RNLS_HUMAN
ID RNLS_HUMAN Reviewed; 342 AA.
AC Q5VYX0; Q9BS33; Q9NUP8;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Renalase {ECO:0000303|PubMed:15841207};
DE EC=1.6.3.5 {ECO:0000269|PubMed:23964689, ECO:0000269|PubMed:25531177};
DE AltName: Full=Monoamine oxidase-C;
DE Short=MAO-C;
DE Flags: Precursor;
GN Name=RNLS; Synonyms=C10orf59;
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=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-37.
RC TISSUE=Kidney;
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).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15841207; DOI=10.1172/jci200524066;
RA Xu J., Li G., Wang P., Velazquez H., Yao X., Li Y., Wu Y., Peixoto A.,
RA Crowley S., Desir G.V.;
RT "Renalase is a novel, soluble monoamine oxidase that regulates cardiac
RT function and blood pressure.";
RL J. Clin. Invest. 115:1275-1280(2005).
RN [5]
RP FUNCTION.
RX PubMed=17385068; DOI=10.1007/s00702-007-0672-1;
RA Boomsma F., Tipton K.F.;
RT "Renalase, a catecholamine-metabolising enzyme?";
RL J. Neural Transm. 114:775-776(2007).
RN [6]
RP CATALYTIC ACTIVITY (ISOFORM 1).
RX PubMed=23964689; DOI=10.1021/ja407384h;
RA Beaupre B.A., Carmichael B.R., Hoag M.R., Shah D.D., Moran G.R.;
RT "Renalase is an alpha-NAD(P)H oxidase/anomerase.";
RL J. Am. Chem. Soc. 135:13980-13987(2013).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=25531177; DOI=10.1021/bi5013436;
RA Beaupre B.A., Hoag M.R., Roman J., Foersterling F.H., Moran G.R.;
RT "Metabolic function for human renalase: oxidation of isomeric forms of
RT beta-NAD(P)H that are inhibitory to primary metabolism.";
RL Biochemistry 54:795-806(2015).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), COFACTOR, AND FAD-BINDING SITES.
RX PubMed=21699903; DOI=10.1016/j.jmb.2011.06.010;
RA Milani M., Ciriello F., Baroni S., Pandini V., Canevari G., Bolognesi M.,
RA Aliverti A.;
RT "FAD-binding site and NADP reactivity in human renalase: a new enzyme
RT involved in blood pressure regulation.";
RL J. Mol. Biol. 411:463-473(2011).
CC -!- FUNCTION: Catalyzes the oxidation of the less abundant 1,2-dihydro-
CC beta-NAD(P) and 1,6-dihydro-beta-NAD(P) to form beta-NAD(P)(+). The
CC enzyme hormone is secreted by the kidney, and circulates in blood and
CC modulates cardiac function and systemic blood pressure. Lowers blood
CC pressure in vivo by decreasing cardiac contractility and heart rate and
CC preventing a compensatory increase in peripheral vascular tone,
CC suggesting a causal link to the increased plasma catecholamine and
CC heightened cardiovascular risk. High concentrations of catecholamines
CC activate plasma renalase and promotes its secretion and synthesis.
CC {ECO:0000269|PubMed:15841207, ECO:0000269|PubMed:17385068,
CC ECO:0000269|PubMed:25531177}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihydro-beta-NAD + H(+) + O2 = H2O2 + NAD(+);
CC Xref=Rhea:RHEA:40395, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:57540, ChEBI:CHEBI:88138; EC=1.6.3.5;
CC Evidence={ECO:0000269|PubMed:23964689, ECO:0000269|PubMed:25531177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihydro-beta-NADP + H(+) + O2 = H2O2 + NADP(+);
CC Xref=Rhea:RHEA:40399, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:58349, ChEBI:CHEBI:88137; EC=1.6.3.5;
CC Evidence={ECO:0000269|PubMed:23964689, ECO:0000269|PubMed:25531177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,6-dihydro-beta-NADP + H(+) + O2 = H2O2 + NADP(+);
CC Xref=Rhea:RHEA:48000, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:58349, ChEBI:CHEBI:88139; EC=1.6.3.5;
CC Evidence={ECO:0000269|PubMed:23964689, ECO:0000269|PubMed:25531177};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,6-dihydro-beta-NAD + H(+) + O2 = H2O2 + NAD(+);
CC Xref=Rhea:RHEA:47996, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:57540, ChEBI:CHEBI:88140; EC=1.6.3.5;
CC Evidence={ECO:0000269|PubMed:23964689, ECO:0000269|PubMed:25531177};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:21699903};
CC -!- INTERACTION:
CC Q5VYX0; P23634: ATP2B4; NbExp=3; IntAct=EBI-3386081, EBI-1174388;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15841207}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5VYX0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5VYX0-2; Sequence=VSP_015211, VSP_015212;
CC -!- TISSUE SPECIFICITY: Secreted into the blood by the kidney. Highly
CC expressed in the kidney, expressed at lower level in heart, skeletal
CC muscle and small intestine. Its plasma concentration is markedly
CC reduced in patients with end-stage renal disease, as compared with
CC healthy subjects. {ECO:0000269|PubMed:15841207}.
CC -!- SIMILARITY: Belongs to the renalase family. {ECO:0000305}.
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DR EMBL; AK002080; BAA92073.1; -; mRNA.
DR EMBL; AL353149; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139406; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC005364; AAH05364.1; -; mRNA.
DR CCDS; CCDS31239.1; -. [Q5VYX0-1]
DR CCDS; CCDS7388.1; -. [Q5VYX0-2]
DR RefSeq; NP_001026879.2; NM_001031709.2. [Q5VYX0-1]
DR RefSeq; NP_060833.1; NM_018363.3. [Q5VYX0-2]
DR RefSeq; XP_011538226.1; XM_011539924.2. [Q5VYX0-2]
DR RefSeq; XP_016871869.1; XM_017016380.1. [Q5VYX0-2]
DR PDB; 3QJ4; X-ray; 2.50 A; A/B=1-342.
DR PDBsum; 3QJ4; -.
DR AlphaFoldDB; Q5VYX0; -.
DR SMR; Q5VYX0; -.
DR BioGRID; 120609; 2.
DR IntAct; Q5VYX0; 13.
DR STRING; 9606.ENSP00000332530; -.
DR iPTMnet; Q5VYX0; -.
DR PhosphoSitePlus; Q5VYX0; -.
DR BioMuta; RNLS; -.
DR DMDM; 73914006; -.
DR MassIVE; Q5VYX0; -.
DR PaxDb; Q5VYX0; -.
DR PeptideAtlas; Q5VYX0; -.
DR PRIDE; Q5VYX0; -.
DR ProteomicsDB; 65655; -. [Q5VYX0-1]
DR ProteomicsDB; 65656; -. [Q5VYX0-2]
DR Antibodypedia; 30183; 293 antibodies from 32 providers.
DR DNASU; 55328; -.
DR Ensembl; ENST00000331772.9; ENSP00000332530.4; ENSG00000184719.12. [Q5VYX0-1]
DR Ensembl; ENST00000371947.7; ENSP00000361015.3; ENSG00000184719.12. [Q5VYX0-2]
DR GeneID; 55328; -.
DR KEGG; hsa:55328; -.
DR MANE-Select; ENST00000331772.9; ENSP00000332530.4; NM_001031709.3; NP_001026879.2.
DR UCSC; uc001kfd.3; human. [Q5VYX0-1]
DR CTD; 55328; -.
DR DisGeNET; 55328; -.
DR GeneCards; RNLS; -.
DR HGNC; HGNC:25641; RNLS.
DR HPA; ENSG00000184719; Low tissue specificity.
DR MIM; 609360; gene.
DR neXtProt; NX_Q5VYX0; -.
DR OpenTargets; ENSG00000184719; -.
DR PharmGKB; PA165549084; -.
DR VEuPathDB; HostDB:ENSG00000184719; -.
DR eggNOG; ENOG502QUZR; Eukaryota.
DR GeneTree; ENSGT00390000016052; -.
DR HOGENOM; CLU_036034_1_0_1; -.
DR InParanoid; Q5VYX0; -.
DR OMA; AFSHSNF; -.
DR OrthoDB; 915997at2759; -.
DR PhylomeDB; Q5VYX0; -.
DR TreeFam; TF332799; -.
DR BioCyc; MetaCyc:G66-32717-MON; -.
DR BRENDA; 1.6.3.5; 2681.
DR PathwayCommons; Q5VYX0; -.
DR Reactome; R-HSA-197264; Nicotinamide salvaging.
DR SignaLink; Q5VYX0; -.
DR BioGRID-ORCS; 55328; 10 hits in 1070 CRISPR screens.
DR ChiTaRS; RNLS; human.
DR GeneWiki; Renalase; -.
DR GenomeRNAi; 55328; -.
DR Pharos; Q5VYX0; Tbio.
DR PRO; PR:Q5VYX0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q5VYX0; protein.
DR Bgee; ENSG00000184719; Expressed in buccal mucosa cell and 153 other tissues.
DR ExpressionAtlas; Q5VYX0; baseline and differential.
DR Genevisible; Q5VYX0; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0051379; F:epinephrine binding; IDA:UniProtKB.
DR GO; GO:0097621; F:monoamine oxidase activity; IMP:UniProtKB.
DR GO; GO:0070404; F:NADH binding; IDA:UniProtKB.
DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IDA:UniProtKB.
DR GO; GO:0045776; P:negative regulation of blood pressure; IDA:UniProtKB.
DR GO; GO:0010459; P:negative regulation of heart rate; IDA:UniProtKB.
DR GO; GO:0071871; P:response to epinephrine; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:1902074; P:response to salt; IEA:Ensembl.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002937; Amino_oxidase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR040174; RNLS.
DR PANTHER; PTHR23357; PTHR23357; 1.
DR Pfam; PF01593; Amino_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; FAD; Flavoprotein; NAD; NADP;
KW Oxidoreductase; Reference proteome; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..342
FT /note="Renalase"
FT /id="PRO_0000019588"
FT BINDING 12
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT BINDING 42
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT BINDING 61..62
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT VAR_SEQ 294..315
FT /note="TNAAANCPGQMTLHHKPFLACG -> PSAGVILGCAKSPWMMAIGFPI (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015211"
FT VAR_SEQ 316..342
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015212"
FT VARIANT 37
FT /note="E -> D (in dbSNP:rs2296545)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_023310"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 11..21
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 74..82
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 113..122
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 125..129
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 139..149
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 173..176
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 179..186
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 211..214
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 219..226
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 248..253
FT /evidence="ECO:0007829|PDB:3QJ4"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 259..273
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 292..295
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:3QJ4"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:3QJ4"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:3QJ4"
FT HELIX 324..338
FT /evidence="ECO:0007829|PDB:3QJ4"
SQ SEQUENCE 342 AA; 37847 MW; 952827FF7926AF48 CRC64;
MAQVLIVGAG MTGSLCAALL RRQTSGPLYL AVWDKAEDSG GRMTTACSPH NPQCTADLGA
QYITCTPHYA KKHQRFYDEL LAYGVLRPLS SPIEGMVMKE GDCNFVAPQG ISSIIKHYLK
ESGAEVYFRH RVTQINLRDD KWEVSKQTGS PEQFDLIVLT MPVPEILQLQ GDITTLISEC
QRQQLEAVSY SSRYALGLFY EAGTKIDVPW AGQYITSNPC IRFVSIDNKK RNIESSEIGP
SLVIHTTVPF GVTYLEHSIE DVQELVFQQL ENILPGLPQP IATKCQKWRH SQVTNAAANC
PGQMTLHHKP FLACGGDGFT QSNFDGCITS ALCVLEALKN YI
