NACA_MOUSE
ID NACA_MOUSE Reviewed; 215 AA.
AC Q60817; Q3THR6; Q4FZL8;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Nascent polypeptide-associated complex subunit alpha;
DE AltName: Full=Alpha-NAC;
DE AltName: Full=Alpha-NAC/1.9.2;
GN Name=Naca;
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 [GENOMIC DNA] (ISOFORM 1), FUNCTION, ALTERNATIVE
RP SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=8698236; DOI=10.1101/gad.10.14.1763;
RA Yotov W.V., St Arnaud R.;
RT "Differential splicing-in of a proline-rich exon converts alphaNAC into a
RT muscle-specific transcription factor.";
RL Genes Dev. 10:1763-1772(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH TBP, AND
RP SUBCELLULAR LOCATION.
RX PubMed=9488445; DOI=10.1128/mcb.18.3.1303;
RA Yotov W.V., Moreau A., St Arnaud R.;
RT "The alpha chain of the nascent polypeptide-associated complex functions as
RT a transcriptional coactivator.";
RL Mol. Cell. Biol. 18:1303-1311(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Yotov W.V., St Arnaud R.;
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ, C57BL/6J, and DBA/2J;
RC TISSUE=Bone marrow, Embryo, Heart, and Kidney;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, Mammary tumor, and Placenta;
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 [6]
RP TISSUE SPECIFICITY.
RX PubMed=9877153; DOI=10.1016/s0014-5793(98)01440-9;
RA Moeller I., Beatrix B., Kreibich G., Sakai H., Lauring B., Wiedmann M.;
RT "Unregulated exposure of the ribosomal M-site caused by NAC depletion
RT results in delivery of non-secretory polypeptides to the Sec61 complex.";
RL FEBS Lett. 441:1-5(1998).
RN [7]
RP FUNCTION, INTERACTION WITH JUN, AND DEVELOPMENTAL STAGE.
RX PubMed=9488446; DOI=10.1128/mcb.18.3.1312;
RA Moreau A., Yotov W.V., Glorieux F.H., St Arnaud R.;
RT "Bone-specific expression of the alpha chain of the nascent polypeptide-
RT associated complex, a coactivator potentiating c-Jun-mediated
RT transcription.";
RL Mol. Cell. Biol. 18:1312-1321(1998).
RN [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=10224091; DOI=10.1074/jbc.274.19.13305;
RA Munz B., Wiedmann M., Lochmueller H., Werner S.;
RT "Cloning of novel injury-regulated genes. Implications for an important
RT role of the muscle-specific protein skNAC in muscle repair.";
RL J. Biol. Chem. 274:13305-13310(1999).
RN [9]
RP SUBCELLULAR LOCATION, DEGRADATION, AND PHOSPHORYLATION AT THR-159.
RX PubMed=15005626; DOI=10.1021/bi036256+;
RA Quelo I., Akhouayri O., Prud'homme J., St Arnaud R.;
RT "GSK3 beta-dependent phosphorylation of the alpha NAC coactivator regulates
RT its nuclear translocation and proteasome-mediated degradation.";
RL Biochemistry 43:2906-2914(2004).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ILK, AND PHOSPHORYLATION
RP AT SER-43.
RX PubMed=15299025; DOI=10.1074/jbc.m406310200;
RA Quelo I., Gauthier C., Hannigan G.E., Dedhar S., St-Arnaud R.;
RT "Integrin-linked kinase regulates the nuclear entry of the c-Jun
RT coactivator alpha-NAC and its coactivation potency.";
RL J. Biol. Chem. 279:43893-43899(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [12]
RP FUNCTION.
RX PubMed=15831452; DOI=10.1128/mcb.25.9.3452-3460.2005;
RA Akhouayri O., Quelo I., St-Arnaud R.;
RT "Sequence-specific DNA binding by the alphaNAC coactivator is required for
RT potentiation of c-Jun-dependent transcription of the osteocalcin gene.";
RL Mol. Cell. Biol. 25:3452-3460(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-159 AND SER-166, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC 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 [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Prevents inappropriate targeting of non-secretory
CC polypeptides to the endoplasmic reticulum (ER). Binds to nascent
CC polypeptide chains as they emerge from the ribosome and blocks their
CC interaction with the signal recognition particle (SRP), which normally
CC targets nascent secretory peptides to the ER. Also reduces the inherent
CC affinity of ribosomes for protein translocation sites in the ER
CC membrane (M sites) (By similarity). Isoform 1 and isoform 2 appear to
CC bind DNA and play roles in transcription. Isoform 1 may function as a
CC specific coactivator for JUN, acting to stabilize the interaction of
CC JUN homodimers with promoter elements. {ECO:0000250,
CC ECO:0000269|PubMed:15299025, ECO:0000269|PubMed:15831452,
CC ECO:0000269|PubMed:8698236, ECO:0000269|PubMed:9488445,
CC ECO:0000269|PubMed:9488446}.
CC -!- SUBUNIT: Part of the nascent polypeptide-associated complex (NAC),
CC which is a heterodimer of NACA and BTF3 (via NAC-A/B domains). NAC
CC associates with ribosomes through the BTF3/NACB subunit and contacts
CC the ribosomal protein L23, which is positioned near the exiting site.
CC Both subunits can contact nascent polypeptide chains. NACA may also
CC form homodimers, and only this form binds DNA (By similarity).
CC Interacts with TBP and JUN. {ECO:0000250, ECO:0000269|PubMed:15299025,
CC ECO:0000269|PubMed:9488445, ECO:0000269|PubMed:9488446}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=The heterodimer is
CC located mainly in the cytosol, and the homodimer in the nucleus.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60817-1; Sequence=Displayed;
CC Name=2; Synonyms=Gp220, skNAC;
CC IsoId=P70670-1; Sequence=External;
CC -!- TISSUE SPECIFICITY: Isoform 1 appears to be ubiquitously expressed.
CC {ECO:0000269|PubMed:10224091, ECO:0000269|PubMed:8698236,
CC ECO:0000269|PubMed:9877153}.
CC -!- DEVELOPMENTAL STAGE: Expressed concomitant with the onset of
CC mineralization in ossification centers of developing bone.
CC {ECO:0000269|PubMed:9488446}.
CC -!- DOMAIN: The positively charged inner surface of the NAC-A/B domain is
CC crucial for NACA localization in the nucleus and DNA-binding. This
CC region is blocked from binding nucleic acids in the heterodimeric
CC complex by a helix region in the beta-subunit, it also displays much
CC higher affinity for RNA than DNA (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation of Ser-43 by ILK during cell adhesion may promote
CC nuclear localization. Phosphorylation of Thr-159 by GSK3B may promote
CC proteasome mediated degradation. {ECO:0000269|PubMed:15005626,
CC ECO:0000269|PubMed:15299025}.
CC -!- SIMILARITY: Belongs to the NAC-alpha family. {ECO:0000305}.
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DR EMBL; U22151; AAB80961.1; -; mRNA.
DR EMBL; U48363; AAB18733.1; -; Genomic_DNA.
DR EMBL; AK146197; BAE26971.1; -; mRNA.
DR EMBL; AK151928; BAE30804.1; -; mRNA.
DR EMBL; AK161678; BAE36526.1; -; mRNA.
DR EMBL; AK168023; BAE40008.1; -; mRNA.
DR EMBL; AK168169; BAE40130.1; -; mRNA.
DR EMBL; AK168607; BAE40474.1; -; mRNA.
DR EMBL; AK169432; BAE41173.1; -; mRNA.
DR EMBL; AK169435; BAE41176.1; -; mRNA.
DR EMBL; BC029830; AAH29830.1; -; mRNA.
DR EMBL; BC083340; AAH83340.1; -; mRNA.
DR EMBL; BC099375; AAH99375.1; -; mRNA.
DR CCDS; CCDS24258.1; -. [Q60817-1]
DR PIR; T30827; T30827.
DR RefSeq; NP_001269905.1; NM_001282976.1. [Q60817-1]
DR RefSeq; NP_038636.2; NM_013608.3. [Q60817-1]
DR AlphaFoldDB; Q60817; -.
DR SMR; Q60817; -.
DR BioGRID; 201682; 16.
DR IntAct; Q60817; 4.
DR iPTMnet; Q60817; -.
DR jPOST; Q60817; -.
DR MaxQB; Q60817; -.
DR PeptideAtlas; Q60817; -.
DR PRIDE; Q60817; -.
DR ProteomicsDB; 287344; -. [Q60817-1]
DR Antibodypedia; 28384; 97 antibodies from 17 providers.
DR DNASU; 17938; -.
DR Ensembl; ENSMUST00000073868; ENSMUSP00000073532; ENSMUSG00000061315. [Q60817-1]
DR GeneID; 17938; -.
DR UCSC; uc007hlb.2; mouse. [Q60817-1]
DR CTD; 4666; -.
DR MGI; MGI:106095; Naca.
DR VEuPathDB; HostDB:ENSMUSG00000061315; -.
DR GeneTree; ENSGT00440000033468; -.
DR HOGENOM; CLU_057806_1_2_1; -.
DR BioGRID-ORCS; 17938; 27 hits in 73 CRISPR screens.
DR ChiTaRS; Naca; mouse.
DR Proteomes; UP000000589; Chromosome 10.
DR Bgee; ENSMUSG00000061315; Expressed in ventricular zone and 67 other tissues.
DR ExpressionAtlas; Q60817; baseline and differential.
DR Genevisible; Q60817; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005854; C:nascent polypeptide-associated complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017025; F:TBP-class protein binding; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:MGI.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0003231; P:cardiac ventricle development; IMP:BHF-UCL.
DR GO; GO:0007507; P:heart development; IMP:BHF-UCL.
DR GO; GO:0061384; P:heart trabecula morphogenesis; IMP:BHF-UCL.
DR GO; GO:0051451; P:myoblast migration; IMP:MGI.
DR GO; GO:1905551; P:negative regulation of protein localization to endoplasmic reticulum; ISO:MGI.
DR GO; GO:0010664; P:negative regulation of striated muscle cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; IMP:BHF-UCL.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0006612; P:protein targeting to membrane; IBA:GO_Central.
DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IMP:BHF-UCL.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IMP:BHF-UCL.
DR GO; GO:0042060; P:wound healing; IMP:BHF-UCL.
DR Gene3D; 2.20.70.30; -; 1.
DR InterPro; IPR016641; EGD2/NACA.
DR InterPro; IPR044034; NAC-like_UBA.
DR InterPro; IPR038187; NAC_A/B_dom_sf.
DR InterPro; IPR002715; Nas_poly-pep-assoc_cplx_dom.
DR PANTHER; PTHR21713; PTHR21713; 1.
DR Pfam; PF19026; HYPK_UBA; 1.
DR Pfam; PF01849; NAC; 1.
DR PIRSF; PIRSF015901; NAC_alpha; 1.
DR SMART; SM01407; NAC; 1.
DR PROSITE; PS51151; NAC_AB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chaperone; Cytoplasm; DNA-binding;
KW Isopeptide bond; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Transcription; Transport; Ubl conjugation.
FT CHAIN 1..215
FT /note="Nascent polypeptide-associated complex subunit
FT alpha"
FT /id="PRO_0000135577"
FT DOMAIN 70..135
FT /note="NAC-A/B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00507"
FT DOMAIN 176..213
FT /note="UBA"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 69..80
FT /note="Required for DNA-binding"
FT REGION 93..108
FT /note="RNA/DNA-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 11..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 43
FT /note="Phosphoserine; by ILK1"
FT /evidence="ECO:0000269|PubMed:15299025"
FT MOD_RES 132
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13765"
FT MOD_RES 142
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 159
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000269|PubMed:15005626,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 161
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13765"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747,
FT ECO:0007744|PubMed:17242355, ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13765"
FT MOD_RES 191
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13765"
FT MOD_RES 203
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13765"
FT CROSSLNK 142
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q13765"
FT CONFLICT 52
FT /note="Q -> K (in Ref. 4; BAE40130)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 215 AA; 23384 MW; 0E7D5D90304E306D CRC64;
MPGEATETVP ATEQELPQPQ AETGSGTESD SDESVPELEE QDSTQTATQQ AQLAAAAEID
EEPVSKAKQS RSEKKARKAM SKLGLRQVTG VTRVTIRKSK NILFVITKPD VYKSPASDTY
IVFGEAKIED LSQQAQLAAA EKFKVQGEAV SNIQENTQTP TVQEESEEEE VDETGVEVKD
IELVMSQANV SRAKAVRALK NNSNDIVNAI MELTM
