Full text data of UBQLN1
UBQLN1
(DA41, PLIC1)
[Confidence: low (only semi-automatic identification from reviews)]
Ubiquilin-1 (Protein linking IAP with cytoskeleton 1; PLIC-1; hPLIC-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ubiquilin-1 (Protein linking IAP with cytoskeleton 1; PLIC-1; hPLIC-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UMX0
ID UBQL1_HUMAN Reviewed; 589 AA.
AC Q9UMX0; Q5T6J5; Q5T6J9; Q8IXS9; Q8N2Q3; Q9H0T8; Q9H3R4; Q9HAZ5;
read moreDT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Ubiquilin-1;
DE AltName: Full=Protein linking IAP with cytoskeleton 1;
DE Short=PLIC-1;
DE Short=hPLIC-1;
GN Name=UBQLN1; Synonyms=DA41, PLIC1;
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), INTERACTION WITH PSEN1 AND
RP PSEN2, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11076969; DOI=10.1083/jcb.151.4.847;
RA Mah A.L., Perry G., Smith M.A., Monteiro M.J.;
RT "Identification of ubiquilin, a novel presenilin interactor that
RT increases presenilin protein accumulation.";
RL J. Cell Biol. 151:847-862(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Mah A.L., Monteiro M.J.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH UBE3A;
RP BTRC AND THE PROTEASOME.
RC TISSUE=B-cell;
RX PubMed=10983987; DOI=10.1016/S1097-2765(00)00040-X;
RA Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E.,
RA Kedersha N.L., Gill G., Howley P.M.;
RT "The hPLIC proteins may provide a link between the ubiquitination
RT machinery and the proteasome.";
RL Mol. Cell 6:409-419(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=10807547; DOI=10.1007/s100380050209;
RA Hanaoka E., Ozaki T., Ohira M., Nakamura Y., Suzuki M., Takahashi E.,
RA Moriya H., Nakagawara A., Sakiyama S.;
RT "Molecular cloning and expression analysis of the human DA41 gene and
RT its mapping to chromosome 9q21.2-q21.3.";
RL J. Hum. Genet. 45:188-191(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Muscle;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-316.
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.,
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 [10]
RP PROTEIN SEQUENCE OF 71-83; 207-236; 244-253 AND 547-582, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PHOSPHORYLATION, INTERACTION WITH MTOR, AND TISSUE SPECIFICITY.
RX PubMed=11853878; DOI=10.1016/S0167-4889(01)00164-1;
RA Wu S., Mikhailov A., Kallo-Hosein H., Hara K., Yonezawa K., Avruch J.;
RT "Characterization of ubiquilin 1, an mTOR-interacting protein.";
RL Biochim. Biophys. Acta 1542:41-56(2002).
RN [12]
RP INTERACTION WITH P4HB.
RX PubMed=12095988; DOI=10.1074/jbc.M203412200;
RA Ko H.S., Uehara T., Nomura Y.;
RT "Role of ubiquilin associated with protein-disulfide isomerase in the
RT endoplasmic reticulum in stress-induced apoptotic cell death.";
RL J. Biol. Chem. 277:35386-35392(2002).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP STRUCTURE BY NMR OF 541-586 ALONE AND IN COMPLEX WITH UBIQUITIN.
RX PubMed=18241885; DOI=10.1016/j.jmb.2007.12.029;
RA Zhang D., Raasi S., Fushman D.;
RT "Affinity makes the difference: nonselective interaction of the UBA
RT domain of Ubiquilin-1 with monomeric ubiquitin and polyubiquitin
RT chains.";
RL J. Mol. Biol. 377:162-180(2008).
CC -!- FUNCTION: Links CD47 to the cytoskeleton. Promotes the surface
CC expression of GABA-A receptors (By similarity). Promotes the
CC accumulation of uncleaved PSEN1 and PSEN2 by stimulating their
CC biosynthesis. Has no effect on PSEN1 and PSEN2 degradation.
CC -!- SUBUNIT: Binds CD47, NBL1, GABRA1, GABRA2, GABRA3, GABRA6, GABRB1,
CC GABRB2 and GABRB3 (By similarity). Binds UBE3A, BTRC, P4HB, MTOR,
CC PSEN1 and PSEN2. Interacts with the proteasome 19S subunit.
CC -!- INTERACTION:
CC Q16186:ADRM1; NbExp=4; IntAct=EBI-741480, EBI-954387;
CC P42566:EPS15; NbExp=5; IntAct=EBI-741480, EBI-396684;
CC P55036:PSMD4; NbExp=6; IntAct=EBI-741480, EBI-359318;
CC Q9NPQ8:RIC8A; NbExp=3; IntAct=EBI-741480, EBI-717509;
CC O75830:SERPINI2; NbExp=3; IntAct=EBI-741480, EBI-750144;
CC P0CG48:UBC; NbExp=3; IntAct=EBI-741480, EBI-3390054;
CC Q9NRR5:UBQLN4; NbExp=8; IntAct=EBI-741480, EBI-711226;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UMX0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UMX0-2; Sequence=VSP_009787;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed throughout the
CC brain; detected in neurons and in neuropathological lesions, such
CC as neurofibrillary tangles and Lewy bodies. Highly expressed in
CC heart, placenta, pancreas, lung, liver, skeletal muscle and
CC kidney.
CC -!- DOMAIN: The UBA domain mediates binding to PSEN1 and PSEN2. It
CC also binds ubiquitin with micromolar affinity, independently of
CC polyubiquitin linkage type.
CC -!- PTM: Phosphorylated.
CC -!- SIMILARITY: Contains 1 UBA domain.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
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DR EMBL; AF176069; AAD49751.3; -; mRNA.
DR EMBL; AF293384; AAG02473.1; -; mRNA.
DR EMBL; AB035275; BAB20436.1; -; mRNA.
DR EMBL; AL136643; CAB66578.1; -; mRNA.
DR EMBL; AL354920; CAI15100.1; -; Genomic_DNA.
DR EMBL; AL354920; CAI15101.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62659.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62661.1; -; Genomic_DNA.
DR EMBL; BC010066; AAH10066.1; -; mRNA.
DR EMBL; BC039294; AAH39294.1; -; mRNA.
DR EMBL; AK074535; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_038466.2; NM_013438.4.
DR RefSeq; NP_444295.1; NM_053067.2.
DR UniGene; Hs.9589; -.
DR PDB; 2JY5; NMR; -; A=541-586.
DR PDB; 2JY6; NMR; -; B=541-586.
DR PDB; 2KLC; NMR; -; A=34-112.
DR PDBsum; 2JY5; -.
DR PDBsum; 2JY6; -.
DR PDBsum; 2KLC; -.
DR ProteinModelPortal; Q9UMX0; -.
DR SMR; Q9UMX0; 1-112, 537-586.
DR IntAct; Q9UMX0; 50.
DR MINT; MINT-150317; -.
DR STRING; 9606.ENSP00000365576; -.
DR PhosphoSite; Q9UMX0; -.
DR DMDM; 48475013; -.
DR REPRODUCTION-2DPAGE; IPI00071180; -.
DR PaxDb; Q9UMX0; -.
DR PRIDE; Q9UMX0; -.
DR Ensembl; ENST00000257468; ENSP00000257468; ENSG00000135018.
DR Ensembl; ENST00000376395; ENSP00000365576; ENSG00000135018.
DR GeneID; 29979; -.
DR KEGG; hsa:29979; -.
DR UCSC; uc004amv.3; human.
DR CTD; 29979; -.
DR GeneCards; GC09M086274; -.
DR HGNC; HGNC:12508; UBQLN1.
DR HPA; CAB037256; -.
DR MIM; 605046; gene.
DR neXtProt; NX_Q9UMX0; -.
DR PharmGKB; PA37155; -.
DR eggNOG; COG5272; -.
DR HOVERGEN; HBG064537; -.
DR InParanoid; Q9UMX0; -.
DR KO; K04523; -.
DR OMA; RSQDHSA; -.
DR OrthoDB; EOG7HF1J8; -.
DR PhylomeDB; Q9UMX0; -.
DR ChiTaRS; UBQLN1; human.
DR EvolutionaryTrace; Q9UMX0; -.
DR GeneWiki; UBQLN1; -.
DR GenomeRNAi; 29979; -.
DR NextBio; 52732; -.
DR PRO; PR:Q9UMX0; -.
DR ArrayExpress; Q9UMX0; -.
DR Bgee; Q9UMX0; -.
DR CleanEx; HS_UBQLN1; -.
DR Genevestigator; Q9UMX0; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; NAS:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0043234; C:protein complex; IDA:LIFEdb.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:BHF-UCL.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:BHF-UCL.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:HGNC.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:BHF-UCL.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR009060; UBA-like.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR InterPro; IPR000449; UBA/Ts_N.
DR InterPro; IPR015496; Ubiquilin.
DR InterPro; IPR000626; Ubiquitin_dom.
DR PANTHER; PTHR10677; PTHR10677; 1.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00727; STI1; 4.
DR SMART; SM00165; UBA; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Nucleus; Phosphoprotein;
KW Proteasome; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 589 Ubiquilin-1.
FT /FTId=PRO_0000211008.
FT DOMAIN 37 111 Ubiquitin-like.
FT DOMAIN 546 586 UBA.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 416 443 Missing (in isoform 2).
FT /FTId=VSP_009787.
FT CONFLICT 25 25 A -> T (in Ref. 8; AAH39294).
FT CONFLICT 41 41 V -> A (in Ref. 4; BAB20436).
FT CONFLICT 61 61 F -> S (in Ref. 4; BAB20436).
FT CONFLICT 91 91 L -> S (in Ref. 4; BAB20436).
FT CONFLICT 125 125 S -> G (in Ref. 5; CAB66578).
FT CONFLICT 202 202 P -> H (in Ref. 8; AAH39294).
FT CONFLICT 537 538 NP -> YS (in Ref. 4; BAB20436).
FT STRAND 37 42
FT STRAND 47 52
FT HELIX 58 69
FT HELIX 73 75
FT STRAND 76 80
FT STRAND 83 85
FT HELIX 92 94
FT STRAND 101 106
FT TURN 543 547
FT HELIX 548 556
FT HELIX 562 572
FT HELIX 576 583
SQ SEQUENCE 589 AA; 62519 MW; 8B4756B6113B7025 CRC64;
MAESGESGGP PGSQDSAAGA EGAGAPAAAA SAEPKIMKVT VKTPKEKEEF AVPENSSVQQ
FKEEISKRFK SHTDQLVLIF AGKILKDQDT LSQHGIHDGL TVHLVIKTQN RPQDHSAQQT
NTAGSNVTTS STPNSNSTSG SATSNPFGLG GLGGLAGLSS LGLNTTNFSE LQSQMQRQLL
SNPEMMVQIM ENPFVQSMLS NPDLMRQLIM ANPQMQQLIQ RNPEISHMLN NPDIMRQTLE
LARNPAMMQE MMRNQDRALS NLESIPGGYN ALRRMYTDIQ EPMLSAAQEQ FGGNPFASLV
SNTSSGEGSQ PSRTENRDPL PNPWAPQTSQ SSSASSGTAS TVGGTTGSTA SGTSGQSTTA
PNLVPGVGAS MFNTPGMQSL LQQITENPQL MQNMLSAPYM RSMMQSLSQN PDLAAQMMLN
NPLFAGNPQL QEQMRQQLPT FLQQMQNPDT LSAMSNPRAM QALLQIQQGL QTLATEAPGL
IPGFTPGLGA LGSTGGSSGT NGSNATPSEN TSPTAGTTEP GHQQFIQQML QALAGVNPQL
QNPEVRFQQQ LEQLSAMGFL NREANLQALI ATGGDINAAI ERLLGSQPS
//
ID UBQL1_HUMAN Reviewed; 589 AA.
AC Q9UMX0; Q5T6J5; Q5T6J9; Q8IXS9; Q8N2Q3; Q9H0T8; Q9H3R4; Q9HAZ5;
read moreDT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 2.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Ubiquilin-1;
DE AltName: Full=Protein linking IAP with cytoskeleton 1;
DE Short=PLIC-1;
DE Short=hPLIC-1;
GN Name=UBQLN1; Synonyms=DA41, PLIC1;
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), INTERACTION WITH PSEN1 AND
RP PSEN2, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11076969; DOI=10.1083/jcb.151.4.847;
RA Mah A.L., Perry G., Smith M.A., Monteiro M.J.;
RT "Identification of ubiquilin, a novel presenilin interactor that
RT increases presenilin protein accumulation.";
RL J. Cell Biol. 151:847-862(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Mah A.L., Monteiro M.J.;
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH UBE3A;
RP BTRC AND THE PROTEASOME.
RC TISSUE=B-cell;
RX PubMed=10983987; DOI=10.1016/S1097-2765(00)00040-X;
RA Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E.,
RA Kedersha N.L., Gill G., Howley P.M.;
RT "The hPLIC proteins may provide a link between the ubiquitination
RT machinery and the proteasome.";
RL Mol. Cell 6:409-419(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=10807547; DOI=10.1007/s100380050209;
RA Hanaoka E., Ozaki T., Ohira M., Nakamura Y., Suzuki M., Takahashi E.,
RA Moriya H., Nakagawara A., Sakiyama S.;
RT "Molecular cloning and expression analysis of the human DA41 gene and
RT its mapping to chromosome 9q21.2-q21.3.";
RL J. Hum. Genet. 45:188-191(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Muscle;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-316.
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.,
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 [10]
RP PROTEIN SEQUENCE OF 71-83; 207-236; 244-253 AND 547-582, AND MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [11]
RP PHOSPHORYLATION, INTERACTION WITH MTOR, AND TISSUE SPECIFICITY.
RX PubMed=11853878; DOI=10.1016/S0167-4889(01)00164-1;
RA Wu S., Mikhailov A., Kallo-Hosein H., Hara K., Yonezawa K., Avruch J.;
RT "Characterization of ubiquilin 1, an mTOR-interacting protein.";
RL Biochim. Biophys. Acta 1542:41-56(2002).
RN [12]
RP INTERACTION WITH P4HB.
RX PubMed=12095988; DOI=10.1074/jbc.M203412200;
RA Ko H.S., Uehara T., Nomura Y.;
RT "Role of ubiquilin associated with protein-disulfide isomerase in the
RT endoplasmic reticulum in stress-induced apoptotic cell death.";
RL J. Biol. Chem. 277:35386-35392(2002).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17323924; DOI=10.1021/bi061994u;
RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.;
RT "Mass spectrometric characterization of the affinity-purified human
RT 26S proteasome complex.";
RL Biochemistry 46:3553-3565(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [16]
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.,
RA Buerckstuemmer T., 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 [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [18]
RP STRUCTURE BY NMR OF 541-586 ALONE AND IN COMPLEX WITH UBIQUITIN.
RX PubMed=18241885; DOI=10.1016/j.jmb.2007.12.029;
RA Zhang D., Raasi S., Fushman D.;
RT "Affinity makes the difference: nonselective interaction of the UBA
RT domain of Ubiquilin-1 with monomeric ubiquitin and polyubiquitin
RT chains.";
RL J. Mol. Biol. 377:162-180(2008).
CC -!- FUNCTION: Links CD47 to the cytoskeleton. Promotes the surface
CC expression of GABA-A receptors (By similarity). Promotes the
CC accumulation of uncleaved PSEN1 and PSEN2 by stimulating their
CC biosynthesis. Has no effect on PSEN1 and PSEN2 degradation.
CC -!- SUBUNIT: Binds CD47, NBL1, GABRA1, GABRA2, GABRA3, GABRA6, GABRB1,
CC GABRB2 and GABRB3 (By similarity). Binds UBE3A, BTRC, P4HB, MTOR,
CC PSEN1 and PSEN2. Interacts with the proteasome 19S subunit.
CC -!- INTERACTION:
CC Q16186:ADRM1; NbExp=4; IntAct=EBI-741480, EBI-954387;
CC P42566:EPS15; NbExp=5; IntAct=EBI-741480, EBI-396684;
CC P55036:PSMD4; NbExp=6; IntAct=EBI-741480, EBI-359318;
CC Q9NPQ8:RIC8A; NbExp=3; IntAct=EBI-741480, EBI-717509;
CC O75830:SERPINI2; NbExp=3; IntAct=EBI-741480, EBI-750144;
CC P0CG48:UBC; NbExp=3; IntAct=EBI-741480, EBI-3390054;
CC Q9NRR5:UBQLN4; NbExp=8; IntAct=EBI-741480, EBI-711226;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UMX0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UMX0-2; Sequence=VSP_009787;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed throughout the
CC brain; detected in neurons and in neuropathological lesions, such
CC as neurofibrillary tangles and Lewy bodies. Highly expressed in
CC heart, placenta, pancreas, lung, liver, skeletal muscle and
CC kidney.
CC -!- DOMAIN: The UBA domain mediates binding to PSEN1 and PSEN2. It
CC also binds ubiquitin with micromolar affinity, independently of
CC polyubiquitin linkage type.
CC -!- PTM: Phosphorylated.
CC -!- SIMILARITY: Contains 1 UBA domain.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
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DR EMBL; AF176069; AAD49751.3; -; mRNA.
DR EMBL; AF293384; AAG02473.1; -; mRNA.
DR EMBL; AB035275; BAB20436.1; -; mRNA.
DR EMBL; AL136643; CAB66578.1; -; mRNA.
DR EMBL; AL354920; CAI15100.1; -; Genomic_DNA.
DR EMBL; AL354920; CAI15101.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62659.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62661.1; -; Genomic_DNA.
DR EMBL; BC010066; AAH10066.1; -; mRNA.
DR EMBL; BC039294; AAH39294.1; -; mRNA.
DR EMBL; AK074535; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_038466.2; NM_013438.4.
DR RefSeq; NP_444295.1; NM_053067.2.
DR UniGene; Hs.9589; -.
DR PDB; 2JY5; NMR; -; A=541-586.
DR PDB; 2JY6; NMR; -; B=541-586.
DR PDB; 2KLC; NMR; -; A=34-112.
DR PDBsum; 2JY5; -.
DR PDBsum; 2JY6; -.
DR PDBsum; 2KLC; -.
DR ProteinModelPortal; Q9UMX0; -.
DR SMR; Q9UMX0; 1-112, 537-586.
DR IntAct; Q9UMX0; 50.
DR MINT; MINT-150317; -.
DR STRING; 9606.ENSP00000365576; -.
DR PhosphoSite; Q9UMX0; -.
DR DMDM; 48475013; -.
DR REPRODUCTION-2DPAGE; IPI00071180; -.
DR PaxDb; Q9UMX0; -.
DR PRIDE; Q9UMX0; -.
DR Ensembl; ENST00000257468; ENSP00000257468; ENSG00000135018.
DR Ensembl; ENST00000376395; ENSP00000365576; ENSG00000135018.
DR GeneID; 29979; -.
DR KEGG; hsa:29979; -.
DR UCSC; uc004amv.3; human.
DR CTD; 29979; -.
DR GeneCards; GC09M086274; -.
DR HGNC; HGNC:12508; UBQLN1.
DR HPA; CAB037256; -.
DR MIM; 605046; gene.
DR neXtProt; NX_Q9UMX0; -.
DR PharmGKB; PA37155; -.
DR eggNOG; COG5272; -.
DR HOVERGEN; HBG064537; -.
DR InParanoid; Q9UMX0; -.
DR KO; K04523; -.
DR OMA; RSQDHSA; -.
DR OrthoDB; EOG7HF1J8; -.
DR PhylomeDB; Q9UMX0; -.
DR ChiTaRS; UBQLN1; human.
DR EvolutionaryTrace; Q9UMX0; -.
DR GeneWiki; UBQLN1; -.
DR GenomeRNAi; 29979; -.
DR NextBio; 52732; -.
DR PRO; PR:Q9UMX0; -.
DR ArrayExpress; Q9UMX0; -.
DR Bgee; Q9UMX0; -.
DR CleanEx; HS_UBQLN1; -.
DR Genevestigator; Q9UMX0; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; NAS:UniProtKB.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0043234; C:protein complex; IDA:LIFEdb.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:BHF-UCL.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:BHF-UCL.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:HGNC.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:BHF-UCL.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR009060; UBA-like.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR InterPro; IPR000449; UBA/Ts_N.
DR InterPro; IPR015496; Ubiquilin.
DR InterPro; IPR000626; Ubiquitin_dom.
DR PANTHER; PTHR10677; PTHR10677; 1.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00727; STI1; 4.
DR SMART; SM00165; UBA; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Cytoplasm; Direct protein sequencing; Nucleus; Phosphoprotein;
KW Proteasome; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 589 Ubiquilin-1.
FT /FTId=PRO_0000211008.
FT DOMAIN 37 111 Ubiquitin-like.
FT DOMAIN 546 586 UBA.
FT MOD_RES 2 2 N-acetylalanine.
FT VAR_SEQ 416 443 Missing (in isoform 2).
FT /FTId=VSP_009787.
FT CONFLICT 25 25 A -> T (in Ref. 8; AAH39294).
FT CONFLICT 41 41 V -> A (in Ref. 4; BAB20436).
FT CONFLICT 61 61 F -> S (in Ref. 4; BAB20436).
FT CONFLICT 91 91 L -> S (in Ref. 4; BAB20436).
FT CONFLICT 125 125 S -> G (in Ref. 5; CAB66578).
FT CONFLICT 202 202 P -> H (in Ref. 8; AAH39294).
FT CONFLICT 537 538 NP -> YS (in Ref. 4; BAB20436).
FT STRAND 37 42
FT STRAND 47 52
FT HELIX 58 69
FT HELIX 73 75
FT STRAND 76 80
FT STRAND 83 85
FT HELIX 92 94
FT STRAND 101 106
FT TURN 543 547
FT HELIX 548 556
FT HELIX 562 572
FT HELIX 576 583
SQ SEQUENCE 589 AA; 62519 MW; 8B4756B6113B7025 CRC64;
MAESGESGGP PGSQDSAAGA EGAGAPAAAA SAEPKIMKVT VKTPKEKEEF AVPENSSVQQ
FKEEISKRFK SHTDQLVLIF AGKILKDQDT LSQHGIHDGL TVHLVIKTQN RPQDHSAQQT
NTAGSNVTTS STPNSNSTSG SATSNPFGLG GLGGLAGLSS LGLNTTNFSE LQSQMQRQLL
SNPEMMVQIM ENPFVQSMLS NPDLMRQLIM ANPQMQQLIQ RNPEISHMLN NPDIMRQTLE
LARNPAMMQE MMRNQDRALS NLESIPGGYN ALRRMYTDIQ EPMLSAAQEQ FGGNPFASLV
SNTSSGEGSQ PSRTENRDPL PNPWAPQTSQ SSSASSGTAS TVGGTTGSTA SGTSGQSTTA
PNLVPGVGAS MFNTPGMQSL LQQITENPQL MQNMLSAPYM RSMMQSLSQN PDLAAQMMLN
NPLFAGNPQL QEQMRQQLPT FLQQMQNPDT LSAMSNPRAM QALLQIQQGL QTLATEAPGL
IPGFTPGLGA LGSTGGSSGT NGSNATPSEN TSPTAGTTEP GHQQFIQQML QALAGVNPQL
QNPEVRFQQQ LEQLSAMGFL NREANLQALI ATGGDINAAI ERLLGSQPS
//
MIM
605046
*RECORD*
*FIELD* NO
605046
*FIELD* TI
*605046 UBIQUILIN 1; UBQLN1
;;DA41, RAT, HOMOLOG OF; DA41;;
PLIC1, MOUSE, HOMOLOG OF; PLIC1;;
read moreUBQN, DROSOPHILA, HOMOLOG OF; UBQN
*FIELD* TX
CLONING
Using a yeast 2-hybrid system to screen an adult rat lung cDNA library,
Ozaki et al. (1997) isolated a cDNA, which they termed DA41, encoding a
cellular protein that can associate with DAN (600613). Expression of DAN
had been found be significantly reduced in rat fibroblast 3Y1 cells
transformed with mouse sarcoma virus and in rodent fibroblasts
transformed with a variety of oncogenes. Ozaki et al. (1997) determined
that the interaction between DAN and DA41 is mediated through the
N-terminal domain and a cystine knot region of DAN. Expression of DA41
is regulated in a cell cycle-dependent manner.
By screening a human lung cDNA library with a rat DA41 cDNA as a probe,
Hanaoka et al. (2000) isolated the human DA41 homolog. Human DA41
encodes a 589-amino acid protein with a predicted molecular mass of 62.4
kD. The protein shows 86% amino acid sequence identity with the rat
protein, indicating the evolutionarily conserved structure and function
of DA41. DA41 was expressed ubiquitously in adult human tissues, with
relatively higher levels in pituitary gland, adrenal gland, kidney,
thymus, and placenta.
By performing independent yeast 2-hybrid screens, Kleijnen et al. (2000)
isolated cDNAs encoding PLIC1 and PLIC2 (UBQLN2; 300264), homologs of
the mouse Plics (proteins linking integrin-associated protein (IAP;
601028) and cytoskeleton) and the yeast Dsk2 protein. PLIC1, also called
UBQLN1, shares 72% amino acid identity with PLIC2. Two motifs are
conserved in the mammalian PLICs and yeast Dsk2, an N-terminal ubiquitin
(191339)-like (UBL) domain and a C-terminal ubiquitin-associated (UBA)
domain. Unlike ubiquitin, the UBL domain of the PLICs does not have a
diglycine motif in its C terminus; the diglycine motif serves as a
target site for cellular hydrolases that release ubiquitin from
precursor fusion proteins. The absence of a GG sequence suggests that
the UBL domain in the PLICs is an integral part of the open reading
frame. The UBA domain is a loosely defined sequence motif present in
multiple enzyme classes of the ubiquitination machinery. The most
notable difference between the mammalian PLICs is the presence of a
collagen-like motif in PLIC2 that is absent in PLIC1 and yeast Dsk2.
This domain is most homologous to the collagen-like oncoprotein of
Herpesvirus saimiri, STP-C488, which is implicated in intracellular
signaling via the RAS-RAF pathway (see 190020). The collagen-like domain
of PLIC2 contains 8 PXGP motifs that are susceptible to cleavage by
collagenase in vitro.
GENE FUNCTION
Kleijnen et al. (2000) showed that the human PLICs physically associate
with both proteasomes and ubiquitin ligases in large complexes.
Overexpression of PLICs interfered with the in vivo degradation of 2
unrelated ubiquitin-dependent proteasome substrates, p53 (191170) and
I-kappa-B-alpha (NFKBIA; 164008), but not a ubiquitin-independent
substrate. These findings raised the possibility that the PLICs, and
possibly related ubiquitin-like family members, may functionally link
the ubiquitination machinery to the proteasome to affect in vivo protein
degradation.
Neurodegenerative Alzheimer disease (AD; 104300) is associated with
extracellular depositions of proteolytic fragments of amyloid precursor
protein (APP; 104760). Using Western blot analysis, Stieren et al.
(2011) found that UBQLN1 expression was reduced in postmortem AD brain
at all stages of AD development except the earliest preclinical stage.
UBQLN1 downregulation preceded significant neuronal cell loss in
preclinical samples. Yeast 2-hybrid analysis of a rat brain cDNA library
showed that human UBQLN1 interacted with the APP intracellular domain.
UBQLN1 also immunoprecipitated with APP in cotransfected HeLa cells. The
amount of UBQLN1 that coprecipitated with APP increased following
crosslinking, suggesting that the complex was transient. Coexpression of
UBQLN1 with APP reduced the content of amyloid deposits in
APP-overexpressing rat PC12 cells and reduced production of pathogenic
amyloid-beta peptides produced by APP-expressing HeLa cells. In vitro,
UBQLN1 significantly protected a test protein against heat denaturation.
Stieren et al. (2011) concluded that UBQLN1 functions as a chaperone for
APP and that diminished UBQLN1 levels in AD may contribute to
pathogenesis.
GENE STRUCTURE
Sweetser et al. (2005) determined that the UBQLN1 gene contains 11
exons.
MAPPING
By fluorescence in situ hybridization, Hanaoka et al. (2000) mapped the
DA41 gene to chromosome 9q21.2-q21.3, a position overlapping a candidate
tumor suppressor locus for bladder cancer (see 109800).
MOLECULAR GENETICS
Bird (2005) reviewed genetic factors in Alzheimer disease (AD; see
104300) and the interrelationship with nongenetic factors. They
commented that UBQLN1 is an intriguing candidate gene because of its
potential role in the proteasome degradation of proteins and its
interaction with PSEN1 and PSEN2.
Bertram et al. (2005) estimated that mutations in the 4 genes that have
been related to Alzheimer disease--APP (104760), PSEN1 (104311), PSEN2
(600759), and APOE4 (107741)--may account for less than half the genetic
variance in Alzheimer disease, and that possibly up to 7 additional
Alzheimer disease genes remained to be identified. They focused on the
fact that the UBQLN1 gene is one of these candidate genes by virtue of
its location at a well-established linkage peak for AD on chromosome
9q22. Bertram et al. (2005) evaluated 19 single-nucleotide polymorphisms
(SNPs) in 3 genes within the 9q22 region in 437 multiplex families with
Alzheimer disease from an NIMH sample. They found a positive association
between Alzheimer disease and various SNPs in UBQLN1 (UBQ-8i, dbSNP
rs2791001, dbSNP 2780995). They confirmed these associations in an
independent sample of families. The risk-conferring haplotype in both
samples was defined by the single intronic SNP located downstream of
exon 8. The risk allele was associated with a dose-dependent increase in
an alternatively spliced UBQLN1 (lacking exon 8) transcript in RNA
extracted from brain samples of patients with Alzheimer disease. Bertram
et al. (2005) interpreted the findings as indicating that genetic
variants in UBQLN1 on 9q22 increase the risk of Alzheimer disease,
possibly by influencing alternative splicing of this gene in the brain.
Slifer et al. (2005) found no association between the risk of Alzheimer
disease and a genetic variant of the UBQ-8i SNP (dbSNP rs12344615) but
did find significant association between this risk allele and an older
age of onset in a recessive disease model in their case-control data
set.
Smemo et al. (2006) found no association between the UBQ-8i SNP and
Alzheimer disease among a group of 1,544 patients with late-onset AD.
There was also no association between AD and 6 other polymorphisms in
the UBQLN1 gene.
Kamboh et al. (2006) studied the association of UBQLN1 gene variation
with Alzheimer disease and examined the association of UBQLN1 SNPs with
quantitative measures of Alzheimer disease progression, namely age at
onset, disease duration, and Mini Mental Status Examination scores. They
examined the association of 3 SNPs in the gene (intron 6 A/C, intron 8
T/C, and intron 9 A/G), all of which are in significant linkage
disequilibrium (p less than 0.0001), in up to 978 late-onset Alzheimer
disease patients and 808 controls. Modestly significant associations
were observed in the single-site regression analysis, but 3-site
haplotype analysis revealed significant associations (p less than
0.0001). One common haplotype, called H4 (ACG for introns 6, 8, and 9,
respectively), was associated with Alzheimer disease risk, and one less
common haplotype, called H5 (CCA for introns 6, 8, and 9, respectively),
was associated with protection. The adjusted odds ratios with
potentially 1 or 2 copies of risk haplotype H4 were 1.5 (95% CI,
0.99-2.26; p = 0.054) and 3.66 (95% CI, 1.43-9.39; p = 0.007),
respectively, and the odds ratio for haplotype H5 carriers was 0.31 (95%
CI, 0.10-0.95; p = 0.0398). Kamboh et al. (2006) suggested that genetic
variation in the UBQLN1 gene has a modest effect on risk, age at onset,
and disease duration of Alzheimer disease and that the presence of
additional putative functional variants either in UBQLN1 or nearby genes
exist.
ANIMAL MODEL
Ganguly et al. (2008) showed that Drosophila Ubqn, the homolog of
UBQLN1, binds to Psen1 (104311) and antagonizes Psen1 function in vivo.
Loss of Ubqn suppressed phenotypes that resulted from loss of Psen1
function in vivo. Overexpression of Ubqn in the eye resulted in
adult-onset, age-dependent retinal degeneration, which could be
suppressed by Psen1 overexpression and enhanced by expression of a
dominant-negative version of Psen1. Expression of a human AD-associated
UBQLN1 variant led to more severe degeneration than expression of
wildtype UBQLN1. The findings identified Ubqn as a regulator of Psen1,
supported a role for UBQLN1 in AD pathogenesis, and suggested that the
expression of a human AD-associated variant can cause neurodegeneration
independent of amyloid production.
*FIELD* RF
1. Bertram, L.; Hiltunen, M.; Parkinson, M.; Ingelsson, M.; Lange,
C.; Ramasamy, K.; Mullin, K.; Menon, R.; Sampson, A. J.; Hsiao, M.
Y.; Elliott, K. J.; Velicelebi, G.; Moscarillo, T.; Hyman, B. T.;
Wagner, S. L.; Becker, K. D.; Blacker, D.; Tanzi, R. E.: Family-based
association between Alzheimer's disease and variants in UBQLN1. New
Eng. J. Med. 352: 884-894, 2005.
2. Bird, T. D.: Genetic factors in Alzheimer's disease. New Eng.
J. Med. 352: 862-864, 2005.
3. Ganguly, A.; Feldman, R. M. R.; Guo, M.: Ubiquilin antagonizes
presenilin and promotes neurodegeneration in Drosophila. Hum. Molec.
Genet. 17: 293-302, 2008.
4. Hanaoka, E.; Ozaki, T.; Ohira, M.; Nakamura, Y.; Suzuki, M.; Takahashi,
E.; Moriya, H.; Nakagawara, A.; Sakiyama, S.: Molecular cloning and
expression analysis of the human DA41 gene and its mapping to chromosome
9q21.2-q21.3. J. Hum. Genet. 45: 188-191, 2000.
5. Kamboh, M. I.; Minster, R. L.; Feingold, E.; DeKosky, S. T.: Genetic
association of ubiquilin with Alzheimer's disease and related quantitative
measures. Molec. Psychiat. 11: 273-279, 2006.
6. Kleijnen, M. F.; Shih, A. H.; Zhou, P.; Kumar, S.; Soccio, R. E.;
Kedersha, N. L.; Gill, G.; Howley, P. M.: The hPLIC proteins may
provide a link between the ubiquitination machinery and the proteasome. Molec.
Cell 6: 409-419, 2000.
7. Ozaki, T.; Hishiki, T.; Toyama, Y.; Yuasa, S.; Nakagawara, A.;
Sakiyama, S.: Identification of a new cellular protein that can interact
specifically with DAN. DNA Cell Biol. 16: 985-991, 1997.
8. Slifer, M. A.; Martin, E. R.; Haines, J. L.; Pericak-Vance, M.
A.: The ubiquilin 1 gene and Alzheimer's disease. (Letter) New Eng.
J. Med. 352: 2752-2753, 2005.
9. Smemo, S.; Nowotny, P.; Hinrichs, A. L.; Kauwe, J. S. K.; Cherny,
S.; Erickson, K.; Myers, A. J.; Kaleem, M.; Marlowe, L.; Gibson, A.
M.; Hollingworth, P.; O'Donovan, M. C.; and 11 others: Ubiquilin
1 polymorphisms are not associated with late-onset Alzheimer's disease. Ann.
Neurol. 59: 21-26, 2006.
10. Stieren, E. S.; El Ayadi, A.; Xiao, Y.; Siller, E.; Landsverk,
M. L.; Oberhauser, A. F.; Barral, J. M.; Boehning, D.: Ubiquilin-1
is a molecular chaperone for the amyloid precursor protein. J. Biol.
Chem. 286: 35689-35698, 2011.
11. Sweetser, D. A.; Peniket, A. J.; Haaland, C.; Blomberg, A. A.;
Zhang, Y.; Zaidi, S. T.; Dayyani, F.; Zhao, Z.; Heerema, N. A.; Boultwood,
J.; Dewald, G. W.; Paietta, E.; Slovak, M. L.; Willman, C. L.; Wainscoat,
J. S.; Bernstein, I. D.; Daly, S. B.: Delineation of the minimal
commonly deleted segment and identification of candidate tumor-suppressor
genes in del(9q) acute myeloid leukemia. Genes Chromosomes Cancer 44:
279-291, 2005.
*FIELD* CN
Patricia A. Hartz - updated: 2/13/2012
Cassandra L. Kniffin - updated: 4/30/2009
Patricia A. Hartz - updated: 8/9/2007
John Logan Black, III - updated: 7/12/2006
Cassandra L. Kniffin - updated: 4/18/2006
Victor A. McKusick - updated: 7/5/2005
Victor A. McKusick - updated: 3/8/2005
Stylianos E. Antonarakis - updated: 9/14/2000
*FIELD* CD
Victor A. McKusick: 6/13/2000
*FIELD* ED
mgross: 02/17/2012
terry: 2/13/2012
alopez: 9/21/2011
terry: 9/9/2010
carol: 7/30/2010
wwang: 5/19/2009
ckniffin: 4/30/2009
mgross: 8/17/2007
terry: 8/9/2007
terry: 7/27/2007
carol: 7/13/2006
terry: 7/12/2006
wwang: 4/24/2006
ckniffin: 4/18/2006
alopez: 7/5/2005
terry: 7/5/2005
alopez: 3/10/2005
terry: 3/8/2005
carol: 5/12/2004
mgross: 9/14/2000
carol: 6/14/2000
carol: 6/13/2000
*RECORD*
*FIELD* NO
605046
*FIELD* TI
*605046 UBIQUILIN 1; UBQLN1
;;DA41, RAT, HOMOLOG OF; DA41;;
PLIC1, MOUSE, HOMOLOG OF; PLIC1;;
read moreUBQN, DROSOPHILA, HOMOLOG OF; UBQN
*FIELD* TX
CLONING
Using a yeast 2-hybrid system to screen an adult rat lung cDNA library,
Ozaki et al. (1997) isolated a cDNA, which they termed DA41, encoding a
cellular protein that can associate with DAN (600613). Expression of DAN
had been found be significantly reduced in rat fibroblast 3Y1 cells
transformed with mouse sarcoma virus and in rodent fibroblasts
transformed with a variety of oncogenes. Ozaki et al. (1997) determined
that the interaction between DAN and DA41 is mediated through the
N-terminal domain and a cystine knot region of DAN. Expression of DA41
is regulated in a cell cycle-dependent manner.
By screening a human lung cDNA library with a rat DA41 cDNA as a probe,
Hanaoka et al. (2000) isolated the human DA41 homolog. Human DA41
encodes a 589-amino acid protein with a predicted molecular mass of 62.4
kD. The protein shows 86% amino acid sequence identity with the rat
protein, indicating the evolutionarily conserved structure and function
of DA41. DA41 was expressed ubiquitously in adult human tissues, with
relatively higher levels in pituitary gland, adrenal gland, kidney,
thymus, and placenta.
By performing independent yeast 2-hybrid screens, Kleijnen et al. (2000)
isolated cDNAs encoding PLIC1 and PLIC2 (UBQLN2; 300264), homologs of
the mouse Plics (proteins linking integrin-associated protein (IAP;
601028) and cytoskeleton) and the yeast Dsk2 protein. PLIC1, also called
UBQLN1, shares 72% amino acid identity with PLIC2. Two motifs are
conserved in the mammalian PLICs and yeast Dsk2, an N-terminal ubiquitin
(191339)-like (UBL) domain and a C-terminal ubiquitin-associated (UBA)
domain. Unlike ubiquitin, the UBL domain of the PLICs does not have a
diglycine motif in its C terminus; the diglycine motif serves as a
target site for cellular hydrolases that release ubiquitin from
precursor fusion proteins. The absence of a GG sequence suggests that
the UBL domain in the PLICs is an integral part of the open reading
frame. The UBA domain is a loosely defined sequence motif present in
multiple enzyme classes of the ubiquitination machinery. The most
notable difference between the mammalian PLICs is the presence of a
collagen-like motif in PLIC2 that is absent in PLIC1 and yeast Dsk2.
This domain is most homologous to the collagen-like oncoprotein of
Herpesvirus saimiri, STP-C488, which is implicated in intracellular
signaling via the RAS-RAF pathway (see 190020). The collagen-like domain
of PLIC2 contains 8 PXGP motifs that are susceptible to cleavage by
collagenase in vitro.
GENE FUNCTION
Kleijnen et al. (2000) showed that the human PLICs physically associate
with both proteasomes and ubiquitin ligases in large complexes.
Overexpression of PLICs interfered with the in vivo degradation of 2
unrelated ubiquitin-dependent proteasome substrates, p53 (191170) and
I-kappa-B-alpha (NFKBIA; 164008), but not a ubiquitin-independent
substrate. These findings raised the possibility that the PLICs, and
possibly related ubiquitin-like family members, may functionally link
the ubiquitination machinery to the proteasome to affect in vivo protein
degradation.
Neurodegenerative Alzheimer disease (AD; 104300) is associated with
extracellular depositions of proteolytic fragments of amyloid precursor
protein (APP; 104760). Using Western blot analysis, Stieren et al.
(2011) found that UBQLN1 expression was reduced in postmortem AD brain
at all stages of AD development except the earliest preclinical stage.
UBQLN1 downregulation preceded significant neuronal cell loss in
preclinical samples. Yeast 2-hybrid analysis of a rat brain cDNA library
showed that human UBQLN1 interacted with the APP intracellular domain.
UBQLN1 also immunoprecipitated with APP in cotransfected HeLa cells. The
amount of UBQLN1 that coprecipitated with APP increased following
crosslinking, suggesting that the complex was transient. Coexpression of
UBQLN1 with APP reduced the content of amyloid deposits in
APP-overexpressing rat PC12 cells and reduced production of pathogenic
amyloid-beta peptides produced by APP-expressing HeLa cells. In vitro,
UBQLN1 significantly protected a test protein against heat denaturation.
Stieren et al. (2011) concluded that UBQLN1 functions as a chaperone for
APP and that diminished UBQLN1 levels in AD may contribute to
pathogenesis.
GENE STRUCTURE
Sweetser et al. (2005) determined that the UBQLN1 gene contains 11
exons.
MAPPING
By fluorescence in situ hybridization, Hanaoka et al. (2000) mapped the
DA41 gene to chromosome 9q21.2-q21.3, a position overlapping a candidate
tumor suppressor locus for bladder cancer (see 109800).
MOLECULAR GENETICS
Bird (2005) reviewed genetic factors in Alzheimer disease (AD; see
104300) and the interrelationship with nongenetic factors. They
commented that UBQLN1 is an intriguing candidate gene because of its
potential role in the proteasome degradation of proteins and its
interaction with PSEN1 and PSEN2.
Bertram et al. (2005) estimated that mutations in the 4 genes that have
been related to Alzheimer disease--APP (104760), PSEN1 (104311), PSEN2
(600759), and APOE4 (107741)--may account for less than half the genetic
variance in Alzheimer disease, and that possibly up to 7 additional
Alzheimer disease genes remained to be identified. They focused on the
fact that the UBQLN1 gene is one of these candidate genes by virtue of
its location at a well-established linkage peak for AD on chromosome
9q22. Bertram et al. (2005) evaluated 19 single-nucleotide polymorphisms
(SNPs) in 3 genes within the 9q22 region in 437 multiplex families with
Alzheimer disease from an NIMH sample. They found a positive association
between Alzheimer disease and various SNPs in UBQLN1 (UBQ-8i, dbSNP
rs2791001, dbSNP 2780995). They confirmed these associations in an
independent sample of families. The risk-conferring haplotype in both
samples was defined by the single intronic SNP located downstream of
exon 8. The risk allele was associated with a dose-dependent increase in
an alternatively spliced UBQLN1 (lacking exon 8) transcript in RNA
extracted from brain samples of patients with Alzheimer disease. Bertram
et al. (2005) interpreted the findings as indicating that genetic
variants in UBQLN1 on 9q22 increase the risk of Alzheimer disease,
possibly by influencing alternative splicing of this gene in the brain.
Slifer et al. (2005) found no association between the risk of Alzheimer
disease and a genetic variant of the UBQ-8i SNP (dbSNP rs12344615) but
did find significant association between this risk allele and an older
age of onset in a recessive disease model in their case-control data
set.
Smemo et al. (2006) found no association between the UBQ-8i SNP and
Alzheimer disease among a group of 1,544 patients with late-onset AD.
There was also no association between AD and 6 other polymorphisms in
the UBQLN1 gene.
Kamboh et al. (2006) studied the association of UBQLN1 gene variation
with Alzheimer disease and examined the association of UBQLN1 SNPs with
quantitative measures of Alzheimer disease progression, namely age at
onset, disease duration, and Mini Mental Status Examination scores. They
examined the association of 3 SNPs in the gene (intron 6 A/C, intron 8
T/C, and intron 9 A/G), all of which are in significant linkage
disequilibrium (p less than 0.0001), in up to 978 late-onset Alzheimer
disease patients and 808 controls. Modestly significant associations
were observed in the single-site regression analysis, but 3-site
haplotype analysis revealed significant associations (p less than
0.0001). One common haplotype, called H4 (ACG for introns 6, 8, and 9,
respectively), was associated with Alzheimer disease risk, and one less
common haplotype, called H5 (CCA for introns 6, 8, and 9, respectively),
was associated with protection. The adjusted odds ratios with
potentially 1 or 2 copies of risk haplotype H4 were 1.5 (95% CI,
0.99-2.26; p = 0.054) and 3.66 (95% CI, 1.43-9.39; p = 0.007),
respectively, and the odds ratio for haplotype H5 carriers was 0.31 (95%
CI, 0.10-0.95; p = 0.0398). Kamboh et al. (2006) suggested that genetic
variation in the UBQLN1 gene has a modest effect on risk, age at onset,
and disease duration of Alzheimer disease and that the presence of
additional putative functional variants either in UBQLN1 or nearby genes
exist.
ANIMAL MODEL
Ganguly et al. (2008) showed that Drosophila Ubqn, the homolog of
UBQLN1, binds to Psen1 (104311) and antagonizes Psen1 function in vivo.
Loss of Ubqn suppressed phenotypes that resulted from loss of Psen1
function in vivo. Overexpression of Ubqn in the eye resulted in
adult-onset, age-dependent retinal degeneration, which could be
suppressed by Psen1 overexpression and enhanced by expression of a
dominant-negative version of Psen1. Expression of a human AD-associated
UBQLN1 variant led to more severe degeneration than expression of
wildtype UBQLN1. The findings identified Ubqn as a regulator of Psen1,
supported a role for UBQLN1 in AD pathogenesis, and suggested that the
expression of a human AD-associated variant can cause neurodegeneration
independent of amyloid production.
*FIELD* RF
1. Bertram, L.; Hiltunen, M.; Parkinson, M.; Ingelsson, M.; Lange,
C.; Ramasamy, K.; Mullin, K.; Menon, R.; Sampson, A. J.; Hsiao, M.
Y.; Elliott, K. J.; Velicelebi, G.; Moscarillo, T.; Hyman, B. T.;
Wagner, S. L.; Becker, K. D.; Blacker, D.; Tanzi, R. E.: Family-based
association between Alzheimer's disease and variants in UBQLN1. New
Eng. J. Med. 352: 884-894, 2005.
2. Bird, T. D.: Genetic factors in Alzheimer's disease. New Eng.
J. Med. 352: 862-864, 2005.
3. Ganguly, A.; Feldman, R. M. R.; Guo, M.: Ubiquilin antagonizes
presenilin and promotes neurodegeneration in Drosophila. Hum. Molec.
Genet. 17: 293-302, 2008.
4. Hanaoka, E.; Ozaki, T.; Ohira, M.; Nakamura, Y.; Suzuki, M.; Takahashi,
E.; Moriya, H.; Nakagawara, A.; Sakiyama, S.: Molecular cloning and
expression analysis of the human DA41 gene and its mapping to chromosome
9q21.2-q21.3. J. Hum. Genet. 45: 188-191, 2000.
5. Kamboh, M. I.; Minster, R. L.; Feingold, E.; DeKosky, S. T.: Genetic
association of ubiquilin with Alzheimer's disease and related quantitative
measures. Molec. Psychiat. 11: 273-279, 2006.
6. Kleijnen, M. F.; Shih, A. H.; Zhou, P.; Kumar, S.; Soccio, R. E.;
Kedersha, N. L.; Gill, G.; Howley, P. M.: The hPLIC proteins may
provide a link between the ubiquitination machinery and the proteasome. Molec.
Cell 6: 409-419, 2000.
7. Ozaki, T.; Hishiki, T.; Toyama, Y.; Yuasa, S.; Nakagawara, A.;
Sakiyama, S.: Identification of a new cellular protein that can interact
specifically with DAN. DNA Cell Biol. 16: 985-991, 1997.
8. Slifer, M. A.; Martin, E. R.; Haines, J. L.; Pericak-Vance, M.
A.: The ubiquilin 1 gene and Alzheimer's disease. (Letter) New Eng.
J. Med. 352: 2752-2753, 2005.
9. Smemo, S.; Nowotny, P.; Hinrichs, A. L.; Kauwe, J. S. K.; Cherny,
S.; Erickson, K.; Myers, A. J.; Kaleem, M.; Marlowe, L.; Gibson, A.
M.; Hollingworth, P.; O'Donovan, M. C.; and 11 others: Ubiquilin
1 polymorphisms are not associated with late-onset Alzheimer's disease. Ann.
Neurol. 59: 21-26, 2006.
10. Stieren, E. S.; El Ayadi, A.; Xiao, Y.; Siller, E.; Landsverk,
M. L.; Oberhauser, A. F.; Barral, J. M.; Boehning, D.: Ubiquilin-1
is a molecular chaperone for the amyloid precursor protein. J. Biol.
Chem. 286: 35689-35698, 2011.
11. Sweetser, D. A.; Peniket, A. J.; Haaland, C.; Blomberg, A. A.;
Zhang, Y.; Zaidi, S. T.; Dayyani, F.; Zhao, Z.; Heerema, N. A.; Boultwood,
J.; Dewald, G. W.; Paietta, E.; Slovak, M. L.; Willman, C. L.; Wainscoat,
J. S.; Bernstein, I. D.; Daly, S. B.: Delineation of the minimal
commonly deleted segment and identification of candidate tumor-suppressor
genes in del(9q) acute myeloid leukemia. Genes Chromosomes Cancer 44:
279-291, 2005.
*FIELD* CN
Patricia A. Hartz - updated: 2/13/2012
Cassandra L. Kniffin - updated: 4/30/2009
Patricia A. Hartz - updated: 8/9/2007
John Logan Black, III - updated: 7/12/2006
Cassandra L. Kniffin - updated: 4/18/2006
Victor A. McKusick - updated: 7/5/2005
Victor A. McKusick - updated: 3/8/2005
Stylianos E. Antonarakis - updated: 9/14/2000
*FIELD* CD
Victor A. McKusick: 6/13/2000
*FIELD* ED
mgross: 02/17/2012
terry: 2/13/2012
alopez: 9/21/2011
terry: 9/9/2010
carol: 7/30/2010
wwang: 5/19/2009
ckniffin: 4/30/2009
mgross: 8/17/2007
terry: 8/9/2007
terry: 7/27/2007
carol: 7/13/2006
terry: 7/12/2006
wwang: 4/24/2006
ckniffin: 4/18/2006
alopez: 7/5/2005
terry: 7/5/2005
alopez: 3/10/2005
terry: 3/8/2005
carol: 5/12/2004
mgross: 9/14/2000
carol: 6/14/2000
carol: 6/13/2000