LOCUS       NP_038472                624 aa            linear   PRI 30-APR-2025
DEFINITION  ubiquilin-2 [Homo sapiens].
ACCESSION   NP_038472
VERSION     NP_038472.2
DBSOURCE    REFSEQ: accession NM_013444.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 624)
  AUTHORS   Thumbadoo,K.M., Dieriks,B.V., Murray,H.C., Swanson,M.E.V.,
            Yoo,J.H., Mehrabi,N.F., Turner,C., Dragunow,M., Faull,R.L.M.,
            Curtis,M.A., Siddique,T., Shaw,C.E., Newell,K.L., Henden,L.,
            Williams,K.L., Nicholson,G.A. and Scotter,E.L.
  TITLE     Hippocampal aggregation signatures of pathogenic UBQLN2 in
            amyotrophic lateral sclerosis and frontotemporal dementia
  JOURNAL   Brain 147 (10), 3547-3561 (2024)
   PUBMED   38703371
  REMARK    GeneRIF: Hippocampal aggregation signatures of pathogenic UBQLN2 in
            amyotrophic lateral sclerosis and frontotemporal dementia.
REFERENCE   2  (residues 1 to 624)
  AUTHORS   Nementzik,L.R., Thumbadoo,K.M., Murray,H.C., Gordon,D., Yang,S.,
            Blair,I.P., Turner,C., Faull,R.L.M., Curtis,M.A., McLean,C.,
            Nicholson,G.A., Swanson,M.E.V. and Scotter,E.L.
  TITLE     Distribution of ubiquilin 2 and TDP-43 aggregates throughout the
            CNS in UBQLN2 p.T487I-linked amyotrophic lateral sclerosis and
            frontotemporal dementia
  JOURNAL   Brain Pathol 34 (3), e13230 (2024)
   PUBMED   38115557
  REMARK    GeneRIF: Distribution of ubiquilin 2 and TDP-43 aggregates
            throughout the CNS in UBQLN2 p.T487I-linked amyotrophic lateral
            sclerosis and frontotemporal dementia.
REFERENCE   3  (residues 1 to 624)
  AUTHORS   Idera,A., Sharkey,L.M., Kurauchi,Y., Kadoyama,K., Paulson,H.L.,
            Katsuki,H. and Seki,T.
  TITLE     Wild-type and pathogenic forms of ubiquilin 2 differentially
            modulate components of the autophagy-lysosome pathways
  JOURNAL   J Pharmacol Sci 152 (3), 182-192 (2023)
   PUBMED   37257946
  REMARK    GeneRIF: Wild-type and pathogenic forms of ubiquilin 2
            differentially modulate components of the autophagy-lysosome
            pathways.
REFERENCE   4  (residues 1 to 624)
  AUTHORS   Black,H.H., Hanson,J.L., Roberts,J.E., Leslie,S.N., Campodonico,W.,
            Ebmeier,C.C., Holling,G.A., Tay,J.W., Matthews,A.M., Ung,E.,
            Lau,C.I. and Whiteley,A.M.
  TITLE     UBQLN2 restrains the domesticated retrotransposon PEG10 to maintain
            neuronal health in ALS
  JOURNAL   Elife 12, e79452 (2023)
   PUBMED   36951542
  REMARK    GeneRIF: UBQLN2 restrains the domesticated retrotransposon PEG10 to
            maintain neuronal health in ALS.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 624)
  AUTHORS   Phung,T.H., Tatman,M. and Monteiro,M.J.
  TITLE     UBQLN2 undergoes a reversible temperature-induced conformational
            switch that regulates binding with HSPA1B: ALS/FTD mutations
            cripple the switch but do not destroy HSPA1B binding
  JOURNAL   Biochim Biophys Acta Gen Subj 1867 (2), 130284 (2023)
   PUBMED   36423739
  REMARK    GeneRIF: UBQLN2 undergoes a reversible temperature-induced
            conformational switch that regulates binding with HSPA1B: ALS/FTD
            mutations cripple the switch but do not destroy HSPA1B binding.
REFERENCE   6  (residues 1 to 624)
  AUTHORS   Murillas,R., Simms,K.S., Hatakeyama,S., Weissman,A.M. and
            Kuehn,M.R.
  TITLE     Identification of developmentally expressed proteins that
            functionally interact with Nedd4 ubiquitin ligase
  JOURNAL   J Biol Chem 277 (4), 2897-2907 (2002)
   PUBMED   11717310
REFERENCE   7  (residues 1 to 624)
  AUTHORS   Kleijnen,M.F., Shih,A.H., Zhou,P., Kumar,S., Soccio,R.E.,
            Kedersha,N.L., Gill,G. and Howley,P.M.
  TITLE     The hPLIC proteins may provide a link between the ubiquitination
            machinery and the proteasome
  JOURNAL   Mol Cell 6 (2), 409-419 (2000)
   PUBMED   10983987
REFERENCE   8  (residues 1 to 624)
  AUTHORS   Kaye,F.J., Modi,S., Ivanovska,I., Koonin,E.V., Thress,K., Kubo,A.,
            Kornbluth,S. and Rose,M.D.
  TITLE     A family of ubiquitin-like proteins binds the ATPase domain of
            Hsp70-like Stch
  JOURNAL   FEBS Lett 467 (2-3), 348-355 (2000)
   PUBMED   10675567
REFERENCE   9  (residues 1 to 624)
  AUTHORS   Kaye,F.J. and Shows,T.B.
  TITLE     Assignment of ubiquilin2 (UBQLN2) to human chromosome xp11.
            23-->p11.1 by GeneBridge radiation hybrids
  JOURNAL   Cytogenet Cell Genet 89 (1-2), 116-117 (2000)
   PUBMED   10894951
REFERENCE   10 (residues 1 to 624)
  AUTHORS   Siddique,N. and Siddique,T.
  TITLE     Amyotrophic Lateral Sclerosis Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301623
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI602998.1, AF189009.1,
            BC069237.1, AU310783.1 and AL354793.11.
            
            On Nov 6, 2001 this sequence version replaced NP_038472.1.
            
            Summary: This gene encodes an ubiquitin-like protein (ubiquilin)
            that shares high degree of similarity with related products in
            yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like
            domain and a C-terminal ubiquitin-associated domain. They
            physically associate with both proteasomes and ubiquitin ligases;
            and thus, are thought to functionally link the ubiquitination
            machinery to the proteasome to affect in vivo protein degradation.
            This ubiquilin has also been shown to bind the ATPase domain of the
            Hsp70-like Stch protein. [provided by RefSeq, Oct 2009].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript is intronless :: AL442081.1, AF189009.1 [ECO:0000345]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000338222.7/ ENSP00000345195.5
            RefSeq Select criteria :: based on single protein-coding transcript
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..624
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="X"
                     /map="Xp11.21"
     Protein         1..624
                     /product="ubiquilin-2"
                     /note="Nedd4 binding protein 4; protein linking IAP with
                     cytoskeleton 2; ubiquitin-like product Chap1/Dsk2"
                     /calculated_mol_wt=65565
     Region          1..32
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UHD9.2)"
     Site            2
                     /site_type="acetylation"
                     /note="N-acetylalanine.
                     /evidence=ECO:0007744|PubMed:19413330,
                     ECO:0007744|PubMed:22814378; propagated from
                     UniProtKB/Swiss-Prot (Q9UHD9.2)"
     Region          31..103
                     /region_name="Ubl_PLICs"
                     /note="ubiquitin-like (Ubl) domain found in eukaryotic
                     protein linking integrin-associated protein (IAP, also
                     known as CD47) with cytoskeleton (PLIC) proteins; cd01808"
                     /db_xref="CDD:340506"
     Site            order(38,75..80,96..99,101,103)
                     /site_type="other"
                     /note="Pru interaction site [polypeptide binding]"
                     /db_xref="CDD:340506"
     Site            order(68,71,75,77..80,82,99,101..103)
                     /site_type="other"
                     /note="putative S5a binding site"
                     /db_xref="CDD:340506"
     Region          106..141
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UHD9.2)"
     Region          182..215
                     /region_name="STI1"
                     /note="Heat shock chaperonin-binding motif; smart00727"
                     /db_xref="CDD:128966"
     Region          208..253
                     /region_name="STI1"
                     /note="STI1 domain; cl17974"
                     /db_xref="CDD:450205"
     Region          287..349
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UHD9.2)"
     Region          382..426
                     /region_name="STI1"
                     /note="Heat shock chaperonin-binding motif; smart00727"
                     /db_xref="CDD:128966"
     Region          491..526
                     /region_name="12 X 3 AA tandem repeats of P-X-X"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UHD9.2)"
     Region          512..556
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q9UHD9.2)"
     Region          581..620
                     /region_name="UBA_PLICs"
                     /note="UBA domain of eukaryotic protein linking
                     integrin-associated protein (IAP, also known as CD47) with
                     cytoskeleton (PLIC) proteins; cd14399"
                     /db_xref="CDD:270582"
     Site            order(591..596,612,615..617,619..620)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:270582"
     CDS             1..624
                     /gene="UBQLN2"
                     /gene_synonym="ALS15; CHAP1; DSK2; HRIHFB2157; N4BP4;
                     PLIC2"
                     /coded_by="NM_013444.4:248..2122"
                     /db_xref="CCDS:CCDS14374.1"
                     /db_xref="GeneID:29978"
                     /db_xref="HGNC:HGNC:12509"
                     /db_xref="MIM:300264"
ORIGIN      
        1 maengessgp prpsrgpaaa qgsaaapaep kiikvtvktp kekeefavpe nssvqqfkea
       61 iskrfksqtd qlvlifagki lkdqdtliqh gihdgltvhl viksqnrpqg qstqpsnaag
      121 tnttsastpr snstpistns npfglgslgg laglsslgls stnfselqsq mqqqlmaspe
      181 mmiqimenpf vqsmlsnpdl mrqlimanpq mqqliqrnpe ishllnnpdi mrqtleiarn
      241 pammqemmrn qdlalsnles ipggynalrr mytdiqepml naaqeqfggn pfasvgssss
      301 sgegtqpsrt enrdplpnpw apppatqssa ttstttstgs gsgnsssnat gntvaaanyv
      361 asifstpgmq sllqqitenp qliqnmlsap ymrsmmqsls qnpdlaaqmm lnsplftanp
      421 qlqeqmrpql paflqqmqnp dtlsamsnpr amqalmqiqq glqtlateap glipsftpgv
      481 gvgvlgtaig pvgpvtpigp igpivpftpi gpigpigptg paappgstgs ggptgptvss
      541 aapsettspt sesgpnqqfi qqmvqalaga napqlpnpev rfqqqleqln amgflnrean
      601 lqaliatggd inaaierllg sqps
//
