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NACA nascent polypeptide associated complex subunit alpha [ Homo sapiens (human) ]

Gene ID: 4666, updated on 7-Apr-2024

Summary

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Official Symbol
NACAprovided by HGNC
Official Full Name
nascent polypeptide associated complex subunit alphaprovided by HGNC
Primary source
HGNC:HGNC:7629
See related
Ensembl:ENSG00000196531 MIM:601234; AllianceGenome:HGNC:7629
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
HSD48; NACA1; skNAC; NAC-alpha
Summary
This gene encodes a protein that associates with basic transcription factor 3 (BTF3) to form the nascent polypeptide-associated complex (NAC). This complex binds to nascent proteins that lack a signal peptide motif as they emerge from the ribosome, blocking interaction with the signal recognition particle (SRP) and preventing mistranslocation to the endoplasmic reticulum. This protein is an IgE autoantigen in atopic dermatitis patients. Alternative splicing results in multiple transcript variants, but the full length nature of some of these variants, including those encoding very large proteins, has not been determined. There are multiple pseudogenes of this gene on different chromosomes. [provided by RefSeq, Feb 2016]
Expression
Ubiquitous expression in ovary (RPKM 104.2), bone marrow (RPKM 62.0) and 25 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
12q13.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (56712427..56725299, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (56680428..56693231, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (57106211..57119083, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57038866-57039576 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57039577-57040285 Neighboring gene ATP synthase F1 subunit beta Neighboring gene small nucleolar RNA, C/D box 59A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6511 Neighboring gene MPRA-validated peak1743 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4563 Neighboring gene prostaglandin E synthase 3 Neighboring gene RNA, 7SL, cytoplasmic 809, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57074705-57075584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6512 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4564 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6514 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6513 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57081953-57082478 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6515 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:57083531-57084056 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:57094539-57094693 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6516 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6517 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6519 Neighboring gene DNA primase subunit 1 Neighboring gene Sharpr-MPRA regulatory region 96 Neighboring gene hydroxysteroid 17-beta dehydrogenase 6

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Dual Role of Ribosome-Binding Domain of NAC as a Potent Suppressor of Protein Aggregation and Aging-Related Proteinopathies. Shen K, et al. Mol Cell, 2019 May 16. PMID 30982745, Free PMC Article
  2. Overexpression of the skNAC gene in human rhabdomyosarcoma cells enhances their differentiation potential and inhibits tumor cell growth and spreading. Berkholz J, et al. Clin Exp Metastasis, 2014 Dec. PMID 25209525
  3. alphaNAC depletion as an initiator of ER stress-induced apoptosis in hypoxia. Hotokezaka Y, et al. Cell Death Differ, 2009 Nov. PMID 19609276
  4. NACA is a positive regulator of human erythroid-cell differentiation. Lopez S, et al. J Cell Sci, 2005 Apr 15. PMID 15784678
  5. Investigation of alpha nascent polypeptide-associated complex functions in a human CD8(+) T cell ex vivo expansion model using antisense oligonucleotides. Al-Shanti N, et al. Immunology, 2004 Jul. PMID 15196207, Free PMC Article

See all (171) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF-alpha.
    Title: The ribosomal chaperone NACA recruits PHD2 to cotranslationally modify HIF-α.
  2. These results suggest that PP1A dephosphorylates NACA at specific residues, impacting cJUN transcriptional activity and osteoblast differentiation and function.
    Title: Dephosphorylation of the transcriptional cofactor NACA by the PP1A phosphatase enhances cJUN transcriptional activity and osteoblast differentiation.
  3. NAC is a potent suppressor of aggregation and proteotoxicity of mutant PolyQ-expanded proteins associated with human diseases like Huntington's disease and spinocerebellar ataxias.
    Title: Dual Role of Ribosome-Binding Domain of NAC as a Potent Suppressor of Protein Aggregation and Aging-Related Proteinopathies.
  4. depletion of alphaNAC in multiple types of cancer cells induce typical apoptotic cell death. This anti-apoptotic function is mediated by the FADD/c-Jun N-terminal kinase pathway.
    Title: αNAC inhibition of the FADD-JNK axis plays anti-apoptotic role in multiple cancer cells.
  5. Low NACA expression is associated with rhabdomyosarcoma.
    Title: Overexpression of the skNAC gene in human rhabdomyosarcoma cells enhances their differentiation potential and inhibits tumor cell growth and spreading.
  6. [review] First evidence of a functional interaction between ATF4, FIAT (factor-inhibiting ATF4-mediated transcription) and alphaNAC (nascent polypeptide-associated complex and coactivator alpha).
    Title: Combinatorial control of ATF4-dependent gene transcription in osteoblasts.
  7. NACA gene expression is decreased in both classic and follicular variants of papillary thyroid carcinoma.
    Title: Differential expression of a set of genes in follicular and classic variants of papillary thyroid carcinoma.
  8. identified a region in the NAC domain of the human NAC alpha-subunit as a new nucleic acid-binding region, which is blocked from binding nucleic acids in the heterodimeric complex by a helix region in the beta-subunit
    Title: The crystal structure of the human nascent polypeptide-associated complex domain reveals a nucleic acid-binding region on the NACA subunit .
  9. Alpha NAC downregulation in hypoxic cells or NAC ablation by NAC short-interfering RNA (siRNA) leads to the initiation of ER stress responses, which results in caspase-dependent apoptosis.
    Title: alphaNAC depletion as an initiator of ER stress-induced apoptosis in hypoxia.
  10. A 220 kDa isoform of Naca is expressed in mouse muscle tissues
    Title: Differential splicing-in of a proline-rich exon converts alphaNAC into a muscle-specific transcription factor.
Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of nascent polypeptide-associated complex alpha subunit in T-cell lines PubMed
Vif vif HIV-1 Vif interacts with NACA; predicted interaction to be relevant to gene regulation and/or protein folding/complex assembly PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC117224

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables unfolded protein binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in protein targeting to membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of nascent polypeptide-associated complex IEA
Inferred from Electronic Annotation
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
nascent polypeptide-associated complex subunit alpha
Names
alpha-NAC, muscle-specific form
nascent-polypeptide-associated complex alpha polypeptide
NP_001106672.1
NP_001106673.1
NP_001106674.2
NP_001307122.1
NP_001307123.1
NP_001352825.1
NP_005585.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_030341.1 RefSeqGene

    Range
    5244..18116
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001113201.3 → NP_001106672.1  nascent polypeptide-associated complex subunit alpha isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains multiple differences in the 5' UTR and lacks three alternate exons in the central coding region, but maintains the reading frame, compared to variant 1. This variant encodes isoform b, which is shorter than isoform a. Variants 2, 3, 4, and 5, encode the same isoform (b).
    Source sequence(s)
    AC117378, AK223085, BC106041
    UniProtKB/Swiss-Prot
    A8MTN7, B2R4P8, F8VU71, Q13765, Q3KQV4, Q53A18, Q53G46
    UniProtKB/TrEMBL
    A0A7I2V2K5
    Related
    ENSP00000447821.1, ENST00000552540.5
    Conserved Domains (2) summary
    cd14415
    Location:169 → 214
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    cd22054
    Location:84 → 131
    NAC_NACA; nascent polypeptide-associated complex (NAC), alpha subunit

  2. NM_001113202.2 → NP_001106673.1  nascent polypeptide-associated complex subunit alpha isoform b

    See identical proteins and their annotated locations for NP_001106673.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks three alternate exons in the central coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform b, which is shorter than isoform a. Variants 2, 3, 4, and 5, encode the same isoform (b).
    Source sequence(s)
    AC117378, AK223085
    Consensus CDS
    CCDS31837.1
    UniProtKB/Swiss-Prot
    A8MTN7, B2R4P8, F8VU71, Q13765, Q3KQV4, Q53A18, Q53G46
    UniProtKB/TrEMBL
    A0A7I2V2K5
    Related
    ENSP00000349212.3, ENST00000356769.7
    Conserved Domains (2) summary
    cd14415
    Location:169 → 214
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    cd22054
    Location:84 → 131
    NAC_NACA; nascent polypeptide-associated complex (NAC), alpha subunit

  3. NM_001113203.3 → NP_001106674.2  nascent polypeptide-associated complex subunit alpha isoform a

    Status: REVIEWED

    Source sequence(s)
    AC117378, AK096699, AK223085
    Consensus CDS
    CCDS44925.2
    UniProtKB/Swiss-Prot
    Q13765
    Related
    ENSP00000448035.1, ENST00000550952.6
    Conserved Domains (3) summary
    COG1308
    Location:784 → 925
    EGD2; Transcription factor homologous to NACalpha-BTF3 [Transcription]
    cd14415
    Location:879 → 924
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    pfam01849
    Location:785 → 838
    NAC; NAC domain

  4. NM_001320193.2 → NP_001307122.1  nascent polypeptide-associated complex subunit alpha isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR and lacks three alternate exons in the central coding region, but maintains the reading frame, compared to variant 1. This variant encodes isoform b, which is shorter than isoform a. Variants 2, 3, 4, and 5, encode the same isoform (b).
    Source sequence(s)
    AC117378, AK223085, BI856347
    Consensus CDS
    CCDS31837.1
    UniProtKB/Swiss-Prot
    A8MTN7, B2R4P8, F8VU71, Q13765, Q3KQV4, Q53A18, Q53G46
    UniProtKB/TrEMBL
    A0A7I2V2K5
    Related
    ENSP00000446801.1, ENST00000546392.6
    Conserved Domains (2) summary
    cd14415
    Location:169 → 214
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    cd22054
    Location:84 → 131
    NAC_NACA; nascent polypeptide-associated complex (NAC), alpha subunit

  5. NM_001320194.2 → NP_001307123.1  nascent polypeptide-associated complex subunit alpha isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks three alternate exons in the central coding region and retains a segment in the 3' region, which results in a different 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (c) is shorter than isoform a and has a distinct C-terminus.
    Source sequence(s)
    AK223085, AW021139, CD104788
    UniProtKB/TrEMBL
    F8W0W4
    Related
    ENSP00000447133.1, ENST00000549259.5
    Conserved Domains (2) summary
    cd14415
    Location:174 → 213
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    cd22054
    Location:84 → 131
    NAC_NACA; nascent polypeptide-associated complex (NAC), alpha subunit

  6. NM_001365896.1 → NP_001352825.1  nascent polypeptide-associated complex subunit alpha isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) contains an alternate segment and encodes a longer protein (isoform d) compared to variant 1.
    Source sequence(s)
    AC117378
    Consensus CDS
    CCDS91708.1
    UniProtKB/Swiss-Prot
    E9PAV3
    Related
    ENSP00000403817.1, ENST00000454682.6
    Conserved Domains (4) summary
    PHA03247
    Location:1273 → 1839
    PHA03247; large tegument protein UL36; Provisional
    PRK12323
    Location:8 → 184
    PRK12323; DNA polymerase III subunit gamma/tau
    cd14415
    Location:2032 → 2077
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    cd22054
    Location:1947 → 1994
    NAC_NACA; nascent polypeptide-associated complex (NAC), alpha subunit

  7. NM_005594.6 → NP_005585.1  nascent polypeptide-associated complex subunit alpha isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in 5' UTR and lacks three alternate exons in the central coding region, but maintains the reading frame, compared to variant 1. This variant encodes isoform b, which is shorter than isoform a. Variants 2, 3, 4, and 5, encode the same isoform (b).
    Source sequence(s)
    AC117378, AK223085, BC105120, BG709003
    UniProtKB/Swiss-Prot
    A8MTN7, B2R4P8, F8VU71, Q13765, Q3KQV4, Q53A18, Q53G46
    UniProtKB/TrEMBL
    A0A7I2V2K5
    Related
    ENSP00000377469.4, ENST00000393891.8
    Conserved Domains (2) summary
    cd14415
    Location:169 → 214
    UBA_NACA_NACP1; UBA-like domain found in nascent polypeptide-associated complex subunit alpha (NACA) and putative NACA-like protein (NACP1)
    cd22054
    Location:84 → 131
    NAC_NACA; nascent polypeptide-associated complex (NAC), alpha subunit

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    56712427..56725299 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    56680428..56693231 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
E9PAV3.1 GenPept UniProtKB/Swiss-Prot:E9PAV3
Q13765.1 GenPept UniProtKB/Swiss-Prot:Q13765

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