ID   FBX25_HUMAN             Reviewed;         367 AA.
AC   Q8TCJ0; Q6PJ83; Q7Z4V4; Q9UKB8;
DT   09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2005, sequence version 3.
DT   27-MAR-2024, entry version 161.
DE   RecName: Full=F-box only protein 25;
GN   Name=FBXO25; Synonyms=FBX25;
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 2).
RC   TISSUE=Prostatic carcinoma;
RA   Tsujiawa K., Mitsui E., Ono Y., Sakamoto K., Konishi N., Yamamoto H.;
RT   "Expression of Fbx25-containing protein in prostate cancer tissues.";
RL   Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Guo J.H., She X.Y., Yu L.;
RL   Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP   HIS-38.
RC   TISSUE=Brain, and Placenta;
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 87-367 (ISOFORM 2).
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   [5]
RP   PROTEIN SEQUENCE OF 110-120; 135-146; 147-154; 190-202 AND 339-366,
RP   INTERACTION WITH BETA-ACTIN AND SKP1, IDENTIFICATION IN A SCF PROTEIN
RP   LIGASE COMPLEX, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=20473970; DOI=10.1002/pmic.200900419;
RA   Teixeira F.R., Yokoo S., Gartner C.A., Manfiolli A.O., Baqui M.M.,
RA   Assmann E.M., Maragno A.L., Yu H., de Lanerolle P., Kobarg J., Gygi S.P.,
RA   Gomes M.D.;
RT   "Identification of FBXO25-interacting proteins using an integrated
RT   proteomics approach.";
RL   Proteomics 10:2746-2757(2010).
RN   [6]
RP   INTERACTION WITH SKP1 AND CUL1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP   AND MUTAGENESIS OF SER-244.
RX   PubMed=16278047; DOI=10.1016/j.bbagen.2005.09.018;
RA   Hagens O., Minina E., Schweiger S., Ropers H.-H., Kalscheuer V.;
RT   "Characterization of FBX25, encoding a novel brain-expressed F-box
RT   protein.";
RL   Biochim. Biophys. Acta 1760:110-118(2006).
RN   [7]
RP   CHROMOSOMAL TRANSLOCATION WITH SHROOM4.
RX   PubMed=16249884; DOI=10.1007/s00439-005-0072-2;
RA   Hagens O., Dubos A., Abidi F., Barbi G., Van Zutven L., Hoeltzenbein M.,
RA   Tommerup N., Moraine C., Fryns J.-P., Chelly J., van Bokhoven H., Gecz J.,
RA   Dollfus H., Ropers H.-H., Schwartz C.E., de Cassia Stocco Dos Santos R.,
RA   Kalscheuer V., Hanauer A.;
RT   "Disruptions of the novel KIAA1202 gene are associated with X-linked mental
RT   retardation.";
RL   Hum. Genet. 118:578-590(2006).
RN   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=18287534; DOI=10.1091/mbc.e07-08-0815;
RA   Manfiolli A.O., Maragno A.L., Baqui M.M., Yokoo S., Teixeira F.R.,
RA   Oliveira E.B., Gomes M.D.;
RT   "FBXO25-associated nuclear domains: a novel subnuclear structure.";
RL   Mol. Biol. Cell 19:1848-1861(2008).
CC   -!- FUNCTION: Substrate-recognition component of the SCF (SKP1-CUL1-F-box
CC       protein)-type E3 ubiquitin ligase complex. May play a role in
CC       accumulation of expanded polyglutamine (polyQ) protein huntingtin (HTT)
CC       (By similarity). {ECO:0000250}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Part of a SCF (SKP1-cullin-F-box) protein ligase complex
CC       consisting of FBXO25, SKP1, CUL1 and RBX1. Interacts directly with SKP1
CC       and CUL1. Interacts (via C-terminus) with beta-actin (via N-terminus).
CC       {ECO:0000269|PubMed:16278047, ECO:0000269|PubMed:20473970}.
CC   -!- INTERACTION:
CC       Q8TCJ0-2; P60709: ACTB; NbExp=3; IntAct=EBI-6264551, EBI-353944;
CC       Q8TCJ0-3; P49821: NDUFV1; NbExp=3; IntAct=EBI-6262578, EBI-748312;
CC       Q8TCJ0-3; P63208: SKP1; NbExp=4; IntAct=EBI-6262578, EBI-307486;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16278047,
CC       ECO:0000269|PubMed:18287534}. Note=In the nucleus, associates with a
CC       subnuclear dot-like structure. Colocalized with SKP1.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q8TCJ0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8TCJ0-2; Sequence=VSP_007374;
CC       Name=3;
CC         IsoId=Q8TCJ0-3; Sequence=VSP_013060, VSP_013061, VSP_007374;
CC   -!- TISSUE SPECIFICITY: Expressed in all brain tissue observed.
CC       {ECO:0000269|PubMed:16278047}.
CC   -!- DOMAIN: The F-box is necessary for the interaction with SKP1.
CC       {ECO:0000250}.
CC   -!- DISEASE: Note=A chromosomal aberration involving FBXO25 is a cause of
CC       X-linked intellectual disability (XLID). Translocation
CC       t(X;8)(p11.22;p23.3) with SHROOM4.
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DR   EMBL; AB070270; BAB85128.1; -; mRNA.
DR   EMBL; AF419858; AAP97293.1; -; mRNA.
DR   EMBL; BC020249; AAH20249.1; -; mRNA.
DR   EMBL; BC050393; AAH50393.1; -; mRNA.
DR   EMBL; AF174605; AAF04526.1; -; mRNA.
DR   CCDS; CCDS5952.1; -. [Q8TCJ0-2]
DR   CCDS; CCDS5953.1; -. [Q8TCJ0-1]
DR   CCDS; CCDS5954.1; -. [Q8TCJ0-3]
DR   RefSeq; NP_036305.2; NM_012173.3. [Q8TCJ0-3]
DR   RefSeq; NP_904356.1; NM_183420.1. [Q8TCJ0-2]
DR   RefSeq; NP_904357.1; NM_183421.1. [Q8TCJ0-1]
DR   RefSeq; XP_011533050.1; XM_011534748.2. [Q8TCJ0-1]
DR   RefSeq; XP_016868802.1; XM_017013313.1. [Q8TCJ0-1]
DR   AlphaFoldDB; Q8TCJ0; -.
DR   BioGRID; 117646; 197.
DR   ComplexPortal; CPX-7965; SCF E3 ubiquitin ligase complex, FBXO25 variant.
DR   IntAct; Q8TCJ0; 16.
DR   STRING; 9606.ENSP00000372274; -.
DR   iPTMnet; Q8TCJ0; -.
DR   PhosphoSitePlus; Q8TCJ0; -.
DR   BioMuta; FBXO25; -.
DR   EPD; Q8TCJ0; -.
DR   MassIVE; Q8TCJ0; -.
DR   MaxQB; Q8TCJ0; -.
DR   PaxDb; 9606-ENSP00000372274; -.
DR   PeptideAtlas; Q8TCJ0; -.
DR   ProteomicsDB; 74143; -. [Q8TCJ0-1]
DR   ProteomicsDB; 74144; -. [Q8TCJ0-2]
DR   ProteomicsDB; 74145; -. [Q8TCJ0-3]
DR   Antibodypedia; 21946; 186 antibodies from 22 providers.
DR   DNASU; 26260; -.
DR   Ensembl; ENST00000276326.9; ENSP00000276326.6; ENSG00000147364.17. [Q8TCJ0-3]
DR   Ensembl; ENST00000350302.8; ENSP00000342077.4; ENSG00000147364.17. [Q8TCJ0-2]
DR   Ensembl; ENST00000352684.2; ENSP00000341345.2; ENSG00000147364.17. [Q8TCJ0-3]
DR   Ensembl; ENST00000382824.5; ENSP00000372274.2; ENSG00000147364.17. [Q8TCJ0-1]
DR   GeneID; 26260; -.
DR   KEGG; hsa:26260; -.
DR   MANE-Select; ENST00000350302.8; ENSP00000342077.4; NM_183420.2; NP_904356.1. [Q8TCJ0-2]
DR   UCSC; uc003woy.4; human. [Q8TCJ0-1]
DR   AGR; HGNC:13596; -.
DR   CTD; 26260; -.
DR   DisGeNET; 26260; -.
DR   GeneCards; FBXO25; -.
DR   HGNC; HGNC:13596; FBXO25.
DR   HPA; ENSG00000147364; Tissue enhanced (testis).
DR   MIM; 609098; gene.
DR   neXtProt; NX_Q8TCJ0; -.
DR   OpenTargets; ENSG00000147364; -.
DR   PharmGKB; PA28038; -.
DR   VEuPathDB; HostDB:ENSG00000147364; -.
DR   eggNOG; KOG3926; Eukaryota.
DR   GeneTree; ENSGT00390000004915; -.
DR   HOGENOM; CLU_065667_0_0_1; -.
DR   InParanoid; Q8TCJ0; -.
DR   OMA; RFNYICK; -.
DR   OrthoDB; 3058135at2759; -.
DR   PhylomeDB; Q8TCJ0; -.
DR   TreeFam; TF313070; -.
DR   PathwayCommons; Q8TCJ0; -.
DR   SignaLink; Q8TCJ0; -.
DR   SIGNOR; Q8TCJ0; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 26260; 18 hits in 1200 CRISPR screens.
DR   ChiTaRS; FBXO25; human.
DR   GenomeRNAi; 26260; -.
DR   Pharos; Q8TCJ0; Tbio.
DR   PRO; PR:Q8TCJ0; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q8TCJ0; Protein.
DR   Bgee; ENSG00000147364; Expressed in left testis and 185 other cell types or tissues.
DR   ExpressionAtlas; Q8TCJ0; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0019005; C:SCF ubiquitin ligase complex; ISS:UniProtKB.
DR   GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR   GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; NAS:UniProtKB.
DR   GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR   CDD; cd22099; F-box_FBXO25; 1.
DR   Gene3D; 1.20.1280.50; -; 1.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR040394; FBX25/32.
DR   PANTHER; PTHR13123:SF8; F-BOX ONLY PROTEIN 25; 1.
DR   PANTHER; PTHR13123; LD30288P; 1.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   Genevisible; Q8TCJ0; HS.
PE   1: Evidence at protein level;
KW   Actin-binding; Alternative splicing; Chromosomal rearrangement;
KW   Direct protein sequencing; Nucleus; Reference proteome;
KW   Ubl conjugation pathway.
FT   CHAIN           1..367
FT                   /note="F-box only protein 25"
FT                   /id="PRO_0000119911"
FT   DOMAIN          226..274
FT                   /note="F-box"
FT   REGION          1..83
FT                   /note="Interaction with beta-actin"
FT   VAR_SEQ         1..67
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013060"
FT   VAR_SEQ         68..96
FT                   /note="KKDHFRNDTNTQSFYREKWIYVHKESTKE -> MEKYSIMKSMNMHRKKGKR
FT                   TILEMTQILK (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_013061"
FT   VAR_SEQ         331..339
FT                   /note="Missing (in isoform 2 and isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:10531035,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|Ref.1,
FT                   ECO:0000303|Ref.2"
FT                   /id="VSP_007374"
FT   VARIANT         36
FT                   /note="N -> D (in dbSNP:rs17665340)"
FT                   /id="VAR_049043"
FT   VARIANT         38
FT                   /note="R -> H (in dbSNP:rs10090550)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_061167"
FT   MUTAGEN         244
FT                   /note="S->L: Loss of SKP1-binding."
FT                   /evidence="ECO:0000269|PubMed:16278047"
FT   CONFLICT        87..96
FT                   /note="IYVHKESTKE -> LILTSVLLFQ (in Ref. 4; AAF04526)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        121
FT                   /note="R -> T (in Ref. 4; AAF04526)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   367 AA;  43313 MW;  1C1C6AD43A92754F CRC64;
     MPFLGQDWRS PGWSWIKTED GWKRCESCSQ KLERENNRCN ISHSIILNSE DGEIFNNEEH
     EYASKKRKKD HFRNDTNTQS FYREKWIYVH KESTKERHGY CTLGEAFNRL DFSSAIQDIR
     RFNYVVKLLQ LIAKSQLTSL SGVAQKNYFN ILDKIVQKVL DDHHNPRLIK DLLQDLSSTL
     CILIRGVGKS VLVGNINIWI CRLETILAWQ QQLQDLQMTK QVNNGLTLSD LPLHMLNNIL
     YRFSDGWDII TLGQVTPTLY MLSEDRQLWK KLCQYHFAEK QFCRHLILSE KGHIEWKLMY
     FALQKHYPAK EQYGDTLHFC RHCSILFWKD YHLALLFKDS GHPCTAADPD SCFTPVSPQH
     FIDLFKF
//