Q13765 (NACA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nascent polypeptide-associated complex subunit alpha
Short name=NAC-alpha

Alternative name(s):
Alpha-NAC
Allergen=Hom s 2

Gene names

Name:	NACA
ORF Names:	HSD48

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	215 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Prevents inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). Binds to nascent polypeptide chains as they emerge from the ribosome and blocks their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. Also reduces the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites). May act as a specific coactivator for JUN, binding to DNA and stabilizing the interaction of JUN homodimers with target gene promoters. Ref.12 Ref.13 Ref.16
Subunit structure	Interacts with TBP and JUN By similarity. Part of the nascent polypeptide-associated complex (NAC), consisting of NACA and BTF3. NAC associates with ribosomes through the BTF3 subunit. Both subunits can contact nascent polypeptide chains. Interacts with ASFV protein H339R. Ref.13 Ref.14
Subcellular location	Cytoplasm. Nucleus. Note: Predominantly cytoplasmic. Also found in nucleus. Ref.13 Ref.15
Tissue specificity	Ubiquitously expressed. Ref.17
Post-translational modification	Phosphorylation of Ser-43 by ILK during cell adhesion may promote nuclear localization. Phosphorylation of Thr-159 by GSK3B may promote proteasome mediated degradation By similarity. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.10 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24
Allergenic properties	Causes an allergic reaction in human. Binds to IgE from atopic dermatitis (AD) patients. Identified as an IgE autoantigen in atopic dermatitis (AD) patients with severe skin manifestations. Ref.11
Sequence similarities	Belongs to the NAC-alpha family. Contains 1 NAC-A/B (NAC-alpha/beta) domain. Contains 1 UBA domain.
Sequence caution	The sequence AAV83778.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction Protein transport Transcription Transport
Cellular component	Cytoplasm Nucleus
Disease	Allergen
Ligand	DNA-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW protein transport Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW translation Traceable author statement. Source: ProtInc
Cellular component	nascent polypeptide-associated complex Traceable author statement. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 215

215

Nascent polypeptide-associated complex subunit alpha

PRO_0000135576

Regions

Domain

70 – 135

66

NAC-A/B

Domain

176 – 213

38

UBA

Region

69 – 80

12

Required for DNA-binding By similarity

Amino acid modifications

Modified residue

43

1

Phosphoserine; by ILK1 By similarity

Modified residue

92

1

Phosphothreonine Ref.18

Modified residue

108

1

N6-acetyllysine Ref.25

Modified residue

142

1

N6-acetyllysine Ref.25

Modified residue

159

1

Phosphothreonine; by GSK3-beta By similarity

Modified residue

161

1

Phosphothreonine Ref.22 Ref.23

Modified residue

166

1

Phosphoserine Ref.10 Ref.19 Ref.21 Ref.22 Ref.23 Ref.24

Modified residue

186

1

Phosphoserine Ref.20

Modified residue

191

1

Phosphoserine Ref.22

Experimental info

Sequence conflict

213

1

L → S in BAD96805. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

215

Helix Strand Turn

Details...

Helix

80 – 82

3

Beta strand

93 – 113

21

Beta strand

120 – 123

4

Beta strand

125 – 130

6

Sequences

	Sequence		Length	Mass (Da)
	Q13765 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 05DC563A8BEF307C	FASTA	215	23,384
	10 20 30 40 50 60 MPGEATETVP ATEQELPQPQ AETGSGTESD SDESVPELEE QDSTQATTQQ AQLAAAAEID 70 80 90 100 110 120 EEPVSKAKQS RSEKKARKAM SKLGLRQVTG VTRVTIRKSK NILFVITKPD VYKSPASDTY 130 140 150 160 170 180 IVFGEAKIED LSQQAQLAAA EKFKVQGEAV SNIQENTQTP TVQEESEEEE VDETGVEVKD 190 200 210 IELVMSQANV SRAKAVRALK NNSNDIVNAI MELTM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel products of the HuD, HuC, NNP-1 and alpha-internexin genes identified by autologous antibody screening of a pediatric neuroblastoma library." Behrends U., Jandl T., Golbeck A., Lechner B., Mueller-Weihrich S., Schmid I., Till H., Berthold F., Voltz R., Mautner J.M. Int. J. Cancer 100:669-677(2002) [PubMed: 12209604] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Neuroblastoma.
[2]	"Investigation of alpha nascent polypeptide-associated complex functions in a human CD8(+) T cell ex vivo expansion model using antisense oligonucleotides." Al-Shanti N., Steward C.G., Garland R.J., Rowbottom A.W. Immunology 112:397-403(2004) [PubMed: 15196207] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Nascent polypeptide-associate complex (NAC): a novel type of polypeptide binding protein." Sakai H., Chew C., Wang S., Wiedmann B., Geromanos S., Tempst P., Wiedmann M. Submitted (AUG-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[4]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Cervix.
[8]	"A new spermatogenesis-related gene." Yuan L.G., Tian Y.Q., Qiao Y., Miao S.Y., Wang L.F. Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-173. Tissue: Testis.
[9]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 101-142 AND 180-192, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[10]	Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 101-142; 145-192 AND 201-215, PHOSPHORYLATION AT SER-166, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Isolation of cDNA clones coding for IgE autoantigens with serum IgE from atopic dermatitis patients." Natter S., Seiberler S., Hufnagl P., Binder B.R., Hirschl A.M., Ring J., Abeck D., Schmidt T., Valent P., Valenta R. FASEB J. 12:1559-1569(1998) [PubMed: 9806765] [Abstract] Cited for: ALLERGEN.
[12]	"Unregulated exposure of the ribosomal M-site caused by NAC depletion results in delivery of non-secretory polypeptides to the Sec61 complex." Moeller I., Beatrix B., Kreibich G., Sakai H., Lauring B., Wiedmann M. FEBS Lett. 441:1-5(1998) [PubMed: 9877153] [Abstract] Cited for: FUNCTION.
[13]	"The alpha and beta subunit of the nascent polypeptide-associated complex have distinct functions." Beatrix B., Sakai H., Wiedmann M. J. Biol. Chem. 275:37838-37845(2000) [PubMed: 10982809] [Abstract] Cited for: FUNCTION, INTERACTION WITH BTF3, ASSOCIATION WITH RIBOSOMES, SUBCELLULAR LOCATION.
[14]	"The alpha-chain of the nascent polypeptide-associated complex binds to and regulates FADD function." Stilo R., Liguoro D., di Jeso B., Leonardi A., Vito P. Biochem. Biophys. Res. Commun. 303:1034-1041(2003) [PubMed: 12684039] [Abstract] Cited for: INTERACTION WITH FADD.
[15]	"Activation of the JNK-AP-1 signal transduction pathway is associated with pathogenesis and progression of human osteosarcomas." Papachristou D.J., Batistatou A., Sykiotis G.P., Varakis I., Papavassiliou A.G. Bone 32:364-371(2003) [PubMed: 12689679] [Abstract] Cited for: SUBCELLULAR LOCATION, POSSIBLE INVOLVEMENT IN OSTEOSARCOMA.
[16]	"NACA is a positive regulator of human erythroid-cell differentiation." Lopez S., Stuhl L., Fichelson S., Dubart-Kupperschmitt A., St Arnaud R., Galindo J.-R., Murati A., Berda N., Dubreuil P., Gomez S. J. Cell Sci. 118:1595-1605(2005) [PubMed: 15784678] [Abstract] Cited for: FUNCTION.
[17]	"Emergence of young human genes after a burst of retroposition in primates." Marques A.C., Dupanloup I., Vinckenbosch N., Reymond A., Kaessmann H. PLoS Biol. 3:E357-E357(2005) [PubMed: 16201836] [Abstract] Cited for: TISSUE SPECIFICITY.
[18]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-92, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[20]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[21]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161; SER-166 AND SER-191, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161 AND SER-166, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[24]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[25]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-108 AND LYS-142, MASS SPECTROMETRY.
[26]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY034001 mRNA. Translation: AAK57544.1.
AY911673 mRNA. Translation: AAX14393.1.
X80909 mRNA. Translation: CAA56869.1.
AF054187 mRNA. Translation: AAC99403.1.
CR450295 mRNA. Translation: CAG29291.1.
AK223085 mRNA. Translation: BAD96805.1.
BC105120 mRNA. Translation: AAI05121.1.
BC105122 mRNA. Translation: AAI05123.1.
BC106041 mRNA. Translation: AAI06042.1.
AY605660 mRNA. Translation: AAV83778.1. Different initiation.

IPI

IPI00023748.

PIR

S49326.

RefSeq

NP_001106673.1. NM_001113202.1.
NP_001106674.2. NM_001113203.2.

UniGene

Hs.505735.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LKX	X-ray	2.50	B	84-136	[»]
3MCB	X-ray	1.90	A	79-132	[»]
3MCE	X-ray	2.40	A/B/C/D	81-133	[»]

ProteinModelPortal

Q13765.

SMR

Q13765. Positions 79-213.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13765. 14 interactions.

MINT

MINT-5000033.

STRING

Q13765.

Protein family/group databases

Allergome

3323. Hom s 2.0101.
412. Hom s 2.

PTM databases

PhosphoSite

Q13765.

Polymorphism databases

DMDM

71151996.

Proteomic databases

PRIDE

Q13765.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356769; ENSP00000349212; ENSG00000196531.
ENST00000393891; ENSP00000377469; ENSG00000196531.
ENST00000435567; ENSP00000397352; ENSG00000196531.

GeneID

4666.

KEGG

hsa:4666.

UCSC

uc001sly.2. human.

Organism-specific databases

CTD

4666.

GeneCards

GC12M057078.

H-InvDB

HIX0034277.
HIX0201818.

HGNC

HGNC:7629. NACA.

MIM

601234. gene.

neXtProt

NX_Q13765.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16779.

HOVERGEN

HBG082004.

OrthoDB

EOG41RPW6.

PhylomeDB

Q13765.

Gene expression databases

ArrayExpress

Q13765.

Bgee

Q13765.

CleanEx

HS_NACA.

Genevestigator

Q13765.

GermOnline

ENSG00000196531. Homo sapiens.

Family and domain databases

InterPro

IPR002715. Nas_poly-pep-assoc_cplx.
IPR016641. Nas_poly-pep-assoc_cplx_asu.
[Graphical view]

KO

K03626.

Pfam

PF01849. NAC. 1 hit.
[Graphical view]

PIRSF

PIRSF015901. NAC_alpha. 1 hit.

PROSITE

PS51151. NAC_AB. 1 hit.
PS50030. UBA. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

17982.

SOURCE

Search...

Entry information

Entry name

NACA_HUMAN

Accession

Primary (citable) accession number: Q13765
Secondary accession number(s): Q3KQV4, Q53A18, Q53G46

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.