Full text data of NACA
NACA
[Confidence: low (only semi-automatic identification from reviews)]
Nascent polypeptide-associated complex subunit alpha; NAC-alpha (Alpha-NAC; Hom s 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Nascent polypeptide-associated complex subunit alpha; NAC-alpha (Alpha-NAC; Hom s 2)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q13765
ID NACA_HUMAN Reviewed; 215 AA.
AC Q13765; F8VU71; Q3KQV4; Q53A18; Q53G46;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Nascent polypeptide-associated complex subunit alpha;
DE Short=NAC-alpha;
DE AltName: Full=Alpha-NAC;
DE AltName: Allergen=Hom s 2;
GN Name=NACA; ORFNames=HSD48;
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).
RC TISSUE=Neuroblastoma;
RX PubMed=12209604; DOI=10.1002/ijc.10550;
RA Behrends U., Jandl T., Golbeck A., Lechner B., Mueller-Weihrich S.,
RA Schmid I., Till H., Berthold F., Voltz R., Mautner J.M.;
RT "Novel products of the HuD, HuC, NNP-1 and alpha-internexin genes
RT identified by autologous antibody screening of a pediatric
RT neuroblastoma library.";
RL Int. J. Cancer 100:669-677(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=15196207; DOI=10.1111/j.1365-2567.2004.01893.x;
RA Al-Shanti N., Steward C.G., Garland R.J., Rowbottom A.W.;
RT "Investigation of alpha nascent polypeptide-associated complex
RT functions in a human CD8(+) T cell ex vivo expansion model using
RT antisense oligonucleotides.";
RL Immunology 112:397-403(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Sakai H., Chew C., Wang S., Wiedmann B., Geromanos S., Tempst P.,
RA Wiedmann M.;
RT "Nascent polypeptide-associate complex (NAC): a novel type of
RT polypeptide binding protein.";
RL Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pericardium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Cervix;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-173 (ISOFORM 1).
RC TISSUE=Testis;
RA Yuan L.G., Tian Y.Q., Qiao Y., Miao S.Y., Wang L.F.;
RT "A new spermatogenesis-related gene.";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 101-142 AND 180-192, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 101-142; 145-192 AND 201-215, PHOSPHORYLATION AT
RP SER-166, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [13]
RP ALLERGEN.
RX PubMed=9806765;
RA Natter S., Seiberler S., Hufnagl P., Binder B.R., Hirschl A.M.,
RA Ring J., Abeck D., Schmidt T., Valent P., Valenta R.;
RT "Isolation of cDNA clones coding for IgE autoantigens with serum IgE
RT from atopic dermatitis patients.";
RL FASEB J. 12:1559-1569(1998).
RN [14]
RP FUNCTION.
RX PubMed=9877153; DOI=10.1016/S0014-5793(98)01440-9;
RA Moeller I., Beatrix B., Kreibich G., Sakai H., Lauring B.,
RA 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
RT complex.";
RL FEBS Lett. 441:1-5(1998).
RN [15]
RP FUNCTION, INTERACTION WITH BTF3, ASSOCIATION WITH RIBOSOMES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10982809; DOI=10.1074/jbc.M006368200;
RA Beatrix B., Sakai H., Wiedmann M.;
RT "The alpha and beta subunit of the nascent polypeptide-associated
RT complex have distinct functions.";
RL J. Biol. Chem. 275:37838-37845(2000).
RN [16]
RP INTERACTION WITH FADD.
RX PubMed=12684039; DOI=10.1016/S0006-291X(03)00487-X;
RA Stilo R., Liguoro D., di Jeso B., Leonardi A., Vito P.;
RT "The alpha-chain of the nascent polypeptide-associated complex binds
RT to and regulates FADD function.";
RL Biochem. Biophys. Res. Commun. 303:1034-1041(2003).
RN [17]
RP SUBCELLULAR LOCATION, AND POSSIBLE INVOLVEMENT IN OSTEOSARCOMA.
RX PubMed=12689679; DOI=10.1016/S8756-3282(03)00026-7;
RA Papachristou D.J., Batistatou A., Sykiotis G.P., Varakis I.,
RA Papavassiliou A.G.;
RT "Activation of the JNK-AP-1 signal transduction pathway is associated
RT with pathogenesis and progression of human osteosarcomas.";
RL Bone 32:364-371(2003).
RN [18]
RP PHOSPHORYLATION AT SER-43, AND SUBCELLULAR LOCATION.
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 [19]
RP FUNCTION.
RX PubMed=15784678; DOI=10.1242/jcs.02295;
RA Lopez S., Stuhl L., Fichelson S., Dubart-Kupperschmitt A.,
RA St Arnaud R., Galindo J.-R., Murati A., Berda N., Dubreuil P.,
RA Gomez S.;
RT "NACA is a positive regulator of human erythroid-cell
RT differentiation.";
RL J. Cell Sci. 118:1595-1605(2005).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16201836; DOI=10.1371/journal.pbio.0030357;
RA Marques A.C., Dupanloup I., Vinckenbosch N., Reymond A., Kaessmann H.;
RT "Emergence of young human genes after a burst of retroposition in
RT primates.";
RL PLoS Biol. 3:E357-E357(2005).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161; SER-166 AND
RP SER-191, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-191 AND
RP SER-203, 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 [29]
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP 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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
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
CC their interaction with the signal recognition particle (SRP),
CC which normally targets nascent secretory peptides to the ER. Also
CC reduces the inherent affinity of ribosomes for protein
CC translocation sites in the ER membrane (M sites). May act as a
CC specific coactivator for JUN, binding to DNA and stabilizing the
CC interaction of JUN homodimers with target gene promoters.
CC -!- SUBUNIT: Interacts with TBP and JUN (By similarity). Part of the
CC nascent polypeptide-associated complex (NAC), consisting of NACA
CC and BTF3. NAC associates with ribosomes through the BTF3 subunit.
CC Both subunits can contact nascent polypeptide chains. Interacts
CC with ASFV protein H339R.
CC -!- INTERACTION:
CC P40222:TXLNA; NbExp=2; IntAct=EBI-712216, EBI-359793;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly
CC cytoplasmic. Also found in nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13765-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13765-2; Sequence=VSP_044825;
CC Note=No experimental confirmation available. May be due to
CC intron retention;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- PTM: Phosphorylation of Thr-159 by GSK3B may promote proteasome
CC mediated degradation (By similarity). Phosphorylation of Ser-43 by
CC ILK during cell adhesion may promote nuclear localization.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE from
CC atopic dermatitis (AD) patients. Identified as an IgE autoantigen
CC in atopic dermatitis (AD) patients with severe skin
CC manifestations.
CC -!- SIMILARITY: Belongs to the NAC-alpha family.
CC -!- SIMILARITY: Contains 1 NAC-A/B (NAC-alpha/beta) domain.
CC -!- SIMILARITY: Contains 1 UBA domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAV83778.1; Type=Erroneous initiation;
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DR EMBL; AY034001; AAK57544.1; -; mRNA.
DR EMBL; AY911673; AAX14393.1; -; mRNA.
DR EMBL; X80909; CAA56869.1; -; mRNA.
DR EMBL; AF054187; AAC99403.1; -; mRNA.
DR EMBL; AK096699; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CR450295; CAG29291.1; -; mRNA.
DR EMBL; AK223085; BAD96805.1; -; mRNA.
DR EMBL; AC117378; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105120; AAI05121.1; -; mRNA.
DR EMBL; BC105122; AAI05123.1; -; mRNA.
DR EMBL; BC106041; AAI06042.1; -; mRNA.
DR EMBL; AY605660; AAV83778.1; ALT_INIT; mRNA.
DR PIR; S49326; S49326.
DR RefSeq; NP_001106673.1; NM_001113202.1.
DR RefSeq; NP_001106674.2; NM_001113203.2.
DR UniGene; Hs.505735; -.
DR PDB; 3LKX; X-ray; 2.50 A; B=84-136.
DR PDB; 3MCB; X-ray; 1.90 A; A=79-132.
DR PDB; 3MCE; X-ray; 2.40 A; A/B/C/D=81-133.
DR PDBsum; 3LKX; -.
DR PDBsum; 3MCB; -.
DR PDBsum; 3MCE; -.
DR ProteinModelPortal; Q13765; -.
DR SMR; Q13765; 79-132.
DR IntAct; Q13765; 23.
DR MINT; MINT-5000033; -.
DR STRING; 9606.ENSP00000403817; -.
DR Allergome; 3323; Hom s 2.0101.
DR Allergome; 412; Hom s 2.
DR PhosphoSite; Q13765; -.
DR DMDM; 71151996; -.
DR PaxDb; Q13765; -.
DR PRIDE; Q13765; -.
DR Ensembl; ENST00000356769; ENSP00000349212; ENSG00000196531.
DR Ensembl; ENST00000393891; ENSP00000377469; ENSG00000196531.
DR Ensembl; ENST00000546392; ENSP00000446801; ENSG00000196531.
DR Ensembl; ENST00000552540; ENSP00000447821; ENSG00000196531.
DR GeneID; 4666; -.
DR KEGG; hsa:4666; -.
DR UCSC; uc001sma.2; human.
DR CTD; 4666; -.
DR GeneCards; GC12M057106; -.
DR H-InvDB; HIX0034277; -.
DR HGNC; HGNC:7629; NACA.
DR MIM; 601234; gene.
DR neXtProt; NX_Q13765; -.
DR PharmGKB; PA31433; -.
DR eggNOG; COG1308; -.
DR HOVERGEN; HBG082004; -.
DR KO; K03626; -.
DR OrthoDB; EOG7RNK24; -.
DR PhylomeDB; Q13765; -.
DR ChiTaRS; NACA; human.
DR EvolutionaryTrace; Q13765; -.
DR GeneWiki; NACA_(gene); -.
DR GenomeRNAi; 4666; -.
DR NextBio; 17982; -.
DR PRO; PR:Q13765; -.
DR ArrayExpress; Q13765; -.
DR Bgee; Q13765; -.
DR CleanEx; HS_NACA; -.
DR Genevestigator; Q13765; -.
DR GO; GO:0005854; C:nascent polypeptide-associated complex; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017025; F:TBP-class protein binding; ISS:BHF-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:BHF-UCL.
DR GO; GO:0003231; P:cardiac ventricle development; ISS:BHF-UCL.
DR GO; GO:0061384; P:heart trabecula morphogenesis; ISS:BHF-UCL.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0010664; P:negative regulation of striated muscle cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:1901227; P:negative regulation of transcription from RNA polymerase II promoter involved in heart development; ISS:BHF-UCL.
DR GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; ISS:BHF-UCL.
DR GO; GO:1901228; P:positive regulation of transcription from RNA polymerase II promoter involved in heart development; ISS:BHF-UCL.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; ISS:BHF-UCL.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISS:BHF-UCL.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006412; P:translation; TAS:ProtInc.
DR InterPro; IPR016641; EGD2/NACA.
DR InterPro; IPR002715; Nas_poly-pep-assoc_cplx_dom.
DR PANTHER; PTHR21713; PTHR21713; 1.
DR Pfam; PF01849; NAC; 1.
DR PIRSF; PIRSF015901; NAC_alpha; 1.
DR PROSITE; PS51151; NAC_AB; 1.
DR PROSITE; PS50030; UBA; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allergen; Alternative splicing;
KW Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding;
KW Host-virus interaction; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Transcription; Transport.
FT CHAIN 1 215 Nascent polypeptide-associated complex
FT subunit alpha.
FT /FTId=PRO_0000135576.
FT DOMAIN 70 135 NAC-A/B.
FT DOMAIN 176 213 UBA.
FT REGION 69 80 Required for DNA-binding (By similarity).
FT MOD_RES 43 43 Phosphoserine; by ILK1.
FT MOD_RES 142 142 N6-acetyllysine.
FT MOD_RES 159 159 Phosphothreonine; by GSK3-beta (By
FT similarity).
FT MOD_RES 161 161 Phosphothreonine.
FT MOD_RES 166 166 Phosphoserine.
FT MOD_RES 186 186 Phosphoserine.
FT MOD_RES 191 191 Phosphoserine.
FT MOD_RES 203 203 Phosphoserine.
FT VAR_SEQ 23 23 T -> TAVLPMSSALSVTAALGQPGPTLPPPCSPAPQQCPL
FT SAANQASPFPSPSTIASTPLEVPFPQSSSGTALPLGTAPEA
FT PTFLPNLIGPPISPAALALASPMIAPTLKGTPSSSAPLALV
FT ALAPHSVQKSSAFPPNLLTSPPSVAVAESGSVITLSAPIAP
FT SEPKTNLNKVPSEVVPNPKGTPSPPCIVSTVPYHCVTPMAS
FT IQSGVASLPQTTPTTTLAIASPQVKDTTISSVLISPQNPGS
FT LSLKGPVSPPAALSLSTQSLPVVTSSQKTAGPNTPPDFPIS
FT LGSHLAPLHQSSFGSVQLLGQTGPSALSDPTEKTISVDHSS
FT TGASYPSQRSVIPPLPSRNEVVPATVAAFPVVAPSVDKGPS
FT TISSITCSPSGSLNVATSSSLSPTTSLILKNSPNATYHYPL
FT VAQMPVSSVGTTPLVVTNPCTIAAAPTTTFEVATCVSPPMS
FT SGPISNIEPTSPAALVMAPVAPKEPSTQVATTLRIPVSPPL
FT PDPEDLKNLSSSVLVKFPTQKDLQTVPASLEGAPFSPAQAG
FT LTTKKDPTVLPLVQAAPKNSPSFQSTSSSPEIPLSPEATLA
FT KKSLGEPLPIVAAFPLESADPAGVAPTTAKAAAFEKVLPKP
FT ESASVSAAPTPPVSLPLAPSPVPTLPPKQQFLPSSPGLVLE
FT SPSKPLAPADEDELPPLIPPEPISGGVPFQSVLVNMPTPKS
FT AGIPVPTPSAKQPVTKNNK (in isoform 2).
FT /FTId=VSP_044825.
FT CONFLICT 213 213 L -> S (in Ref. 7; BAD96805).
FT HELIX 80 83
FT STRAND 86 88
FT STRAND 91 108
FT STRAND 110 113
FT STRAND 117 124
FT STRAND 126 130
SQ SEQUENCE 215 AA; 23384 MW; 05DC563A8BEF307C CRC64;
MPGEATETVP ATEQELPQPQ AETGSGTESD SDESVPELEE QDSTQATTQQ AQLAAAAEID
EEPVSKAKQS RSEKKARKAM SKLGLRQVTG VTRVTIRKSK NILFVITKPD VYKSPASDTY
IVFGEAKIED LSQQAQLAAA EKFKVQGEAV SNIQENTQTP TVQEESEEEE VDETGVEVKD
IELVMSQANV SRAKAVRALK NNSNDIVNAI MELTM
//
ID NACA_HUMAN Reviewed; 215 AA.
AC Q13765; F8VU71; Q3KQV4; Q53A18; Q53G46;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Nascent polypeptide-associated complex subunit alpha;
DE Short=NAC-alpha;
DE AltName: Full=Alpha-NAC;
DE AltName: Allergen=Hom s 2;
GN Name=NACA; ORFNames=HSD48;
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).
RC TISSUE=Neuroblastoma;
RX PubMed=12209604; DOI=10.1002/ijc.10550;
RA Behrends U., Jandl T., Golbeck A., Lechner B., Mueller-Weihrich S.,
RA Schmid I., Till H., Berthold F., Voltz R., Mautner J.M.;
RT "Novel products of the HuD, HuC, NNP-1 and alpha-internexin genes
RT identified by autologous antibody screening of a pediatric
RT neuroblastoma library.";
RL Int. J. Cancer 100:669-677(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=15196207; DOI=10.1111/j.1365-2567.2004.01893.x;
RA Al-Shanti N., Steward C.G., Garland R.J., Rowbottom A.W.;
RT "Investigation of alpha nascent polypeptide-associated complex
RT functions in a human CD8(+) T cell ex vivo expansion model using
RT antisense oligonucleotides.";
RL Immunology 112:397-403(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Sakai H., Chew C., Wang S., Wiedmann B., Geromanos S., Tempst P.,
RA Wiedmann M.;
RT "Nascent polypeptide-associate complex (NAC): a novel type of
RT polypeptide binding protein.";
RL Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for
RT 300 previously undefined genes expressed in CD34+ hematopoietic
RT stem/progenitor cells.";
RL Genome Res. 10:1546-1560(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pericardium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M.,
RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M.,
RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D.,
RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA Kucherlapati R., Weinstock G., Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Cervix;
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-173 (ISOFORM 1).
RC TISSUE=Testis;
RA Yuan L.G., Tian Y.Q., Qiao Y., Miao S.Y., Wang L.F.;
RT "A new spermatogenesis-related gene.";
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP PROTEIN SEQUENCE OF 101-142 AND 180-192, AND MASS SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [12]
RP PROTEIN SEQUENCE OF 101-142; 145-192 AND 201-215, PHOSPHORYLATION AT
RP SER-166, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [13]
RP ALLERGEN.
RX PubMed=9806765;
RA Natter S., Seiberler S., Hufnagl P., Binder B.R., Hirschl A.M.,
RA Ring J., Abeck D., Schmidt T., Valent P., Valenta R.;
RT "Isolation of cDNA clones coding for IgE autoantigens with serum IgE
RT from atopic dermatitis patients.";
RL FASEB J. 12:1559-1569(1998).
RN [14]
RP FUNCTION.
RX PubMed=9877153; DOI=10.1016/S0014-5793(98)01440-9;
RA Moeller I., Beatrix B., Kreibich G., Sakai H., Lauring B.,
RA 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
RT complex.";
RL FEBS Lett. 441:1-5(1998).
RN [15]
RP FUNCTION, INTERACTION WITH BTF3, ASSOCIATION WITH RIBOSOMES, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10982809; DOI=10.1074/jbc.M006368200;
RA Beatrix B., Sakai H., Wiedmann M.;
RT "The alpha and beta subunit of the nascent polypeptide-associated
RT complex have distinct functions.";
RL J. Biol. Chem. 275:37838-37845(2000).
RN [16]
RP INTERACTION WITH FADD.
RX PubMed=12684039; DOI=10.1016/S0006-291X(03)00487-X;
RA Stilo R., Liguoro D., di Jeso B., Leonardi A., Vito P.;
RT "The alpha-chain of the nascent polypeptide-associated complex binds
RT to and regulates FADD function.";
RL Biochem. Biophys. Res. Commun. 303:1034-1041(2003).
RN [17]
RP SUBCELLULAR LOCATION, AND POSSIBLE INVOLVEMENT IN OSTEOSARCOMA.
RX PubMed=12689679; DOI=10.1016/S8756-3282(03)00026-7;
RA Papachristou D.J., Batistatou A., Sykiotis G.P., Varakis I.,
RA Papavassiliou A.G.;
RT "Activation of the JNK-AP-1 signal transduction pathway is associated
RT with pathogenesis and progression of human osteosarcomas.";
RL Bone 32:364-371(2003).
RN [18]
RP PHOSPHORYLATION AT SER-43, AND SUBCELLULAR LOCATION.
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 [19]
RP FUNCTION.
RX PubMed=15784678; DOI=10.1242/jcs.02295;
RA Lopez S., Stuhl L., Fichelson S., Dubart-Kupperschmitt A.,
RA St Arnaud R., Galindo J.-R., Murati A., Berda N., Dubreuil P.,
RA Gomez S.;
RT "NACA is a positive regulator of human erythroid-cell
RT differentiation.";
RL J. Cell Sci. 118:1595-1605(2005).
RN [20]
RP TISSUE SPECIFICITY.
RX PubMed=16201836; DOI=10.1371/journal.pbio.0030357;
RA Marques A.C., Dupanloup I., Vinckenbosch N., Reymond A., Kaessmann H.;
RT "Emergence of young human genes after a burst of retroposition in
RT primates.";
RL PLoS Biol. 3:E357-E357(2005).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161; SER-166 AND
RP SER-191, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-191 AND
RP SER-203, 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 [29]
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP 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 [31]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
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
CC their interaction with the signal recognition particle (SRP),
CC which normally targets nascent secretory peptides to the ER. Also
CC reduces the inherent affinity of ribosomes for protein
CC translocation sites in the ER membrane (M sites). May act as a
CC specific coactivator for JUN, binding to DNA and stabilizing the
CC interaction of JUN homodimers with target gene promoters.
CC -!- SUBUNIT: Interacts with TBP and JUN (By similarity). Part of the
CC nascent polypeptide-associated complex (NAC), consisting of NACA
CC and BTF3. NAC associates with ribosomes through the BTF3 subunit.
CC Both subunits can contact nascent polypeptide chains. Interacts
CC with ASFV protein H339R.
CC -!- INTERACTION:
CC P40222:TXLNA; NbExp=2; IntAct=EBI-712216, EBI-359793;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly
CC cytoplasmic. Also found in nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13765-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13765-2; Sequence=VSP_044825;
CC Note=No experimental confirmation available. May be due to
CC intron retention;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC -!- PTM: Phosphorylation of Thr-159 by GSK3B may promote proteasome
CC mediated degradation (By similarity). Phosphorylation of Ser-43 by
CC ILK during cell adhesion may promote nuclear localization.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE from
CC atopic dermatitis (AD) patients. Identified as an IgE autoantigen
CC in atopic dermatitis (AD) patients with severe skin
CC manifestations.
CC -!- SIMILARITY: Belongs to the NAC-alpha family.
CC -!- SIMILARITY: Contains 1 NAC-A/B (NAC-alpha/beta) domain.
CC -!- SIMILARITY: Contains 1 UBA domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAV83778.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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DR EMBL; AY034001; AAK57544.1; -; mRNA.
DR EMBL; AY911673; AAX14393.1; -; mRNA.
DR EMBL; X80909; CAA56869.1; -; mRNA.
DR EMBL; AF054187; AAC99403.1; -; mRNA.
DR EMBL; AK096699; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; CR450295; CAG29291.1; -; mRNA.
DR EMBL; AK223085; BAD96805.1; -; mRNA.
DR EMBL; AC117378; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105120; AAI05121.1; -; mRNA.
DR EMBL; BC105122; AAI05123.1; -; mRNA.
DR EMBL; BC106041; AAI06042.1; -; mRNA.
DR EMBL; AY605660; AAV83778.1; ALT_INIT; mRNA.
DR PIR; S49326; S49326.
DR RefSeq; NP_001106673.1; NM_001113202.1.
DR RefSeq; NP_001106674.2; NM_001113203.2.
DR UniGene; Hs.505735; -.
DR PDB; 3LKX; X-ray; 2.50 A; B=84-136.
DR PDB; 3MCB; X-ray; 1.90 A; A=79-132.
DR PDB; 3MCE; X-ray; 2.40 A; A/B/C/D=81-133.
DR PDBsum; 3LKX; -.
DR PDBsum; 3MCB; -.
DR PDBsum; 3MCE; -.
DR ProteinModelPortal; Q13765; -.
DR SMR; Q13765; 79-132.
DR IntAct; Q13765; 23.
DR MINT; MINT-5000033; -.
DR STRING; 9606.ENSP00000403817; -.
DR Allergome; 3323; Hom s 2.0101.
DR Allergome; 412; Hom s 2.
DR PhosphoSite; Q13765; -.
DR DMDM; 71151996; -.
DR PaxDb; Q13765; -.
DR PRIDE; Q13765; -.
DR Ensembl; ENST00000356769; ENSP00000349212; ENSG00000196531.
DR Ensembl; ENST00000393891; ENSP00000377469; ENSG00000196531.
DR Ensembl; ENST00000546392; ENSP00000446801; ENSG00000196531.
DR Ensembl; ENST00000552540; ENSP00000447821; ENSG00000196531.
DR GeneID; 4666; -.
DR KEGG; hsa:4666; -.
DR UCSC; uc001sma.2; human.
DR CTD; 4666; -.
DR GeneCards; GC12M057106; -.
DR H-InvDB; HIX0034277; -.
DR HGNC; HGNC:7629; NACA.
DR MIM; 601234; gene.
DR neXtProt; NX_Q13765; -.
DR PharmGKB; PA31433; -.
DR eggNOG; COG1308; -.
DR HOVERGEN; HBG082004; -.
DR KO; K03626; -.
DR OrthoDB; EOG7RNK24; -.
DR PhylomeDB; Q13765; -.
DR ChiTaRS; NACA; human.
DR EvolutionaryTrace; Q13765; -.
DR GeneWiki; NACA_(gene); -.
DR GenomeRNAi; 4666; -.
DR NextBio; 17982; -.
DR PRO; PR:Q13765; -.
DR ArrayExpress; Q13765; -.
DR Bgee; Q13765; -.
DR CleanEx; HS_NACA; -.
DR Genevestigator; Q13765; -.
DR GO; GO:0005854; C:nascent polypeptide-associated complex; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0017025; F:TBP-class protein binding; ISS:BHF-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:BHF-UCL.
DR GO; GO:0003231; P:cardiac ventricle development; ISS:BHF-UCL.
DR GO; GO:0061384; P:heart trabecula morphogenesis; ISS:BHF-UCL.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0010664; P:negative regulation of striated muscle cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:1901227; P:negative regulation of transcription from RNA polymerase II promoter involved in heart development; ISS:BHF-UCL.
DR GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; ISS:BHF-UCL.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; ISS:BHF-UCL.
DR GO; GO:1901228; P:positive regulation of transcription from RNA polymerase II promoter involved in heart development; ISS:BHF-UCL.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; ISS:BHF-UCL.
DR GO; GO:0043403; P:skeletal muscle tissue regeneration; ISS:BHF-UCL.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0006412; P:translation; TAS:ProtInc.
DR InterPro; IPR016641; EGD2/NACA.
DR InterPro; IPR002715; Nas_poly-pep-assoc_cplx_dom.
DR PANTHER; PTHR21713; PTHR21713; 1.
DR Pfam; PF01849; NAC; 1.
DR PIRSF; PIRSF015901; NAC_alpha; 1.
DR PROSITE; PS51151; NAC_AB; 1.
DR PROSITE; PS50030; UBA; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allergen; Alternative splicing;
KW Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding;
KW Host-virus interaction; Nucleus; Phosphoprotein; Protein transport;
KW Reference proteome; Transcription; Transport.
FT CHAIN 1 215 Nascent polypeptide-associated complex
FT subunit alpha.
FT /FTId=PRO_0000135576.
FT DOMAIN 70 135 NAC-A/B.
FT DOMAIN 176 213 UBA.
FT REGION 69 80 Required for DNA-binding (By similarity).
FT MOD_RES 43 43 Phosphoserine; by ILK1.
FT MOD_RES 142 142 N6-acetyllysine.
FT MOD_RES 159 159 Phosphothreonine; by GSK3-beta (By
FT similarity).
FT MOD_RES 161 161 Phosphothreonine.
FT MOD_RES 166 166 Phosphoserine.
FT MOD_RES 186 186 Phosphoserine.
FT MOD_RES 191 191 Phosphoserine.
FT MOD_RES 203 203 Phosphoserine.
FT VAR_SEQ 23 23 T -> TAVLPMSSALSVTAALGQPGPTLPPPCSPAPQQCPL
FT SAANQASPFPSPSTIASTPLEVPFPQSSSGTALPLGTAPEA
FT PTFLPNLIGPPISPAALALASPMIAPTLKGTPSSSAPLALV
FT ALAPHSVQKSSAFPPNLLTSPPSVAVAESGSVITLSAPIAP
FT SEPKTNLNKVPSEVVPNPKGTPSPPCIVSTVPYHCVTPMAS
FT IQSGVASLPQTTPTTTLAIASPQVKDTTISSVLISPQNPGS
FT LSLKGPVSPPAALSLSTQSLPVVTSSQKTAGPNTPPDFPIS
FT LGSHLAPLHQSSFGSVQLLGQTGPSALSDPTEKTISVDHSS
FT TGASYPSQRSVIPPLPSRNEVVPATVAAFPVVAPSVDKGPS
FT TISSITCSPSGSLNVATSSSLSPTTSLILKNSPNATYHYPL
FT VAQMPVSSVGTTPLVVTNPCTIAAAPTTTFEVATCVSPPMS
FT SGPISNIEPTSPAALVMAPVAPKEPSTQVATTLRIPVSPPL
FT PDPEDLKNLSSSVLVKFPTQKDLQTVPASLEGAPFSPAQAG
FT LTTKKDPTVLPLVQAAPKNSPSFQSTSSSPEIPLSPEATLA
FT KKSLGEPLPIVAAFPLESADPAGVAPTTAKAAAFEKVLPKP
FT ESASVSAAPTPPVSLPLAPSPVPTLPPKQQFLPSSPGLVLE
FT SPSKPLAPADEDELPPLIPPEPISGGVPFQSVLVNMPTPKS
FT AGIPVPTPSAKQPVTKNNK (in isoform 2).
FT /FTId=VSP_044825.
FT CONFLICT 213 213 L -> S (in Ref. 7; BAD96805).
FT HELIX 80 83
FT STRAND 86 88
FT STRAND 91 108
FT STRAND 110 113
FT STRAND 117 124
FT STRAND 126 130
SQ SEQUENCE 215 AA; 23384 MW; 05DC563A8BEF307C CRC64;
MPGEATETVP ATEQELPQPQ AETGSGTESD SDESVPELEE QDSTQATTQQ AQLAAAAEID
EEPVSKAKQS RSEKKARKAM SKLGLRQVTG VTRVTIRKSK NILFVITKPD VYKSPASDTY
IVFGEAKIED LSQQAQLAAA EKFKVQGEAV SNIQENTQTP TVQEESEEEE VDETGVEVKD
IELVMSQANV SRAKAVRALK NNSNDIVNAI MELTM
//
MIM
601234
*RECORD*
*FIELD* NO
601234
*FIELD* TI
*601234 NASCENT POLYPEPTIDE-ASSOCIATED COMPLEX, ALPHA POLYPEPTIDE; NACA
SKELETAL MUSCLE NACA, INCLUDED; SKNAC, INCLUDED
read more*FIELD* TX
CLONING
Wiedmann et al. (1994) purified the heterodimeric nascent
polypeptide-associated complex (NAC) from bovine cytosol and determined
that it contains Naca, which migrated at an apparent molecular mass of
about 33 kD, and Btf3b (602542), which migrated at an apparent molecular
mass of about 21 kD. Using peptide sequences from the purified proteins,
they cloned human NACA and BTF3B.
Yotov and St-Arnaud (1996) cloned a splice variant of mouse Naca, which
they called Sknac, from a skeletal muscle cDNA library. The deduced
protein contains 2,187 amino acids. Sknac contains a large in-frame
insertion of a proline-rich sequence encoded by Naca exon 3. The first
23 residues and last 192 residues of Naca and Sknac are identical. Both
Naca and Sknac have a C-terminal putative nuclear localization signal
and calcium-binding EF-hand motif. Northern blot analysis detected a
0.9-kb Naca transcript in all mouse tissues examined, and a 7.0-kb Sknac
transcript in skeletal muscle, with weaker expression in heart only.
Western blot analysis detected Naca at an apparent molecular mass of 35
kD in mouse osteoblastic cells, embryonal carcinoma cells,
undifferentiated C1C12 myoblasts, and differentiated C2C12 myotubes.
Sknac was detected at an apparent molecular mass of 220 kD in
differentiated C2C12 myotubes only.
Li et al. (2009) stated that orthologs of NACA are found in all
eukaryotes; however, they found orthologs of the muscle-specific exon 3
in vertebrates only. The deduced human SKNAC protein contains 2,078
amino acids. The first 23 N-terminal amino acids of SKNAC are identical
to the N terminus of the deduced 215-amino acid NACA protein. In SKNAC,
the N-terminal domain is followed by a 1,863- amino acid domain
containing 18 repeats of a 23-amino acid proline- rich sequence. The C
terminus of SKNAC is identical to the remainder of the NACA protein. In
zebrafish embryos, Li et al. (2009) found ubiquitous Naca expression,
but Sknac was expressed in skeletal and cardiac muscle only. In situ
hybridization of zebrafish embryos showed Sknac expression increased
significantly during somitogenesis and myogenesis. Epitope-tagged Sknac
localized to the cytosol at all stages of muscle development, while
epitope-tagged Naca was expressed in the nucleus and translocated to the
cytosol during differentiation of myotubes into myofibers.
GENE STRUCTURE
Li et al. (2009) determined that the NACA gene contains 9 exons. Exon 3
is very large and encodes the proline-rich repeat region of the striated
muscle isoform of NACA. Introns 2 and 5 contain Alu repeats.
MAPPING
Yotov and St-Arnaud (1996) used somatic cell hybrids and fluorescence in
situ hybridization to assign the NACA gene to chromosome 12q23-q24.1.
GENE FUNCTION
Wiedmann et al. (1994) showed that NAC bound ubiquitously to nascent
polypeptides unless a signal peptide was fully exposed. NAC did not bind
to fully emerged signal peptides. In the absence of NAC, the signal
recognition particle (SRP; see 604857) interacted with polypeptides even
in the absence of a signal peptide and allowed mistargeting of the
protein to the SRP receptor (see 600867) at the endoplasmic reticulum
membrane. Readdition of purified NAC prevented mistranslocation.
Yotov and St-Arnaud (1996) stated that the NACA protein is specifically
expressed in bone during development and acts as a transcriptional
coactivator in conjunction with acidic activators.
Mossabeb et al. (2002) showed that an 86-amino acid C-terminal fragment
of NACA, which they called 'Hom s 2.02,' bound IgE autoantibodies.
Using a gel mobility shift assay, Yotov and St-Arnaud (1996) found that
both mouse Naca and Sknac bound the same consensus DNA sequence.
However, only Sknac activated transcription of a reporter gene
containing the motif. Sknac, but not Naca, increased expression of
murine myoglobin (160000), which contains 3 putative Naca-binding sites.
Naca did not competitively inhibit the transactivating activity of Sknac
in vivo. Overexpression of Naca inhibited differentiation in C2C12
skeletal myoblasts, while overexpression of Sknac induced
differentiation of C2C12 cells into gigantic, myosin heavy chain (MHC;
see MYH1, 160730)-positive multinucleated myosacs. Sknac had no effect
on the phenotype of mouse embryonic fibroblasts. Yotov and St-Arnaud
(1996) concluded that Sknac, but not Naca, functions as a transactivator
for skeletal muscle cell differentiation in mouse.
ANIMAL MODEL
Using morpholinos that blocked splicing of Naca exon 3, Li et al. (2009)
specifically knocked down Sknac expression in zebrafish. Knockdown of
Sknac resulted in paralysis, cardiac edema, and embryonic death around
days 5 and 6. Specification of slow and fast muscles appeared normal,
but expression of Mhc was reduced, resulting in disruption of thick- and
thin-filament assembly in both slow and fast muscle fibers. Mhc mRNA
expression was normal, suggesting that Sknac is required for Mhc protein
translation or stabilization.
Park et al. (2010) created a line of Sknac-specific knockout mice.
Although Sknac -/- embryos initially developed normally, many died
between embryonic days 10.5 and 12.5 with cardiac defects, including
thin myocardial wall, interventricular septal defects, and poorly
developed trabeculae, likely due to a proliferation defect. Expression
of chamber-specific markers and markers of valve-forming regions
revealed appropriate specification of subdomains within the heart. mRNA
microarray analysis of Sknac -/- and wildtype hearts at embryonic day
10.5 detected dysregulation of genes involved in cardiac proliferation
and differentiation. Surviving Sknac -/- mice showed a growth defect and
reduced skeletal muscle mass accompanied by reduced myofiber number and
switching of myofiber type from oxidative to glycolytic fibers. Sknac
-/- muscle was impaired in regeneration following necrotic injury, and
showed replacement of myofibers with adipocytes. In culture, Sknac -/-
satellite cells showed more cell death than wildtype satellite cells.
*FIELD* RF
1. Li, H.; Randall, W. R.; Du, S.-J.: skNAC (skeletal Naca), a muscle-specific
isoform of Naca (nascent polypeptide-associated complex alpha), is
required for myofibril organization. FASEB J. 23: 1988-2000, 2009.
2. Mossabeb, R.; Seiberler, S.; Mittermann, I.; Reininger, R.; Spitzauer,
S.; Natter, S.; Verdino, P.; Keller, W.; Kraft, D.; Valenta, R.:
Characterization of a novel isoform of alpha-nascent polypeptide-associated
complex as IgE-defined autoantigen. J. Invest. Derm. 119: 820-829,
2002.
3. Park, C. Y.; Pierce, S. A.; von Drehle, M.; Ivey, K. N.; Morgan,
J. A.; Blau, H. M.; Srivastava, D.: skNAC, a Smyd1-interacting transcription
factor, is involved in cardiac development and skeletal muscle growth
and regeneration. Proc. Nat. Acad. Sci. 107: 20750-20755, 2010.
4. Wiedmann, B.; Sakai, H.; Davis, T. A.; Wiedmann, M.: A protein
complex required for signal-sequence-specific sorting and translocation. Nature 370:
434-440, 1994.
5. Yotov, W. V.; St-Arnaud, R.: Differential splicing-in of a proline-rich
exon converts alpha-NAC into a muscle-specific transcription factor. Genes
Dev. 10: 1763-1772, 1996.
6. Yotov, W. V.; St-Arnaud, R.: Mapping of the human gene for the
alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to chromosome
12q23-24.1. Mammalian Genome 7: 163-164, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 07/31/2013
Patricia A. Hartz - updated: 3/25/2005
Patricia A. Hartz - updated: 10/27/2003
*FIELD* CD
Victor A. McKusick: 4/29/1996
*FIELD* ED
alopez: 07/31/2013
mgross: 3/25/2005
mgross: 11/4/2003
terry: 10/27/2003
terry: 1/17/1997
mark: 4/29/1996
terry: 4/29/1996
*RECORD*
*FIELD* NO
601234
*FIELD* TI
*601234 NASCENT POLYPEPTIDE-ASSOCIATED COMPLEX, ALPHA POLYPEPTIDE; NACA
SKELETAL MUSCLE NACA, INCLUDED; SKNAC, INCLUDED
read more*FIELD* TX
CLONING
Wiedmann et al. (1994) purified the heterodimeric nascent
polypeptide-associated complex (NAC) from bovine cytosol and determined
that it contains Naca, which migrated at an apparent molecular mass of
about 33 kD, and Btf3b (602542), which migrated at an apparent molecular
mass of about 21 kD. Using peptide sequences from the purified proteins,
they cloned human NACA and BTF3B.
Yotov and St-Arnaud (1996) cloned a splice variant of mouse Naca, which
they called Sknac, from a skeletal muscle cDNA library. The deduced
protein contains 2,187 amino acids. Sknac contains a large in-frame
insertion of a proline-rich sequence encoded by Naca exon 3. The first
23 residues and last 192 residues of Naca and Sknac are identical. Both
Naca and Sknac have a C-terminal putative nuclear localization signal
and calcium-binding EF-hand motif. Northern blot analysis detected a
0.9-kb Naca transcript in all mouse tissues examined, and a 7.0-kb Sknac
transcript in skeletal muscle, with weaker expression in heart only.
Western blot analysis detected Naca at an apparent molecular mass of 35
kD in mouse osteoblastic cells, embryonal carcinoma cells,
undifferentiated C1C12 myoblasts, and differentiated C2C12 myotubes.
Sknac was detected at an apparent molecular mass of 220 kD in
differentiated C2C12 myotubes only.
Li et al. (2009) stated that orthologs of NACA are found in all
eukaryotes; however, they found orthologs of the muscle-specific exon 3
in vertebrates only. The deduced human SKNAC protein contains 2,078
amino acids. The first 23 N-terminal amino acids of SKNAC are identical
to the N terminus of the deduced 215-amino acid NACA protein. In SKNAC,
the N-terminal domain is followed by a 1,863- amino acid domain
containing 18 repeats of a 23-amino acid proline- rich sequence. The C
terminus of SKNAC is identical to the remainder of the NACA protein. In
zebrafish embryos, Li et al. (2009) found ubiquitous Naca expression,
but Sknac was expressed in skeletal and cardiac muscle only. In situ
hybridization of zebrafish embryos showed Sknac expression increased
significantly during somitogenesis and myogenesis. Epitope-tagged Sknac
localized to the cytosol at all stages of muscle development, while
epitope-tagged Naca was expressed in the nucleus and translocated to the
cytosol during differentiation of myotubes into myofibers.
GENE STRUCTURE
Li et al. (2009) determined that the NACA gene contains 9 exons. Exon 3
is very large and encodes the proline-rich repeat region of the striated
muscle isoform of NACA. Introns 2 and 5 contain Alu repeats.
MAPPING
Yotov and St-Arnaud (1996) used somatic cell hybrids and fluorescence in
situ hybridization to assign the NACA gene to chromosome 12q23-q24.1.
GENE FUNCTION
Wiedmann et al. (1994) showed that NAC bound ubiquitously to nascent
polypeptides unless a signal peptide was fully exposed. NAC did not bind
to fully emerged signal peptides. In the absence of NAC, the signal
recognition particle (SRP; see 604857) interacted with polypeptides even
in the absence of a signal peptide and allowed mistargeting of the
protein to the SRP receptor (see 600867) at the endoplasmic reticulum
membrane. Readdition of purified NAC prevented mistranslocation.
Yotov and St-Arnaud (1996) stated that the NACA protein is specifically
expressed in bone during development and acts as a transcriptional
coactivator in conjunction with acidic activators.
Mossabeb et al. (2002) showed that an 86-amino acid C-terminal fragment
of NACA, which they called 'Hom s 2.02,' bound IgE autoantibodies.
Using a gel mobility shift assay, Yotov and St-Arnaud (1996) found that
both mouse Naca and Sknac bound the same consensus DNA sequence.
However, only Sknac activated transcription of a reporter gene
containing the motif. Sknac, but not Naca, increased expression of
murine myoglobin (160000), which contains 3 putative Naca-binding sites.
Naca did not competitively inhibit the transactivating activity of Sknac
in vivo. Overexpression of Naca inhibited differentiation in C2C12
skeletal myoblasts, while overexpression of Sknac induced
differentiation of C2C12 cells into gigantic, myosin heavy chain (MHC;
see MYH1, 160730)-positive multinucleated myosacs. Sknac had no effect
on the phenotype of mouse embryonic fibroblasts. Yotov and St-Arnaud
(1996) concluded that Sknac, but not Naca, functions as a transactivator
for skeletal muscle cell differentiation in mouse.
ANIMAL MODEL
Using morpholinos that blocked splicing of Naca exon 3, Li et al. (2009)
specifically knocked down Sknac expression in zebrafish. Knockdown of
Sknac resulted in paralysis, cardiac edema, and embryonic death around
days 5 and 6. Specification of slow and fast muscles appeared normal,
but expression of Mhc was reduced, resulting in disruption of thick- and
thin-filament assembly in both slow and fast muscle fibers. Mhc mRNA
expression was normal, suggesting that Sknac is required for Mhc protein
translation or stabilization.
Park et al. (2010) created a line of Sknac-specific knockout mice.
Although Sknac -/- embryos initially developed normally, many died
between embryonic days 10.5 and 12.5 with cardiac defects, including
thin myocardial wall, interventricular septal defects, and poorly
developed trabeculae, likely due to a proliferation defect. Expression
of chamber-specific markers and markers of valve-forming regions
revealed appropriate specification of subdomains within the heart. mRNA
microarray analysis of Sknac -/- and wildtype hearts at embryonic day
10.5 detected dysregulation of genes involved in cardiac proliferation
and differentiation. Surviving Sknac -/- mice showed a growth defect and
reduced skeletal muscle mass accompanied by reduced myofiber number and
switching of myofiber type from oxidative to glycolytic fibers. Sknac
-/- muscle was impaired in regeneration following necrotic injury, and
showed replacement of myofibers with adipocytes. In culture, Sknac -/-
satellite cells showed more cell death than wildtype satellite cells.
*FIELD* RF
1. Li, H.; Randall, W. R.; Du, S.-J.: skNAC (skeletal Naca), a muscle-specific
isoform of Naca (nascent polypeptide-associated complex alpha), is
required for myofibril organization. FASEB J. 23: 1988-2000, 2009.
2. Mossabeb, R.; Seiberler, S.; Mittermann, I.; Reininger, R.; Spitzauer,
S.; Natter, S.; Verdino, P.; Keller, W.; Kraft, D.; Valenta, R.:
Characterization of a novel isoform of alpha-nascent polypeptide-associated
complex as IgE-defined autoantigen. J. Invest. Derm. 119: 820-829,
2002.
3. Park, C. Y.; Pierce, S. A.; von Drehle, M.; Ivey, K. N.; Morgan,
J. A.; Blau, H. M.; Srivastava, D.: skNAC, a Smyd1-interacting transcription
factor, is involved in cardiac development and skeletal muscle growth
and regeneration. Proc. Nat. Acad. Sci. 107: 20750-20755, 2010.
4. Wiedmann, B.; Sakai, H.; Davis, T. A.; Wiedmann, M.: A protein
complex required for signal-sequence-specific sorting and translocation. Nature 370:
434-440, 1994.
5. Yotov, W. V.; St-Arnaud, R.: Differential splicing-in of a proline-rich
exon converts alpha-NAC into a muscle-specific transcription factor. Genes
Dev. 10: 1763-1772, 1996.
6. Yotov, W. V.; St-Arnaud, R.: Mapping of the human gene for the
alpha-NAC/1.9.2 (NACA/1.9.2) transcriptional coactivator to chromosome
12q23-24.1. Mammalian Genome 7: 163-164, 1996.
*FIELD* CN
Patricia A. Hartz - updated: 07/31/2013
Patricia A. Hartz - updated: 3/25/2005
Patricia A. Hartz - updated: 10/27/2003
*FIELD* CD
Victor A. McKusick: 4/29/1996
*FIELD* ED
alopez: 07/31/2013
mgross: 3/25/2005
mgross: 11/4/2003
terry: 10/27/2003
terry: 1/17/1997
mark: 4/29/1996
terry: 4/29/1996