ID   FBSP1_HUMAN             Reviewed;         286 AA.
AC   P0C2W1; A6NF90; D3DXB5;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2007, sequence version 1.
DT   05-FEB-2025, entry version 144.
DE   RecName: Full=F-box/SPRY domain-containing protein 1;
DE   AltName: Full=F-box only protein 45;
DE            Short=hFbxo45;
GN   Name=FBXO45; Synonyms=FBX45;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA   Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA   Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA   Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA   Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA   Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA   Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA   Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA   Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA   Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA   Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA   Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA   Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA   Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA   Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 107-286.
RC   TISSUE=Hepatoma;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NOMENCLATURE, AND IDENTIFICATION.
RX   PubMed=15520277; DOI=10.1101/gad.1255304;
RA   Jin J., Cardozo T., Lovering R.C., Elledge S.J., Pagano M., Harper J.W.;
RT   "Systematic analysis and nomenclature of mammalian F-box proteins.";
RL   Genes Dev. 18:2573-2580(2004).
RN   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [6]
RP   FUNCTION, AND INDUCTION.
RX   PubMed=19581926; DOI=10.1038/onc.2009.177;
RA   Peschiaroli A., Scialpi F., Bernassola F., Pagano M., Melino G.;
RT   "The F-box protein FBXO45 promotes the proteasome-dependent degradation of
RT   p73.";
RL   Oncogene 28:3157-3166(2009).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [8]
RP   INTERACTION WITH HEY1, AND SUBCELLULAR LOCATION.
RX   PubMed=26068074; DOI=10.1371/journal.pone.0130288;
RA   Salat D., Winkler A., Urlaub H., Gessler M.;
RT   "Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase
RT   Complex and Induce Its Translocation into the Nucleus.";
RL   PLoS ONE 10:e0130288-e0130288(2015).
RN   [9]
RP   FUNCTION, AND INTERACTION WITH MYCBP2 AND SKP1.
RX   PubMed=29997255; DOI=10.1074/jbc.ra118.002176;
RA   Desbois M., Crawley O., Evans P.R., Baker S.T., Masuho I., Yasuda R.,
RA   Grill B.;
RT   "PAM forms an atypical SCF ubiquitin ligase complex that ubiquitinates and
RT   degrades NMNAT2.";
RL   J. Biol. Chem. 293:13897-13909(2018).
RN   [10]
RP   FUNCTION.
RX   PubMed=31285543; DOI=10.1038/s41418-019-0385-7;
RA   Richter K.T., Kschonsak Y.T., Vodicska B., Hoffmann I.;
RT   "FBXO45-MYCBP2 regulates mitotic cell fate by targeting FBXW7 for
RT   degradation.";
RL   Cell Death Differ. 27:758-772(2020).
RN   [11]
RP   FUNCTION, AND INDUCTION BY INFLUENZA INFECTION.
RX   PubMed=36379255; DOI=10.1016/j.jbc.2022.102698;
RA   Tsai M., Osman W., Adair J., ElMergawy R., Chafin L., Johns F., Farkas D.,
RA   Elhance A., Londino J., Mallampalli R.K.;
RT   "The E3 ligase subunit FBXO45 binds the interferon-lambda receptor and
RT   promotes its degradation during influenza virus infection.";
RL   J. Biol. Chem. 298:102698-102698(2022).
RN   [12]
RP   INTERACTION WITH CDH2, AND SUBCELLULAR LOCATION.
RX   PubMed=32341084; DOI=10.1128/mcb.00539-19;
RA   Na Y., Calvo-Jimenez E., Kon E., Cao H., Jossin Y., Cooper J.A.;
RT   "Fbxo45 Binds SPRY Motifs in the Extracellular Domain of N-Cadherin and
RT   Regulates Neuron Migration during Brain Development.";
RL   Mol. Cell. Biol. 40:0-0(2020).
CC   -!- FUNCTION: Component of E3 ubiquitin ligase complex consisting of
CC       FBXO45, MYCBP2 and SKP1 (PubMed:29997255). Functions in substrate
CC       recognition but plays also an important role in assembly of the complex
CC       (PubMed:29997255). Required for normal neuromuscular synaptogenesis,
CC       axon pathfinding and neuronal migration (By similarity). Regulates
CC       neuron migration during brain development through interaction with N-
CC       cadherin/CDH2 after secretion via a non-classical mechanism (By
CC       similarity). Plays a role in the regulation of neurotransmission at
CC       mature neurons (By similarity). May control synaptic activity by
CC       controlling UNC13A via ubiquitin dependent pathway (By similarity).
CC       Specifically recognizes TP73, promoting its ubiquitination and
CC       degradation. Polyubiquitinates NMNAT2, an adenylyltransferase that acts
CC       as an axon maintenance factor, and regulates its stability and
CC       degradation by the proteasome (PubMed:29997255). Acts also by
CC       ubiquitinating FBXW7 during prolonged mitotic arrest and promotes FBXW7
CC       proteasomal degradation (PubMed:31285543). Induces subsequently an
CC       increase in mitotic slippage and prevents mitotic cell death
CC       (PubMed:31285543). In response to influenza infection, mediates
CC       interferon-lambda receptor IFNLR1 polyubiquitination and degradation
CC       through the ubiquitin-proteasome system by docking with its
CC       intracellular receptor domain (PubMed:36379255).
CC       {ECO:0000250|UniProtKB:P0CH38, ECO:0000250|UniProtKB:Q8K3B1,
CC       ECO:0000269|PubMed:19581926, ECO:0000269|PubMed:29997255,
CC       ECO:0000269|PubMed:31285543, ECO:0000269|PubMed:36379255}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Forms a complex with MYCBP2 and SKP1 (PubMed:29997255).
CC       Interacts with HEY1; leading to FBXO45 nuclear translocation. Interacts
CC       (via SPRY domain) with CDH2 (PubMed:32341084).
CC       {ECO:0000269|PubMed:19581926, ECO:0000269|PubMed:32341084}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32341084}.
CC       Postsynaptic cell membrane {ECO:0000250|UniProtKB:P0CH38}. Presynaptic
CC       cell membrane {ECO:0000250|UniProtKB:P0CH38}. Nucleus
CC       {ECO:0000269|PubMed:26068074}. Note=Secreted by a non-classical
CC       mechanism. {ECO:0000269|PubMed:32341084}.
CC   -!- INDUCTION: Down-regulated in response to DNA-damage (PubMed:19581926).
CC       Induced upon influenza infection (PubMed:36379255).
CC       {ECO:0000269|PubMed:19581926, ECO:0000269|PubMed:36379255}.
CC   -!- SIMILARITY: Belongs to the FBXO45/Fsn family. {ECO:0000305}.
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DR   EMBL; AC092933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471191; EAW53643.1; -; Genomic_DNA.
DR   EMBL; CH471191; EAW53644.1; -; Genomic_DNA.
DR   EMBL; AK025697; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS46985.1; -.
DR   RefSeq; NP_001099043.1; NM_001105573.1.
DR   AlphaFoldDB; P0C2W1; -.
DR   SMR; P0C2W1; -.
DR   BioGRID; 128358; 194.
DR   ComplexPortal; CPX-8004; Non-canonical FBXO45-MYCBP2-SKP1 E3 ubiquitin ligase complex.
DR   IntAct; P0C2W1; 61.
DR   STRING; 9606.ENSP00000310332; -.
DR   GlyGen; P0C2W1; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P0C2W1; -.
DR   PhosphoSitePlus; P0C2W1; -.
DR   BioMuta; FBXO45; -.
DR   DMDM; 146286173; -.
DR   jPOST; P0C2W1; -.
DR   MassIVE; P0C2W1; -.
DR   PaxDb; 9606-ENSP00000310332; -.
DR   PeptideAtlas; P0C2W1; -.
DR   ProteomicsDB; 52305; -.
DR   Pumba; P0C2W1; -.
DR   Antibodypedia; 51201; 91 antibodies from 16 providers.
DR   DNASU; 200933; -.
DR   Ensembl; ENST00000311630.7; ENSP00000310332.6; ENSG00000174013.8.
DR   GeneID; 200933; -.
DR   KEGG; hsa:200933; -.
DR   MANE-Select; ENST00000311630.7; ENSP00000310332.6; NM_001105573.2; NP_001099043.1.
DR   UCSC; uc010iai.4; human.
DR   AGR; HGNC:29148; -.
DR   CTD; 200933; -.
DR   DisGeNET; 200933; -.
DR   GeneCards; FBXO45; -.
DR   HGNC; HGNC:29148; FBXO45.
DR   HPA; ENSG00000174013; Low tissue specificity.
DR   MIM; 609112; gene.
DR   neXtProt; NX_P0C2W1; -.
DR   OpenTargets; ENSG00000174013; -.
DR   PharmGKB; PA134904114; -.
DR   VEuPathDB; HostDB:ENSG00000174013; -.
DR   eggNOG; KOG3953; Eukaryota.
DR   GeneTree; ENSGT01030000234629; -.
DR   HOGENOM; CLU_046756_1_0_1; -.
DR   InParanoid; P0C2W1; -.
DR   OMA; ATKRASM; -.
DR   OrthoDB; 2398163at2759; -.
DR   PhylomeDB; P0C2W1; -.
DR   TreeFam; TF312822; -.
DR   PathwayCommons; P0C2W1; -.
DR   SignaLink; P0C2W1; -.
DR   SIGNOR; P0C2W1; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 200933; 9 hits in 1187 CRISPR screens.
DR   ChiTaRS; FBXO45; human.
DR   GenomeRNAi; 200933; -.
DR   Pharos; P0C2W1; Tbio.
DR   PRO; PR:P0C2W1; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; P0C2W1; protein.
DR   Bgee; ENSG00000174013; Expressed in secondary oocyte and 194 other cell types or tissues.
DR   ExpressionAtlas; P0C2W1; baseline and differential.
DR   GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR   GO; GO:0005737; C:cytoplasm; IC:UniProt.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0099524; C:postsynaptic cytosol; IEA:Ensembl.
DR   GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0099523; C:presynaptic cytosol; IEA:Ensembl.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019005; C:SCF ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:1990756; F:ubiquitin-like ligase-substrate adaptor activity; IDA:UniProt.
DR   GO; GO:0021960; P:anterior commissure morphogenesis; IEA:Ensembl.
DR   GO; GO:0021799; P:cerebral cortex radially oriented cell migration; IEA:Ensembl.
DR   GO; GO:0021800; P:cerebral cortex tangential migration; IEA:Ensembl.
DR   GO; GO:0021957; P:corticospinal tract morphogenesis; IEA:Ensembl.
DR   GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR   GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR   GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProt.
DR   GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR   GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR   GO; GO:0060386; P:synapse assembly involved in innervation; IBA:GO_Central.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR   CDD; cd22111; F-box_FBXO45; 1.
DR   CDD; cd12907; SPRY_Fbox; 1.
DR   FunFam; 1.20.1280.50:FF:000024; F-box/SPRY domain-containing protein 1; 1.
DR   FunFam; 2.60.120.920:FF:000017; F-box/SPRY domain-containing protein 1; 1.
DR   Gene3D; 1.20.1280.50; -; 1.
DR   Gene3D; 2.60.120.920; -; 1.
DR   InterPro; IPR001870; B30.2/SPRY.
DR   InterPro; IPR043136; B30.2/SPRY_sf.
DR   InterPro; IPR013320; ConA-like_dom_sf.
DR   InterPro; IPR036047; F-box-like_dom_sf.
DR   InterPro; IPR001810; F-box_dom.
DR   InterPro; IPR050672; FBXO45-Fsn/SPSB_families.
DR   InterPro; IPR003877; SPRY_dom.
DR   InterPro; IPR035784; SPRY_FBXO45.
DR   PANTHER; PTHR12245:SF7; F-BOX_SPRY DOMAIN-CONTAINING PROTEIN 1; 1.
DR   PANTHER; PTHR12245; SPRY DOMAIN CONTAINING SOCS BOX PROTEIN; 1.
DR   Pfam; PF12937; F-box-like; 1.
DR   Pfam; PF00622; SPRY; 1.
DR   SMART; SM00256; FBOX; 1.
DR   SMART; SM00449; SPRY; 1.
DR   SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1.
DR   SUPFAM; SSF81383; F-box domain; 1.
DR   PROSITE; PS50188; B302_SPRY; 1.
DR   PROSITE; PS50181; FBOX; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cell membrane; Cell projection; Developmental protein;
KW   Membrane; Neurogenesis; Nucleus; Postsynaptic cell membrane;
KW   Proteomics identification; Reference proteome; Secreted; Synapse;
KW   Ubl conjugation pathway.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:19413330"
FT   CHAIN           2..286
FT                   /note="F-box/SPRY domain-containing protein 1"
FT                   /id="PRO_0000285933"
FT   DOMAIN          33..82
FT                   /note="F-box"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT   DOMAIN          92..284
FT                   /note="B30.2/SPRY"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00548"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0007744|PubMed:19413330"
SQ   SEQUENCE   286 AA;  30633 MW;  C2CF11ED007CC837 CRC64;
     MAAPAPGAGA ASGGAGCSGG GAGAGAGSGS GAAGAGGRLP SRVLELVFSY LELSELRSCA
     LVCKHWYRCL HGDENSEVWR SLCARSLAEE ALRTDILCNL PSYKAKIRAF QHAFSTNDCS
     RNVYIKKNGF TLHRNPIAQS TDGARTKIGF SEGRHAWEVW WEGPLGTVAV IGIATKRAPM
     QCQGYVALLG SDDQSWGWNL VDNNLLHNGE VNGSFPQCNN APKYQIGERI RVILDMEDKT
     LAFERGYEFL GVAFRGLPKV CLYPAVSAVY GNTEVTLVYL GKPLDG
//