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

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

Summary

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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
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Genomic context

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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

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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. 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

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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

Associated conditions

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

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
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

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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

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

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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)

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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.

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

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