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 27-MAR-2024, entry version 163. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; Q8IWF2; -. DR BioGRID; 123074; 155. DR DIP; DIP-48946N; -. DR IntAct; Q8IWF2; 37. DR MINT; Q8IWF2; -. DR STRING; 9606.ENSP00000380401; -. DR GlyCosmos; Q8IWF2; 1 site, No reported glycans. 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; 9606-ENSP00000380401; -. DR PeptideAtlas; Q8IWF2; -. DR ProteomicsDB; 70851; -. [Q8IWF2-1] DR ProteomicsDB; 70852; -. [Q8IWF2-2] DR Pumba; Q8IWF2; -. DR Antibodypedia; 25683; 130 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 AGR; HGNC:26264; -. 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; DQRAWNG; -. DR OrthoDB; 2665879at2759; -. DR PhylomeDB; Q8IWF2; -. DR TreeFam; TF324712; -. DR PathwayCommons; Q8IWF2; -. DR SignaLink; Q8IWF2; -. DR BioGRID-ORCS; 80020; 17 hits in 1161 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 160 other cell types or tissues. DR ExpressionAtlas; Q8IWF2; baseline and differential. 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; FAD/NAD(P)-binding domain; 2. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR PANTHER; PTHR43539:SF78; FAD-DEPENDENT OXIDOREDUCTASE DOMAIN-CONTAINING PROTEIN 2; 1. DR PANTHER; PTHR43539; FLAVIN-BINDING MONOOXYGENASE-LIKE PROTEIN (AFU_ORTHOLOGUE AFUA_4G09220); 1. DR Pfam; PF13738; Pyr_redox_3; 1. DR PRINTS; PR00419; ADXRDTASE. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. DR PROSITE; PS00014; ER_TARGET; 1. DR Genevisible; Q8IWF2; HS. 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 //