ID   FXL22_HUMAN             Reviewed;         231 AA.
AC   Q6P050; A0A1W2PQW8;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   28-JAN-2026, sequence version 3.
DT   10-JUN-2026, entry version 150.
DE   RecName: Full=F-box and leucine-rich protein 22;
GN   Name=FBXL22;
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 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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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   [3]
RP   NOMENCLATURE.
RX   PubMed=15520277; DOI=10.1101/gad.1255304;
RA   Jin J., Cardozo T., Lovering R.C., Elledge S.J., Pagano M., Harper J.W.;
RT   "Systematic analysis and nomenclature of mammalian F-box proteins.";
RL   Genes Dev. 18:2573-2580(2004).
RN   [4]
RP   FUNCTION, PATHWAY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND SUBUNIT.
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).
CC   -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box
CC       protein)-type E3 ubiquitin ligase complex. Promotes ubiquitination of
CC       sarcomeric proteins alpha-actinin-2 (ACTN2) and filamin-C (FLNC).
CC       {ECO:0000269|PubMed:22972877}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000269|PubMed:22972877}.
CC   -!- SUBUNIT: Directly interacts with SKP1 and CUL1.
CC       {ECO:0000269|PubMed:22972877}.
CC   -!- INTERACTION:
CC       Q6P050; P35609: ACTN2; NbExp=3; IntAct=EBI-24224082, EBI-77797;
CC       Q6P050; Q14315: FLNC; NbExp=3; IntAct=EBI-24224082, EBI-489954;
CC       Q6P050; P63208: SKP1; NbExp=7; IntAct=EBI-24224082, EBI-307486;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC       {ECO:0000269|PubMed:22972877}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q6P050-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6P050-2; Sequence=VSP_062729;
CC   -!- TISSUE SPECIFICITY: Enriched in cardiac muscle.
CC       {ECO:0000269|PubMed:22972877}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH65833.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AC118274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC065833; AAH65833.1; ALT_INIT; mRNA.
DR   CCDS; CCDS10187.2; -. [Q6P050-1]
DR   RefSeq; NP_001354736.1; NM_001367807.1. [Q6P050-1]
DR   RefSeq; NP_976307.2; NM_203373.3. [Q6P050-2]
DR   AlphaFoldDB; Q6P050; -.
DR   BioGRID; 129675; 16.
DR   ComplexPortal; CPX-2489; SCF E3 ubiquitin ligase complex, FBXL22 variant.
DR   FunCoup; Q6P050; 8.
DR   IntAct; Q6P050; 12.
DR   STRING; 9606.ENSP00000353794; -.
DR   GlyGen; Q6P050; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; Q6P050; -.
DR   BioMuta; FBXL22; -.
DR   DMDM; 519668655; -.
DR   MassIVE; Q6P050; -.
DR   PaxDb; 9606-ENSP00000353794; -.
DR   PeptideAtlas; Q6P050; -.
DR   ProteomicsDB; 66802; -.
DR   Antibodypedia; 25713; 55 antibodies from 12 providers.
DR   DNASU; 283807; -.
DR   Ensembl; ENST00000360587.2; ENSP00000353794.3; ENSG00000197361.8. [Q6P050-2]
DR   Ensembl; ENST00000638704.2; ENSP00000492359.1; ENSG00000197361.8. [Q6P050-1]
DR   GeneID; 283807; -.
DR   KEGG; hsa:283807; -.
DR   MANE-Select; ENST00000638704.2; ENSP00000492359.1; NM_001367807.1; NP_001354736.1.
DR   UCSC; uc002amn.5; human. [Q6P050-1]
DR   AGR; HGNC:27537; -.
DR   ClinPGx; PA134959373; -.
DR   CTD; 283807; -.
DR   DisGeNET; 283807; -.
DR   GeneCards; FBXL22; -.
DR   HGNC; HGNC:27537; FBXL22.
DR   HPA; ENSG00000197361; Tissue enhanced (endometrium, intestine).
DR   MIM; 609088; gene.
DR   OpenTargets; ENSG00000197361; -.
DR   VEuPathDB; HostDB:ENSG00000197361; -.
DR   eggNOG; KOG1947; Eukaryota.
DR   GeneTree; ENSGT00390000003748; -.
DR   HOGENOM; CLU_100261_0_0_1; -.
DR   InParanoid; Q6P050; -.
DR   OMA; LQVCNIE; -.
DR   OrthoDB; 549243at2759; -.
DR   PAN-GO; Q6P050; 0 GO annotations based on evolutionary models.
DR   PhylomeDB; Q6P050; -.
DR   PathwayCommons; Q6P050; -.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q6P050; -.
DR   UniPathway; UPA00143; -.
DR   Agora; ENSG00000197361; -.
DR   BioGRID-ORCS; 283807; 5 hits in 1173 CRISPR screens.
DR   GenomeRNAi; 283807; -.
DR   Pharos; Q6P050; Tdark.
DR   PRO; PR:Q6P050; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q6P050; protein.
DR   Bgee; ENSG00000197361; Expressed in muscle layer of sigmoid colon and 100 other cell types or tissues.
DR   ExpressionAtlas; Q6P050; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; NAS:ComplexPortal.
DR   CDD; cd22129; F-box_FBXL22; 1.
DR   FunFam; 1.20.1280.50:FF:000036; F-box and leucine rich repeat protein 22; 1.
DR   FunFam; 3.80.10.10:FF:000454; F-box and leucine-rich repeat protein 22; 1.
DR   Gene3D; 1.20.1280.50; -; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR050648; F-box_LRR-repeat.
DR   InterPro; IPR006553; Leu-rich_rpt_Cys-con_subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   PANTHER; PTHR13382; MITOCHONDRIAL ATP SYNTHASE COUPLING FACTOR B; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   SMART; SM00367; LRR_CC; 3.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   SUPFAM; SSF52047; RNI-like; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Leucine-rich repeat;
KW   Proteomics identification; Reference proteome; Repeat;
KW   Ubl conjugation pathway.
FT   CHAIN           1..231
FT                   /note="F-box and leucine-rich protein 22"
FT                   /id="PRO_0000247149"
FT   DOMAIN          6..52
FT                   /note="F-box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT   REPEAT          21..46
FT                   /note="LRR 1"
FT   REPEAT          49..78
FT                   /note="LRR 2"
FT   REPEAT          101..129
FT                   /note="LRR 3"
FT   REPEAT          130..155
FT                   /note="LRR 4"
FT   REPEAT          156..181
FT                   /note="LRR 5"
FT   REPEAT          182..207
FT                   /note="LRR 6"
FT   REGION          208..231
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         119..231
FT                   /note="CPNLASVTLSGCGHVTDDCLARLLRCCPRLRALRLENCARVTNRTLAAVAAD
FT                   GRALQTLHVDFCRNVSAAGLRRLRAACPRLALRAEHSAAMLPDQPPRPRAPAAALGKLL
FT                   QR -> LSAVRSPRRREAPAPSSGTPIAVGPKSPRWGGPDHSEFADLRSGVTGARAAAR
FT                   RGLGSLRAERPSETPPAPGVSWGPPPPGAPVVISVKQEEGKQGRTGRRSHRAAPPCGFA
FT                   RTRVCPPTFPGADAFPQ (in isoform 2)"
FT                   /id="VSP_062729"
FT   VARIANT         115
FT                   /note="V -> L (in dbSNP:rs8035931)"
FT                   /id="VAR_033940"
SQ   SEQUENCE   231 AA;  26028 MW;  5C84AA5C25BCE054 CRC64;
     MWPLLTMHIT QLNRECLLHL FSFLDKDSRK SLARTCSQLH DVFEDPALWS LLHFRSLTEL
     QKDNFLLGPA LRSLSICWHS SRVQVCSIED WLKSAFQRSI CSRHESLVND FLLRVCDRCP
     NLASVTLSGC GHVTDDCLAR LLRCCPRLRA LRLENCARVT NRTLAAVAAD GRALQTLHVD
     FCRNVSAAGL RRLRAACPRL ALRAEHSAAM LPDQPPRPRA PAAALGKLLQ R
//