FXRD2_HUMAN
ID FXRD2_HUMAN Reviewed; 684 AA.
AC Q8IWF2; B2RDI4; Q8N378; Q96BD1; Q9H5L5; Q9H6M8;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=FAD-dependent oxidoreductase domain-containing protein 2;
DE AltName: Full=Endoplasmic reticulum flavoprotein associated with degradation;
DE Flags: Precursor;
GN Name=FOXRED2 {ECO:0000312|HGNC:HGNC:26264};
GN Synonyms=ERFAD {ECO:0000303|PubMed:21359175};
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 1), AND VARIANTS LEU-179
RP AND SER-308.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-308.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LEU-179
RP AND SER-308.
RC TISSUE=Brain, Colon, and Eye;
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 [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-143.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [7]
RP FUNCTION, FAD-BINDING, GLYCOSYLATION, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH DNAJC10; OS9 AND SEL1L.
RX PubMed=19706418; DOI=10.1073/pnas.0900742106;
RA Riemer J., Appenzeller-Herzog C., Johansson L., Bodenmiller B.,
RA Hartmann-Petersen R., Ellgaard L.;
RT "A luminal flavoprotein in endoplasmic reticulum-associated degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:14831-14836(2009).
RN [8]
RP INTERACTION WITH TXNDC16.
RX PubMed=21359175; DOI=10.1371/journal.pone.0017037;
RA Riemer J., Hansen H.G., Appenzeller-Herzog C., Johansson L., Ellgaard L.;
RT "Identification of the PDI-family member ERp90 as an interaction partner of
RT ERFAD.";
RL PLoS ONE 6:E17037-E17037(2011).
CC -!- FUNCTION: Probable flavoprotein which may function in endoplasmic
CC reticulum associated degradation (ERAD). May bind non-native proteins
CC in the endoplasmic reticulum and target them to the ubiquitination
CC machinery for subsequent degradation. {ECO:0000269|PubMed:19706418}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:19706418};
CC -!- SUBUNIT: Interacts with SEL1L. May interact with OS9 and DNAJC10.
CC Interacts with TXNDC16 (PubMed:21359175). {ECO:0000269|PubMed:19706418,
CC ECO:0000269|PubMed:21359175}.
CC -!- INTERACTION:
CC Q8IWF2; Q8IXB1: DNAJC10; NbExp=2; IntAct=EBI-10763361, EBI-2949763;
CC Q8IWF2; Q9UBV2: SEL1L; NbExp=6; IntAct=EBI-10763361, EBI-358766;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-
CC ProRule:PRU10138, ECO:0000269|PubMed:19706418}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8IWF2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IWF2-2; Sequence=VSP_033997;
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19159218,
CC ECO:0000269|PubMed:19706418}.
CC -!- SIMILARITY: Belongs to the FOXRED2 family. {ECO:0000305}.
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DR EMBL; CR456444; CAG30330.1; -; mRNA.
DR EMBL; AK025714; BAB15227.1; -; mRNA.
DR EMBL; AK026975; BAB15610.1; -; mRNA.
DR EMBL; AK315555; BAG37931.1; -; mRNA.
DR EMBL; AL022313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471095; EAW60106.1; -; Genomic_DNA.
DR EMBL; BC015726; AAH15726.1; -; mRNA.
DR EMBL; BC027716; AAH27716.1; -; mRNA.
DR EMBL; BC040351; AAH40351.1; -; mRNA.
DR CCDS; CCDS13929.1; -. [Q8IWF2-1]
DR RefSeq; NP_001095841.1; NM_001102371.1. [Q8IWF2-1]
DR RefSeq; NP_079231.4; NM_024955.5. [Q8IWF2-1]
DR AlphaFoldDB; Q8IWF2; -.
DR BioGRID; 123074; 153.
DR DIP; DIP-48946N; -.
DR IntAct; Q8IWF2; 37.
DR MINT; Q8IWF2; -.
DR STRING; 9606.ENSP00000380401; -.
DR GlyGen; Q8IWF2; 1 site.
DR iPTMnet; Q8IWF2; -.
DR PhosphoSitePlus; Q8IWF2; -.
DR BioMuta; FOXRED2; -.
DR DMDM; 74759632; -.
DR EPD; Q8IWF2; -.
DR jPOST; Q8IWF2; -.
DR MassIVE; Q8IWF2; -.
DR MaxQB; Q8IWF2; -.
DR PaxDb; Q8IWF2; -.
DR PeptideAtlas; Q8IWF2; -.
DR PRIDE; Q8IWF2; -.
DR ProteomicsDB; 70851; -. [Q8IWF2-1]
DR ProteomicsDB; 70852; -. [Q8IWF2-2]
DR Antibodypedia; 25683; 98 antibodies from 22 providers.
DR DNASU; 80020; -.
DR Ensembl; ENST00000216187.10; ENSP00000216187.6; ENSG00000100350.16. [Q8IWF2-1]
DR Ensembl; ENST00000397223.4; ENSP00000380400.4; ENSG00000100350.16. [Q8IWF2-1]
DR Ensembl; ENST00000397224.9; ENSP00000380401.4; ENSG00000100350.16. [Q8IWF2-1]
DR Ensembl; ENST00000684868.1; ENSP00000510800.1; ENSG00000100350.16. [Q8IWF2-1]
DR GeneID; 80020; -.
DR KEGG; hsa:80020; -.
DR MANE-Select; ENST00000397224.9; ENSP00000380401.4; NM_001102371.2; NP_001095841.1.
DR UCSC; uc003apn.5; human. [Q8IWF2-1]
DR CTD; 80020; -.
DR GeneCards; FOXRED2; -.
DR HGNC; HGNC:26264; FOXRED2.
DR HPA; ENSG00000100350; Low tissue specificity.
DR MIM; 613777; gene.
DR neXtProt; NX_Q8IWF2; -.
DR OpenTargets; ENSG00000100350; -.
DR PharmGKB; PA145148808; -.
DR VEuPathDB; HostDB:ENSG00000100350; -.
DR eggNOG; KOG1399; Eukaryota.
DR GeneTree; ENSGT00640000091519; -.
DR HOGENOM; CLU_014290_1_0_1; -.
DR InParanoid; Q8IWF2; -.
DR OMA; FIHMVSR; -.
DR OrthoDB; 461621at2759; -.
DR PhylomeDB; Q8IWF2; -.
DR TreeFam; TF324712; -.
DR PathwayCommons; Q8IWF2; -.
DR SignaLink; Q8IWF2; -.
DR BioGRID-ORCS; 80020; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; FOXRED2; human.
DR GenomeRNAi; 80020; -.
DR Pharos; Q8IWF2; Tdark.
DR PRO; PR:Q8IWF2; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8IWF2; protein.
DR Bgee; ENSG00000100350; Expressed in buccal mucosa cell and 159 other tissues.
DR ExpressionAtlas; Q8IWF2; baseline and differential.
DR Genevisible; Q8IWF2; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IDA:UniProtKB.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:UniProtKB.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IMP:UniProtKB.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR SUPFAM; SSF51905; SSF51905; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; FAD; Flavoprotein;
KW Glycoprotein; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..684
FT /note="FAD-dependent oxidoreductase domain-containing
FT protein 2"
FT /id="PRO_0000337692"
FT REGION 649..684
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 681..684
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 1..327
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_033997"
FT VARIANT 71
FT /note="R -> C (in dbSNP:rs56767103)"
FT /id="VAR_062247"
FT VARIANT 179
FT /note="F -> L (in dbSNP:rs760718)"
FT /evidence="ECO:0000269|PubMed:15461802,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_043704"
FT VARIANT 308
FT /note="N -> S (in dbSNP:rs2277841)"
FT /evidence="ECO:0000269|PubMed:15461802,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.4"
FT /id="VAR_043705"
FT VARIANT 374
FT /note="K -> R (in dbSNP:rs35813894)"
FT /id="VAR_043706"
FT VARIANT 637
FT /note="E -> D (in dbSNP:rs35748020)"
FT /id="VAR_043707"
FT CONFLICT 345
FT /note="F -> S (in Ref. 2; BAB15610)"
FT /evidence="ECO:0000305"
FT CONFLICT 607
FT /note="T -> A (in Ref. 2; BAB15227)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 684 AA; 77791 MW; 8209FFAF6289DDAF CRC64;
MGLSAAAPLW GPPGLLLAIA LHPALSVPPR RDYCVLGAGP AGLQMAYFLQ RAGRDYAVFE
RAPRPGSFFT RYPRHRKLIS INKRYTGKAN AEFNLRHDWN SLLSHDPRLL FRHYSRAYFP
DARDMVRYLG DFADTLGLRV QYNTTIAHVT LDKDRQAWNG HYFILTDQKG QVHQCSVLFV
ATGLSVPNQV DFPGSEYAEG YESVSVDPED FVGQNVLILG RGNSAFETAE NILGVTNFIH
MLSRSRVRLS WATHYVGDLR AINNGLLDTY QLKSLDGLLE SDLTDLAILK DSKGKFHVTP
KFFLEEANTN QSADSITLPQ DDNDNFAMRV PYDRVIRCLG WNFDFSIFNK SLRLNSGNAF
GKKYPLIRAS YESKGSRGLF ILGTASHSVD YRKSAGGFIH GFRYTVRAVH RLLEHRHHSV
TWPATELPIT QLTSSIVRRV NEASGLYQMF GVLADVILLK ENSTAFEYLE EFPIQMLAQL
ETLTGRKAKH GLFVINMEYG RNFSGPDKDV FFDDRSVGHT EDAWQSNFLH PVIYYYRYLP
TEQEVRFRPA HWPLPRPTAI HHIVEDFLTD WTAPIGHILP LRRFLENCLD TDLRSFYAES
CFLFALTRQK LPPFCQQGYL RMQGLVSTES LWQHRVESRL LRDYAPTGRR LEDSSQQLGD
QEPLGSPLAP GPLAQSVDSN KEEL
