Full text data of FBXO7
FBXO7
(FBX7)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
F-box only protein 7
Note: presumably soluble (membrane word is not in UniProt keywords or features)
F-box only protein 7
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00294567
IPI00294567 F-box only protein 7 Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00294567 F-box only protein 7 Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q9Y3I1
ID FBX7_HUMAN Reviewed; 522 AA.
AC Q9Y3I1; B4DNB3; B4DWX5; Q5TGC4; Q5TI86; Q96HM6; Q9UF21; Q9UKT2;
read moreDT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 124.
DE RecName: Full=F-box only protein 7;
GN Name=FBXO7; Synonyms=FBX7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10945468; DOI=10.1006/geno.2000.6211;
RA Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.;
RT "cDNA cloning and expression analysis of new members of the mammalian
RT F-box protein family.";
RL Genomics 67:40-47(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12529303; DOI=10.1101/gr.695703;
RA Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J.,
RA Knowles S., Bye J.M., Beare D.M., Dunham I.;
RT "Reevaluating human gene annotation: a second-generation analysis of
RT chromosome 22.";
RL Genome Res. 13:27-36(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ILE-115.
RC TISSUE=Heart, and Testis;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ILE-115.
RC TISSUE=Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-522 (ISOFORM 1), AND VARIANT ILE-115.
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 [8]
RP INTERACTION WITH DLGAP5, AND IDENTIFICATION IN SCF COMPLEX.
RX PubMed=12527899; DOI=10.1038/sj.onc.1206129;
RA Tsou A.-P., Yang C.-W., Huang C.-Y.F., Yu R.C.-T., Lee Y.-C.G.,
RA Chang C.-W., Chen B.-R., Chung Y.-F., Fann M.-J., Chi C.-W.,
RA Chiu J.-H., Chou C.-K.;
RT "Identification of a novel cell cycle regulated gene, HURP,
RT overexpressed in human hepatocellular carcinoma.";
RL Oncogene 22:298-307(2003).
RN [9]
RP INTERACTION WITH DLGAP5; CUL1 AND SKP1, AND FUNCTION IN UBIQUITINATION
RP OF DLGAP5.
RX PubMed=15145941; DOI=10.1074/jbc.M404950200;
RA Hsu J.-M., Lee Y.-C.G., Yu C.-T.R., Huang C.-Y.F.;
RT "Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-
RT phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a
RT proline-rich region.";
RL J. Biol. Chem. 279:32592-32602(2004).
RN [10]
RP INTERACTION WITH CDK6, AND SUBCELLULAR LOCATION.
RX PubMed=16096642; DOI=10.1038/sj.emboj.7600775;
RA Laman H., Funes J.M., Ye H., Henderson S., Galinanes-Garcia L.,
RA Hara E., Knowles P., McDonald N., Boshoff C.;
RT "Transforming activity of Fbxo7 is mediated specifically through
RT regulation of cyclin D/cdk6.";
RL EMBO J. 24:3104-3116(2005).
RN [11]
RP INTERACTION WITH BIRC2, AND FUNCTION IN UBIQUITINATION OF BIRC2.
RX PubMed=16510124; DOI=10.1016/j.bbrc.2006.02.061;
RA Chang Y.F., Cheng C.M., Chang L.K., Jong Y.J., Yuo C.Y.;
RT "The F-box protein Fbxo7 interacts with human inhibitor of apoptosis
RT protein cIAP1 and promotes cIAP1 ubiquitination.";
RL Biochem. Biophys. Res. Commun. 342:1022-1026(2006).
RN [12]
RP VARIANT PARK15 GLY-378, AND VARIANT ILE-115.
RX PubMed=18513678; DOI=10.1016/j.ajhg.2008.05.005;
RA Shojaee S., Sina F., Banihosseini S.S., Kazemi M.H., Kalhor R.,
RA Shahidi G.-A., Fakhrai-Rad H., Ronaghi M., Elahi E.;
RT "Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome
RT pedigree by 500 K SNP arrays.";
RL Am. J. Hum. Genet. 82:1375-1384(2008).
RN [13]
RP VARIANT CYS-481.
RX PubMed=20853184; DOI=10.1007/s10048-010-0259-0;
RA Santoro L., Breedveld G.J., Manganelli F., Iodice R., Pisciotta C.,
RA Nolano M., Punzo F., Quarantelli M., Pappata S., Di Fonzo A.,
RA Oostra B.A., Bonifati V.;
RT "Novel ATP13A2 (PARK9) homozygous mutation in a family with marked
RT phenotype variability.";
RL Neurogenetics 12:33-39(2011).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-
CC box protein) E3 ubiquitin-protein ligase complex which mediates
CC the ubiquitination and subsequent proteasomal degradation of
CC target proteins. Recognizes BIRC2 and DLGAP5.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein
CC ligase complex SCF(FBXO7) formed of CUL1, SKP1, RBX1 and FBXO7.
CC Interacts via its C-terminal proline-rich region with DLGAP5.
CC Interacts with BIRC2. Interacts with CDK6 and promotes its
CC interaction with D-type cyclin.
CC -!- INTERACTION:
CC P63208:SKP1; NbExp=2; IntAct=EBI-1161222, EBI-307486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y3I1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3I1-2; Sequence=VSP_041073, VSP_041074;
CC Name=3;
CC IsoId=Q9Y3I1-3; Sequence=VSP_044723;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Parkinson disease 15 (PARK15) [MIM:260300]: A
CC neurodegenerative disorder characterized by parkinsonian and
CC pyramidal signs. Clinical manifestations include tremor,
CC bradykinesia, rigidity, postural instability, spasticity, mainly
CC in the lower limbs, and hyperreflexia. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 F-box domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF04471.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF233225; AAF67155.1; -; mRNA.
DR EMBL; AL050254; CAB43356.1; -; mRNA.
DR EMBL; CR456491; CAG30377.1; -; mRNA.
DR EMBL; AK297841; BAG60175.1; -; mRNA.
DR EMBL; AK301716; BAG63187.1; -; mRNA.
DR EMBL; AL021937; CAI19587.1; -; Genomic_DNA.
DR EMBL; AL035068; CAI19587.1; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19587.1; JOINED; Genomic_DNA.
DR EMBL; AL021937; CAI19588.2; -; Genomic_DNA.
DR EMBL; AL035068; CAI19588.2; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19588.2; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI19333.1; -; Genomic_DNA.
DR EMBL; AL021937; CAI19333.1; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19333.1; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI19334.2; -; Genomic_DNA.
DR EMBL; AL021937; CAI19334.2; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19334.2; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI18782.1; -; Genomic_DNA.
DR EMBL; AL021937; CAI18782.1; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI18782.1; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI18783.2; -; Genomic_DNA.
DR EMBL; AL021937; CAI18783.2; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI18783.2; JOINED; Genomic_DNA.
DR EMBL; BC008361; AAH08361.1; -; mRNA.
DR EMBL; AF129537; AAF04471.1; ALT_INIT; mRNA.
DR RefSeq; NP_001028196.1; NM_001033024.1.
DR RefSeq; NP_001244919.1; NM_001257990.1.
DR RefSeq; NP_036311.3; NM_012179.3.
DR UniGene; Hs.5912; -.
DR ProteinModelPortal; Q9Y3I1; -.
DR DIP; DIP-36125N; -.
DR IntAct; Q9Y3I1; 7.
DR MINT; MINT-108554; -.
DR STRING; 9606.ENSP00000266087; -.
DR PhosphoSite; Q9Y3I1; -.
DR DMDM; 13124249; -.
DR PaxDb; Q9Y3I1; -.
DR PRIDE; Q9Y3I1; -.
DR DNASU; 25793; -.
DR Ensembl; ENST00000266087; ENSP00000266087; ENSG00000100225.
DR Ensembl; ENST00000382058; ENSP00000371490; ENSG00000100225.
DR Ensembl; ENST00000397426; ENSP00000380571; ENSG00000100225.
DR GeneID; 25793; -.
DR KEGG; hsa:25793; -.
DR UCSC; uc003amq.3; human.
DR CTD; 25793; -.
DR GeneCards; GC22P032870; -.
DR HGNC; HGNC:13586; FBXO7.
DR HPA; CAB034296; -.
DR HPA; HPA032114; -.
DR MIM; 260300; phenotype.
DR MIM; 605648; gene.
DR neXtProt; NX_Q9Y3I1; -.
DR Orphanet; 171695; Parkinsonian-pyramidal syndrome.
DR PharmGKB; PA28047; -.
DR eggNOG; NOG78399; -.
DR HOGENOM; HOG000112551; -.
DR HOVERGEN; HBG005648; -.
DR KO; K10293; -.
DR OMA; PLCEGGS; -.
DR OrthoDB; EOG7S7SDG; -.
DR PhylomeDB; Q9Y3I1; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; FBXO7; human.
DR GeneWiki; FBXO7; -.
DR GenomeRNAi; 25793; -.
DR NextBio; 46969; -.
DR PRO; PR:Q9Y3I1; -.
DR ArrayExpress; Q9Y3I1; -.
DR Bgee; Q9Y3I1; -.
DR CleanEx; HS_FBXO7; -.
DR Genevestigator; Q9Y3I1; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:ProtInc.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; TAS:ProtInc.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR021625; FP_dom.
DR Pfam; PF00646; F-box; 1.
DR Pfam; PF11566; PI31_Prot_N; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Disease mutation;
KW Neurodegeneration; Nucleus; Parkinsonism; Polymorphism;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1 522 F-box only protein 7.
FT /FTId=PRO_0000119885.
FT DOMAIN 329 375 F-box.
FT VAR_SEQ 1 114 Missing (in isoform 3).
FT /FTId=VSP_044723.
FT VAR_SEQ 1 79 Missing (in isoform 2).
FT /FTId=VSP_041073.
FT VAR_SEQ 80 91 DDIPAPNIPSST -> MARPPGGSGPLL (in isoform
FT 2).
FT /FTId=VSP_041074.
FT VARIANT 115 115 M -> I (in dbSNP:rs11107).
FT /FTId=VAR_021408.
FT VARIANT 378 378 R -> G (in PARK15; dbSNP:rs71799110).
FT /FTId=VAR_047938.
FT VARIANT 481 481 R -> C (found in two patients with Kufor-
FT Rakeb syndrome also carrying R-877 in
FT ATP13A2).
FT /FTId=VAR_066022.
FT CONFLICT 79 79 Q -> H (in Ref. 7; AAF04471).
FT CONFLICT 84 84 A -> P (in Ref. 7; AAF04471).
FT CONFLICT 154 154 N -> S (in Ref. 4; BAG63187).
FT CONFLICT 169 169 M -> L (in Ref. 7; AAF04471).
FT CONFLICT 224 224 M -> L (in Ref. 7; AAF04471).
FT CONFLICT 241 241 P -> H (in Ref. 7; AAF04471).
FT CONFLICT 328 328 D -> N (in Ref. 7; AAF04471).
FT CONFLICT 413 413 M -> L (in Ref. 7; AAF04471).
FT CONFLICT 475 475 F -> L (in Ref. 7; AAF04471).
SQ SEQUENCE 522 AA; 58503 MW; C4E5E70A0747287A CRC64;
MRLRVRLLKR TWPLEVPETE PTLGHLRSHL RQSLLCTWGY SSNTRFTITL NYKDPLTGDE
ETLASYGIVS GDLICLILQD DIPAPNIPSS TDSEHSSLQN NEQPSLATSS NQTSMQDEQP
SDSFQGQAAQ SGVWNDDSML GPSQNFEAES IQDNAHMAEG TGFYPSEPML CSESVEGQVP
HSLETLYQSA DCSDANDALI VLIHLLMLES GYIPQGTEAK ALSMPEKWKL SGVYKLQYMH
PLCEGSSATL TCVPLGNLIV VNATLKINNE IRSVKRLQLL PESFICKEKL GENVANIYKD
LQKLSRLFKD QLVYPLLAFT RQALNLPDVF GLVVLPLELK LRIFRLLDVR SVLSLSAVCR
DLFTASNDPL LWRFLYLRDF RDNTVRVQDT DWKELYRKRH IQRKESPKGR FVMLLPSSTH
TIPFYPNPLH PRPFPSSRLP PGIIGGEYDQ RPTLPYVGDP ISSLIPGPGE TPSQFPPLRP
RFDPVGPLPG PNPILPGRGG PNDRFPFRPS RGRPTDGRLS FM
//
ID FBX7_HUMAN Reviewed; 522 AA.
AC Q9Y3I1; B4DNB3; B4DWX5; Q5TGC4; Q5TI86; Q96HM6; Q9UF21; Q9UKT2;
read moreDT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 124.
DE RecName: Full=F-box only protein 7;
GN Name=FBXO7; Synonyms=FBX7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10945468; DOI=10.1006/geno.2000.6211;
RA Ilyin G.P., Rialland M., Pigeon C., Guguen-Guillouzo C.;
RT "cDNA cloning and expression analysis of new members of the mammalian
RT F-box protein family.";
RL Genomics 67:40-47(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12529303; DOI=10.1101/gr.695703;
RA Collins J.E., Goward M.E., Cole C.G., Smink L.J., Huckle E.J.,
RA Knowles S., Bye J.M., Beare D.M., Dunham I.;
RT "Reevaluating human gene annotation: a second-generation analysis of
RT chromosome 22.";
RL Genome Res. 13:27-36(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANT
RP ILE-115.
RC TISSUE=Heart, and Testis;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP ILE-115.
RC TISSUE=Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-522 (ISOFORM 1), AND VARIANT ILE-115.
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 [8]
RP INTERACTION WITH DLGAP5, AND IDENTIFICATION IN SCF COMPLEX.
RX PubMed=12527899; DOI=10.1038/sj.onc.1206129;
RA Tsou A.-P., Yang C.-W., Huang C.-Y.F., Yu R.C.-T., Lee Y.-C.G.,
RA Chang C.-W., Chen B.-R., Chung Y.-F., Fann M.-J., Chi C.-W.,
RA Chiu J.-H., Chou C.-K.;
RT "Identification of a novel cell cycle regulated gene, HURP,
RT overexpressed in human hepatocellular carcinoma.";
RL Oncogene 22:298-307(2003).
RN [9]
RP INTERACTION WITH DLGAP5; CUL1 AND SKP1, AND FUNCTION IN UBIQUITINATION
RP OF DLGAP5.
RX PubMed=15145941; DOI=10.1074/jbc.M404950200;
RA Hsu J.-M., Lee Y.-C.G., Yu C.-T.R., Huang C.-Y.F.;
RT "Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-
RT phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a
RT proline-rich region.";
RL J. Biol. Chem. 279:32592-32602(2004).
RN [10]
RP INTERACTION WITH CDK6, AND SUBCELLULAR LOCATION.
RX PubMed=16096642; DOI=10.1038/sj.emboj.7600775;
RA Laman H., Funes J.M., Ye H., Henderson S., Galinanes-Garcia L.,
RA Hara E., Knowles P., McDonald N., Boshoff C.;
RT "Transforming activity of Fbxo7 is mediated specifically through
RT regulation of cyclin D/cdk6.";
RL EMBO J. 24:3104-3116(2005).
RN [11]
RP INTERACTION WITH BIRC2, AND FUNCTION IN UBIQUITINATION OF BIRC2.
RX PubMed=16510124; DOI=10.1016/j.bbrc.2006.02.061;
RA Chang Y.F., Cheng C.M., Chang L.K., Jong Y.J., Yuo C.Y.;
RT "The F-box protein Fbxo7 interacts with human inhibitor of apoptosis
RT protein cIAP1 and promotes cIAP1 ubiquitination.";
RL Biochem. Biophys. Res. Commun. 342:1022-1026(2006).
RN [12]
RP VARIANT PARK15 GLY-378, AND VARIANT ILE-115.
RX PubMed=18513678; DOI=10.1016/j.ajhg.2008.05.005;
RA Shojaee S., Sina F., Banihosseini S.S., Kazemi M.H., Kalhor R.,
RA Shahidi G.-A., Fakhrai-Rad H., Ronaghi M., Elahi E.;
RT "Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome
RT pedigree by 500 K SNP arrays.";
RL Am. J. Hum. Genet. 82:1375-1384(2008).
RN [13]
RP VARIANT CYS-481.
RX PubMed=20853184; DOI=10.1007/s10048-010-0259-0;
RA Santoro L., Breedveld G.J., Manganelli F., Iodice R., Pisciotta C.,
RA Nolano M., Punzo F., Quarantelli M., Pappata S., Di Fonzo A.,
RA Oostra B.A., Bonifati V.;
RT "Novel ATP13A2 (PARK9) homozygous mutation in a family with marked
RT phenotype variability.";
RL Neurogenetics 12:33-39(2011).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-
CC box protein) E3 ubiquitin-protein ligase complex which mediates
CC the ubiquitination and subsequent proteasomal degradation of
CC target proteins. Recognizes BIRC2 and DLGAP5.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein
CC ligase complex SCF(FBXO7) formed of CUL1, SKP1, RBX1 and FBXO7.
CC Interacts via its C-terminal proline-rich region with DLGAP5.
CC Interacts with BIRC2. Interacts with CDK6 and promotes its
CC interaction with D-type cyclin.
CC -!- INTERACTION:
CC P63208:SKP1; NbExp=2; IntAct=EBI-1161222, EBI-307486;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9Y3I1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y3I1-2; Sequence=VSP_041073, VSP_041074;
CC Name=3;
CC IsoId=Q9Y3I1-3; Sequence=VSP_044723;
CC Note=No experimental confirmation available;
CC -!- DISEASE: Parkinson disease 15 (PARK15) [MIM:260300]: A
CC neurodegenerative disorder characterized by parkinsonian and
CC pyramidal signs. Clinical manifestations include tremor,
CC bradykinesia, rigidity, postural instability, spasticity, mainly
CC in the lower limbs, and hyperreflexia. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 F-box domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF04471.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF233225; AAF67155.1; -; mRNA.
DR EMBL; AL050254; CAB43356.1; -; mRNA.
DR EMBL; CR456491; CAG30377.1; -; mRNA.
DR EMBL; AK297841; BAG60175.1; -; mRNA.
DR EMBL; AK301716; BAG63187.1; -; mRNA.
DR EMBL; AL021937; CAI19587.1; -; Genomic_DNA.
DR EMBL; AL035068; CAI19587.1; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19587.1; JOINED; Genomic_DNA.
DR EMBL; AL021937; CAI19588.2; -; Genomic_DNA.
DR EMBL; AL035068; CAI19588.2; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19588.2; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI19333.1; -; Genomic_DNA.
DR EMBL; AL021937; CAI19333.1; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19333.1; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI19334.2; -; Genomic_DNA.
DR EMBL; AL021937; CAI19334.2; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI19334.2; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI18782.1; -; Genomic_DNA.
DR EMBL; AL021937; CAI18782.1; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI18782.1; JOINED; Genomic_DNA.
DR EMBL; Z71183; CAI18783.2; -; Genomic_DNA.
DR EMBL; AL021937; CAI18783.2; JOINED; Genomic_DNA.
DR EMBL; AL035068; CAI18783.2; JOINED; Genomic_DNA.
DR EMBL; BC008361; AAH08361.1; -; mRNA.
DR EMBL; AF129537; AAF04471.1; ALT_INIT; mRNA.
DR RefSeq; NP_001028196.1; NM_001033024.1.
DR RefSeq; NP_001244919.1; NM_001257990.1.
DR RefSeq; NP_036311.3; NM_012179.3.
DR UniGene; Hs.5912; -.
DR ProteinModelPortal; Q9Y3I1; -.
DR DIP; DIP-36125N; -.
DR IntAct; Q9Y3I1; 7.
DR MINT; MINT-108554; -.
DR STRING; 9606.ENSP00000266087; -.
DR PhosphoSite; Q9Y3I1; -.
DR DMDM; 13124249; -.
DR PaxDb; Q9Y3I1; -.
DR PRIDE; Q9Y3I1; -.
DR DNASU; 25793; -.
DR Ensembl; ENST00000266087; ENSP00000266087; ENSG00000100225.
DR Ensembl; ENST00000382058; ENSP00000371490; ENSG00000100225.
DR Ensembl; ENST00000397426; ENSP00000380571; ENSG00000100225.
DR GeneID; 25793; -.
DR KEGG; hsa:25793; -.
DR UCSC; uc003amq.3; human.
DR CTD; 25793; -.
DR GeneCards; GC22P032870; -.
DR HGNC; HGNC:13586; FBXO7.
DR HPA; CAB034296; -.
DR HPA; HPA032114; -.
DR MIM; 260300; phenotype.
DR MIM; 605648; gene.
DR neXtProt; NX_Q9Y3I1; -.
DR Orphanet; 171695; Parkinsonian-pyramidal syndrome.
DR PharmGKB; PA28047; -.
DR eggNOG; NOG78399; -.
DR HOGENOM; HOG000112551; -.
DR HOVERGEN; HBG005648; -.
DR KO; K10293; -.
DR OMA; PLCEGGS; -.
DR OrthoDB; EOG7S7SDG; -.
DR PhylomeDB; Q9Y3I1; -.
DR UniPathway; UPA00143; -.
DR ChiTaRS; FBXO7; human.
DR GeneWiki; FBXO7; -.
DR GenomeRNAi; 25793; -.
DR NextBio; 46969; -.
DR PRO; PR:Q9Y3I1; -.
DR ArrayExpress; Q9Y3I1; -.
DR Bgee; Q9Y3I1; -.
DR CleanEx; HS_FBXO7; -.
DR Genevestigator; Q9Y3I1; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; TAS:ProtInc.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; TAS:ProtInc.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR021625; FP_dom.
DR Pfam; PF00646; F-box; 1.
DR Pfam; PF11566; PI31_Prot_N; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Disease mutation;
KW Neurodegeneration; Nucleus; Parkinsonism; Polymorphism;
KW Reference proteome; Ubl conjugation pathway.
FT CHAIN 1 522 F-box only protein 7.
FT /FTId=PRO_0000119885.
FT DOMAIN 329 375 F-box.
FT VAR_SEQ 1 114 Missing (in isoform 3).
FT /FTId=VSP_044723.
FT VAR_SEQ 1 79 Missing (in isoform 2).
FT /FTId=VSP_041073.
FT VAR_SEQ 80 91 DDIPAPNIPSST -> MARPPGGSGPLL (in isoform
FT 2).
FT /FTId=VSP_041074.
FT VARIANT 115 115 M -> I (in dbSNP:rs11107).
FT /FTId=VAR_021408.
FT VARIANT 378 378 R -> G (in PARK15; dbSNP:rs71799110).
FT /FTId=VAR_047938.
FT VARIANT 481 481 R -> C (found in two patients with Kufor-
FT Rakeb syndrome also carrying R-877 in
FT ATP13A2).
FT /FTId=VAR_066022.
FT CONFLICT 79 79 Q -> H (in Ref. 7; AAF04471).
FT CONFLICT 84 84 A -> P (in Ref. 7; AAF04471).
FT CONFLICT 154 154 N -> S (in Ref. 4; BAG63187).
FT CONFLICT 169 169 M -> L (in Ref. 7; AAF04471).
FT CONFLICT 224 224 M -> L (in Ref. 7; AAF04471).
FT CONFLICT 241 241 P -> H (in Ref. 7; AAF04471).
FT CONFLICT 328 328 D -> N (in Ref. 7; AAF04471).
FT CONFLICT 413 413 M -> L (in Ref. 7; AAF04471).
FT CONFLICT 475 475 F -> L (in Ref. 7; AAF04471).
SQ SEQUENCE 522 AA; 58503 MW; C4E5E70A0747287A CRC64;
MRLRVRLLKR TWPLEVPETE PTLGHLRSHL RQSLLCTWGY SSNTRFTITL NYKDPLTGDE
ETLASYGIVS GDLICLILQD DIPAPNIPSS TDSEHSSLQN NEQPSLATSS NQTSMQDEQP
SDSFQGQAAQ SGVWNDDSML GPSQNFEAES IQDNAHMAEG TGFYPSEPML CSESVEGQVP
HSLETLYQSA DCSDANDALI VLIHLLMLES GYIPQGTEAK ALSMPEKWKL SGVYKLQYMH
PLCEGSSATL TCVPLGNLIV VNATLKINNE IRSVKRLQLL PESFICKEKL GENVANIYKD
LQKLSRLFKD QLVYPLLAFT RQALNLPDVF GLVVLPLELK LRIFRLLDVR SVLSLSAVCR
DLFTASNDPL LWRFLYLRDF RDNTVRVQDT DWKELYRKRH IQRKESPKGR FVMLLPSSTH
TIPFYPNPLH PRPFPSSRLP PGIIGGEYDQ RPTLPYVGDP ISSLIPGPGE TPSQFPPLRP
RFDPVGPLPG PNPILPGRGG PNDRFPFRPS RGRPTDGRLS FM
//
MIM
260300
*RECORD*
*FIELD* NO
260300
*FIELD* TI
#260300 PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE EARLY-ONSET; PARK15
;;PARKINSONIAN-PYRAMIDAL SYNDROME; PKPS;;
read morePALLIDOPYRAMIDAL SYNDROME;;
PALLIDO-PYRAMIDAL SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because Parkinson disease-15
(PARK15), also known as the parkinsonian-pyramidal syndrome, is caused
by mutation in the FBXO7 gene (605648).
For a phenotypic description and a discussion of genetic heterogeneity
of Parkinson disease, see PD (168600).
CLINICAL FEATURES
Davison (1954) described 5 affected cases in 3 families. In 1 family, a
brother and sister with first-cousin parents were affected, and in
another family, a brother and sister with uncle-niece parents were
affected. The illness began in the second or early third decade with the
picture of paralysis agitans and pyramidal tract signs. Postmortem
examination showed pallor of the pallidal segments, thinning of the ansa
lenticularis, slight shrinkage and cellular change in the substantia
nigra, and early demyelination of the pyramids and crossed pyramidal
tracts. One of Davison's cases had been reported by Ramsey Hunt (1917).
Tremor and rigidity of 'paralysis agitans' type, parkinsonism, began at
age 13. Clinically, Wilson disease was considered likely for a time. The
patient survived until age 65 years. Lange and Poppe (1963) may have
described the same disorder as familial progressive pallidum atrophy in
6 sibs. Lange et al. (1970) gave information on the autopsy findings.
Horowitz and Greenberg (1975) reported a brother and sister who
developed parkinsonism in the first decade of life. They both later
developed symptoms of cortical spinal tract disease, similar to the
disorder described by Davison (1954). Clinical features included tremor,
rigidity, akinesia, scissor gait, and hyperreflexia. The disorder was
progressive until the institution of levodopa treatment at the ages of
18 and 20 years, respectively. The extremely favorable response of the
extrapyramidal signs and the lack of equal response of the pyramidal
tract signs demonstrated the specificity of the pharmacologic agent.
Livingstone (1983) described a family with affected brother and sister.
Nisipeanu et al. (1994) reported 2 unrelated consanguineous families in
which 2 sibs each had levodopa-responsive parkinsonian-pyramidal
syndrome. In the first family, of Libyan Jewish descent, a brother and
sister both developed spasticity and hyperreflexia of the lower limbs at
age 12 years. The disorder was progressive and resulted in impaired gait
and later development of extrapyramidal signs, including tremor and
bradykinesia. Two brothers in the second family, born of consanguineous
Iraqi Jewish parents, developed lower limb spasticity at ages 21 and 23
years, respectively. Extrapyramidal signs became apparent about 3 years
later. All 4 patients showed good response to levodopa treatment.
Nisipeanu et al. (1994) noted that since no autopsy information was
available in their patients to identify precise anatomic involvement,
the term 'parkinsonian-pyramidal syndrome' would be more appropriate
than 'pallido-pyramidal syndrome.'
Srivastava et al. (2005) reported a 22-year-old Indian woman, born of
consanguineous parents, with a history of progressive bradykinesia and
stiffness from age 12 years. From age 20, she developed blepharospasm
with rapid worsening of the bradykinesia, stiffness, and postural
instability confining her to bed. She also reported urinary frequency
and urgency as well as ankle clonus. Physical examination showed
mask-like face, monotonous speech, slow saccades, hyperreflexia,
extensor plantar responses, and mild intention tremor. Cognition was
normal. Brain MRI showed bilateral calcifications in the basal ganglia,
which the authors suggested may be idiopathic. She had a favorable
clinical response to L-dopa.
Panagariya et al. (2007) reported a 19-year-old Indian man with an
18-month history of gradually progressive difficulty in walking,
abnormal movements of the neck, and slow monotonous voice. He later
developed postural tremors in both upper limbs, abnormal body posturing,
and perioral dyskinesias. There was no family history of a neurologic
disorder, and he had no memory impairment. Physical examination showed
asymmetric pyramidal weakness and cogwheel rigidity in all 4 limbs.
Single photon emission tomography (SPECT) scan revealed hypoperfusion in
the left frontoparietal region and left basal ganglia and minimal
hypoperfusion in left temporal lobe. He had excellent clinical response
to L-dopa.
Shojaee et al. (2008) reported a large Iranian family with
parkinsonian-pyramidal syndrome. Inheritance was autosomal recessive.
All affected exhibited equinovarus deformity since childhood, but
pyramidal signs did not become apparent until young adulthood in the
third decade of life. All exhibited Babinski signs, hyperreflexia, and
spasticity restricted mainly to lower limbs. At the time of the report,
only the 3 most severely affected individuals showed detectable
extrapyramidal symptoms, including rigidity, bradykinesia, hypomimia,
and monotone speech. These symptoms became evident 5 to 20 years after
appearance of pyramidal symptoms. One patient who agreed to treatment
showed favorable response to L-dopa. None of the patients exhibited
tremor, upgaze paresis, dementia, or cerebellar signs.
Di Fonzo et al. (2009) reported 2 unrelated families, of Italian and
Dutch descent, respectively, with PARK15. Affected individuals had
juvenile onset (range, 10 to 19 years) of progressive parkinsonism
associated with spasticity, hyperreflexia, and variable response to
L-dopa. Disease progression was slow, and all patients were alive
decades after symptom onset.
MAPPING
Shojaee et al. (2008) performed genomewide linkage analysis of an
Iranian family with parkinsonian-pyramidal syndrome using 500 K SNP
arrays. The maximum parametric lod score under an autosomal recessive
model was 3.39 on chromosome 22q. The authors noted that the linkage may
have been missed had they used chips containing less than 100,000 SNPs
across the genome.
MOLECULAR GENETICS
In affected members of an Iranian family with parkinsonian-pyramidal
syndrome, Shojaee et al. (2008) identified a homozygous mutation in the
FBXO7 gene (605648.0001).
In affected members of an Italian and a Dutch family with PARK15, Di
Fonzo et al. (2009) identified homozygous (605648.0002) and compound
heterozygous (605648.0003 and 605648.0004) mutations in the FBXO7 gene,
respectively.
*FIELD* SA
Jellinger (1968)
*FIELD* RF
1. Davison, C.: Pallido-pyramidal disease. J. Neuropath. Exp. Neurol. 13:
50-59, 1954.
2. Di Fonzo, A.; Dekker, M. C. J.; Montagna, P.; Baruzzi, A.; Yonova,
E. H.; Correia Guedes, L.; Szczerbinska, A.; Zhao, T.; Dubbel-Hulsman,
L. O. M.; Wouters, C. H.; de Graaff, E.; Oyen, W. J. G.; Simons, E.
J.; Breedveld, G. J.; Oostra, B. A.; Horstink, M. W.; Bonifati, V.
: FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal
syndrome. Neurology 72: 240-245, 2009.
3. Horowitz, G.; Greenberg, J.: Pallido-pyramidal syndrome treated
with levodopa. J. Neurol. Neurosurg. Psychiat. 38: 238-240, 1975.
4. Hunt, J. R.: Progressive atrophy of the globus pallidus (primary
atrophy of the pallidal system): a system disease of the paralysis
agitans type, characterized by atrophy of the motor cells of the corpus
striatum; a contribution to the functions of the corpus striatum. Brain 40:
58-148, 1917.
5. Jellinger, K.: Progressive Pallidumatrophie. J. Neurol. Sci. 6:
19-44, 1968.
6. Lange, E.; Poppe, W.: Klinischer Beitrag zum Krankheitsbild der
progressiven Pallidumatrophie (van Bogaert). Psychiat. Neurol. 146:
176-192, 1963.
7. Lange, E.; Poppe, W.; Scholtze, P.: Familial progressive pallidum
atrophy. Europ. Neurol. 3: 265-267, 1970.
8. Livingstone, I. R.: Personal Communication. Baltimore, Md.
3/3/1983.
9. Nisipeanu, P.; Kuritzky, A.; Korczyn, A. D.: Familial levodopa-responsive
parkinsonian-pyramidal syndrome Mov. Disord. 9: 673-675, 1994.
10. Panagariya, A.; Sharma, B.; Dev, A.: Pallido-pyramidal syndrome:
a rare entity. (Letter) Indian J. Med. Sci. 61: 156-157, 2007.
11. Shojaee, S.; Sina, F.; Banihosseini, S. S.; Kazemi, M. H.; Kalhor,
R.; Shahidi, G.-A.; Fakhrai-Rad, H.; Ronaghi, M.; Elahi, E.: Genome-wide
linkage analysis of a parkinsonian-pyramidal syndrome pedigree by
500 K SNP arrays. Am. J. Hum. Genet. 82: 1375-1384, 2008.
12. Srivastava, T.; Goyal, V.; Singh, S.; Shukla, G.; Behari, M.:
Pallido-pyramidal syndrome with blepharospasm and good response to
levodopa. J. Neurol. 252: 1537-1538, 2005.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Reduced upgaze;
Slow saccades
SKELETAL:
[Feet];
Pes equinovarus
NEUROLOGIC:
[Central nervous system];
Pyramidal signs;
Spasticity, mainly in the lower limbs;
Hyperreflexia;
Scissor gait;
Extensor plantar responses;
Dystonia;
Extrapyramidal signs;
Parkinsonism;
Rigidity;
Bradykinesia;
Hypomimia;
Dysarthria;
Tremor;
Monotone speech;
Postural instability
VOICE:
Monotone speech
MISCELLANEOUS:
Onset in adolescence or young adulthood;
Childhood onset has been reported in 1 family;
Slow progression;
Extrapyramidal signs show a favorable response to levodopa
MOLECULAR BASIS:
Caused by mutation in the F-box only protein 7 gene (FBXO7, 605648.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 03/12/2009
Cassandra L. Kniffin - revised: 9/11/2008
*FIELD* ED
ckniffin: 03/12/2009
joanna: 10/10/2008
ckniffin: 9/11/2008
*FIELD* CN
Cassandra L. Kniffin - updated: 3/12/2009
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
ckniffin: 11/16/2010
alopez: 1/4/2010
wwang: 3/25/2009
ckniffin: 3/12/2009
wwang: 9/16/2008
ckniffin: 9/11/2008
mgross: 3/17/2004
warfield: 4/20/1994
mimadm: 3/11/1994
supermim: 3/17/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
*RECORD*
*FIELD* NO
260300
*FIELD* TI
#260300 PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE EARLY-ONSET; PARK15
;;PARKINSONIAN-PYRAMIDAL SYNDROME; PKPS;;
read morePALLIDOPYRAMIDAL SYNDROME;;
PALLIDO-PYRAMIDAL SYNDROME
*FIELD* TX
A number sign (#) is used with this entry because Parkinson disease-15
(PARK15), also known as the parkinsonian-pyramidal syndrome, is caused
by mutation in the FBXO7 gene (605648).
For a phenotypic description and a discussion of genetic heterogeneity
of Parkinson disease, see PD (168600).
CLINICAL FEATURES
Davison (1954) described 5 affected cases in 3 families. In 1 family, a
brother and sister with first-cousin parents were affected, and in
another family, a brother and sister with uncle-niece parents were
affected. The illness began in the second or early third decade with the
picture of paralysis agitans and pyramidal tract signs. Postmortem
examination showed pallor of the pallidal segments, thinning of the ansa
lenticularis, slight shrinkage and cellular change in the substantia
nigra, and early demyelination of the pyramids and crossed pyramidal
tracts. One of Davison's cases had been reported by Ramsey Hunt (1917).
Tremor and rigidity of 'paralysis agitans' type, parkinsonism, began at
age 13. Clinically, Wilson disease was considered likely for a time. The
patient survived until age 65 years. Lange and Poppe (1963) may have
described the same disorder as familial progressive pallidum atrophy in
6 sibs. Lange et al. (1970) gave information on the autopsy findings.
Horowitz and Greenberg (1975) reported a brother and sister who
developed parkinsonism in the first decade of life. They both later
developed symptoms of cortical spinal tract disease, similar to the
disorder described by Davison (1954). Clinical features included tremor,
rigidity, akinesia, scissor gait, and hyperreflexia. The disorder was
progressive until the institution of levodopa treatment at the ages of
18 and 20 years, respectively. The extremely favorable response of the
extrapyramidal signs and the lack of equal response of the pyramidal
tract signs demonstrated the specificity of the pharmacologic agent.
Livingstone (1983) described a family with affected brother and sister.
Nisipeanu et al. (1994) reported 2 unrelated consanguineous families in
which 2 sibs each had levodopa-responsive parkinsonian-pyramidal
syndrome. In the first family, of Libyan Jewish descent, a brother and
sister both developed spasticity and hyperreflexia of the lower limbs at
age 12 years. The disorder was progressive and resulted in impaired gait
and later development of extrapyramidal signs, including tremor and
bradykinesia. Two brothers in the second family, born of consanguineous
Iraqi Jewish parents, developed lower limb spasticity at ages 21 and 23
years, respectively. Extrapyramidal signs became apparent about 3 years
later. All 4 patients showed good response to levodopa treatment.
Nisipeanu et al. (1994) noted that since no autopsy information was
available in their patients to identify precise anatomic involvement,
the term 'parkinsonian-pyramidal syndrome' would be more appropriate
than 'pallido-pyramidal syndrome.'
Srivastava et al. (2005) reported a 22-year-old Indian woman, born of
consanguineous parents, with a history of progressive bradykinesia and
stiffness from age 12 years. From age 20, she developed blepharospasm
with rapid worsening of the bradykinesia, stiffness, and postural
instability confining her to bed. She also reported urinary frequency
and urgency as well as ankle clonus. Physical examination showed
mask-like face, monotonous speech, slow saccades, hyperreflexia,
extensor plantar responses, and mild intention tremor. Cognition was
normal. Brain MRI showed bilateral calcifications in the basal ganglia,
which the authors suggested may be idiopathic. She had a favorable
clinical response to L-dopa.
Panagariya et al. (2007) reported a 19-year-old Indian man with an
18-month history of gradually progressive difficulty in walking,
abnormal movements of the neck, and slow monotonous voice. He later
developed postural tremors in both upper limbs, abnormal body posturing,
and perioral dyskinesias. There was no family history of a neurologic
disorder, and he had no memory impairment. Physical examination showed
asymmetric pyramidal weakness and cogwheel rigidity in all 4 limbs.
Single photon emission tomography (SPECT) scan revealed hypoperfusion in
the left frontoparietal region and left basal ganglia and minimal
hypoperfusion in left temporal lobe. He had excellent clinical response
to L-dopa.
Shojaee et al. (2008) reported a large Iranian family with
parkinsonian-pyramidal syndrome. Inheritance was autosomal recessive.
All affected exhibited equinovarus deformity since childhood, but
pyramidal signs did not become apparent until young adulthood in the
third decade of life. All exhibited Babinski signs, hyperreflexia, and
spasticity restricted mainly to lower limbs. At the time of the report,
only the 3 most severely affected individuals showed detectable
extrapyramidal symptoms, including rigidity, bradykinesia, hypomimia,
and monotone speech. These symptoms became evident 5 to 20 years after
appearance of pyramidal symptoms. One patient who agreed to treatment
showed favorable response to L-dopa. None of the patients exhibited
tremor, upgaze paresis, dementia, or cerebellar signs.
Di Fonzo et al. (2009) reported 2 unrelated families, of Italian and
Dutch descent, respectively, with PARK15. Affected individuals had
juvenile onset (range, 10 to 19 years) of progressive parkinsonism
associated with spasticity, hyperreflexia, and variable response to
L-dopa. Disease progression was slow, and all patients were alive
decades after symptom onset.
MAPPING
Shojaee et al. (2008) performed genomewide linkage analysis of an
Iranian family with parkinsonian-pyramidal syndrome using 500 K SNP
arrays. The maximum parametric lod score under an autosomal recessive
model was 3.39 on chromosome 22q. The authors noted that the linkage may
have been missed had they used chips containing less than 100,000 SNPs
across the genome.
MOLECULAR GENETICS
In affected members of an Iranian family with parkinsonian-pyramidal
syndrome, Shojaee et al. (2008) identified a homozygous mutation in the
FBXO7 gene (605648.0001).
In affected members of an Italian and a Dutch family with PARK15, Di
Fonzo et al. (2009) identified homozygous (605648.0002) and compound
heterozygous (605648.0003 and 605648.0004) mutations in the FBXO7 gene,
respectively.
*FIELD* SA
Jellinger (1968)
*FIELD* RF
1. Davison, C.: Pallido-pyramidal disease. J. Neuropath. Exp. Neurol. 13:
50-59, 1954.
2. Di Fonzo, A.; Dekker, M. C. J.; Montagna, P.; Baruzzi, A.; Yonova,
E. H.; Correia Guedes, L.; Szczerbinska, A.; Zhao, T.; Dubbel-Hulsman,
L. O. M.; Wouters, C. H.; de Graaff, E.; Oyen, W. J. G.; Simons, E.
J.; Breedveld, G. J.; Oostra, B. A.; Horstink, M. W.; Bonifati, V.
: FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal
syndrome. Neurology 72: 240-245, 2009.
3. Horowitz, G.; Greenberg, J.: Pallido-pyramidal syndrome treated
with levodopa. J. Neurol. Neurosurg. Psychiat. 38: 238-240, 1975.
4. Hunt, J. R.: Progressive atrophy of the globus pallidus (primary
atrophy of the pallidal system): a system disease of the paralysis
agitans type, characterized by atrophy of the motor cells of the corpus
striatum; a contribution to the functions of the corpus striatum. Brain 40:
58-148, 1917.
5. Jellinger, K.: Progressive Pallidumatrophie. J. Neurol. Sci. 6:
19-44, 1968.
6. Lange, E.; Poppe, W.: Klinischer Beitrag zum Krankheitsbild der
progressiven Pallidumatrophie (van Bogaert). Psychiat. Neurol. 146:
176-192, 1963.
7. Lange, E.; Poppe, W.; Scholtze, P.: Familial progressive pallidum
atrophy. Europ. Neurol. 3: 265-267, 1970.
8. Livingstone, I. R.: Personal Communication. Baltimore, Md.
3/3/1983.
9. Nisipeanu, P.; Kuritzky, A.; Korczyn, A. D.: Familial levodopa-responsive
parkinsonian-pyramidal syndrome Mov. Disord. 9: 673-675, 1994.
10. Panagariya, A.; Sharma, B.; Dev, A.: Pallido-pyramidal syndrome:
a rare entity. (Letter) Indian J. Med. Sci. 61: 156-157, 2007.
11. Shojaee, S.; Sina, F.; Banihosseini, S. S.; Kazemi, M. H.; Kalhor,
R.; Shahidi, G.-A.; Fakhrai-Rad, H.; Ronaghi, M.; Elahi, E.: Genome-wide
linkage analysis of a parkinsonian-pyramidal syndrome pedigree by
500 K SNP arrays. Am. J. Hum. Genet. 82: 1375-1384, 2008.
12. Srivastava, T.; Goyal, V.; Singh, S.; Shukla, G.; Behari, M.:
Pallido-pyramidal syndrome with blepharospasm and good response to
levodopa. J. Neurol. 252: 1537-1538, 2005.
*FIELD* CS
INHERITANCE:
Autosomal recessive
HEAD AND NECK:
[Eyes];
Reduced upgaze;
Slow saccades
SKELETAL:
[Feet];
Pes equinovarus
NEUROLOGIC:
[Central nervous system];
Pyramidal signs;
Spasticity, mainly in the lower limbs;
Hyperreflexia;
Scissor gait;
Extensor plantar responses;
Dystonia;
Extrapyramidal signs;
Parkinsonism;
Rigidity;
Bradykinesia;
Hypomimia;
Dysarthria;
Tremor;
Monotone speech;
Postural instability
VOICE:
Monotone speech
MISCELLANEOUS:
Onset in adolescence or young adulthood;
Childhood onset has been reported in 1 family;
Slow progression;
Extrapyramidal signs show a favorable response to levodopa
MOLECULAR BASIS:
Caused by mutation in the F-box only protein 7 gene (FBXO7, 605648.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 03/12/2009
Cassandra L. Kniffin - revised: 9/11/2008
*FIELD* ED
ckniffin: 03/12/2009
joanna: 10/10/2008
ckniffin: 9/11/2008
*FIELD* CN
Cassandra L. Kniffin - updated: 3/12/2009
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
ckniffin: 11/16/2010
alopez: 1/4/2010
wwang: 3/25/2009
ckniffin: 3/12/2009
wwang: 9/16/2008
ckniffin: 9/11/2008
mgross: 3/17/2004
warfield: 4/20/1994
mimadm: 3/11/1994
supermim: 3/17/1992
supermim: 3/20/1990
ddp: 10/27/1989
marie: 3/25/1988
MIM
605648
*RECORD*
*FIELD* NO
605648
*FIELD* TI
*605648 F-BOX ONLY PROTEIN 7; FBXO7
;;FBX7;;
FBX
*FIELD* TX
DESCRIPTION
The F box, named after cyclin F (CCNF; 600227), in which it was
read moreoriginally observed, is an approximately 40-amino acid motif that binds
SKP1 (601434). F-box proteins, such as FBXO7, are components of modular
E3 ubiquitin protein ligases called SCFs (SKP1, cullin (see 603134),
F-box proteins), which function in phosphorylation-dependent
ubiquitination.
CLONING
Using a yeast 2-hybrid screen with SKP1 as bait, followed by searching
sequence databases, Winston et al. (1999) and Cenciarelli et al. (1999)
identified 33 mammalian and 26 human F-box proteins, respectively. These
contained C termini with leucine-rich repeats (FBXLs, e.g., SKP2
(601436)), WD40 domains (FBXWs, e.g., BTRCP (603482)), or no
recognizable motifs (FBXOs, e.g., CCNF). Using RT-PCR analysis, Winston
et al. (1999) found high expression of FBXO7 in brain, heart, kidney,
liver, lung, skeletal muscle, and placenta, with lower levels in
pancreas.
By searching sequence databases, Ilyin et al. (2000) identified a cDNA
encoding FBXO7, which they termed FBX. The deduced 522-amino acid
protein contains an F box in its C-terminal half. RNA blot analysis
detected ubiquitous expression, with greater abundance in bone marrow,
fetal liver, testis, and thyroid glands, followed by corpus callosum.
Jin et al. (2004) reported that the FBXO7 protein contains a
ubiquitin-like fold in its N-terminal half and an F box in its
C-terminal half.
Di Fonzo et al. (2009) identified 4 isoforms of FBXO7 expressed by
alternative combinations of exon 1A with exon 2A alone or exon 2A/2B and
of exon 1B with exon 2A alone or exon 2A/2B.
GENE STRUCTURE
Di Fonzo et al. (2009) noted that the FBXO7 gene contains 9 exons with a
translation start site in exons 1A and 1B, respectively, and alternative
splicing of exons 2A and 2B.
MAPPING
By genomic sequence analysis using mapped clones, Ilyin et al. (2000)
mapped the FBXO7 gene to chromosome 22q12-q13.
Jin et al. (2004) stated that the mouse Fbxo7 gene maps to chromosome
10C1.
GENE FUNCTION
Winston et al. (1999) showed that mouse Fbx7 interacted with SKP1 in
vitro and in transfected human embryonic kidney cells.
MOLECULAR GENETICS
In affected members of an Iranian family with parkinsonian-pyramidal
syndrome (PARK15; 260300), Shojaee et al. (2008) identified a homozygous
mutation in the FBXO7 gene (605648.0001).
In affected members of Italian and Dutch families with PARK15, Di Fonzo
et al. (2009) identified homozygous (605648.0002) and compound
heterozygous (605648.0003; 605648.0004) mutations in the FBXO7 gene,
respectively.
*FIELD* AV
.0001
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, ARG378GLY
In affected members of a large Iranian family with
parkinsonian-pyramidal syndrome (PARK15; 260300), Shojaee et al. (2008)
identified a homozygous 1132C-G transversion in the FBXO7 gene,
resulting in an arg378-to-gly (R378G) substitution in a highly conserved
residue. The mutation was not identified in 800 control individuals.
.0002
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, ARG498TER
In affected members of an Italian family with PARK15 (260300), Di Fonzo
et al. (2009) identified a homozygous 1492C-T transition in exon 9 of
the FBXO7 gene, resulting in an arg498-to-ter (R498X) substitution. The
unaffected parents were heterozygous for the mutation. The mutation was
not identified in 364 control chromosomes from the Italian population.
.0003
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, IVS7DS, G-T, +1
In affected members of a Dutch family with PARK15 (260300), Di Fonzo et
al. (2009) identified compound heterozygosity for 2 mutations in the
FBXO7 gene: a G-to-T transversion in intron 7, resulting in a splice
site mutation, and a 65C-T transition, resulting in a thr22-to-met
(T22M; 605648.0004) substitution in a highly conserved residue in the
N-terminal ubiquitin-like domain. The T22M mutation affects only the
isoforms containing exon 1A. The mutations were not identified in about
300 control chromosomes from the Dutch population.
.0004
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, THR22MET
See 605648.0003 and Di Fonzo et al. (2009).
*FIELD* RF
1. Cenciarelli, C.; Chiaur, D. S.; Guardavaccaro, D.; Parks, W.; Vidal,
M.; Pagano, M.: Identification of a family of human F-box proteins. Curr.
Biol. 9: 1177-1179, 1999.
2. Di Fonzo, A.; Dekker, M. C. J.; Montagna, P.; Baruzzi, A.; Yonova,
E. H.; Correia Guedes, L.; Szczerbinska, A.; Zhao, T.; Dubbel-Hulsman,
L. O. M.; Wouters, C. H.; de Graaff, E.; Oyen, W. J. G.; Simons, E.
J.; Breedveld, G. J.; Oostra, B. A.; Horstink, M. W.; Bonifati, V.
: FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal
syndrome. Neurology 72: 240-245, 2009.
3. Ilyin, G. P.; Rialland, M.; Pigeon, C.; Guguen-Guillouzo, C.:
cDNA cloning and expression analysis of new members of the mammalian
F-box protein family. Genomics 67: 40-47, 2000.
4. Jin, J.; Cardozo, T.; Lovering, R. C.; Elledge, S. J.; Pagano,
M.; Harper, J. W.: Systematic analysis and nomenclature of mammalian
F-box proteins. Genes Dev. 18: 2573-2580, 2004.
5. Shojaee, S.; Sina, F.; Banihosseini, S. S.; Kazemi, M. H.; Kalhor,
R.; Shahidi, G.-A.; Fakhrai-Rad, H.; Ronaghi, M.; Elahi, E.: Genome-wide
linkage analysis of a parkinsonian-pyramidal syndrome pedigree by
500 K SNP arrays. Am. J. Hum. Genet. 82: 1375-1384, 2008.
6. Winston, J. T.; Koepp, D. M.; Zhu, C.; Elledge, S. J.; Harper,
J. W.: A family of mammalian F-box proteins. Curr. Biol. 9: 1180-1182,
1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 3/12/2009
Cassandra L. Kniffin - updated: 9/11/2008
Patricia A. Hartz - updated: 12/16/2004
*FIELD* CD
Paul J. Converse: 2/15/2001
*FIELD* ED
wwang: 03/25/2009
ckniffin: 3/12/2009
wwang: 9/16/2008
ckniffin: 9/11/2008
mgross: 12/16/2004
mgross: 2/16/2001
mgross: 2/15/2001
*RECORD*
*FIELD* NO
605648
*FIELD* TI
*605648 F-BOX ONLY PROTEIN 7; FBXO7
;;FBX7;;
FBX
*FIELD* TX
DESCRIPTION
The F box, named after cyclin F (CCNF; 600227), in which it was
read moreoriginally observed, is an approximately 40-amino acid motif that binds
SKP1 (601434). F-box proteins, such as FBXO7, are components of modular
E3 ubiquitin protein ligases called SCFs (SKP1, cullin (see 603134),
F-box proteins), which function in phosphorylation-dependent
ubiquitination.
CLONING
Using a yeast 2-hybrid screen with SKP1 as bait, followed by searching
sequence databases, Winston et al. (1999) and Cenciarelli et al. (1999)
identified 33 mammalian and 26 human F-box proteins, respectively. These
contained C termini with leucine-rich repeats (FBXLs, e.g., SKP2
(601436)), WD40 domains (FBXWs, e.g., BTRCP (603482)), or no
recognizable motifs (FBXOs, e.g., CCNF). Using RT-PCR analysis, Winston
et al. (1999) found high expression of FBXO7 in brain, heart, kidney,
liver, lung, skeletal muscle, and placenta, with lower levels in
pancreas.
By searching sequence databases, Ilyin et al. (2000) identified a cDNA
encoding FBXO7, which they termed FBX. The deduced 522-amino acid
protein contains an F box in its C-terminal half. RNA blot analysis
detected ubiquitous expression, with greater abundance in bone marrow,
fetal liver, testis, and thyroid glands, followed by corpus callosum.
Jin et al. (2004) reported that the FBXO7 protein contains a
ubiquitin-like fold in its N-terminal half and an F box in its
C-terminal half.
Di Fonzo et al. (2009) identified 4 isoforms of FBXO7 expressed by
alternative combinations of exon 1A with exon 2A alone or exon 2A/2B and
of exon 1B with exon 2A alone or exon 2A/2B.
GENE STRUCTURE
Di Fonzo et al. (2009) noted that the FBXO7 gene contains 9 exons with a
translation start site in exons 1A and 1B, respectively, and alternative
splicing of exons 2A and 2B.
MAPPING
By genomic sequence analysis using mapped clones, Ilyin et al. (2000)
mapped the FBXO7 gene to chromosome 22q12-q13.
Jin et al. (2004) stated that the mouse Fbxo7 gene maps to chromosome
10C1.
GENE FUNCTION
Winston et al. (1999) showed that mouse Fbx7 interacted with SKP1 in
vitro and in transfected human embryonic kidney cells.
MOLECULAR GENETICS
In affected members of an Iranian family with parkinsonian-pyramidal
syndrome (PARK15; 260300), Shojaee et al. (2008) identified a homozygous
mutation in the FBXO7 gene (605648.0001).
In affected members of Italian and Dutch families with PARK15, Di Fonzo
et al. (2009) identified homozygous (605648.0002) and compound
heterozygous (605648.0003; 605648.0004) mutations in the FBXO7 gene,
respectively.
*FIELD* AV
.0001
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, ARG378GLY
In affected members of a large Iranian family with
parkinsonian-pyramidal syndrome (PARK15; 260300), Shojaee et al. (2008)
identified a homozygous 1132C-G transversion in the FBXO7 gene,
resulting in an arg378-to-gly (R378G) substitution in a highly conserved
residue. The mutation was not identified in 800 control individuals.
.0002
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, ARG498TER
In affected members of an Italian family with PARK15 (260300), Di Fonzo
et al. (2009) identified a homozygous 1492C-T transition in exon 9 of
the FBXO7 gene, resulting in an arg498-to-ter (R498X) substitution. The
unaffected parents were heterozygous for the mutation. The mutation was
not identified in 364 control chromosomes from the Italian population.
.0003
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, IVS7DS, G-T, +1
In affected members of a Dutch family with PARK15 (260300), Di Fonzo et
al. (2009) identified compound heterozygosity for 2 mutations in the
FBXO7 gene: a G-to-T transversion in intron 7, resulting in a splice
site mutation, and a 65C-T transition, resulting in a thr22-to-met
(T22M; 605648.0004) substitution in a highly conserved residue in the
N-terminal ubiquitin-like domain. The T22M mutation affects only the
isoforms containing exon 1A. The mutations were not identified in about
300 control chromosomes from the Dutch population.
.0004
PARKINSON DISEASE 15, AUTOSOMAL RECESSIVE
FBXO7, THR22MET
See 605648.0003 and Di Fonzo et al. (2009).
*FIELD* RF
1. Cenciarelli, C.; Chiaur, D. S.; Guardavaccaro, D.; Parks, W.; Vidal,
M.; Pagano, M.: Identification of a family of human F-box proteins. Curr.
Biol. 9: 1177-1179, 1999.
2. Di Fonzo, A.; Dekker, M. C. J.; Montagna, P.; Baruzzi, A.; Yonova,
E. H.; Correia Guedes, L.; Szczerbinska, A.; Zhao, T.; Dubbel-Hulsman,
L. O. M.; Wouters, C. H.; de Graaff, E.; Oyen, W. J. G.; Simons, E.
J.; Breedveld, G. J.; Oostra, B. A.; Horstink, M. W.; Bonifati, V.
: FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal
syndrome. Neurology 72: 240-245, 2009.
3. Ilyin, G. P.; Rialland, M.; Pigeon, C.; Guguen-Guillouzo, C.:
cDNA cloning and expression analysis of new members of the mammalian
F-box protein family. Genomics 67: 40-47, 2000.
4. Jin, J.; Cardozo, T.; Lovering, R. C.; Elledge, S. J.; Pagano,
M.; Harper, J. W.: Systematic analysis and nomenclature of mammalian
F-box proteins. Genes Dev. 18: 2573-2580, 2004.
5. Shojaee, S.; Sina, F.; Banihosseini, S. S.; Kazemi, M. H.; Kalhor,
R.; Shahidi, G.-A.; Fakhrai-Rad, H.; Ronaghi, M.; Elahi, E.: Genome-wide
linkage analysis of a parkinsonian-pyramidal syndrome pedigree by
500 K SNP arrays. Am. J. Hum. Genet. 82: 1375-1384, 2008.
6. Winston, J. T.; Koepp, D. M.; Zhu, C.; Elledge, S. J.; Harper,
J. W.: A family of mammalian F-box proteins. Curr. Biol. 9: 1180-1182,
1999.
*FIELD* CN
Cassandra L. Kniffin - updated: 3/12/2009
Cassandra L. Kniffin - updated: 9/11/2008
Patricia A. Hartz - updated: 12/16/2004
*FIELD* CD
Paul J. Converse: 2/15/2001
*FIELD* ED
wwang: 03/25/2009
ckniffin: 3/12/2009
wwang: 9/16/2008
ckniffin: 9/11/2008
mgross: 12/16/2004
mgross: 2/16/2001
mgross: 2/15/2001