FBX22_HUMAN
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 03-AUG-2022, entry version 158.
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, 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 [10]
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 [11]
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 [12]
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).
CC -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box
CC protein)-type E3 ubiquitin ligase complex. Promotes the proteasome-
CC dependent degradation of key sarcomeric proteins, such as alpha-actinin
CC (ACTN2) and filamin-C (FLNC), essential for maintenance of normal
CC contractile function. {ECO:0000269|PubMed:22972877}.
CC -!- SUBUNIT: Directly interacts with SKP1 and CUL1.
CC {ECO:0000269|PubMed:22972877}.
CC -!- INTERACTION:
CC Q8NEZ5; Q13616: CUL1; NbExp=4; IntAct=EBI-2510137, EBI-359390;
CC Q8NEZ5; P63208: SKP1; NbExp=7; IntAct=EBI-2510137, EBI-307486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000250}.
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 -!- 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};
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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_012170.3. [Q8NEZ5-3]
DR RefSeq; NP_671717.1; NM_147188.2. [Q8NEZ5-1]
DR RefSeq; XP_011519749.1; XM_011521447.2.
DR AlphaFoldDB; Q8NEZ5; -.
DR BioGRID; 117649; 46.
DR IntAct; Q8NEZ5; 18.
DR MINT; Q8NEZ5; -.
DR STRING; 9606.ENSP00000307833; -.
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 EPD; Q8NEZ5; -.
DR jPOST; Q8NEZ5; -.
DR MassIVE; Q8NEZ5; -.
DR MaxQB; Q8NEZ5; -.
DR PaxDb; Q8NEZ5; -.
DR PeptideAtlas; Q8NEZ5; -.
DR PRIDE; Q8NEZ5; -.
DR ProteomicsDB; 73255; -. [Q8NEZ5-1]
DR ProteomicsDB; 73256; -. [Q8NEZ5-2]
DR ProteomicsDB; 73257; -. [Q8NEZ5-3]
DR Antibodypedia; 27397; 187 antibodies from 25 providers.
DR DNASU; 26263; -.
DR Ensembl; ENST00000308275.8; ENSP00000307833.3; ENSG00000167196.14. [Q8NEZ5-1]
DR Ensembl; ENST00000453211.6; ENSP00000396442.2; ENSG00000167196.14. [Q8NEZ5-3]
DR Ensembl; ENST00000569022.1; ENSP00000457531.1; ENSG00000167196.14. [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 CTD; 26263; -.
DR DisGeNET; 26263; -.
DR GeneCards; FBXO22; -.
DR HGNC; HGNC:13593; FBXO22.
DR HPA; ENSG00000167196; Low tissue specificity.
DR MIM; 609096; gene.
DR neXtProt; NX_Q8NEZ5; -.
DR OpenTargets; ENSG00000167196; -.
DR PharmGKB; PA28035; -.
DR VEuPathDB; HostDB:ENSG00000167196; -.
DR eggNOG; ENOG502QSZ2; Eukaryota.
DR GeneTree; ENSGT00390000013049; -.
DR HOGENOM; CLU_042854_0_0_1; -.
DR InParanoid; Q8NEZ5; -.
DR OMA; GCDRIIK; -.
DR OrthoDB; 681238at2759; -.
DR PhylomeDB; Q8NEZ5; -.
DR TreeFam; TF328809; -.
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 BioGRID-ORCS; 26263; 21 hits in 1124 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 176 other tissues.
DR ExpressionAtlas; Q8NEZ5; baseline and differential.
DR Genevisible; Q8NEZ5; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; TAS:ProtInc.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0006913; P:nucleocytoplasmic transport; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
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:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR019494; FIST_C.
DR Pfam; PF00646; F-box; 1.
DR Pfam; PF10442; FIST_C; 1.
DR SMART; SM01204; FIST_C; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Phosphoprotein;
KW Reference proteome; 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 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 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"
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
