Q5T6S3 · PHF19_HUMAN
- ProteinPHD finger protein 19
- GenePHF19
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids580 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Polycomb group (PcG) protein that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex, thus enhancing PRC2 H3K27me3 methylation activity (PubMed:15563832, PubMed:18691976, PubMed:23104054, PubMed:23160351, PubMed:23228662, PubMed:23273982, PubMed:29499137, PubMed:31959557).
Probably involved in the transition from an active state to a repressed state in embryonic stem cells: acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting H3K36me3 histone demethylases RIOX1 or KDM2B, leading to demethylation of H3K36 and recruitment of the PRC2 complex that mediates H3K27me3 methylation, followed by de novo silencing (PubMed:23160351).
Recruits the PRC2 complex to CpG islands and contributes to embryonic stem cell self-renewal. Also binds histone H3 dimethylated at 'Lys-36' (H3K36me2) (PubMed:23104054).
Isoform 1 and isoform 2 inhibit transcription from an HSV-tk promoter (PubMed:15563832).
Probably involved in the transition from an active state to a repressed state in embryonic stem cells: acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting H3K36me3 histone demethylases RIOX1 or KDM2B, leading to demethylation of H3K36 and recruitment of the PRC2 complex that mediates H3K27me3 methylation, followed by de novo silencing (PubMed:23160351).
Recruits the PRC2 complex to CpG islands and contributes to embryonic stem cell self-renewal. Also binds histone H3 dimethylated at 'Lys-36' (H3K36me2) (PubMed:23104054).
Isoform 1 and isoform 2 inhibit transcription from an HSV-tk promoter (PubMed:15563832).
Miscellaneous
Down-regulated in spheroid melanoma cells that display an invasive phenotype, characterized by a higher motility, a poor proliferation rate and a gain of pluripotency gene expression. PHF19 favors the proliferation and reduces the transmigration capacity of melanoma cell lines, 2 properties of invasive cells, suggesting that down-regulation may participate in the switch from proliferative to invasive states in melanoma cells (PubMed:22487681).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 47 | Histone H3K36me3 binding | ||||
Sequence: L | ||||||
Site | 55 | Histone H3K36me3 binding | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | ESC/E(Z) complex | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | chromatin binding | |
Molecular Function | DNA binding | |
Molecular Function | metal ion binding | |
Molecular Function | methylated histone binding | |
Biological Process | negative regulation of gene expression, epigenetic | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | stem cell differentiation | |
Biological Process | stem cell population maintenance |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePHD finger protein 19
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ5T6S3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to chromatin as part of the PRC2 complex.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 50 | In muthPhf19; abolishes histone H3K36me3-binding and impaired activity of the PRC2 complex and subsequent H3K27me3 methylation. | ||||
Sequence: W → A | ||||||
Mutagenesis | 50 | Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and RIOX1; when associated with A-56. | ||||
Sequence: W → C | ||||||
Mutagenesis | 56 | Abolishes histone H3K36me3-binding. Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and RIOX1; when associated with C-50. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 331-332 | Impairs chromatin binding as part of the PRC2 complex. | ||||
Sequence: KK → AA |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 520 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000318570 | 1-580 | UniProt | PHD finger protein 19 | |||
Sequence: MENRALDPGTRDSYGATSHLPNKGALAKVKNNFKDLMSKLTEGQYVLCRWTDGLYYLGKIKRVSSSKQSCLVTFEDNSKYWVLWKDIQHAGVPGEEPKCNICLGKTSGPLNEILICGKCGLGYHQQCHIPIAGSADQPLLTPWFCRRCIFALAVRKGGALKKGAIARTLQAVKMVLSYQPEELEWDSPHRTNQQQCYCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVCNQGPEYIERLPLRWVDVVHLALYNLGVQSKKKYFDFEEILAFVNHHWELLQLGKLTSTPVTDRGPHLLNALNSYKSRFLCGKEIKKKKCIFRLRIRVPPNPPGKLLPDKGLLPNENSASSELRKRGKSKPGLLPHEFQQQKRRVYRRKRSKFLLEDAIPSSDFTSAWSTNHHLASIFDFTLDEIQSLKSASSGQTFFSDVDSTDAASTSGSASTSLSYDSRWTVGSRKRKLAAKAYMPLRAKRWAAELDGRCPSDSSAEGASVPERPDEGIDSHTFESISEDDSSLSHLKSSITNYFGAAGRLACGEKYQVLARRVTPEGKVQYLVEWEGTTPY | |||||||
Modified residue | 13 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 13 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 166 | UniProt | In isoform Q5T6S3-2; Phosphoserine | ||||
Sequence: A | |||||||
Modified residue | 187 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 365 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 366 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 366 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 538 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Isoform 1 is expressed in thymus, heart, lung and kidney. Isoform 2 is predominantly expressed in placenta, skeletal muscle and kidney, whereas isoform 1 is predominantly expressed in liver and peripheral blood leukocytes. Overexpressed in many types of cancers, including colon, skin, lung, rectal, cervical, uterus, liver cancers, in cell lines derived from different stages of melanoma and in glioma cell lines.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:23104054, PubMed:29499137, PubMed:31959557).
Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin (PubMed:31959557).
Interacts with SUZ12; competes with AEBP2 for SUZ12 binding (PubMed:29499137, PubMed:31959557).
Interacts with EZH2 (via its Tudor domain) (PubMed:21143197).
Isoform 1 interacts with SUZ12; isoform 2 does not interact with SUZ12 (PubMed:23104054).
Interacts with RIOX1 (PubMed:23160351).
Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19 or MTF2; PHF19 and MTF2 stabilize the dimeric structure which enhances PRC2 interaction with chromatin (PubMed:31959557).
Interacts with SUZ12; competes with AEBP2 for SUZ12 binding (PubMed:29499137, PubMed:31959557).
Interacts with EZH2 (via its Tudor domain) (PubMed:21143197).
Isoform 1 interacts with SUZ12; isoform 2 does not interact with SUZ12 (PubMed:23104054).
Interacts with RIOX1 (PubMed:23160351).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 40-93 | Tudor | ||||
Sequence: LTEGQYVLCRWTDGLYYLGKIKRVSSSKQSCLVTFEDNSKYWVLWKDIQHAGVP | ||||||
Region | 74-80 | Histone H3K36me3 binding | ||||
Sequence: FEDNSKY | ||||||
Zinc finger | 96-151 | PHD-type 1 | ||||
Sequence: EPKCNICLGKTSGPLNEILICGKCGLGYHQQCHIPIAGSADQPLLTPWFCRRCIFA | ||||||
Zinc finger | 195-249 | PHD-type 2 | ||||
Sequence: QCYCYCGGPGEWYLRMLQCYRCRQWFHEACTQCLNEPMMFGDRFYLFFCSVCNQG | ||||||
Region | 347-390 | Disordered | ||||
Sequence: PPGKLLPDKGLLPNENSASSELRKRGKSKPGLLPHEFQQQKRRV | ||||||
Region | 496-521 | Disordered | ||||
Sequence: GRCPSDSSAEGASVPERPDEGIDSHT | ||||||
Region | 531-544 | Important for PRC2 dimer stability | ||||
Sequence: SLSHLKSSITNYFG | ||||||
Region | 531-580 | Interaction with SUZ12 | ||||
Sequence: SLSHLKSSITNYFGAAGRLACGEKYQVLARRVTPEGKVQYLVEWEGTTPY |
Domain
The Tudor domain recognizes and binds H3K36me3 (PubMed:23104054, PubMed:23160351, PubMed:23228662, PubMed:23273982).
May also bind H3K27me3, with a lower affinity (PubMed:23160351).
May also bind H3K27me3, with a lower affinity (PubMed:23160351).
Sequence similarities
Belongs to the Polycomblike family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q5T6S3-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsPCL3L, hPCL3L
- Length580
- Mass (Da)65,591
- Last updated2004-12-21 v1
- Checksum17CCF21BA2827826
Q5T6S3-2
- Name2
- SynonymsPCL3S, hPCL3S
Q5T6S3-3
- Name3
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_031222 | 122-130 | in isoform 3 | |||
Sequence: GYHQQCHIP → VPHPHSGQC | ||||||
Alternative sequence | VSP_031223 | 131-580 | in isoform 3 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_031224 | 155-207 | in isoform 2 | |||
Sequence: RKGGALKKGAIARTLQAVKMVLSYQPEELEWDSPHRTNQQQCYCYCGGPGEWY → RVSLPSSPVPASPASSSGADQRLPSQSLSSKQKGHTWALETDSASATVLGQDL | ||||||
Sequence conflict | 181 | in Ref. 1; CAE45832 | ||||
Sequence: E → G | ||||||
Alternative sequence | VSP_031225 | 208-580 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL117477 EMBL· GenBank· DDBJ | CAB55950.1 EMBL· GenBank· DDBJ | mRNA | ||
BX640713 EMBL· GenBank· DDBJ | CAE45832.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AL161911 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL354792 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC022374 EMBL· GenBank· DDBJ | AAH22374.1 EMBL· GenBank· DDBJ | mRNA | ||
BC108663 EMBL· GenBank· DDBJ | AAI08664.1 EMBL· GenBank· DDBJ | mRNA | ||
BC125076 EMBL· GenBank· DDBJ | AAI25077.1 EMBL· GenBank· DDBJ | mRNA | ||
BC125077 EMBL· GenBank· DDBJ | AAI25078.1 EMBL· GenBank· DDBJ | mRNA |