ENOX1_HUMAN
ID ENOX1_HUMAN Reviewed; 643 AA.
AC Q8TC92; A4GU15; A6NMH9; B7Z5K1; Q2TU81; Q5VT11; Q9NWE0;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Ecto-NOX disulfide-thiol exchanger 1;
DE AltName: Full=Candidate growth-related and time keeping constitutive hydroquinone [NADH] oxidase;
DE Short=cCNOX;
DE AltName: Full=Cell proliferation-inducing gene 38 protein;
DE AltName: Full=Constitutive Ecto-NOX;
DE Short=cNOX;
DE Includes:
DE RecName: Full=Hydroquinone [NADH] oxidase;
DE EC=1.-.-.-;
DE Includes:
DE RecName: Full=Protein disulfide-thiol oxidoreductase;
DE EC=1.-.-.-;
GN Name=ENOX1; ORFNames=PIG38;
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 [MRNA] (ISOFORM 1), FUNCTION, AND VARIANT ASP-16.
RC TISSUE=Cervix carcinoma;
RX PubMed=19055324; DOI=10.1021/bi801073p;
RA Jiang Z., Gorenstein N.M., Morre D.M., Morre D.J.;
RT "Molecular cloning and characterization of a candidate human growth-related
RT and time-keeping constitutive cell surface hydroquinone (NADH) oxidase.";
RL Biochemistry 47:14028-14038(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human cell proliferation inducing gene.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Embryo;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=11360993; DOI=10.1006/abbi.2000.2180;
RA Sedlak D., Moore D.M., Moore D.J.;
RT "A drug-unresponsive and protease-resistant CNOX protein from human sera.";
RL Arch. Biochem. Biophys. 386:106-116(2001).
RN [8]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=12565167; DOI=10.1016/s0304-3835(02)00616-x;
RA Wang S., Morre D.M., Morre D.J.;
RT "Sera from cancer patients contain two oscillating ECTO-NOX activities with
RT different period lengths.";
RL Cancer Lett. 190:135-141(2003).
RN [9]
RP FUNCTION, AND COFACTOR.
RX PubMed=17027975; DOI=10.1016/j.jinorgbio.2006.08.007;
RA Jiang Z., Morre D.M., Morre D.J.;
RT "A role for copper in biological time-keeping.";
RL J. Inorg. Biochem. 100:2140-2149(2006).
CC -!- FUNCTION: Probably acts as a terminal oxidase of plasma electron
CC transport from cytosolic NAD(P)H via hydroquinones to acceptors at the
CC cell surface. Hydroquinone oxidase activity alternates with a protein
CC disulfide-thiol interchange/oxidoreductase activity which may control
CC physical membrane displacements associated with vesicle budding or cell
CC enlargement. The activities oscillate with a period length of 24
CC minutes and play a role in control of the ultradian cellular biological
CC clock. {ECO:0000269|PubMed:11360993, ECO:0000269|PubMed:12565167,
CC ECO:0000269|PubMed:17027975, ECO:0000269|PubMed:19055324}.
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000269|PubMed:17027975};
CC -!- ACTIVITY REGULATION: Not inhibited by the antitumor sulfonylurea
CC LY181984, the vabilloid capsaicin, and retinoids.
CC {ECO:0000269|PubMed:11360993, ECO:0000269|PubMed:12565167}.
CC -!- INTERACTION:
CC Q8TC92; Q16206-2: ENOX2; NbExp=3; IntAct=EBI-713221, EBI-10179508;
CC Q8TC92; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-713221, EBI-739467;
CC Q8TC92; Q8TBB1: LNX1; NbExp=4; IntAct=EBI-713221, EBI-739832;
CC Q8TC92; O00560: SDCBP; NbExp=3; IntAct=EBI-713221, EBI-727004;
CC Q8TC92; Q96BQ3: TRIM43; NbExp=6; IntAct=EBI-713221, EBI-2129899;
CC Q8TC92; Q96E35: ZMYND19; NbExp=6; IntAct=EBI-713221, EBI-746595;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11360993}.
CC Secreted, extracellular space {ECO:0000269|PubMed:11360993}.
CC Note=Extracellular and plasma membrane-associated.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TC92-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TC92-2; Sequence=VSP_056985, VSP_056986, VSP_056987;
CC -!- TISSUE SPECIFICITY: Expressed in lymphocyte cells, breast and breast
CC cancer (at protein level). Found in the sera of cancer patients with a
CC wide variety of cancers including breast, prostate, lung and ovarian
CC cancers, leukemias, and lymphomas. Found also in the serum of healthy
CC volunteers or patients with disorders other than cancer. Probably shed
CC into serum by cancer cells.
CC -!- SIMILARITY: Belongs to the ENOX family. {ECO:0000305}.
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DR EMBL; EF432052; ABO28524.1; -; mRNA.
DR EMBL; AY513282; AAT08035.1; -; mRNA.
DR EMBL; AK000956; BAA91442.1; -; mRNA.
DR EMBL; AK299053; BAH12937.1; -; mRNA.
DR EMBL; AL136959; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161714; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162713; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445703; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138823; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL607148; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL627430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08693.1; -; Genomic_DNA.
DR EMBL; BC024178; AAH24178.1; -; mRNA.
DR CCDS; CCDS9389.1; -. [Q8TC92-1]
DR RefSeq; NP_001121087.1; NM_001127615.2. [Q8TC92-1]
DR RefSeq; NP_001229792.1; NM_001242863.2. [Q8TC92-1]
DR RefSeq; NP_001334893.1; NM_001347964.1. [Q8TC92-1]
DR RefSeq; NP_001334894.1; NM_001347965.1. [Q8TC92-1]
DR RefSeq; NP_001334895.1; NM_001347966.1. [Q8TC92-1]
DR RefSeq; NP_001334896.1; NM_001347967.1. [Q8TC92-1]
DR RefSeq; NP_001334897.1; NM_001347968.1. [Q8TC92-1]
DR RefSeq; NP_001334898.1; NM_001347969.1. [Q8TC92-1]
DR RefSeq; NP_060463.2; NM_017993.4. [Q8TC92-1]
DR RefSeq; XP_011533428.1; XM_011535126.2. [Q8TC92-1]
DR RefSeq; XP_011533429.1; XM_011535127.2. [Q8TC92-1]
DR RefSeq; XP_016876126.1; XM_017020637.1. [Q8TC92-1]
DR RefSeq; XP_016876127.1; XM_017020638.1.
DR AlphaFoldDB; Q8TC92; -.
DR BioGRID; 120385; 20.
DR IntAct; Q8TC92; 15.
DR STRING; 9606.ENSP00000261488; -.
DR iPTMnet; Q8TC92; -.
DR PhosphoSitePlus; Q8TC92; -.
DR BioMuta; ENOX1; -.
DR DMDM; 74760449; -.
DR MassIVE; Q8TC92; -.
DR MaxQB; Q8TC92; -.
DR PaxDb; Q8TC92; -.
DR PeptideAtlas; Q8TC92; -.
DR PRIDE; Q8TC92; -.
DR ProteomicsDB; 6698; -.
DR ProteomicsDB; 74102; -. [Q8TC92-1]
DR Antibodypedia; 23523; 94 antibodies from 22 providers.
DR DNASU; 55068; -.
DR Ensembl; ENST00000261488.10; ENSP00000261488.6; ENSG00000120658.14. [Q8TC92-1]
DR Ensembl; ENST00000690772.1; ENSP00000509229.1; ENSG00000120658.14. [Q8TC92-1]
DR GeneID; 55068; -.
DR KEGG; hsa:55068; -.
DR MANE-Select; ENST00000690772.1; ENSP00000509229.1; NM_001347969.2; NP_001334898.1.
DR UCSC; uc001uzc.5; human. [Q8TC92-1]
DR CTD; 55068; -.
DR DisGeNET; 55068; -.
DR GeneCards; ENOX1; -.
DR HGNC; HGNC:25474; ENOX1.
DR HPA; ENSG00000120658; Tissue enhanced (brain).
DR MIM; 610914; gene.
DR neXtProt; NX_Q8TC92; -.
DR OpenTargets; ENSG00000120658; -.
DR PharmGKB; PA162385069; -.
DR VEuPathDB; HostDB:ENSG00000120658; -.
DR eggNOG; ENOG502QQ8G; Eukaryota.
DR GeneTree; ENSGT00390000006788; -.
DR HOGENOM; CLU_019282_1_1_1; -.
DR InParanoid; Q8TC92; -.
DR OMA; MSDDETC; -.
DR OrthoDB; 357901at2759; -.
DR PhylomeDB; Q8TC92; -.
DR TreeFam; TF323802; -.
DR PathwayCommons; Q8TC92; -.
DR SignaLink; Q8TC92; -.
DR SIGNOR; Q8TC92; -.
DR BioGRID-ORCS; 55068; 9 hits in 1069 CRISPR screens.
DR ChiTaRS; ENOX1; human.
DR GenomeRNAi; 55068; -.
DR Pharos; Q8TC92; Tbio.
DR PRO; PR:Q8TC92; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q8TC92; protein.
DR Bgee; ENSG00000120658; Expressed in sperm and 140 other tissues.
DR ExpressionAtlas; Q8TC92; baseline and differential.
DR Genevisible; Q8TC92; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0003954; F:NADH dehydrogenase activity; IDA:FlyBase.
DR GO; GO:0003756; F:protein disulfide isomerase activity; IDA:FlyBase.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IBA:GO_Central.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
DR GO; GO:0007624; P:ultradian rhythm; IEA:InterPro.
DR CDD; cd12228; RRM_ENOX; 1.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR038876; ENOX.
DR InterPro; IPR034140; ENOX_RRM.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR PANTHER; PTHR16001; PTHR16001; 1.
DR Pfam; PF00076; RRM_1; 1.
DR SMART; SM00360; RRM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50102; RRM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Biological rhythms; Cell membrane; Coiled coil;
KW Copper; Electron transport; Membrane; NAD; Oxidoreductase;
KW Reference proteome; Secreted; Transport.
FT CHAIN 1..643
FT /note="Ecto-NOX disulfide-thiol exchanger 1"
FT /id="PRO_0000295900"
FT DOMAIN 142..221
FT /note="RRM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT COILED 307..342
FT /evidence="ECO:0000255"
FT COILED 425..570
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..187
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056985"
FT VAR_SEQ 421..422
FT /note="AL -> GA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056986"
FT VAR_SEQ 423..643
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056987"
FT VARIANT 16
FT /note="E -> D (in dbSNP:rs7338624)"
FT /evidence="ECO:0000269|PubMed:19055324"
FT /id="VAR_052205"
FT CONFLICT 62
FT /note="L -> S (in Ref. 2; AAT08035)"
FT /evidence="ECO:0000305"
FT CONFLICT 279
FT /note="F -> S (in Ref. 2; AAT08035 and 3; BAA91442)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 643 AA; 73348 MW; 501DC6905F326610 CRC64;
MVDAGGVENI TQLPQELPQM MAAAADGLGS IAIDTTQLNM SVTDPTAWAT AMNNLGMVPV
GLPGQQLVSD SICVPGFDPS LNMMTGITPI NPMIPGLGLV PPPPPTEVAV VKEIIHCKSC
TLFPQNPNLP PPSTRERPPG CKTVFVGGLP ENATEEIIQE VFEQCGDITA IRKSKKNFCH
IRFAEEFMVD KAIYLSGYRM RLGSSTDKKD SGRLHVDFAQ ARDDFYEWEC KQRMRAREER
HRRKLEEDRL RPPSPPAIMH YSEHEAALLA EKLKDDSKFS EAITVLLSWI ERGEVNRRSA
NQFYSMVQSA NSHVRRLMNE KATHEQEMEE AKENFKNALT GILTQFEQIV AVFNASTRQK
AWDHFSKAQR KNIDIWRKHS EELRNAQSEQ LMGIRREEEM EMSDDENCDS PTKKMRVDES
ALAAQAYALK EENDSLRWQL DAYRNEVELL KQEKEQLFRT EENLTKDQQL QFLQQTMQGM
QQQLLTIQEE LNNKKSELEQ AKEEQSHTQA LLKVLQEQLK GTKELVETNG HSHEDSNEIN
VLTVALVNQD RENNIEKRSQ GLKSEKEALL IGIISTFLHV HPFGANIEYL WSYMQQLDSK
ISANEIEMLL MRLPRMFKQE FTGVGATLEK RWKLCAFEGI KTT
