U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from MedGen

    • Showing Current items.

    CPSF3 cleavage and polyadenylation specific factor 3 [ Homo sapiens (human) ]

    Gene ID: 51692, updated on 11-Apr-2024

    Summary

    Go to the top of the page Help
    Official Symbol
    CPSF3provided by HGNC
    Official Full Name
    cleavage and polyadenylation specific factor 3provided by HGNC
    Primary source
    HGNC:HGNC:2326
    See related
    Ensembl:ENSG00000119203 MIM:606029; AllianceGenome:HGNC:2326
    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
    CPSF73; NEDMHS; CPSF-73; NEDMHSN
    Summary
    This gene encodes a member of the metallo-beta-lactamase family. The encoded protein is a 73kDa subunit of the cleavage and polyadenylation specificity factor and functions as an endonuclease that recognizes the pre-mRNA 3'-cleavage site AAUAAA prior to polyadenylation. It also cleaves after the pre-mRNA sequence ACCCA during histone 3'-end pre-mRNA processing. [provided by RefSeq, Oct 2012]
    Expression
    Broad expression in testis (RPKM 20.7), lymph node (RPKM 8.6) and 24 other tissues See more
    Orthologs
    mouse all
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Go to the top of the page Help
    Location:
    2p25.1
    Exon count:
    19
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (9423654..9473101)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (9448733..9498144)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (9563783..9613230)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 Neighboring gene uncharacterized LOC124907730 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:9532979-9533616 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:9533617-9534254 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:9540673-9541236 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:9562108-9562966 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11133 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15276 Neighboring gene integrin subunit beta 1 binding protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15277 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15278 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:9614491-9615258 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:9615739-9616299 Neighboring gene isoamyl acetate hydrolyzing esterase 1 (putative) Neighboring gene ADAM metallopeptidase domain 17 Neighboring gene small nucleolar RNA U13

    Genomic regions, transcripts, and products

    Go to the top of the page Help

    Go to nucleotide: Graphics FASTA GenBank

    Expression

    Go to the top of the page Help
    • 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

    Go to the top of the pageHelp

    Related articles in PubMed

    1. Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene. Arnadottir GA, et al. Nat Commun, 2022 Feb 4. PMID 35121750, Free PMC Article
    2. A real-time fluorescence assay for CPSF73, the nuclease for pre-mRNA 3'-end processing. Gutierrez PA, et al. RNA, 2021 Oct. PMID 34230059, Free PMC Article
    3. Cleavage and polyadenylation-specific factor 3 induces cell cycle arrest via PI3K/Akt/GSK-3β signaling pathways and predicts a negative prognosis in hepatocellular carcinoma. Li N, et al. Biomark Med, 2021 Apr. PMID 33666519
    4. CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma. Ross NT, et al. Nat Chem Biol, 2020 Jan. PMID 31819276, Free PMC Article
    5. An examination of the metal ion content in the active sites of human endonucleases CPSF73 and INTS11. Huang J, et al. J Biol Chem, 2023 Apr. PMID 36822327, Free PMC Article

    See all (120) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing.
      Title: CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing.
    2. Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer.
      Title: Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer.
    3. An examination of the metal ion content in the active sites of human endonucleases CPSF73 and INTS11.
      Title: An examination of the metal ion content in the active sites of human endonucleases CPSF73 and INTS11.
    4. Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.
      Title: Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.
    5. Cleavage and polyadenylation-specific factor 3 induces cell cycle arrest via PI3K/Akt/GSK-3beta signaling pathways and predicts a negative prognosis in hepatocellular carcinoma.
      Title: Cleavage and polyadenylation-specific factor 3 induces cell cycle arrest via PI3K/Akt/GSK-3β signaling pathways and predicts a negative prognosis in hepatocellular carcinoma.
    6. A real-time fluorescence assay for CPSF73, the nuclease for pre-mRNA 3'-end processing.
      Title: A real-time fluorescence assay for CPSF73, the nuclease for pre-mRNA 3'-end processing.
    7. CPSF3 represents a synthetic lethal node in a subset of acute myeloid leukemia and Ewing's sarcoma cancer cell lines
      Title: CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.
    8. CASC9 is a promising prognostic predictor for patients with CRC and the CASC9-CPSF3-TGFbeta2 axis is a potential therapeutic target for CRC treatment.
      Title: LncRNA CASC9 interacts with CPSF3 to regulate TGF-β signaling in colorectal cancer.
    9. the molecular mechanism that recruits the CPSF73 endonuclease to histone pre-mRNAs
      Title: A complex containing the CPSF73 endonuclease and other polyadenylation factors associates with U7 snRNP and is recruited to histone pre-mRNA for 3'-end processing.
    10. The data support a model where Star-PAP binds to the pre-mRNA, recruits the CPSF complex to the 3'-end of pre-mRNA and then defines cleavage by CPSF 73 and subsequent polyadenylation of its target mRNAs.
      Title: The poly A polymerase Star-PAP controls 3'-end cleavage by promoting CPSF interaction and specificity toward the pre-mRNA.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

    Go to the top of the page Help

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

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures
    MedGen: C5676986 OMIM: 619876 GeneReviews: Not available
    		not available

    Variation

    Go to the top of the page Help

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

    Go to the top of the page Help

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat 73 kDa subunit of the cleavage and polyadenylation specificity factor (CPSF-73) and its homologue RC-68 repress the HIV-1 LTR promoter. The LTR region between -275 to -110 within the 5' upstream region is necessary for the CPSF-73 interaction PubMed
    tat HIV-1 Tat interacts with CPSF-73 and counteracts its repressive activity on the HIV-1 LTR promoter. The N-terminal 48 amino acid residues of Tat are sufficient to mediate the interaction with CPSF-73 PubMed
    tat HIV-1 Tat specifically increases the expression of the cleavage and polyadenylation specificity factor 73-kDa subunit (CPSF3), and this upregulation is an important regulatory step for both viral and cellular gene expression PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Go to the top of the page

    Interactions

    Go to the top of the page Help
    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Go to the top of the page Help

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 5'-3' RNA exonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 5'-3' RNA exonuclease activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables RNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables RNA endonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA endonuclease activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables RNA endonuclease activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables metal ion binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in co-transcriptional mRNA 3'-end processing, cleavage and polyadenylation pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mRNA 3'-end processing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mRNA 3'-end processing by stem-loop binding and cleavage IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mRNA 3'-end processing by stem-loop binding and cleavage IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of G1/S transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of mRNA cleavage and polyadenylation specificity factor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of mRNA cleavage and polyadenylation specificity factor complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    part_of ribonucleoprotein complex IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

    Go to the top of the page Help
    Preferred Names
    cleavage and polyadenylation specificity factor subunit 3
    Names
    cleavage and polyadenylation specific factor 3, 73kDa
    mRNA 3'-end-processing endonuclease CPSF-73

    NCBI Reference Sequences (RefSeq)

    Go to the top of the page Help

    NEW Try the new Transcript table

    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.

    mRNA and Protein(s)

    1. NM_001321833.2 → NP_001308762.1  cleavage and polyadenylation specificity factor subunit 3 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) and variant 3 both encode the same isoform (b).
      Source sequence(s)
      AA635764, BC014106, DA455023, DC420903
      Consensus CDS
      CCDS82417.1
      UniProtKB/TrEMBL
      G5E9W3, Q53F02
      Conserved Domains (5) summary
      smart01027
      Location:209 → 330
      Beta-Casp; Beta-Casp domain
      smart01098
      Location:440 → 646
      CPSF73-100_C; This is the C-terminal conserved region of the pre-mRNA 3'-end-processing of the polyadenylation factor CPSF-73/CPSF-100 proteins
      COG1236
      Location:1 → 417
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:343 → 383
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16292
      Location:1 → 168
      CPSF3-like_MBL-fold; cleavage and polyadenylation specificity factor (CPSF) subunit 3 and related proteins; MBL-fold metallo-hydrolase domain

    2. NM_001321834.2 → NP_001308763.1  cleavage and polyadenylation specificity factor subunit 3 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) and variant 2 both encode the same isoform (b).
      Source sequence(s)
      AA635764, BC014106, DA455023, DC420903
      Consensus CDS
      CCDS82417.1
      UniProtKB/TrEMBL
      G5E9W3, Q53F02
      Related
      ENSP00000418957.1, ENST00000460593.1
      Conserved Domains (5) summary
      smart01027
      Location:209 → 330
      Beta-Casp; Beta-Casp domain
      smart01098
      Location:440 → 646
      CPSF73-100_C; This is the C-terminal conserved region of the pre-mRNA 3'-end-processing of the polyadenylation factor CPSF-73/CPSF-100 proteins
      COG1236
      Location:1 → 417
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:343 → 383
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16292
      Location:1 → 168
      CPSF3-like_MBL-fold; cleavage and polyadenylation specificity factor (CPSF) subunit 3 and related proteins; MBL-fold metallo-hydrolase domain

    3. NM_001321835.2 → NP_001308764.1  cleavage and polyadenylation specificity factor subunit 3 isoform c

      Status: REVIEWED

      Source sequence(s)
      AA635764, BC014106, DA478774, DC420903
      Conserved Domains (5) summary
      smart01027
      Location:107 → 228
      Beta-Casp; Beta-Casp domain
      smart01098
      Location:338 → 544
      CPSF73-100_C; This is the C-terminal conserved region of the pre-mRNA 3'-end-processing of the polyadenylation factor CPSF-73/CPSF-100 proteins
      COG1236
      Location:18 → 315
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:241 → 281
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cl23716
      Location:18 → 66
      metallo-hydrolase-like_MBL-fold; mainly hydrolytic enzymes and related proteins which carry out various biological functions; MBL-fold metallohydrolase domain

    4. NM_001321836.2 → NP_001308765.1  cleavage and polyadenylation specificity factor subunit 3 isoform d

      Status: REVIEWED

      Source sequence(s)
      AA635764, AC080162, BC014106, BG773037, DA455023, DC420903
      UniProtKB/TrEMBL
      Q53F02
      Conserved Domains (5) summary
      smart01027
      Location:250 → 371
      Beta-Casp; Beta-Casp domain
      smart01098
      Location:481 → 687
      CPSF73-100_C; This is the C-terminal conserved region of the pre-mRNA 3'-end-processing of the polyadenylation factor CPSF-73/CPSF-100 proteins
      COG1236
      Location:22 → 458
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      pfam07521
      Location:384 → 424
      RMMBL; RNA-metabolizing metallo-beta-lactamase
      cd16292
      Location:22 → 209
      CPSF3-like_MBL-fold; cleavage and polyadenylation specificity factor (CPSF) subunit 3 and related proteins; MBL-fold metallo-hydrolase domain

    5. NM_016207.4 → NP_057291.1  cleavage and polyadenylation specificity factor subunit 3 isoform a

      See identical proteins and their annotated locations for NP_057291.1

      Status: REVIEWED

      Source sequence(s)
      AA635764, BC020211, DC420903
      Consensus CDS
      CCDS1664.1
      UniProtKB/Swiss-Prot
      O14769, Q53RS2, Q96F36, Q9UKF6
      UniProtKB/TrEMBL
      Q53F02
      Related
      ENSP00000238112.3, ENST00000238112.8
      Conserved Domains (3) summary
      COG1236
      Location:14 → 454
      YSH1; RNA processing exonuclease, beta-lactamase fold, Cft2 family [Translation, ribosomal structure and biogenesis]
      cd16292
      Location:12 → 205
      CPSF3-like_MBL-fold; cleavage and polyadenylation specificity factor (CPSF) subunit 3 and related proteins; MBL-fold metallo-hydrolase domain
      pfam11718
      Location:479 → 682
      CPSF73-100_C; Pre-mRNA 3'-end-processing endonuclease polyadenylation factor C-term

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      9423654..9473101
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047444745.1 → XP_047300701.1  cleavage and polyadenylation specificity factor subunit 3 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      9448733..9498144
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054342551.1 → XP_054198526.1  cleavage and polyadenylation specificity factor subunit 3 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UKF6.1 GenPept UniProtKB/Swiss-Prot:Q9UKF6

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous