FXL22_HUMAN
ID FXL22_HUMAN Reviewed; 247 AA.
AC Q6P050;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2013, sequence version 2.
DT 03-AUG-2022, entry version 135.
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].
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, 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 -!- SUBUNIT: Directly interacts with SKP1 and CUL1.
CC {ECO:0000269|PubMed:22972877}.
CC -!- INTERACTION:
CC Q6P050; P63208: SKP1; NbExp=3; IntAct=EBI-24224082, EBI-307486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:22972877}.
CC -!- TISSUE SPECIFICITY: Enriched in cardiac muscle.
CC {ECO:0000269|PubMed:22972877}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-7 is the initiator.
CC {ECO:0000305}.
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; -.
DR RefSeq; NP_976307.2; NM_203373.2.
DR AlphaFoldDB; Q6P050; -.
DR BioGRID; 129675; 16.
DR IntAct; Q6P050; 1.
DR STRING; 9606.ENSP00000353794; -.
DR BioMuta; FBXL22; -.
DR DMDM; 519668655; -.
DR MassIVE; Q6P050; -.
DR PaxDb; Q6P050; -.
DR PeptideAtlas; Q6P050; -.
DR PRIDE; Q6P050; -.
DR ProteomicsDB; 66802; -.
DR Antibodypedia; 25713; 64 antibodies from 13 providers.
DR DNASU; 283807; -.
DR Ensembl; ENST00000360587.2; ENSP00000353794.3; ENSG00000197361.8.
DR GeneID; 283807; -.
DR KEGG; hsa:283807; -.
DR UCSC; uc002amn.5; human.
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 neXtProt; NX_Q6P050; -.
DR OpenTargets; ENSG00000197361; -.
DR PharmGKB; PA134959373; -.
DR VEuPathDB; HostDB:ENSG00000197361; -.
DR eggNOG; KOG1947; Eukaryota.
DR GeneTree; ENSGT00390000003748; -.
DR HOGENOM; CLU_100261_0_0_1; -.
DR InParanoid; Q6P050; -.
DR OrthoDB; 1332077at2759; -.
DR PhylomeDB; Q6P050; -.
DR TreeFam; TF332457; -.
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 BioGRID-ORCS; 283807; 5 hits in 1095 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 99 other tissues.
DR ExpressionAtlas; Q6P050; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IBA:GO_Central.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR Pfam; PF12937; F-box-like; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..247
FT /note="F-box and leucine-rich protein 22"
FT /id="PRO_0000247149"
FT DOMAIN 6..52
FT /note="F-box"
FT REGION 124..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..202
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 115
FT /note="V -> L (in dbSNP:rs8035931)"
FT /id="VAR_033940"
SQ SEQUENCE 247 AA; 27269 MW; 9966D98688B8FF26 CRC64;
MWPLLTMHIT QLNRECLLHL FSFLDKDSRK SLARTCSQLH DVFEDPALWS LLHFRSLTEL
QKDNFLLGPA LRSLSICWHS SRVQVCSIED WLKSAFQRSI CSRHESLVND FLLRVCDRLS
AVRSPRRREA PAPSSGTPIA VGPKSPRWGG PDHSEFADLR SGVTGARAAA RRGLGSLRAE
RPSETPPAPG VSWGPPPPGA PVVISVKQEE GKQGRTGRRS HRAAPPCGFA RTRVCPPTFP
GADAFPQ
