Full text data of FBXO4
FBXO4
(FBX4)
[Confidence: low (only semi-automatic identification from reviews)]
F-box only protein 4
Note: presumably soluble (membrane word is not in UniProt keywords or features)
F-box only protein 4
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UKT5
ID FBX4_HUMAN Reviewed; 387 AA.
AC Q9UKT5; Q68CU8; Q86VT8; Q9UK98;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2005, sequence version 2.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=F-box only protein 4;
GN Name=FBXO4; Synonyms=FBX4;
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), FUNCTION, AND INTERACTION WITH
RP SKP1 AND CUL1.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=10531037; DOI=10.1016/S0960-9822(00)80021-4;
RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.;
RT "A family of mammalian F-box proteins.";
RL Curr. Biol. 9:1180-1182(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-387.
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP INTERACTION WITH TERF1, AND FUNCTION IN UBIQUITINATION OF TERF1.
RX PubMed=16275645; DOI=10.1074/jbc.M509855200;
RA Lee T.H., Perrem K., Harper J.W., Lu K.P., Zhou X.Z.;
RT "The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated
RT degradation and regulates telomere maintenance.";
RL J. Biol. Chem. 281:759-768(2006).
RN [6]
RP FUNCTION, SUBUNIT, INTERACTION WITH SKP1, PHOSPHORYLATION AT SER-12,
RP VARIANTS ARG-8; LEU-12; SER-13; GLN-23 AND THR-76, AND
RP CHARACTERIZATION OF VARIANTS LEU-12; SER-13 AND GLN-23.
RX PubMed=18598945; DOI=10.1016/j.ccr.2008.05.017;
RA Barbash O., Zamfirova P., Lin D.I., Chen X., Yang K., Nakagawa H.,
RA Lu F., Rustgi A.K., Diehl J.A.;
RT "Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and
RT contribute to cyclin D1 overexpression in human cancer.";
RL Cancer Cell 14:68-78(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 162-387 IN COMPLEX WITH
RP TERF1, FUNCTION, MUTAGENESIS OF CYS-341 AND ALA-345, AND SUBUNIT.
RX PubMed=20159592; DOI=10.1016/j.devcel.2010.01.007;
RA Zeng Z., Wang W., Yang Y., Chen Y., Yang X., Diehl J.A., Liu X.,
RA Lei M.;
RT "Structural basis of selective ubiquitination of TRF1 by SCFFbx4.";
RL Dev. Cell 18:214-225(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 55-387 IN COMPLEX WITH SKP1,
RP FUNCTION, AND SUBUNIT.
RX PubMed=20181953; DOI=10.1074/jbc.M110.111518;
RA Li Y., Hao B.;
RT "Structural basis of dimerization-dependent ubiquitination by the
RT SCF(Fbx4) ubiquitin ligase.";
RL J. Biol. Chem. 285:13896-13906(2010).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-
CC box protein) E3 ubiquitin-protein ligase complex that mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. Promotes ubiquitination of CCND1 and its subsequent
CC proteasomal degradation. Recognizes TERF1 and promotes its
CC ubiquitination together with UBE2D1.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Directly interacts with SKP1 and CUL1. Part of
CC the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex
CC SCF(FBXO4) formed of CUL1, SKP1, RBX1 and FBXO4. Interacts with
CC TERF1. This interaction is prevented in the presence of GNL3L.
CC Identified in a complex with CRYAB and CCND1.
CC -!- INTERACTION:
CC Q13616:CUL1; NbExp=2; IntAct=EBI-960409, EBI-359390;
CC P54274:TERF1; NbExp=2; IntAct=EBI-960421, EBI-710997;
CC P54274-2:TERF1; NbExp=3; IntAct=EBI-960421, EBI-711018;
CC P62258:YWHAE; NbExp=5; IntAct=EBI-960409, EBI-356498;
CC P62260:Ywhae (xeno); NbExp=2; IntAct=EBI-960409, EBI-356462;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UKT5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKT5-2; Sequence=VSP_012977, VSP_012978;
CC Note=No experimental confirmation available;
CC -!- PTM: Phosphorylation at Ser-12 varies during the cell cycle. It is
CC low in resting cells and high in the S phase and the G2/M phase of
CC the cell cycle. Phosphorylation is decreased during late G1 phase
CC (By similarity). Phosphorylation at Ser-12 promotes
CC homodimerization and is necessary for optimal ubiquitin ligase
CC activity towards CCND1.
CC -!- SIMILARITY: Contains 1 F-box domain.
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; AF176703; AAF03703.1; -; mRNA.
DR EMBL; BC048098; AAH48098.1; -; mRNA.
DR EMBL; CR749719; CAH18486.1; -; mRNA.
DR EMBL; AF129534; AAF04468.1; -; mRNA.
DR RefSeq; NP_036308.1; NM_012176.2.
DR RefSeq; NP_277019.1; NM_033484.2.
DR UniGene; Hs.165575; -.
DR PDB; 3L2O; X-ray; 2.80 A; B=55-387.
DR PDB; 3L82; X-ray; 2.40 A; B=162-387.
DR PDBsum; 3L2O; -.
DR PDBsum; 3L82; -.
DR ProteinModelPortal; Q9UKT5; -.
DR SMR; Q9UKT5; 55-383.
DR IntAct; Q9UKT5; 8.
DR MINT; MINT-108507; -.
DR STRING; 9606.ENSP00000281623; -.
DR PhosphoSite; Q9UKT5; -.
DR DMDM; 60416426; -.
DR PaxDb; Q9UKT5; -.
DR PRIDE; Q9UKT5; -.
DR DNASU; 26272; -.
DR Ensembl; ENST00000281623; ENSP00000281623; ENSG00000151876.
DR Ensembl; ENST00000296812; ENSP00000296812; ENSG00000151876.
DR GeneID; 26272; -.
DR KEGG; hsa:26272; -.
DR UCSC; uc003jmq.3; human.
DR CTD; 26272; -.
DR GeneCards; GC05P041925; -.
DR HGNC; HGNC:13583; FBXO4.
DR MIM; 609090; gene.
DR neXtProt; NX_Q9UKT5; -.
DR PharmGKB; PA28044; -.
DR eggNOG; NOG39270; -.
DR HOGENOM; HOG000112550; -.
DR HOVERGEN; HBG051585; -.
DR InParanoid; Q9UKT5; -.
DR KO; K10291; -.
DR OMA; HEWQDEF; -.
DR PhylomeDB; Q9UKT5; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; Q9UKT5; -.
DR GeneWiki; FBXO4; -.
DR GenomeRNAi; 26272; -.
DR NextBio; 48565; -.
DR PRO; PR:Q9UKT5; -.
DR ArrayExpress; Q9UKT5; -.
DR Bgee; Q9UKT5; -.
DR CleanEx; HS_FBXO4; -.
DR Genevestigator; Q9UKT5; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR InterPro; IPR001810; F-box_dom.
DR Pfam; PF00646; F-box; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 387 F-box only protein 4.
FT /FTId=PRO_0000119879.
FT DOMAIN 56 102 F-box.
FT MOD_RES 12 12 Phosphoserine.
FT VAR_SEQ 300 307 RHEWQDEF -> SKYSYVHF (in isoform 2).
FT /FTId=VSP_012977.
FT VAR_SEQ 308 387 Missing (in isoform 2).
FT /FTId=VSP_012978.
FT VARIANT 8 8 S -> R (in esophagus cancer samples;
FT dbSNP:rs2231917).
FT /FTId=VAR_063500.
FT VARIANT 12 12 S -> L (in esophagus cancer sample;
FT impairs homodimerization and reduces
FT ubiquitin ligase activity).
FT /FTId=VAR_063501.
FT VARIANT 13 13 P -> S (in esophagus cancer sample).
FT /FTId=VAR_063502.
FT VARIANT 23 23 L -> Q (in esophagus cancer samples).
FT /FTId=VAR_063503.
FT VARIANT 76 76 P -> T (in esophagus cancer samples;
FT impairs interaction with SKP1).
FT /FTId=VAR_063504.
FT MUTAGEN 12 12 S->A: Reduces homodimerization. Reduces
FT ubiquitination of CCND1.
FT MUTAGEN 12 12 S->E: No effect on homodimerization.
FT MUTAGEN 13 13 P->A: Reduces homodimerization.
FT MUTAGEN 23 23 L->A: Abolishes homodimerization.
FT MUTAGEN 341 341 C->W: Abolishes interaction with TERF1.
FT MUTAGEN 345 345 A->R: Abolishes interaction with TERF1.
FT CONFLICT 41 41 E -> D (in Ref. 1; AAF04468).
FT CONFLICT 95 95 D -> N (in Ref. 1; AAF04468).
FT CONFLICT 120 122 DLE -> YLQ (in Ref. 1; AAF04468).
FT CONFLICT 132 132 T -> S (in Ref. 1; AAF04468).
FT CONFLICT 144 144 R -> L (in Ref. 1; AAF04468).
FT CONFLICT 174 174 Q -> P (in Ref. 1; AAF04468).
FT CONFLICT 181 181 M -> L (in Ref. 1; AAF04468).
FT CONFLICT 185 185 G -> R (in Ref. 1; AAF04468).
FT CONFLICT 188 188 E -> Q (in Ref. 1; AAF04468).
FT CONFLICT 198 198 M -> L (in Ref. 1; AAF04468).
FT CONFLICT 268 269 QQ -> RP (in Ref. 1; AAF04468).
FT CONFLICT 282 282 V -> L (in Ref. 1; AAF04468).
FT HELIX 58 61
FT HELIX 64 72
FT HELIX 76 83
FT HELIX 87 93
FT HELIX 96 104
FT HELIX 107 109
FT HELIX 115 117
FT HELIX 122 125
FT HELIX 139 146
FT STRAND 167 169
FT STRAND 178 182
FT HELIX 184 186
FT STRAND 188 191
FT HELIX 193 198
FT HELIX 201 203
FT HELIX 210 212
FT STRAND 215 217
FT STRAND 221 228
FT STRAND 230 235
FT HELIX 279 285
FT STRAND 287 294
FT HELIX 303 313
FT HELIX 316 319
FT STRAND 325 333
FT HELIX 341 347
FT HELIX 350 353
FT STRAND 357 363
FT TURN 364 366
FT HELIX 370 377
FT TURN 378 383
SQ SEQUENCE 387 AA; 44136 MW; BD5E8DD14B9733E9 CRC64;
MAGSEPRSGT NSPPPPFSDW GRLEAAILSG WKTFWQSVSK ERVARTTSRE EVDEAASTLT
RLPIDVQLYI LSFLSPHDLC QLGSTNHYWN ETVRDPILWR YFLLRDLPSW SSVDWKSLPD
LEILKKPISE VTDGAFFDYM AVYRMCCPYT RRASKSSRPM YGAVTSFLHS LIIQNEPRFA
MFGPGLEELN TSLVLSLMSS EELCPTAGLP QRQIDGIGSG VNFQLNNQHK FNILILYSTT
RKERDRAREE HTSAVNKMFS RHNEGDDQQG SRYSVIPQIQ KVCEVVDGFI YVANAEAHKR
HEWQDEFSHI MAMTDPAFGS SGRPLLVLSC ISQGDVKRMP CFYLAHELHL NLLNHPWLVQ
DTEAETLTGF LNGIEWILEE VESKRAR
//
ID FBX4_HUMAN Reviewed; 387 AA.
AC Q9UKT5; Q68CU8; Q86VT8; Q9UK98;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2005, sequence version 2.
DT 22-JAN-2014, entry version 109.
DE RecName: Full=F-box only protein 4;
GN Name=FBXO4; Synonyms=FBX4;
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), FUNCTION, AND INTERACTION WITH
RP SKP1 AND CUL1.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=10531037; DOI=10.1016/S0960-9822(00)80021-4;
RA Winston J.T., Koepp D.M., Zhu C., Elledge S.J., Harper J.W.;
RT "A family of mammalian F-box proteins.";
RL Curr. Biol. 9:1180-1182(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-387.
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP INTERACTION WITH TERF1, AND FUNCTION IN UBIQUITINATION OF TERF1.
RX PubMed=16275645; DOI=10.1074/jbc.M509855200;
RA Lee T.H., Perrem K., Harper J.W., Lu K.P., Zhou X.Z.;
RT "The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated
RT degradation and regulates telomere maintenance.";
RL J. Biol. Chem. 281:759-768(2006).
RN [6]
RP FUNCTION, SUBUNIT, INTERACTION WITH SKP1, PHOSPHORYLATION AT SER-12,
RP VARIANTS ARG-8; LEU-12; SER-13; GLN-23 AND THR-76, AND
RP CHARACTERIZATION OF VARIANTS LEU-12; SER-13 AND GLN-23.
RX PubMed=18598945; DOI=10.1016/j.ccr.2008.05.017;
RA Barbash O., Zamfirova P., Lin D.I., Chen X., Yang K., Nakagawa H.,
RA Lu F., Rustgi A.K., Diehl J.A.;
RT "Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and
RT contribute to cyclin D1 overexpression in human cancer.";
RL Cancer Cell 14:68-78(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 162-387 IN COMPLEX WITH
RP TERF1, FUNCTION, MUTAGENESIS OF CYS-341 AND ALA-345, AND SUBUNIT.
RX PubMed=20159592; DOI=10.1016/j.devcel.2010.01.007;
RA Zeng Z., Wang W., Yang Y., Chen Y., Yang X., Diehl J.A., Liu X.,
RA Lei M.;
RT "Structural basis of selective ubiquitination of TRF1 by SCFFbx4.";
RL Dev. Cell 18:214-225(2010).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 55-387 IN COMPLEX WITH SKP1,
RP FUNCTION, AND SUBUNIT.
RX PubMed=20181953; DOI=10.1074/jbc.M110.111518;
RA Li Y., Hao B.;
RT "Structural basis of dimerization-dependent ubiquitination by the
RT SCF(Fbx4) ubiquitin ligase.";
RL J. Biol. Chem. 285:13896-13906(2010).
CC -!- FUNCTION: Substrate recognition component of a SCF (SKP1-CUL1-F-
CC box protein) E3 ubiquitin-protein ligase complex that mediates the
CC ubiquitination and subsequent proteasomal degradation of target
CC proteins. Promotes ubiquitination of CCND1 and its subsequent
CC proteasomal degradation. Recognizes TERF1 and promotes its
CC ubiquitination together with UBE2D1.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Directly interacts with SKP1 and CUL1. Part of
CC the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex
CC SCF(FBXO4) formed of CUL1, SKP1, RBX1 and FBXO4. Interacts with
CC TERF1. This interaction is prevented in the presence of GNL3L.
CC Identified in a complex with CRYAB and CCND1.
CC -!- INTERACTION:
CC Q13616:CUL1; NbExp=2; IntAct=EBI-960409, EBI-359390;
CC P54274:TERF1; NbExp=2; IntAct=EBI-960421, EBI-710997;
CC P54274-2:TERF1; NbExp=3; IntAct=EBI-960421, EBI-711018;
CC P62258:YWHAE; NbExp=5; IntAct=EBI-960409, EBI-356498;
CC P62260:Ywhae (xeno); NbExp=2; IntAct=EBI-960409, EBI-356462;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UKT5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UKT5-2; Sequence=VSP_012977, VSP_012978;
CC Note=No experimental confirmation available;
CC -!- PTM: Phosphorylation at Ser-12 varies during the cell cycle. It is
CC low in resting cells and high in the S phase and the G2/M phase of
CC the cell cycle. Phosphorylation is decreased during late G1 phase
CC (By similarity). Phosphorylation at Ser-12 promotes
CC homodimerization and is necessary for optimal ubiquitin ligase
CC activity towards CCND1.
CC -!- SIMILARITY: Contains 1 F-box domain.
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; AF176703; AAF03703.1; -; mRNA.
DR EMBL; BC048098; AAH48098.1; -; mRNA.
DR EMBL; CR749719; CAH18486.1; -; mRNA.
DR EMBL; AF129534; AAF04468.1; -; mRNA.
DR RefSeq; NP_036308.1; NM_012176.2.
DR RefSeq; NP_277019.1; NM_033484.2.
DR UniGene; Hs.165575; -.
DR PDB; 3L2O; X-ray; 2.80 A; B=55-387.
DR PDB; 3L82; X-ray; 2.40 A; B=162-387.
DR PDBsum; 3L2O; -.
DR PDBsum; 3L82; -.
DR ProteinModelPortal; Q9UKT5; -.
DR SMR; Q9UKT5; 55-383.
DR IntAct; Q9UKT5; 8.
DR MINT; MINT-108507; -.
DR STRING; 9606.ENSP00000281623; -.
DR PhosphoSite; Q9UKT5; -.
DR DMDM; 60416426; -.
DR PaxDb; Q9UKT5; -.
DR PRIDE; Q9UKT5; -.
DR DNASU; 26272; -.
DR Ensembl; ENST00000281623; ENSP00000281623; ENSG00000151876.
DR Ensembl; ENST00000296812; ENSP00000296812; ENSG00000151876.
DR GeneID; 26272; -.
DR KEGG; hsa:26272; -.
DR UCSC; uc003jmq.3; human.
DR CTD; 26272; -.
DR GeneCards; GC05P041925; -.
DR HGNC; HGNC:13583; FBXO4.
DR MIM; 609090; gene.
DR neXtProt; NX_Q9UKT5; -.
DR PharmGKB; PA28044; -.
DR eggNOG; NOG39270; -.
DR HOGENOM; HOG000112550; -.
DR HOVERGEN; HBG051585; -.
DR InParanoid; Q9UKT5; -.
DR KO; K10291; -.
DR OMA; HEWQDEF; -.
DR PhylomeDB; Q9UKT5; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR Reactome; REACT_6900; Immune System.
DR UniPathway; UPA00143; -.
DR EvolutionaryTrace; Q9UKT5; -.
DR GeneWiki; FBXO4; -.
DR GenomeRNAi; 26272; -.
DR NextBio; 48565; -.
DR PRO; PR:Q9UKT5; -.
DR ArrayExpress; Q9UKT5; -.
DR Bgee; Q9UKT5; -.
DR CleanEx; HS_FBXO4; -.
DR Genevestigator; Q9UKT5; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019005; C:SCF ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0031146; P:SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR InterPro; IPR001810; F-box_dom.
DR Pfam; PF00646; F-box; 1.
DR SMART; SM00256; FBOX; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm;
KW Phosphoprotein; Polymorphism; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1 387 F-box only protein 4.
FT /FTId=PRO_0000119879.
FT DOMAIN 56 102 F-box.
FT MOD_RES 12 12 Phosphoserine.
FT VAR_SEQ 300 307 RHEWQDEF -> SKYSYVHF (in isoform 2).
FT /FTId=VSP_012977.
FT VAR_SEQ 308 387 Missing (in isoform 2).
FT /FTId=VSP_012978.
FT VARIANT 8 8 S -> R (in esophagus cancer samples;
FT dbSNP:rs2231917).
FT /FTId=VAR_063500.
FT VARIANT 12 12 S -> L (in esophagus cancer sample;
FT impairs homodimerization and reduces
FT ubiquitin ligase activity).
FT /FTId=VAR_063501.
FT VARIANT 13 13 P -> S (in esophagus cancer sample).
FT /FTId=VAR_063502.
FT VARIANT 23 23 L -> Q (in esophagus cancer samples).
FT /FTId=VAR_063503.
FT VARIANT 76 76 P -> T (in esophagus cancer samples;
FT impairs interaction with SKP1).
FT /FTId=VAR_063504.
FT MUTAGEN 12 12 S->A: Reduces homodimerization. Reduces
FT ubiquitination of CCND1.
FT MUTAGEN 12 12 S->E: No effect on homodimerization.
FT MUTAGEN 13 13 P->A: Reduces homodimerization.
FT MUTAGEN 23 23 L->A: Abolishes homodimerization.
FT MUTAGEN 341 341 C->W: Abolishes interaction with TERF1.
FT MUTAGEN 345 345 A->R: Abolishes interaction with TERF1.
FT CONFLICT 41 41 E -> D (in Ref. 1; AAF04468).
FT CONFLICT 95 95 D -> N (in Ref. 1; AAF04468).
FT CONFLICT 120 122 DLE -> YLQ (in Ref. 1; AAF04468).
FT CONFLICT 132 132 T -> S (in Ref. 1; AAF04468).
FT CONFLICT 144 144 R -> L (in Ref. 1; AAF04468).
FT CONFLICT 174 174 Q -> P (in Ref. 1; AAF04468).
FT CONFLICT 181 181 M -> L (in Ref. 1; AAF04468).
FT CONFLICT 185 185 G -> R (in Ref. 1; AAF04468).
FT CONFLICT 188 188 E -> Q (in Ref. 1; AAF04468).
FT CONFLICT 198 198 M -> L (in Ref. 1; AAF04468).
FT CONFLICT 268 269 QQ -> RP (in Ref. 1; AAF04468).
FT CONFLICT 282 282 V -> L (in Ref. 1; AAF04468).
FT HELIX 58 61
FT HELIX 64 72
FT HELIX 76 83
FT HELIX 87 93
FT HELIX 96 104
FT HELIX 107 109
FT HELIX 115 117
FT HELIX 122 125
FT HELIX 139 146
FT STRAND 167 169
FT STRAND 178 182
FT HELIX 184 186
FT STRAND 188 191
FT HELIX 193 198
FT HELIX 201 203
FT HELIX 210 212
FT STRAND 215 217
FT STRAND 221 228
FT STRAND 230 235
FT HELIX 279 285
FT STRAND 287 294
FT HELIX 303 313
FT HELIX 316 319
FT STRAND 325 333
FT HELIX 341 347
FT HELIX 350 353
FT STRAND 357 363
FT TURN 364 366
FT HELIX 370 377
FT TURN 378 383
SQ SEQUENCE 387 AA; 44136 MW; BD5E8DD14B9733E9 CRC64;
MAGSEPRSGT NSPPPPFSDW GRLEAAILSG WKTFWQSVSK ERVARTTSRE EVDEAASTLT
RLPIDVQLYI LSFLSPHDLC QLGSTNHYWN ETVRDPILWR YFLLRDLPSW SSVDWKSLPD
LEILKKPISE VTDGAFFDYM AVYRMCCPYT RRASKSSRPM YGAVTSFLHS LIIQNEPRFA
MFGPGLEELN TSLVLSLMSS EELCPTAGLP QRQIDGIGSG VNFQLNNQHK FNILILYSTT
RKERDRAREE HTSAVNKMFS RHNEGDDQQG SRYSVIPQIQ KVCEVVDGFI YVANAEAHKR
HEWQDEFSHI MAMTDPAFGS SGRPLLVLSC ISQGDVKRMP CFYLAHELHL NLLNHPWLVQ
DTEAETLTGF LNGIEWILEE VESKRAR
//
MIM
609090
*RECORD*
*FIELD* NO
609090
*FIELD* TI
*609090 F-BOX ONLY PROTEIN 4; FBXO4
;;FBX4
*FIELD* TX
DESCRIPTION
Members of the F-box protein family, such as FBXO4, are characterized by
read morean approximately 40-amino acid F-box motif. SCF complexes, formed by
SKP1 (601434), cullin (see CUL1; 603134), and F-box proteins, act as
protein-ubiquitin ligases. F-box proteins interact with SKP1 through the
F box, and they interact with ubiquitination targets through other
protein interaction domains (Jin et al., 2004).
CLONING
Using SKP1 as bait in a yeast 2-hybrid screen and by searching DNA
databases, Cenciarelli et al. (1999) identified FBXO4, which they
designated FBX4. The deduced protein contains an F box in its N-terminal
half. Northern blot analysis detected nearly ubiquitous expression of a
4.4-kb FBX4 transcript. Immunofluorescence localization detected
epitope-tagged FBX4 in the cytoplasm and nucleus of transfected HeLa
cells.
By PCR, Winston et al. (1999) found expression of FBX4 in heart, kidney,
liver, lung, pancreas, and placenta, but not in brain and skeletal
muscle.
GENE FUNCTION
By coexpression and immunoprecipitation in HeLa cells, Cenciarelli et
al. (1999) demonstrated that FBX4 interacts with CUL1 and SKP1, but not
with CUL2 (603135). The FBX4 F box was required for this interaction.
FBX4 supported ubiquitin ligase activity in HeLa cells when
cotransfected with CUL1 and SKP1.
MAPPING
By FISH, Chiaur et al. (2000) mapped the FBXO4 gene to chromosome 5p12.
Jin et al. (2004) stated that the mouse Fbxo4 gene maps to chromosome
15A1.
*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. Chiaur, D. S.; Murthy, S.; Cenciarelli, C.; Parks, W.; Loda, M.;
Inghirami, G.; Demetrick, D.; Pagano, M.: Five human genes encoding
F-box proteins: chromosome mapping and analysis in human tumors. Cytogenet.
Cell Genet. 88: 255-258, 2000.
3. 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.
4. 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* CD
Patricia A. Hartz: 12/14/2004
*FIELD* ED
mgross: 12/15/2004
*RECORD*
*FIELD* NO
609090
*FIELD* TI
*609090 F-BOX ONLY PROTEIN 4; FBXO4
;;FBX4
*FIELD* TX
DESCRIPTION
Members of the F-box protein family, such as FBXO4, are characterized by
read morean approximately 40-amino acid F-box motif. SCF complexes, formed by
SKP1 (601434), cullin (see CUL1; 603134), and F-box proteins, act as
protein-ubiquitin ligases. F-box proteins interact with SKP1 through the
F box, and they interact with ubiquitination targets through other
protein interaction domains (Jin et al., 2004).
CLONING
Using SKP1 as bait in a yeast 2-hybrid screen and by searching DNA
databases, Cenciarelli et al. (1999) identified FBXO4, which they
designated FBX4. The deduced protein contains an F box in its N-terminal
half. Northern blot analysis detected nearly ubiquitous expression of a
4.4-kb FBX4 transcript. Immunofluorescence localization detected
epitope-tagged FBX4 in the cytoplasm and nucleus of transfected HeLa
cells.
By PCR, Winston et al. (1999) found expression of FBX4 in heart, kidney,
liver, lung, pancreas, and placenta, but not in brain and skeletal
muscle.
GENE FUNCTION
By coexpression and immunoprecipitation in HeLa cells, Cenciarelli et
al. (1999) demonstrated that FBX4 interacts with CUL1 and SKP1, but not
with CUL2 (603135). The FBX4 F box was required for this interaction.
FBX4 supported ubiquitin ligase activity in HeLa cells when
cotransfected with CUL1 and SKP1.
MAPPING
By FISH, Chiaur et al. (2000) mapped the FBXO4 gene to chromosome 5p12.
Jin et al. (2004) stated that the mouse Fbxo4 gene maps to chromosome
15A1.
*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. Chiaur, D. S.; Murthy, S.; Cenciarelli, C.; Parks, W.; Loda, M.;
Inghirami, G.; Demetrick, D.; Pagano, M.: Five human genes encoding
F-box proteins: chromosome mapping and analysis in human tumors. Cytogenet.
Cell Genet. 88: 255-258, 2000.
3. 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.
4. 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* CD
Patricia A. Hartz: 12/14/2004
*FIELD* ED
mgross: 12/15/2004