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

Summary

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

Location:: 2p25.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (9423654..9473101)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (9448733..9498144)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (9563783..9613230)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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 page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CPSF3 regulates alternative polyadenylation of CNIH2 to promote esophageal squamous cell carcinoma progression.
Title: CPSF3 regulates alternative polyadenylation of CNIH2 to promote esophageal squamous cell carcinoma progression.
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.
Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer.
Title: Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer.
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.
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.
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.
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.
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.
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.
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.

Submit: New GeneRIF Correction See all GeneRIFs (18)

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)

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

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

D2S287 (e-PCR), detects polymorphism
- UniSTS:1176

RH78234 (e-PCR)
- UniSTS:11687

D2S287 (e-PCR), detects polymorphism
- UniSTS:72412

WI-11400 (e-PCR)
- UniSTS:41443

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)

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
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
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
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
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