UBQL4_MOUSE
ID UBQL4_MOUSE Reviewed; 596 AA.
AC Q99NB8; Q8BP88;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ubiquilin-4 {ECO:0000305};
DE AltName: Full=Ataxin-1 interacting ubiquitin-like protein {ECO:0000305};
DE Short=A1Up {ECO:0000250|UniProtKB:Q9NRR5};
DE AltName: Full=Ataxin-1 ubiquitin-like-interacting protein A1U;
DE AltName: Full=Connexin43-interacting protein of 75 kDa {ECO:0000303|PubMed:18079109};
DE Short=CIP75 {ECO:0000303|PubMed:18079109};
GN Name=Ubqln4 {ECO:0000312|MGI:MGI:2150152};
GN Synonyms=Cip75 {ECO:0000303|PubMed:18079109},
GN Ubin {ECO:0000303|PubMed:11162551};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SIGNAL SEQUENCES, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=11162551; DOI=10.1006/bbrc.2000.4149;
RA Matsuda M., Koide T., Yorihuzi T., Hosokawa N., Nagata K.;
RT "Molecular cloning of a novel ubiquitin-like protein, UBIN, that binds to
RT ER targeting signal sequences.";
RL Biochem. Biophys. Res. Commun. 280:535-540(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 549-596.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PSMD2; PSMD4 AND GJA1.
RX PubMed=18079109; DOI=10.1074/jbc.m709288200;
RA Li X., Su V., Kurata W.E., Jin C., Lau A.F.;
RT "A novel connexin43-interacting protein, CIP75, which belongs to the UbL-
RT UBA protein family, regulates the turnover of connexin43.";
RL J. Biol. Chem. 283:5748-5759(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH UBIQUITIN AND GJA1, AND
RP TISSUE SPECIFICITY.
RX PubMed=20940304; DOI=10.1074/jbc.m110.170753;
RA Su V., Nakagawa R., Koval M., Lau A.F.;
RT "Ubiquitin-independent proteasomal degradation of endoplasmic reticulum-
RT localized connexin43 mediated by CIP75.";
RL J. Biol. Chem. 285:40979-40990(2010).
RN [7]
RP STRUCTURE BY NMR OF 549-596, AND INTERACTION WITH GJA1.
RX PubMed=20127391; DOI=10.1007/s10858-010-9397-9;
RA Kieken F., Spagnol G., Su V., Lau A.F., Sorgen P.L.;
RT "NMR structure note: UBA domain of CIP75.";
RL J. Biomol. NMR 46:245-250(2010).
CC -!- FUNCTION: Regulator of protein degradation that mediates the
CC proteasomal targeting of misfolded, mislocalized or accumulated
CC proteins (By similarity). Acts by binding polyubiquitin chains of
CC target proteins via its UBA domain and by interacting with subunits of
CC the proteasome via its ubiquitin-like domain (By similarity). Key
CC regulator of DNA repair that represses homologous recombination repair:
CC in response to DNA damage, recruited to sites of DNA damage following
CC phosphorylation by ATM and acts by binding and removing ubiquitinated
CC MRE11 from damaged chromatin, leading to MRE11 degradation by the
CC proteasome (By similarity). MRE11 degradation prevents homologous
CC recombination repair, redirecting double-strand break repair toward
CC non-homologous end joining (NHEJ) (By similarity). Specifically
CC recognizes and binds mislocalized transmembrane-containing proteins and
CC targets them to proteasomal degradation (By similarity). Collaborates
CC with DESI1/POST in the export of ubiquitinated proteins from the
CC nucleus to the cytoplasm (By similarity). Plays a role in the
CC regulation of the proteasomal degradation of non-ubiquitinated GJA1
CC (PubMed:18079109, PubMed:20940304). Acts as an adapter protein that
CC recruits UBQLN1 to the autophagy machinery (By similarity). Mediates
CC the association of UBQLN1 with autophagosomes and the autophagy-related
CC protein LC3 (MAP1LC3A/B/C) and may assist in the maturation of
CC autophagosomes to autolysosomes by mediating autophagosome-lysosome
CC fusion (By similarity). {ECO:0000250|UniProtKB:Q9NRR5,
CC ECO:0000269|PubMed:18079109, ECO:0000269|PubMed:20940304}.
CC -!- SUBUNIT: Homooligomer (By similarity). Binds signal sequences of
CC proteins that are targeted to the endoplasmic reticulum
CC (PubMed:11162551). Interacts (via UBA domain) with GJA1 (not
CC ubiquitinated) and with ubiquitin; both compete for the same binding
CC site (PubMed:18079109, PubMed:20127391, PubMed:20940304). Interacts
CC (via UBA domain) with ubiquitin and with polyubiquitin chains
CC (PubMed:20940304). Interacts (via ubiquitin-like domain) with PSMD2 and
CC PSMD4, regulatory subunits of the 26S proteasome (PubMed:18079109).
CC Interacts with ATXN1/SCA1; interaction with ATXN1 inhibits
CC polyubiquitination of UBQLN4 and interferes with PSMD4 binding (By
CC similarity). Interacts with HERPUD1 (By similarity). Interacts (via
CC ubiquitin-like domain) with UBQLN1 (via UBA domain) (By similarity).
CC Interacts with UBQLN2 (By similarity). Interacts (via STI1 1 and 2
CC domains) with MAP1LC3A/B/C (By similarity). Interacts with BAG6 (By
CC similarity). Interacts with MRE11 (when ubiquitinated); interaction
CC with ubiquitinated MRE11 leads to MRE11 removal from chromatin (By
CC similarity). Interacts with DESI1/POST; leading to nuclear export (By
CC similarity). Interacts with BCL2A1 and BCL2L10 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NRR5, ECO:0000269|PubMed:11162551,
CC ECO:0000269|PubMed:18079109, ECO:0000269|PubMed:20127391,
CC ECO:0000269|PubMed:20940304}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11162551}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9NRR5}. Chromosome
CC {ECO:0000250|UniProtKB:Q9NRR5}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:11162551, ECO:0000269|PubMed:18079109,
CC ECO:0000269|PubMed:20940304}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:18079109}. Cytoplasmic vesicle, autophagosome
CC {ECO:0000250|UniProtKB:Q9NRR5}. Note=Colocalizes with the proteasome,
CC both in nucleus and cytoplasm. Exported from the nucleus following
CC interaction with DESI1/POST. In response to DNA damage and
CC phosphorylation at Ser-318 by ATM, localizes to the nucleus and is
CC recruited to sites of DNA damage. {ECO:0000250|UniProtKB:Q9NRR5}.
CC -!- TISSUE SPECIFICITY: Detected in testis, ovary, thyroid, kidney, thymus,
CC heart, liver, lung and spleen (at protein level). Highly expressed in
CC heart, skeletal muscle, kidney, liver and brain. Detected at lower
CC levels in testis, lung and spleen. {ECO:0000269|PubMed:11162551,
CC ECO:0000269|PubMed:20940304}.
CC -!- PTM: Phosphorylated by ATM at Ser-313 in response to DNA damage,
CC leading to localization in the nucleus and recruitment to sites of DNA
CC damage. {ECO:0000250|UniProtKB:Q9NRR5}.
CC -!- PTM: Ubiquitinated; this does not lead to proteasomal degradation. May
CC undergo both 'Lys-48'- and 'Lys-63'-linked polyubiquitination.
CC {ECO:0000250|UniProtKB:Q9NRR5}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB040050; BAB40326.1; -; mRNA.
DR EMBL; BC017686; AAH17686.1; -; mRNA.
DR EMBL; AK077511; BAC36837.1; -; mRNA.
DR CCDS; CCDS17479.1; -.
DR RefSeq; NP_277068.1; NM_033526.2.
DR PDB; 2KNZ; NMR; -; A=549-596.
DR PDBsum; 2KNZ; -.
DR AlphaFoldDB; Q99NB8; -.
DR BMRB; Q99NB8; -.
DR SMR; Q99NB8; -.
DR BioGRID; 220488; 48.
DR IntAct; Q99NB8; 3.
DR STRING; 10090.ENSMUSP00000008748; -.
DR iPTMnet; Q99NB8; -.
DR PhosphoSitePlus; Q99NB8; -.
DR EPD; Q99NB8; -.
DR MaxQB; Q99NB8; -.
DR PaxDb; Q99NB8; -.
DR PeptideAtlas; Q99NB8; -.
DR PRIDE; Q99NB8; -.
DR ProteomicsDB; 298423; -.
DR Antibodypedia; 34204; 116 antibodies from 26 providers.
DR DNASU; 94232; -.
DR Ensembl; ENSMUST00000008748; ENSMUSP00000008748; ENSMUSG00000008604.
DR GeneID; 94232; -.
DR KEGG; mmu:94232; -.
DR UCSC; uc008pvq.1; mouse.
DR CTD; 56893; -.
DR MGI; MGI:2150152; Ubqln4.
DR VEuPathDB; HostDB:ENSMUSG00000008604; -.
DR eggNOG; KOG0010; Eukaryota.
DR GeneTree; ENSGT00940000155620; -.
DR HOGENOM; CLU_024293_4_0_1; -.
DR InParanoid; Q99NB8; -.
DR OMA; GVKMADQ; -.
DR OrthoDB; 1553668at2759; -.
DR PhylomeDB; Q99NB8; -.
DR TreeFam; TF314412; -.
DR BioGRID-ORCS; 94232; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Ubqln4; mouse.
DR EvolutionaryTrace; Q99NB8; -.
DR PRO; PR:Q99NB8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q99NB8; protein.
DR Bgee; ENSMUSG00000008604; Expressed in ventricular zone and 254 other tissues.
DR ExpressionAtlas; Q99NB8; baseline and differential.
DR Genevisible; Q99NB8; MM.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0031597; C:cytosolic proteasome complex; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:MGI.
DR GO; GO:0031595; C:nuclear proteasome complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0036435; F:K48-linked polyubiquitin modification-dependent protein binding; ISO:MGI.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:1901097; P:negative regulation of autophagosome maturation; ISO:MGI.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
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 SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Chromosome; Cytoplasm; Cytoplasmic vesicle;
KW DNA damage; DNA repair; Endoplasmic reticulum; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..596
FT /note="Ubiquilin-4"
FT /id="PRO_0000211016"
FT DOMAIN 13..87
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 187..224
FT /note="STI1 1"
FT /evidence="ECO:0000255"
FT DOMAIN 225..256
FT /note="STI1 2"
FT /evidence="ECO:0000255"
FT DOMAIN 388..435
FT /note="STI1 3"
FT /evidence="ECO:0000255"
FT DOMAIN 439..471
FT /note="STI1 4"
FT /evidence="ECO:0000255"
FT DOMAIN 548..593
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 89..148
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 482..528
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 90..135
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 297..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 335..361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 487..528
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR5"
FT MOD_RES 282
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR5"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR5"
FT CROSSLNK 23
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR5"
FT CROSSLNK 62
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9NRR5"
FT HELIX 551..562
FT /evidence="ECO:0007829|PDB:2KNZ"
FT TURN 563..565
FT /evidence="ECO:0007829|PDB:2KNZ"
FT HELIX 569..579
FT /evidence="ECO:0007829|PDB:2KNZ"
FT HELIX 583..592
FT /evidence="ECO:0007829|PDB:2KNZ"
SQ SEQUENCE 596 AA; 63506 MW; 77CC85B49FD083C4 CRC64;
MAEPSGAETR PQIRVTVKTP KDKEEIVICD QASVKEFKEE ISRRFKAQQD QLVLIFAGKI
LKDGDTLSQH GIKDGLTVHL VIKTPQKAQD PVTAAASPPS TPDSASAPST TPASPAAAPV
QPCSSGNTTS DAGSGGGPSP VAAEGPSSAT ASILSGFGGI LGLGSLGLGS ANFMELQQQM
QRQLMSNPEM LSQIMENPLV QDMMSNPDLM RHMIMANPQM QQLMERNPEI SHMLNNPELM
RQTMELARNP AMMQEMMRNQ DRALSNLESV PGGYNALRRM YTDIQEPMFT AAREQFGNNP
FSSLAGNSDN SSSQPLRTEN REPLPNPWSP SPPTSQAPGS GGEGTGGSGT SQVHPTVSNP
FGINAASLGS GMFNSPEMQA LLQQISENPQ LMQNVISAPY MRTMMQTLAQ NPDFAAQMMV
NVPLFAGNPQ LQEQLRLQLP VFLQQMQNPE SLSILTNPRA MQALLQIQQG LQTLQTEAPG
LVPSLGSFGT PRTSVPLAGS NSGSSAEAPT SSPGVPATSP PSAGSNAQQQ LMQQMIQLLS
GSGNSQVPMP EVRFQQQLEQ LNSMGFINRE ANLQALIATG GDINAAIERL LGSQLS
