NB5R5_HUMAN
ID NB5R5_HUMAN Reviewed; 315 AA.
AC Q6IPT4; B7ZBS4; Q8NF25;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=NADH-cytochrome b5 reductase-like;
DE EC=1.6.2.2;
GN Name=CYB5RL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT LYS-47.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: NADH-cytochrome b5 reductases are involved in desaturation
CC and elongation of fatty acids, cholesterol biosynthesis, drug
CC metabolism, and, in erythrocyte, methemoglobin reduction.
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(III)-[cytochrome b5] + NADH = 2 Fe(II)-[cytochrome b5] +
CC H(+) + NAD(+); Xref=Rhea:RHEA:46680, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.6.2.2;
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6IPT4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6IPT4-3; Sequence=VSP_033845;
CC Name=3;
CC IsoId=Q6IPT4-4; Sequence=VSP_040404;
CC -!- SIMILARITY: Belongs to the flavoprotein pyridine nucleotide cytochrome
CC reductase family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC03437.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CD515193; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK090456; BAC03437.1; ALT_INIT; mRNA.
DR EMBL; AL357673; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CD515193; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS44151.1; -. [Q6IPT4-1]
DR RefSeq; NP_001026842.2; NM_001031672.2. [Q6IPT4-1]
DR AlphaFoldDB; Q6IPT4; -.
DR SMR; Q6IPT4; -.
DR STRING; 9606.ENSP00000434343; -.
DR iPTMnet; Q6IPT4; -.
DR PhosphoSitePlus; Q6IPT4; -.
DR BioMuta; CYB5RL; -.
DR DMDM; 317373410; -.
DR MassIVE; Q6IPT4; -.
DR PaxDb; Q6IPT4; -.
DR PeptideAtlas; Q6IPT4; -.
DR PRIDE; Q6IPT4; -.
DR ProteomicsDB; 66459; -. [Q6IPT4-1]
DR ProteomicsDB; 66461; -. [Q6IPT4-4]
DR Antibodypedia; 46895; 30 antibodies from 11 providers.
DR DNASU; 606495; -.
DR Ensembl; ENST00000287899.13; ENSP00000287899.8; ENSG00000215883.11. [Q6IPT4-4]
DR Ensembl; ENST00000534324.6; ENSP00000434343.1; ENSG00000215883.11. [Q6IPT4-1]
DR GeneID; 606495; -.
DR KEGG; hsa:606495; -.
DR MANE-Select; ENST00000534324.6; ENSP00000434343.1; NM_001031672.4; NP_001026842.2.
DR UCSC; uc057gtt.1; human. [Q6IPT4-1]
DR CTD; 606495; -.
DR GeneCards; CYB5RL; -.
DR HGNC; HGNC:32220; CYB5RL.
DR HPA; ENSG00000215883; Low tissue specificity.
DR neXtProt; NX_Q6IPT4; -.
DR OpenTargets; ENSG00000215883; -.
DR PharmGKB; PA164718527; -.
DR VEuPathDB; HostDB:ENSG00000215883; -.
DR eggNOG; KOG0534; Eukaryota.
DR GeneTree; ENSGT00920000149170; -.
DR HOGENOM; CLU_003827_9_3_1; -.
DR InParanoid; Q6IPT4; -.
DR OMA; DIPPGHH; -.
DR OrthoDB; 1311668at2759; -.
DR PhylomeDB; Q6IPT4; -.
DR TreeFam; TF336549; -.
DR PathwayCommons; Q6IPT4; -.
DR Reactome; R-HSA-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR BioGRID-ORCS; 606495; 17 hits in 1078 CRISPR screens.
DR ChiTaRS; CYB5RL; human.
DR GenomeRNAi; 606495; -.
DR Pharos; Q6IPT4; Tdark.
DR PRO; PR:Q6IPT4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6IPT4; protein.
DR Bgee; ENSG00000215883; Expressed in gluteal muscle and 187 other tissues.
DR ExpressionAtlas; Q6IPT4; baseline and differential.
DR Genevisible; Q6IPT4; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004128; F:cytochrome-b5 reductase activity, acting on NAD(P)H; IBA:GO_Central.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR Gene3D; 3.40.50.80; -; 1.
DR InterPro; IPR001834; CBR-like.
DR InterPro; IPR008333; Cbr1-like_FAD-bd_dom.
DR InterPro; IPR017927; FAD-bd_FR_type.
DR InterPro; IPR039261; FNR_nucleotide-bd.
DR InterPro; IPR019180; Oxidoreductase-like_N.
DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd.
DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl.
DR PANTHER; PTHR19370; PTHR19370; 1.
DR Pfam; PF00970; FAD_binding_6; 1.
DR Pfam; PF00175; NAD_binding_1; 1.
DR Pfam; PF09791; Oxidored-like; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; FAD; Flavoprotein; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..315
FT /note="NADH-cytochrome b5 reductase-like"
FT /id="PRO_0000337041"
FT DOMAIN 19..55
FT /note="Oxidoreductase-like"
FT DOMAIN 75..177
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT BINDING 157..172
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 182..214
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..148
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_033845"
FT VAR_SEQ 180..247
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040404"
FT VARIANT 47
FT /note="R -> K (in dbSNP:rs946448)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_043577"
FT CONFLICT 267
FT /note="H -> P (in Ref. 3; CD515193)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="C -> W (in Ref. 3; CD515193)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 315 AA; 35892 MW; 0C1788B5980AA86E CRC64;
MMAEREEDDD TEEAWMQLRP TEPLPSQCCG SGCSPCVFDL YHRDLARWEA AQASKDRSLL
RGPESQSCPS KLNPETFVAF CIIAMDRLTK DTYRVRFALP GNSQLGLRPG QHLILRGIVD
DLEIQRAYTP ISPANAEGYF EVLIKCYQMG LMSRYVESWR VGDTAFWRGP FGDFFYKPNQ
YGELLLLAAG TGLAPMVPIL QSITDNENDE TFVTLVGCFK TFESIYLKTF LQEQARFWNV
RTFFVLSQES SSEQLPWSYQ EKTHFGHLGQ DLIKELVSCC RRKPFALVCG SAEFTKDIAR
CLLCAGLTED SYFLF
