ID   NACA_HUMAN              Reviewed;         215 AA.
AC   Q13765; Q3KQV4; Q53A18; Q53G46;
DT   19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   07-JUL-2009, entry version 74.
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].
RC   TISSUE=Neuroblastoma;
RX   MEDLINE=22198197; 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].
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].
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].
RC   TISSUE=Umbilical cord blood;
RX   MEDLINE=20499367; 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].
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-173.
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   [9]
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   [10]
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   [11]
RP   ALLERGENICITY.
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   [12]
RP   FUNCTION.
RX   MEDLINE=99092980; 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   [13]
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   [14]
RP   INTERACTION WITH FADD.
RX   MEDLINE=22570630; 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   [15]
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   [16]
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   [17]
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. 3:1970-1979(2005).
RN   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-92, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Epithelium;
RX   PubMed=17924679; DOI=10.1021/pr070152u;
RA   Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT   "Improved titanium dioxide enrichment of phosphopeptides from HeLa
RT   cells and high confident phosphopeptide identification by cross-
RT   validation of MS/MS and MS/MS/MS spectra.";
RL   J. Proteome Res. 6:4150-4162(2007).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP   SPECTROMETRY.
RX   PubMed=17287340; DOI=10.1073/pnas.0611217104;
RA   Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.;
RT   "Global proteomic profiling of phosphopeptides using electron transfer
RT   dissociation tandem mass spectrometry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007).
RN   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND MASS
RP   SPECTROMETRY.
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   [21]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND MASS
RP   SPECTROMETRY.
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   [22]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161; SER-166 AND
RP   SER-191, AND MASS SPECTROMETRY.
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   [23]
RP   IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RA   Colinge J., Superti-Furga G., Bennett K.L.;
RL   Submitted (OCT-2008) to UniProtKB.
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   -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly
CC       cytoplasmic. Also found in nucleus.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC   -!- PTM: Phosphorylation of Ser-43 by ILK during cell adhesion may
CC       promote nuclear localization. Phosphorylation of Thr-159 by GSK3B
CC       may promote proteasome mediated degradation (By similarity).
CC       Phosphorylated upon DNA damage, probably by ATM or ATR.
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   ---------------------------------------------------------------------------
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; AY034001; AAK57544.1; -; mRNA.
DR   EMBL; AY911673; AAX14393.1; -; mRNA.
DR   EMBL; X80909; CAA56869.1; -; mRNA.
DR   EMBL; AF054187; AAC99403.1; -; mRNA.
DR   EMBL; CR450295; CAG29291.1; -; mRNA.
DR   EMBL; AK223085; BAD96805.1; -; mRNA.
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   IPI; IPI00023748; -.
DR   PIR; S49326; S49326.
DR   RefSeq; NP_001106672.1; -.
DR   RefSeq; NP_001106673.1; -.
DR   RefSeq; NP_001106674.1; -.
DR   RefSeq; NP_005585.1; -.
DR   UniGene; Hs.505735; -.
DR   IntAct; Q13765; 6.
DR   PhosphoSite; Q13765; -.
DR   PRIDE; Q13765; -.
DR   Ensembl; ENSG00000196531; Homo sapiens.
DR   GeneID; 4666; -.
DR   KEGG; hsa:4666; -.
DR   UCSC; uc001sly.2; human.
DR   GeneCards; GC12M055392; -.
DR   H-InvDB; HIX0010738; -.
DR   H-InvDB; HIX0034277; -.
DR   HGNC; HGNC:7629; NACA.
DR   MIM; 601234; gene.
DR   PharmGKB; PA31433; -.
DR   HOGENOM; Q13765; -.
DR   HOVERGEN; Q13765; -.
DR   OMA; Q13765; IVNAIMS.
DR   NextBio; 17982; -.
DR   Bgee; Q13765; -.
DR   CleanEx; HS_NACA; -.
DR   GermOnline; ENSG00000196531; Homo sapiens.
DR   GO; GO:0005854; C:nascent polypeptide-associated complex; TAS:ProtInc.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0044419; P:interspecies interaction between organisms; IEA:UniProtKB-KW.
DR   GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR   GO; GO:0006350; P:transcription; IEA:UniProtKB-KW.
DR   GO; GO:0006412; P:translation; TAS:ProtInc.
DR   InterPro; IPR002715; Nas_poly-pep-assoc_cplx.
DR   InterPro; IPR016641; Nas_poly-pep-assoc_cplx_asu.
DR   InterPro; IPR000449; UBA/transl_elong_EF1B_N.
DR   Pfam; PF01849; NAC; 1.
DR   Pfam; PF00627; UBA; 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   Allergen; Complete proteome; Cytoplasm; Direct protein sequencing;
KW   DNA-binding; Host-virus interaction; Nucleus; Phosphoprotein;
KW   Protein transport; 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 (By similarity).
FT   MOD_RES      92     92       Phosphothreonine.
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   CONFLICT    213    213       L -> S (in Ref. 6; BAD96805).
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
//