ID FBX22_HUMAN Reviewed; 403 AA. AC Q8NEZ5; Q0D2P8; Q6PIL5; Q8IXW3; Q9H824; Q9UKC0; DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 10-JUN-2026, entry version 176. DE RecName: Full=F-box only protein 22; DE AltName: Full=F-box protein FBX22p44; GN Name=FBXO22; Synonyms=FBX22; 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). RA Tan P., Pan Z.-Q.; RT "FBX22p44: a novel human F-box protein predominantly expressed in the RT liver."; RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, Colon, and Lung; 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 [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-82. RX PubMed=10531035; DOI=10.1016/s0960-9822(00)80020-2; RA Cenciarelli C., Chiaur D.S., Guardavaccaro D., Parks W., Vidal M., RA Pagano M.; RT "Identification of a family of human F-box proteins."; RL Curr. Biol. 9:1177-1179(1999). RN [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-194, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP FUNCTION, AND INTERACTION WITH KDM4A; CUL1 AND SKP1. RX PubMed=21768309; DOI=10.1128/mcb.05746-11; RA Tan M.K., Lim H.J., Harper J.W.; RT "SCF(FBXO22) regulates histone H3 lysine 9 and 36 methylation levels by RT targeting histone demethylase KDM4A for ubiquitin-mediated proteasomal RT degradation."; RL Mol. Cell. Biol. 31:3687-3699(2011). RN [10] RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH SKP1 AND CUL1. RX PubMed=22972877; DOI=10.1161/circresaha.112.271007; RA Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D., Berger I.M., RA Wiemann S., Korn B., Koegl M., Backs J., Katus H.A., Rottbauer W., Frey N.; RT "F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box RT protein that regulates sarcomeric protein turnover and is essential for RT maintenance of contractile function in vivo."; RL Circ. Res. 111:1504-1516(2012). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP FUNCTION, AND INTERACTION WITH TP53. RX PubMed=26868148; DOI=10.1038/ncomms10574; RA Johmura Y., Sun J., Kitagawa K., Nakanishi K., Kuno T., Naiki-Ito A., RA Sawada Y., Miyamoto T., Okabe A., Aburatani H., Li S., Miyoshi I., RA Takahashi S., Kitagawa M., Nakanishi M.; RT "SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates RT senescence."; RL Nat. Commun. 7:10574-10574(2016). RN [15] RP FUNCTION, PHOSPHORYLATION AT THR-127, INTERACTION WITH MTOR, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF THR-127. RX PubMed=37979583; DOI=10.1016/j.cmet.2023.10.016; RA Ge M.K., Zhang C., Zhang N., He P., Cai H.Y., Li S., Wu S., Chu X.L., RA Zhang Y.X., Ma H.M., Xia L., Yang S., Yu J.X., Yao S.Y., Zhou X.L., Su B., RA Chen G.Q., Shen S.M.; RT "The tRNA-GCN2-FBXO22-axis-mediated mTOR ubiquitination senses amino acid RT insufficiency."; RL Cell Metab. 35:2216-2230.e8(2023). RN [16] RP FUNCTION, INTERACTION WITH SARS-COV-2 3C-LIKE PROTEINASE NSP5 (MICROBIAL RP INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=39223933; DOI=10.1002/jmv.29891; RA Zhou Y., Feng W., Yang C., Wei X., Fan L., Wu Y., Gao X., Shen X., RA Zhang Z., Zhao J.; RT "E3 ubiquitin ligase FBXO22 inhibits SARS-CoV-2 replication via promoting RT proteasome-dependent degradation of NSP5."; RL J. Med. Virol. 96:e29891-e29891(2024). RN [17] RP FUNCTION, AND INTERACTION WITH BACH1. RX PubMed=39504958; DOI=10.1016/j.cell.2024.10.012; RA Cao S., Garcia S.F., Shi H., James E.I., Kito Y., Shi H., Mao H., RA Kaisari S., Rona G., Deng S., Goldberg H.V., Ponce J., Ueberheide B., RA Lignitto L., Guttman M., Pagano M., Zheng N.; RT "Recognition of BACH1 quaternary structure degrons by two F-box proteins RT under oxidative stress."; RL Cell 0:0-0(2024). RN [18] RP VARIANT TYMAS VAL-222 DEL, AND INVOLVEMENT IN TYMAS. RX PubMed=40215970; DOI=10.1016/j.ajhg.2025.03.013; RA Ramakrishna N.B., Mohamad Sahari U.B., Johmura Y., Ali N.A., Alghamdi M., RA Bauer P., Khan S., Ordonez N., Ferreira M., Pinto Basto J., Alkuraya F.S., RA Faqeih E.A., Mori M., Almontashiri N.A.M., Al Shamsi A., ElGhazali G., RA Abu Subieh H., Al Ojaimi M., El-Hattab A.W., Said Al-Kindi S.A., RA Alhashmi N., Alhabshan F., Al Saman A., Tfayli H., Arabi M., Khalifeh S., RA Taylor A., Alfadhel M., Jain R., Sinha S., Shenbagam S., Ramachandran R., RA Altunoglu U., Jacob A., Thalange N., El Bejjani M., Perrin A., Shin J.W., RA Al-Maawali A., Al-Shidhani A., Al-Futaisi A., Rabea F., Chekroun I., RA Almarri M.A., Ohta T., Nakanishi M., Alsheikh-Ali A., Ali F.R., RA Bertoli-Avella A.M., Reversade B., Abou Tayoun A.; RT "FBXO22 deficiency defines a pleiotropic syndrome of growth restriction and RT multi-system anomalies associated with a unique epigenetic signature."; RL Am. J. Hum. Genet. 112:1233-1246(2025). CC -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box CC protein)-type E3 ubiquitin ligase complex that is implicated in the CC control of various cellular processes such as cell cycle control, CC transcriptional regulation, DNA damage repair, and apoptosis. Promotes CC the proteasome-dependent degradation of key sarcomeric proteins, such CC as alpha-actinin (ACTN2) and filamin-C (FLNC), essential for CC maintenance of normal contractile function. Acts as a key regulator of CC histone methylation marks namely H3K9 and H3K36 methylation through the CC regulation of histone demethylase KDM4A protein levels CC (PubMed:21768309). In complex with KDM4A, also regulates the abundance CC of TP53 by targeting methylated TP53 for degradation at the late CC senescent stage (PubMed:26868148). Under oxidative stress, promotes the CC ubiquitination and degradation of BACH1. Mechanistically, reactive CC oxygen species (ROS) covalently modify cysteine residues on the bZIP CC domain of BACH1, leading to its release from chromatin and making it CC accessible to FBXO22 (PubMed:39504958). Upon amino acid depletion, CC mediates 'Lys-27'-linked ubiquitination of MTOR and thereby inhibits CC substrate recruitment to mTORC1 (PubMed:37979583). Also inhibits SARS- CC CoV-2 replication by inducing NSP5 degradation (PubMed:39223933). CC {ECO:0000269|PubMed:21768309, ECO:0000269|PubMed:22972877, CC ECO:0000269|PubMed:26868148, ECO:0000269|PubMed:37979583, CC ECO:0000269|PubMed:39223933, ECO:0000269|PubMed:39504958}. CC -!- SUBUNIT: Directly interacts with SKP1 and CUL1 (PubMed:21768309, CC PubMed:22972877). Interacts (via C-terminal) with KDM4A CC (PubMed:21768309). Interacts with TP53 (PubMed:26868148). Interacts CC with MTOR; this interaction promotes 'lys-27'-linked ubiquitination of CC MTOR (PubMed:37979583). {ECO:0000269|PubMed:21768309, CC ECO:0000269|PubMed:22972877}. CC -!- SUBUNIT: (Microbial infection) Interacts with SARS_COV-2 protein NSP5; CC this interaction attenuates NSP5-mediated inhibition of innate CC immunity. {ECO:0000269|PubMed:39223933}. CC -!- INTERACTION: CC Q8NEZ5; Q13616: CUL1; NbExp=4; IntAct=EBI-2510137, EBI-359390; CC Q8NEZ5; P63208: SKP1; NbExp=11; IntAct=EBI-2510137, EBI-307486; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:37979583, CC ECO:0000269|PubMed:39223933}. Nucleus {ECO:0000269|PubMed:37979583, CC ECO:0000269|PubMed:39223933}. Cytoplasm, myofibril, sarcomere, Z line CC {ECO:0000250}. Note=Amino acid depletion lead to a time-dependent CC increase of FBXO22 in the cytoplasm. {ECO:0000269|PubMed:37979583}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8NEZ5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8NEZ5-2; Sequence=VSP_041821; CC Name=3; CC IsoId=Q8NEZ5-3; Sequence=VSP_013058, VSP_013059; CC -!- TISSUE SPECIFICITY: Predominantly expressed in liver, also enriched in CC cardiac muscle. {ECO:0000269|PubMed:22972877}. CC -!- PTM: Phosphorylated by EIF2AK4 at Thr-127 causes cytoplasmic retention CC of FBXO22. {ECO:0000269|PubMed:37979583}. CC -!- DISEASE: Tayoun-Maawali syndrome (TYMAS) [MIM:621184]: An autosomal CC recessive pleiotropic syndrome characterized by multiple abnormalities CC encompassing early growth restriction, neurodevelopmental delay, and CC craniofacial, cardiovascular, gastrointestinal, urinary and endocrine CC anomalies. {ECO:0000269|PubMed:40215970}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH39024.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={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; AY005144; AAF89095.1; -; mRNA. DR EMBL; AK024048; BAB14798.1; -; mRNA. DR EMBL; AC027104; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC032540; AAH32540.1; -; mRNA. DR EMBL; BC020204; AAH20204.2; -; mRNA. DR EMBL; BC039024; AAH39024.1; ALT_SEQ; mRNA. DR EMBL; BC041691; AAH41691.1; -; mRNA. DR EMBL; AF174602; AAF04523.1; -; Genomic_DNA. DR CCDS; CCDS10287.1; -. [Q8NEZ5-1] DR CCDS; CCDS45310.1; -. [Q8NEZ5-3] DR RefSeq; NP_036302.1; NM_012170.4. [Q8NEZ5-3] DR RefSeq; NP_671717.1; NM_147188.3. [Q8NEZ5-1] DR PDB; 8S7D; EM; 3.20 A; D=12-403. DR PDB; 8S7E; EM; 3.40 A; B=12-403. DR PDB; 8UA3; EM; 3.80 A; C=1-403. DR PDB; 8UA6; EM; 3.90 A; C=1-403. DR PDBsum; 8S7D; -. DR PDBsum; 8S7E; -. DR PDBsum; 8UA3; -. DR PDBsum; 8UA6; -. DR AlphaFoldDB; Q8NEZ5; -. DR EMDB; EMD-19766; -. DR EMDB; EMD-19768; -. DR EMDB; EMD-42049; -. DR EMDB; EMD-42051; -. DR SMR; Q8NEZ5; -. DR BioGRID; 117649; 548. DR ComplexPortal; CPX-7962; SCF E3 ubiquitin ligase complex, FBXO22 variant. DR FunCoup; Q8NEZ5; 1392. DR IntAct; Q8NEZ5; 32. DR MINT; Q8NEZ5; -. DR STRING; 9606.ENSP00000307833; -. DR ChEMBL; CHEMBL5724687; -. DR GlyGen; Q8NEZ5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q8NEZ5; -. DR MetOSite; Q8NEZ5; -. DR PhosphoSitePlus; Q8NEZ5; -. DR BioMuta; FBXO22; -. DR DMDM; 30580428; -. DR jPOST; Q8NEZ5; -. DR MassIVE; Q8NEZ5; -. DR PaxDb; 9606-ENSP00000307833; -. DR PeptideAtlas; Q8NEZ5; -. DR ProteomicsDB; 73255; -. [Q8NEZ5-1] DR ProteomicsDB; 73256; -. [Q8NEZ5-2] DR ProteomicsDB; 73257; -. [Q8NEZ5-3] DR Pumba; Q8NEZ5; -. DR Antibodypedia; 27397; 184 antibodies from 26 providers. DR DNASU; 26263; -. DR Ensembl; ENST00000308275.8; ENSP00000307833.3; ENSG00000167196.15. [Q8NEZ5-1] DR Ensembl; ENST00000453211.6; ENSP00000396442.2; ENSG00000167196.15. [Q8NEZ5-3] DR Ensembl; ENST00000569022.1; ENSP00000457531.1; ENSG00000167196.15. [Q8NEZ5-2] DR GeneID; 26263; -. DR KEGG; hsa:26263; -. DR MANE-Select; ENST00000308275.8; ENSP00000307833.3; NM_147188.3; NP_671717.1. DR UCSC; uc002bbj.3; human. [Q8NEZ5-1] DR AGR; HGNC:13593; -. DR ClinPGx; PA28035; -. DR CTD; 26263; -. DR DisGeNET; 26263; -. DR GeneCards; FBXO22; -. DR HGNC; HGNC:13593; FBXO22. DR HPA; ENSG00000167196; Low tissue specificity. DR MalaCards; FBXO22; -. DR MIM; 609096; gene. DR MIM; 621184; phenotype. DR OpenTargets; ENSG00000167196; -. DR VEuPathDB; HostDB:ENSG00000167196; -. DR eggNOG; ENOG502QSZ2; Eukaryota. DR GeneTree; ENSGT00390000013049; -. DR HOGENOM; CLU_042854_0_0_1; -. DR InParanoid; Q8NEZ5; -. DR OMA; LWRECSR; -. DR OrthoDB; 509497at2759; -. DR PAN-GO; Q8NEZ5; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q8NEZ5; -. DR PathwayCommons; Q8NEZ5; -. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q8NEZ5; -. DR SIGNOR; Q8NEZ5; -. DR Agora; ENSG00000167196; -. DR BioGRID-ORCS; 26263; 22 hits in 1203 CRISPR screens. DR ChiTaRS; FBXO22; human. DR GenomeRNAi; 26263; -. DR Pharos; Q8NEZ5; Tbio. DR PRO; PR:Q8NEZ5; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q8NEZ5; protein. DR Bgee; ENSG00000167196; Expressed in endothelial cell and 178 other cell types or tissues. DR ExpressionAtlas; Q8NEZ5; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:ProtInc. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central. DR GO; GO:0036211; P:protein modification process; TAS:ProtInc. DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central. DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IBA:GO_Central. DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc. DR CDD; cd22097; F-box_FBXO22; 1. DR Gene3D; 1.20.1280.50; -; 1. DR InterPro; IPR036047; F-box-like_dom_sf. DR InterPro; IPR001810; F-box_dom. DR InterPro; IPR019494; FIST_C. DR PANTHER; PTHR14939; F-BOX ONLY PROTEIN 22; 1. DR PANTHER; PTHR14939:SF5; F-BOX ONLY PROTEIN 22; 1. DR Pfam; PF00646; F-box; 1. DR Pfam; PF10442; FIST_C; 1. DR SMART; SM01204; FIST_C; 1. DR SUPFAM; SSF81383; F-box domain; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Nucleus; KW Phosphoprotein; Proteomics identification; Reference proteome; KW Ubl conjugation pathway. FT CHAIN 1..403 FT /note="F-box only protein 22" FT /id="PRO_0000119906" FT DOMAIN 21..67 FT /note="F-box" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 127 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:37979583" FT MOD_RES 128 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 194 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 47..403 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_041821" FT VAR_SEQ 266..276 FT /note="NPLDIDASGVV -> YVLCASDFVCE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_013058" FT VAR_SEQ 277..403 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_013059" FT VARIANT 222 FT /note="Missing (in TYMAS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:40215970" FT /id="VAR_090580" FT MUTAGEN 127 FT /note="T->A: Loss of EIF2AK4-induced cytoplasmic retention FT of FBXO22." FT /evidence="ECO:0000269|PubMed:37979583" FT CONFLICT 4..11 FT /note="VGCCGECR -> AGACGGP (in Ref. 5; AAF04523)" FT /evidence="ECO:0000305" FT CONFLICT 349 FT /note="F -> L (in Ref. 4; AAH32540)" FT /evidence="ECO:0000305" FT HELIX 19..25 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 27..35 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 39..45 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 50..61 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:8S7E" FT HELIX 84..91 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 99..107 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 108..111 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 129..137 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 141..151 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 166..170 FT /evidence="ECO:0007829|PDB:8S7E" FT STRAND 174..180 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 191..193 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 203..208 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 246..261 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 274..280 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 282..285 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 286..291 FT /evidence="ECO:0007829|PDB:8S7E" FT HELIX 299..310 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 319..326 FT /evidence="ECO:0007829|PDB:8S7D" FT TURN 331..333 FT /evidence="ECO:0007829|PDB:8S7D" FT HELIX 341..348 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 354..363 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 368..370 FT /evidence="ECO:0007829|PDB:8S7E" FT STRAND 371..378 FT /evidence="ECO:0007829|PDB:8S7D" FT TURN 382..386 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 387..390 FT /evidence="ECO:0007829|PDB:8S7D" FT STRAND 393..399 FT /evidence="ECO:0007829|PDB:8S7D" SQ SEQUENCE 403 AA; 44508 MW; D96712BAA1149D8D CRC64; MEPVGCCGEC RGSSVDPRST FVLSNLAEVV ERVLTFLPAK ALLRVACVCR LWRECVRRVL RTHRSVTWIS AGLAEAGHLE GHCLVRVVAE ELENVRILPH TVLYMADSET FISLEECRGH KRARKRTSME TALALEKLFP KQCQVLGIVT PGIVVTPMGS GSNRPQEIEI GESGFALLFP QIEGIKIQPF HFIKDPKNLT LERHQLTEVG LLDNPELRVV LVFGYNCCKV GASNYLQQVV STFSDMNIIL AGGQVDNLSS LTSEKNPLDI DASGVVGLSF SGHRIQSATV LLNEDVSDEK TAEAAMQRLK AANIPEHNTI GFMFACVGRG FQYYRAKGNV EADAFRKFFP SVPLFGFFGN GEIGCDRIVT GNFILRKCNE VKDDDLFHSY TTIMALIHLG SSK //