FBX32_HUMAN
ID FBX32_HUMAN Reviewed; 355 AA.
AC Q969P5; A4KYM0;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=F-box only protein 32;
DE AltName: Full=Atrogin-1;
DE AltName: Full=Muscle atrophy F-box protein;
DE Short=MAFbx;
GN Name=FBXO32;
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).
RC TISSUE=Skeletal muscle;
RX PubMed=11679633; DOI=10.1126/science.1065874;
RA Bodine S.C., Latres E., Baumhueter S., Lai V.K.-M., Nunez L., Clarke B.A.,
RA Poueymirou W.T., Panaro F.J., Na E., Dharmarajan K., Pan Z.-Q.,
RA Valenzuela D.M., DeChiara T.M., Stitt T.N., Yancopoulos G.D., Glass D.J.;
RT "Identification of ubiquitin ligases required for skeletal muscle
RT atrophy.";
RL Science 294:1704-1708(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Sivertsen E.A., Aasheim H.-C.;
RT "The FBXO32 gene encodes a novel F-box protein selectively expressed in
RT muscle tissue.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Pescatori M., Bugli F., Sali M., Tonali P.A., Fadda G., Tasca G., Ricci E.;
RT "Atrogin 1 expression in human DMD muscle.";
RL Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [6]
RP RECONSTITUTION OF THE SCF(FBXO32) COMPLEX, AND FUNCTION IN UBIQUITINATION
RP OF MYOD1.
RX PubMed=15531760; DOI=10.1074/jbc.m411346200;
RA Tintignac L.A., Lagirand J., Batonnet S., Sirri V., Leibovitch M.P.,
RA Leibovitch S.A.;
RT "Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase.";
RL J. Biol. Chem. 280:2847-2856(2005).
RN [7]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNALS, AND MUTAGENESIS OF
RP LEU-169.
RX PubMed=22249105; DOI=10.1016/j.febslet.2011.12.031;
RA Julie L.C., Sabrina B.P., Marie-Pierre L., Leibovitch S.A.;
RT "Identification of essential sequences for cellular localization in the
RT muscle-specific ubiquitin E3 ligase MAFbx/Atrogin 1.";
RL FEBS Lett. 586:362-367(2012).
RN [8]
RP INVOLVEMENT IN DCM, VARIANT ARG-243, AND SUBCELLULAR LOCATION.
RX PubMed=26768247; DOI=10.1186/s12881-016-0267-5;
RA Al-Hassnan Z.N., Shinwari Z.M., Wakil S.M., Tulbah S., Mohammed S.,
RA Rahbeeni Z., Alghamdi M., Rababh M., Colak D., Kaya N., Al-Fayyadh M.,
RA Alburaiki J.;
RT "A substitution mutation in cardiac ubiquitin ligase, FBXO32, is associated
RT with an autosomal recessive form of dilated cardiomyopathy.";
RL BMC Med. Genet. 17:3-3(2016).
RN [9]
RP INVOLVEMENT IN DCM, VARIANT ARG-243, CHARACTERIZATION OF VARIANT ARG-243,
RP AND SUBUNIT.
RX PubMed=26753747; DOI=10.1186/s13059-015-0861-4;
RA Al-Yacoub N., Shaheen R., Awad S.M., Kunhi M., Dzimiri N., Nguyen H.C.,
RA Xiong Y., Al-Buraiki J., Al-Habeeb W., Alkuraya F.S., Poizat C.;
RT "FBXO32, encoding a member of the SCF complex, is mutated in dilated
RT cardiomyopathy.";
RL Genome Biol. 17:R2.1-R2.11(2016).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex which mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. Probably recognizes and binds to phosphorylated target
CC proteins during skeletal muscle atrophy. Recognizes TERF1.
CC {ECO:0000269|PubMed:15531760}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase
CC complex SCF(FBXO32) formed of CUL1, SKP1, RBX1 and FBXO32.
CC {ECO:0000269|PubMed:26753747}.
CC -!- INTERACTION:
CC Q969P5; O00303: EIF3F; NbExp=7; IntAct=EBI-2932534, EBI-711990;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22249105,
CC ECO:0000269|PubMed:26768247}. Nucleus {ECO:0000269|PubMed:22249105}.
CC Note=Shuttles between cytoplasm and the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969P5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969P5-2; Sequence=VSP_042744;
CC -!- TISSUE SPECIFICITY: Specifically expressed in cardiac and skeletal
CC muscle.
CC -!- DISEASE: Note=Defects in FBXO32 are associated with susceptibility to
CC dilated cardiomyopathy (DCM). A disorder characterized by ventricular
CC and impaired systolic function, resulting in heart failure and
CC arrhythmia. Patient are at risk of premature death.
CC {ECO:0000269|PubMed:26753747, ECO:0000269|PubMed:26768247}.
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; AY059629; AAL16407.1; -; mRNA.
DR EMBL; AJ420108; CAD12251.1; -; mRNA.
DR EMBL; EF143260; ABO37797.1; -; mRNA.
DR EMBL; AK056986; BAB71333.1; -; mRNA.
DR EMBL; AC090193; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS56553.1; -. [Q969P5-2]
DR CCDS; CCDS6345.1; -. [Q969P5-1]
DR RefSeq; NP_001229392.1; NM_001242463.1. [Q969P5-2]
DR RefSeq; NP_478136.1; NM_058229.3. [Q969P5-1]
DR AlphaFoldDB; Q969P5; -.
DR BioGRID; 125395; 244.
DR IntAct; Q969P5; 6.
DR MINT; Q969P5; -.
DR STRING; 9606.ENSP00000428205; -.
DR iPTMnet; Q969P5; -.
DR PhosphoSitePlus; Q969P5; -.
DR BioMuta; FBXO32; -.
DR DMDM; 20177894; -.
DR EPD; Q969P5; -.
DR MassIVE; Q969P5; -.
DR PaxDb; Q969P5; -.
DR PeptideAtlas; Q969P5; -.
DR PRIDE; Q969P5; -.
DR ProteomicsDB; 75810; -. [Q969P5-1]
DR ProteomicsDB; 75811; -. [Q969P5-2]
DR Antibodypedia; 27004; 340 antibodies from 37 providers.
DR DNASU; 114907; -.
DR Ensembl; ENST00000443022.2; ENSP00000390790.2; ENSG00000156804.7. [Q969P5-2]
DR Ensembl; ENST00000517956.5; ENSP00000428205.1; ENSG00000156804.7. [Q969P5-1]
DR GeneID; 114907; -.
DR KEGG; hsa:114907; -.
DR MANE-Select; ENST00000517956.5; ENSP00000428205.1; NM_058229.4; NP_478136.1.
DR UCSC; uc003yqr.4; human. [Q969P5-1]
DR CTD; 114907; -.
DR DisGeNET; 114907; -.
DR GeneCards; FBXO32; -.
DR HGNC; HGNC:16731; FBXO32.
DR HPA; ENSG00000156804; Tissue enriched (skeletal).
DR MIM; 606604; gene.
DR neXtProt; NX_Q969P5; -.
DR OpenTargets; ENSG00000156804; -.
DR PharmGKB; PA28043; -.
DR VEuPathDB; HostDB:ENSG00000156804; -.
DR eggNOG; KOG3926; Eukaryota.
DR GeneTree; ENSGT00390000004915; -.
DR HOGENOM; CLU_065667_0_0_1; -.
DR InParanoid; Q969P5; -.
DR OMA; QNWVKTE; -.
DR PhylomeDB; Q969P5; -.
DR TreeFam; TF313070; -.
DR PathwayCommons; Q969P5; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q969P5; -.
DR SIGNOR; Q969P5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 114907; 13 hits in 1109 CRISPR screens.
DR ChiTaRS; FBXO32; human.
DR GeneWiki; FBXO32; -.
DR GenomeRNAi; 114907; -.
DR Pharos; Q969P5; Tbio.
DR PRO; PR:Q969P5; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q969P5; protein.
DR Bgee; ENSG00000156804; Expressed in cardiac muscle of right atrium and 180 other tissues.
DR ExpressionAtlas; Q969P5; baseline and differential.
DR Genevisible; Q969P5; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:UniProtKB.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR040394; FBX25/32.
DR PANTHER; PTHR13123; PTHR13123; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Disease variant; Nucleus;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..355
FT /note="F-box only protein 32"
FT /id="PRO_0000119922"
FT DOMAIN 223..271
FT /note="F-box"
FT MOTIF 62..67
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:22249105"
FT MOTIF 169..173
FT /note="Nuclear export signal"
FT MOTIF 280..295
FT /note="Bipartite nuclear localization signal"
FT VAR_SEQ 124..216
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_042744"
FT VARIANT 56
FT /note="N -> S (in dbSNP:rs6988591)"
FT /id="VAR_049045"
FT VARIANT 89
FT /note="G -> A (in dbSNP:rs11786471)"
FT /id="VAR_049046"
FT VARIANT 243
FT /note="G -> R (probable disease-associated variant found in
FT patients with familial dilated cardiomyopathy; impairs the
FT formation of SCF complex; reduced ubiquitination of
FT cellular proteins; dbSNP:rs771939133)"
FT /evidence="ECO:0000269|PubMed:26753747,
FT ECO:0000269|PubMed:26768247"
FT /id="VAR_076453"
FT MUTAGEN 169
FT /note="L->Q: Significantly increases nuclear localization."
FT /evidence="ECO:0000269|PubMed:22249105"
SQ SEQUENCE 355 AA; 41637 MW; A0258E5DBEF5CC0E CRC64;
MPFLGQDWRS PGQNWVKTAD GWKRFLDEKS GSFVSDLSSY CNKEVYNKEN LFNSLNYDVA
AKKRKKDMLN SKTKTQYFHQ EKWIYVHKGS TKERHGYCTL GEAFNRLDFS TAILDSRRFN
YVVRLLELIA KSQLTSLSGI AQKNFMNILE KVVLKVLEDQ QNIRLIRELL QTLYTSLCTL
VQRVGKSVLV GNINMWVYRM ETILHWQQQL NNIQITRPAF KGLTFTDLPL CLQLNIMQRL
SDGRDLVSLG QAAPDLHVLS EDRLLWKKLC QYHFSERQIR KRLILSDKGQ LDWKKMYFKL
VRCYPRKEQY GDTLQLCKHC HILSWKGTDH PCTANNPESC SVSLSPQDFI NLFKF
