., Xia Z.-X., Wang Y.-H., Wang W.-H., Xue L.-L., Xie Y.,
RA   Huang Z.-X.;
RT   "Crystal structure of recombinant trypsin-solubilized fragment of
RT   cytochrome b5 and the structural comparison with Val61His mutant.";
RL   Proteins 40:249-257(2000).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY, AND MUTAGENESIS.
RX   PubMed=12136141; DOI=10.1107/s0907444902010016;
RA   Gan J.-H., Wu J., Wang Z.-Q., Wang Y.-H., Huang Z.-X., Xia Z.-X.;
RT   "Structures of V45E and V45Y mutants and structure comparison of a variety
RT   of cytochrome b5 mutants.";
RL   Acta Crystallogr. D 58:1298-1306(2002).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY, CIRCULAR DICHROISM ANALYSIS, AND MUTAGENESIS.
RX   PubMed=12199707; DOI=10.1046/j.1432-1033.2002.03120.x;
RA   Yao P., Wu J., Wang Y.-H., Sun B.-Y., Xia Z.-X., Huang Z.-X.;
RT   "X-ray crystallography, CD and kinetic studies revealed the essence of the
RT   abnormal behaviors of the cytochrome b5 Phe35->Tyr mutant.";
RL   Eur. J. Biochem. 269:4287-4296(2002).
RN   [16]
RP   STRUCTURE BY NMR.
RX   PubMed=8613986; DOI=10.1006/jmbi.1996.0241;
RA   Muskett F.W., Kelly G.P., Whitford D.;
RT   "The solution structure of bovine ferricytochrome b5 determined using
RT   heteronuclear NMR methods.";
RL   J. Mol. Biol. 258:172-189(1996).
RN   [17]
RP   STRUCTURE BY NMR OF 8-89, AND MUTAGENESIS.
RX   PubMed=11248680; DOI=10.1046/j.1432-1327.2001.02033.x;
RA   Wu Y., Wang Y., Qian C., Lu J., Li E., Wang W., Lu J., Xie Y., Wang J.,
RA   Zhu D., Huang Z., Tang W.;
RT   "Solution structure of cytochrome b5 mutant (E44/48/56A/D60A) and its
RT   interaction with cytochrome c.";
RL   Eur. J. Biochem. 268:1620-1630(2001).
RN   [18]
RP   STRUCTURE BY NMR OF 8-89, AND MUTAGENESIS.
RX   PubMed=11714912; DOI=10.1110/ps.12401;
RA   Qian C., Yao Y., Ye K., Wang J., Tang W., Wang Y., Wang W., Lu J., Xie Y.,
RA   Huang Z.;
RT   "Effects of charged amino-acid mutation on the solution structure of
RT   cytochrome b5 and binding between cytochrome b5 and cytochrome c.";
RL   Protein Sci. 10:2451-2459(2001).
RN   [19]
RP   STRUCTURE BY NMR OF 8-89, AND MUTAGENESIS.
RX   PubMed=12893266; DOI=10.1016/s0006-291x(03)01225-7;
RA   Cao C., Zhang Q., Xue L.-L., Ma J., Wang Y.-H., Wu H., Huang Z.-X.;
RT   "The solution structure of the oxidized bovine microsomal cytochrome b5
RT   mutant V61H.";
RL   Biochem. Biophys. Res. Commun. 307:600-609(2003).
CC   -!- FUNCTION: Cytochrome b5 is a membrane-bound hemoprotein functioning as
CC       an electron carrier for several membrane-bound oxygenases.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC       membrane protein; Cytoplasmic side. Microsome membrane; Single-pass
CC       membrane protein; Cytoplasmic side.
CC   -!- SIMILARITY: Belongs to the cytochrome b5 family. {ECO:0000305}.
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DR   EMBL; X13617; CAA31949.1; -; mRNA.
DR   EMBL; M63328; AAC14455.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; M63326; AAC14455.1; JOINED; Genomic_DNA.
DR   EMBL; M63327; AAC14455.1; JOINED; Genomic_DNA.
DR   EMBL; L22966; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC108113; AAI08114.1; -; mRNA.
DR   PIR; A47215; CBBO5.
DR   RefSeq; NP_776458.1; NM_174033.3.
DR   PDB; 1CYO; X-ray; 1.50 A; A=6-98.
DR   PDB; 1EHB; X-ray; 1.90 A; A=8-89.
DR   PDB; 1ES1; X-ray; 2.10 A; A=8-89.
DR   PDB; 1F03; NMR; -; A=8-89.
DR   PDB; 1F04; NMR; -; A=8-89.
DR   PDB; 1HKO; NMR; -; A=2-105.
DR   PDB; 1I5U; NMR; -; A=8-89.
DR   PDB; 1J0Q; NMR; -; A=8-89.
DR   PDB; 1LQX; X-ray; 1.80 A; A=8-89.
DR   PDB; 1LR6; X-ray; 1.90 A; A=8-89.
DR   PDB; 1M20; X-ray; 1.80 A; A=8-89.
DR   PDB; 1M2I; X-ray; 1.80 A; A=8-89.
DR   PDB; 1M2M; X-ray; 1.80 A; A=8-89.
DR   PDB; 1M59; X-ray; 1.90 A; A=8-89.
DR   PDB; 1NX7; NMR; -; A=8-89.
DR   PDB; 1SH4; NMR; -; A=8-89.
DR   PDB; 1U9M; X-ray; 2.00 A; A/B/C/D/E/F=8-89.
DR   PDB; 1U9U; X-ray; 1.86 A; A=8-89.
DR   PDB; 3OZZ; X-ray; 1.70 A; B=8-89.
DR   PDB; 4HIN; X-ray; 2.40 A; A/B/C/D=8-89.
DR   AlphaFoldDB; P00171; -.
DR   BMRB; P00171; -.
DR   MDposit; P00171; -.
DR   SMR; P00171; -.
DR   FunCoup; P00171; 2716.
DR   STRING; 9913.ENSBTAP00000067864; -.
DR   iPTMnet; P00171; -.
DR   PaxDb; 9913-ENSBTAP00000067864; -.
DR   PeptideAtlas; P00171; -.
DR   Ensembl; ENSBTAT00000072295.2; ENSBTAP00000067864.1; ENSBTAG00000012012.8.
DR   Ensembl; ENSBTAT00090025311; ENSBTAP00090013121; ENSBTAG00090012783.
DR   GeneID; 281110; -.
DR   KEGG; bta:281110; -.
DR   CTD; 1528; -.
DR   VEuPathDB; HostDB:ENSBTAG00000012012; -.
DR   VGNC; VGNC:50260; CYB5A.
DR   eggNOG; KOG0537; Eukaryota.
DR   GeneTree; ENSGT00940000156770; -.
DR   HOGENOM; CLU_102602_3_3_1; -.
DR   InParanoid; P00171; -.
DR   OMA; AEKSCWI; -.
DR   OrthoDB; 260519at2759; -.
DR   Reactome; R-BTA-196836; Vitamin C (ascorbate) metabolism.
DR   Reactome; R-BTA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR   SABIO-RK; P00171; -.
DR   EvolutionaryTrace; P00171; -.
DR   Proteomes; UP000009136; Chromosome 24.
DR   Bgee; ENSBTAG00000012012; Expressed in liver and 103 other cell types or tissues.
DR   ExpressionAtlas; P00171; baseline.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR   GO; GO:0020037; F:heme binding; IBA:GO_Central.
DR   FunFam; 3.10.120.10:FF:000002; Cytochrome b5 type B; 1.
DR   Gene3D; 3.10.120.10; Cytochrome b5-like heme/steroid binding domain; 1.
DR   InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR   InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR   InterPro; IPR018506; Cyt_B5_heme-BS.
DR   InterPro; IPR050668; Cytochrome_b5.
DR   PANTHER; PTHR19359; CYTOCHROME B5; 1.
DR   PANTHER; PTHR19359:SF154; CYTOCHROME B5; 1.
DR   Pfam; PF00173; Cyt-b5; 1.
DR   PRINTS; PR00363; CYTOCHROMEB5.
DR   SMART; SM01117; Cyt-b5; 1.
DR   SUPFAM; SSF55856; Cytochrome b5-like heme/steroid binding domain; 1.
DR   PROSITE; PS00191; CYTOCHROME_B5_1; 1.
DR   PROSITE; PS50255; CYTOCHROME_B5_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Direct protein sequencing; Electron transport;
KW   Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:2752049,
FT                   ECO:0000269|PubMed:4030743, ECO:0000269|PubMed:4810060"
FT   CHAIN           2..134
FT                   /note="Cytochrome b5"
FT                   /id="PRO_0000166008"
FT   TRANSMEM        109..131
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          9..85
FT                   /note="Cytochrome b5 heme-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT   BINDING         44
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00279,
FT                   ECO:0000269|PubMed:15299727"
FT   BINDING         68
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00279,
FT                   ECO:0000269|PubMed:15299727"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000269|PubMed:2752049,
FT                   ECO:0000269|PubMed:4030743"
FT   MOD_RES         7
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P56395"
FT   MOD_RES         10
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P56395"
FT   MOD_RES         19
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P56395"
FT   CONFLICT        2..5
FT                   /note="AEES -> ZSZZBA (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        16..18
FT                   /note="EIQ -> QIE (in Ref. 7; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        18
FT                   /note="Q -> E (in Ref. 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        62
FT                   /note="N -> D (in Ref. 7; AA sequence and 8; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        134
FT                   /note="N -> D (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          9..12
FT                   /evidence="ECO:0007829|PDB:1U9M"
FT   HELIX           14..17
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   STRAND          21..24
FT                   /evidence="ECO:0007829|PDB:1M20"
FT   STRAND          25..30
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   STRAND          33..36
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   TURN            38..43
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   HELIX           49..54
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   STRAND          56..58
FT                   /evidence="ECO:0007829|PDB:1HKO"
FT   HELIX           60..65
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   HELIX           70..76
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   TURN            77..79
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   STRAND          80..84
FT                   /evidence="ECO:0007829|PDB:1CYO"
FT   HELIX           86..91
FT                   /evidence="ECO:0007829|PDB:1CYO"
SQ   SEQUENCE   134 AA;  15329 MW;  7B7B605158D97525 CRC64;
     MAEESSKAVK YYTLEEIQKH NNSKSTWLIL HYKVYDLTKF LEEHPGGEEV LREQAGGDAT
     ENFEDVGHST DARELSKTFI IGELHPDDRS KITKPSESII TTIDSNPSWW TNWLIPAISA
     LFVALIYHLY TSEN
//