ID   BEX4_HUMAN              Reviewed;         120 AA.
AC   Q9NWD9;
DT   04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   24-JAN-2024, entry version 149.
DE   RecName: Full=Protein BEX4 {ECO:0000305};
DE   AltName: Full=BEX1-like protein 1 {ECO:0000312|HGNC:HGNC:25475};
DE   AltName: Full=Brain-expressed X-linked protein 4 {ECO:0000303|PubMed:15958283, ECO:0000312|HGNC:HGNC:25475};
DE   AltName: Full=Nerve growth factor receptor-associated protein 3 {ECO:0000303|PubMed:15958283};
GN   Name=BEX4 {ECO:0000303|PubMed:15958283, ECO:0000312|HGNC:HGNC:25475};
GN   Synonyms=BEXL1 {ECO:0000312|HGNC:HGNC:25475}, NADE3
GN   {ECO:0000303|PubMed:15958283};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=15958283; DOI=10.1016/j.gene.2005.05.012;
RA   Alvarez E., Zhou W., Witta S.E., Freed C.R.;
RT   "Characterization of the Bex gene family in humans, mice, and rats.";
RL   Gene 357:18-28(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [4]
RP   FUNCTION, INTERACTION WITH ALPHA-TUBULIN AND SIRT2, SUBCELLULAR LOCATION,
RP   AND REGION.
RX   PubMed=27512957; DOI=10.1038/cddis.2016.240;
RA   Lee J.K., Lee J., Go H., Lee C.G., Kim S., Kim H.S., Cho H., Choi K.S.,
RA   Ha G.H., Lee C.W.;
RT   "Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2
RT   inhibition.";
RL   Cell Death Dis. 7:E2336-E2336(2016).
CC   -!- FUNCTION: May play a role in microtubule deacetylation by negatively
CC       regulating the SIRT2 deacetylase activity toward alpha-tubulin and
CC       thereby participate in the control of cell cycle progression and
CC       genomic stability (PubMed:27512957). In absence of reductive stress,
CC       acts as a pseudosubstrate for the CRL2(FEM1B) complex: associates with
CC       FEM1B via zinc, thereby preventing association between FEM1B and its
CC       substrates (By similarity). {ECO:0000250|UniProtKB:Q9CWT2,
CC       ECO:0000269|PubMed:27512957}.
CC   -!- SUBUNIT: Interacts with alpha-tubulin (PubMed:27512957). Interacts with
CC       SIRT2 (PubMed:27512957). {ECO:0000269|PubMed:27512957}.
CC   -!- INTERACTION:
CC       Q9NWD9; Q15777: MPPED2; NbExp=3; IntAct=EBI-15105944, EBI-2350461;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle pole
CC       {ECO:0000269|PubMed:27512957}. Nucleus {ECO:0000269|PubMed:27512957}.
CC       Cytoplasm {ECO:0000269|PubMed:27512957}. Note=Also localizes to
CC       microtubules. {ECO:0000269|PubMed:27512957}.
CC   -!- TISSUE SPECIFICITY: Very high expression in heart, skeletal muscle,
CC       liver, and kidney. The levels of expression are uniform throughout the
CC       brain. {ECO:0000269|PubMed:15958283}.
CC   -!- PTM: Ubiquitinated and degraded by the proteasome.
CC       {ECO:0000250|UniProtKB:Q3MKP9}.
CC   -!- SIMILARITY: Belongs to the BEX family. {ECO:0000305}.
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DR   EMBL; AK000959; BAA91443.1; -; mRNA.
DR   EMBL; AY833563; AAX40681.1; -; mRNA.
DR   EMBL; AL035494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS35355.1; -.
DR   RefSeq; NP_001073894.1; NM_001080425.3.
DR   RefSeq; NP_001121160.1; NM_001127688.2.
DR   AlphaFoldDB; Q9NWD9; -.
DR   BioGRID; 121131; 18.
DR   IntAct; Q9NWD9; 4.
DR   MINT; Q9NWD9; -.
DR   STRING; 9606.ENSP00000361780; -.
DR   iPTMnet; Q9NWD9; -.
DR   PhosphoSitePlus; Q9NWD9; -.
DR   BioMuta; BEX4; -.
DR   DMDM; 74753015; -.
DR   MassIVE; Q9NWD9; -.
DR   PaxDb; 9606-ENSP00000361780; -.
DR   PeptideAtlas; Q9NWD9; -.
DR   ProteomicsDB; 82929; -.
DR   Pumba; Q9NWD9; -.
DR   Antibodypedia; 29002; 131 antibodies from 16 providers.
DR   DNASU; 56271; -.
DR   Ensembl; ENST00000372691.3; ENSP00000361776.3; ENSG00000102409.10.
DR   Ensembl; ENST00000372695.6; ENSP00000361780.5; ENSG00000102409.10.
DR   GeneID; 56271; -.
DR   KEGG; hsa:56271; -.
DR   MANE-Select; ENST00000372695.6; ENSP00000361780.5; NM_001080425.4; NP_001073894.1.
DR   UCSC; uc004ejv.5; human.
DR   AGR; HGNC:25475; -.
DR   CTD; 56271; -.
DR   DisGeNET; 56271; -.
DR   GeneCards; BEX4; -.
DR   HGNC; HGNC:25475; BEX4.
DR   HPA; ENSG00000102409; Low tissue specificity.
DR   MIM; 300692; gene.
DR   neXtProt; NX_Q9NWD9; -.
DR   OpenTargets; ENSG00000102409; -.
DR   PharmGKB; PA162377543; -.
DR   VEuPathDB; HostDB:ENSG00000102409; -.
DR   eggNOG; ENOG502TDUR; Eukaryota.
DR   GeneTree; ENSGT00940000162932; -.
DR   HOGENOM; CLU_123122_0_0_1; -.
DR   InParanoid; Q9NWD9; -.
DR   OMA; WAIPSRH; -.
DR   OrthoDB; 5264682at2759; -.
DR   PhylomeDB; Q9NWD9; -.
DR   TreeFam; TF337909; -.
DR   PathwayCommons; Q9NWD9; -.
DR   SignaLink; Q9NWD9; -.
DR   BioGRID-ORCS; 56271; 6 hits in 785 CRISPR screens.
DR   ChiTaRS; BEX4; human.
DR   GenomeRNAi; 56271; -.
DR   Pharos; Q9NWD9; Tbio.
DR   PRO; PR:Q9NWD9; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9NWD9; Protein.
DR   Bgee; ENSG00000102409; Expressed in prefrontal cortex and 207 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0000922; C:spindle pole; IDA:UniProtKB.
DR   GO; GO:0043014; F:alpha-tubulin binding; IDA:UniProtKB.
DR   GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0140678; F:molecular function inhibitor activity; ISS:UniProtKB.
DR   GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR   GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR   GO; GO:1904428; P:negative regulation of tubulin deacetylation; IMP:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB.
DR   InterPro; IPR007623; BEX.
DR   InterPro; IPR021156; TF_A-like/BEX.
DR   PANTHER; PTHR13987; PROTEIN BEX4; 1.
DR   PANTHER; PTHR13987:SF3; PROTEIN BEX4; 1.
DR   Pfam; PF04538; BEX; 1.
DR   PIRSF; PIRSF008633; BEX; 1.
DR   Genevisible; Q9NWD9; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; Cytoskeleton; Metal-binding; Nucleus; Reference proteome;
KW   Ubl conjugation; Zinc.
FT   CHAIN           1..120
FT                   /note="Protein BEX4"
FT                   /id="PRO_0000229783"
FT   REGION          1..54
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          31..120
FT                   /note="Interaction with alpha-tubulin"
FT                   /evidence="ECO:0000269|PubMed:27512957"
FT   REGION          31..90
FT                   /note="Interaction with SIRT2"
FT                   /evidence="ECO:0000269|PubMed:27512957"
FT   COMPBIAS        9..28
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         117
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="ligand shared with FEM1B"
FT                   /evidence="ECO:0000250|UniProtKB:Q9WTZ9"
SQ   SEQUENCE   120 AA;  14067 MW;  AD9527B5587622D4 CRC64;
     MESKEELAAN NLNGENAQQE NEGGEQAPTQ NEEESRHLGG GEGQKPGGNI RRGRVRRLVP
     NFRWAIPNRH IEHNEARDDV ERFVGQMMEI KRKTREQQMR HYMRFQTPEP DNHYDFCLIP
//