CPSF3
Cleavage and polyadenylation specificity factor subunit 3
Also known as: CPSF-73, CPSF3_HUMAN, CPSF73, YSH1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9UKF6
- Gene
- CPSF3
- Ensembl
- ENSG00000119203
- Chromosome
- 2
- Canonical length
- 684 aa
- Protein class
- Disease related genes, Predicted intracellular proteins
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
684 residues, UniProt reviewed canonical sequence.
>Q9UKF6|CPSF3
1 MSAIPAEESD QLLIRPLGAG QEVGRSCIIL EFKGRKIMLD CGIHPGLEGM DALPYIDLID
61 PAEIDLLLIS HFHLDHCGAL PWFLQKTSFK GRTFMTHATK AIYRWLLSDY VKVSNISADD
121 MLYTETDLEE SMDKIETINF HEVKEVAGIK FWCYHAGHVL GAAMFMIEIA GVKLLYTGDF
181 SRQEDRHLMA AEIPNIKPDI LIIESTYGTH IHEKREEREA RFCNTVHDIV NRGGRGLIPV
241 FALGRAQELL LILDEYWQNH PELHDIPIYY ASSLAKKCMA VYQTYVNAMN DKIRKQININ
301 NPFVFKHISN LKSMDHFDDI GPSVVMASPG MMQSGLSREL FESWCTDKRN GVIIAGYCVE
361 GTLAKHIMSE PEEITTMSGQ KLPLKMSVDY ISFSAHTDYQ QTSEFIRALK PPHVILVHGE
421 QNEMARLKAA LIREYEDNDE VHIEVHNPRN TEAVTLNFRG EKLAKVMGFL ADKKPEQGQR
481 VSGILVKRNF NYHILSPCDL SNYTDLAMST VKQTQAIPYT GPFNLLCYQL QKLTGDVEEL
541 EIQEKPALKV FKNITVIQEP GMVVLEWLAN PSNDMYADTV TTVILEVQSN PKIRKGAVQK
601 VSKKLEMHVY SKRLEIMLQD IFGEDCVSVK DDSILSVTVD GKTANLNLET RTVECEEGSE
661 DDESLREMVE LAAQRLYEAL TPVHLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CPSF3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.26
- Highest tissue expression
- 48 nTPM
Expression across tissuesHPA
Tissue
- testis: 48 nTPM
- thymus: 30 nTPM
- tonsil: 29 nTPM
- lymph node: 25 nTPM
- bone marrow: 22 nTPM
- epididymis: 22 nTPM
Single-cell type
- late primary spermatocytes: 367 nCPM
- early spermatids: 157 nCPM
- early primary spermatocytes: 115 nCPM
- epicardial cells: 84 nCPM
- erythrocyte progenitors: 74 nCPM
- neutrophil progenitors: 74 nCPM
Immune cell
- myeloid DC: 50 nTPM
- intermediate monocyte: 40 nTPM
- non-classical monocyte: 39 nTPM
- NK-cell: 38 nTPM
- T-reg: 37 nTPM
- classical monocyte: 35 nTPM
Brain region
- white matter: 21 nTPM
- thalamus: 20 nTPM
- choroid plexus: 19 nTPM
- pons: 19 nTPM
- medulla oblongata: 18 nTPM
- basal ganglia: 18 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CPSF3.
Disease | AllUniProt
Conditions CPSF3 is implicated in, by any mechanism.
- Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures (NEDMHS) MIM:619876
Disease | GeneticClinVar
3 pathogenic / likely-pathogenic of 91 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Neurodevelopmental disorder with hypotonia, microcephaly, and seizures
- Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures
- HP:0001252
- HP:0001776
- HP:0000252
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.7
- gnomAD pLI
- 0
- gnomAD missense Z
- 3.61
- DepMap mean gene effect
- -1.66
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- co-transcriptional mRNA 3'-end processing, cleavage and polyadenylation pathway
- mRNA 3'-end processing
- mRNA 3'-end processing by stem-loop binding and cleavage
- positive regulation of G1/S transition of mitotic cell cycle
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Metallo-beta-lactamase
- Zn-dependent metallo-hydrolase, RNA specificity domain
- Beta-Casp domain
- Ribonuclease Z/Hydroxyacylglutathione hydrolase-like
- RNA Processing Metallo-Beta-Lactamase
- Metallo-beta-lactamase superfamily
- Zn-dependent metallo-hydrolase RNA specificity domain
- Beta-Casp domain
- Pre-mRNA 3'-end-processing endonuclease polyadenylation factor C-term
- Pre-mRNA 3'-end-processing endonuclease polyadenylation factor C-term
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CPSF3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CPSF3 as an antibody target. Whether an autoantibody or antibody against CPSF3 could matter depends on whether native CPSF3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CPSF3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CPSF3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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