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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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    See NACA in Genome Data Viewer
    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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