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Q5T6S3 (PHF19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
PHD finger protein 19
Alternative name(s):
Polycomb-like protein 3
Short name=hPCL3
Gene names
Name:PHF19
Synonyms:PCL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length580 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. 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 NO66 or KDM2B, leading to demethylation of H3K36 and recruitment of the PRC2 complex that mediates H3K27me3 methylation, followed by de novo silencing. Recruits the PRC2 complex to CpG islands and contributes to embryonic stem cell self-renewal. Also binds dimethylated at 'Lys-36' (H3K36me2). Isoform 1 and isoform 2 inhibit transcription from an HSV-tk promoter. Ref.4 Ref.6 Ref.8 Ref.12

Subunit structure

Associated component of the PRC2 complex. Interacts with EZH2 (via its Tudor domain). Isoform 1 interacts with SUZ12; isoform 2 does not interact with SUZ12. Interacts with NO66. Ref.6 Ref.8 Ref.12

Subcellular location

Nucleus Ref.4.

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. Ref.4

Domain

The Tudor domain recognizes and binds H3K36me3 (Ref.10, Ref.8, Ref.12 and Ref.9). May also bind H3K27me3, with a lower affinity (Ref.8). Ref.8 Ref.12

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 (Ref.7).

Sequence similarities

Belongs to the Polycomblike family.

Contains 2 PHD-type zinc fingers.

Contains 1 Tudor domain.

Sequence caution

The sequence CAE45832.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q5T6S3-1)

Also known as: PCL3L; hPCL3L;

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.
Isoform 2 (identifier: Q5T6S3-2)

Also known as: PCL3S; hPCL3S;

The sequence of this isoform differs from the canonical sequence as follows:
     155-207: RKGGALKKGA...CYCGGPGEWY → RVSLPSSPVP...ASATVLGQDL
     208-580: Missing.
Note: Contains a phosphoserine at position 166.
Isoform 3 (identifier: Q5T6S3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     122-130: GYHQQCHIP → VPHPHSGQC
     131-580: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 580580PHD finger protein 19
PRO_0000318570

Regions

Domain40 – 9354Tudor
Zinc finger96 – 15156PHD-type 1
Zinc finger195 – 24955PHD-type 2
Region74 – 807Histone H3K36me3 binding

Sites

Binding site471Histone H3K36me3
Binding site551Histone H3K36me3

Natural variations

Alternative sequence122 – 1309GYHQQCHIP → VPHPHSGQC in isoform 3.
VSP_031222
Alternative sequence131 – 580450Missing in isoform 3.
VSP_031223
Alternative sequence155 – 20753RKGGA…PGEWY → RVSLPSSPVPASPASSSGAD QRLPSQSLSSKQKGHTWALE TDSASATVLGQDL in isoform 2.
VSP_031224
Alternative sequence208 – 580373Missing in isoform 2.
VSP_031225

Experimental info

Mutagenesis501W → A in muthPhf19; abolishes histone H3K36me3-binding and impaired activity of the PRC2 complex and subsequent H3K27me3 methylation. Ref.8 Ref.12
Mutagenesis501W → C: Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and NO66; when associated with A-56. Ref.8 Ref.12
Mutagenesis561Y → A: Abolishes histone H3K36me3-binding. Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and NO66; when associated with C-50. Ref.8 Ref.10
Sequence conflict1811E → G in CAE45832. Ref.1

Secondary structure

........... 580
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (PCL3L) (hPCL3L) [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: 17CCF21BA2827826

FASTA58065,591
        10         20         30         40         50         60 
MENRALDPGT RDSYGATSHL PNKGALAKVK NNFKDLMSKL TEGQYVLCRW TDGLYYLGKI 

        70         80         90        100        110        120 
KRVSSSKQSC LVTFEDNSKY WVLWKDIQHA GVPGEEPKCN ICLGKTSGPL NEILICGKCG 

       130        140        150        160        170        180 
LGYHQQCHIP IAGSADQPLL TPWFCRRCIF ALAVRKGGAL KKGAIARTLQ AVKMVLSYQP 

       190        200        210        220        230        240 
EELEWDSPHR TNQQQCYCYC GGPGEWYLRM LQCYRCRQWF HEACTQCLNE PMMFGDRFYL 

       250        260        270        280        290        300 
FFCSVCNQGP EYIERLPLRW VDVVHLALYN LGVQSKKKYF DFEEILAFVN HHWELLQLGK 

       310        320        330        340        350        360 
LTSTPVTDRG PHLLNALNSY KSRFLCGKEI KKKKCIFRLR IRVPPNPPGK LLPDKGLLPN 

       370        380        390        400        410        420 
ENSASSELRK RGKSKPGLLP HEFQQQKRRV YRRKRSKFLL EDAIPSSDFT SAWSTNHHLA 

       430        440        450        460        470        480 
SIFDFTLDEI QSLKSASSGQ TFFSDVDSTD AASTSGSAST SLSYDSRWTV GSRKRKLAAK 

       490        500        510        520        530        540 
AYMPLRAKRW AAELDGRCPS DSSAEGASVP ERPDEGIDSH TFESISEDDS SLSHLKSSIT 

       550        560        570        580 
NYFGAAGRLA CGEKYQVLAR RVTPEGKVQY LVEWEGTTPY 

« Hide

Isoform 2 (PCL3S) (hPCL3S) [UniParc].

Checksum: 34F3EF834B17FAF0
Show »

FASTA20722,512
Isoform 3 [UniParc].

Checksum: E10645A3F782774C
Show »

FASTA13014,386

References

« Hide 'large scale' references
[1]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Esophageal carcinoma and Mammary cancer.
[2]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Prostate and Skin.
[4]"A novel human homologue of Drosophila polycomblike gene is up-regulated in multiple cancers."
Wang S., Robertson G.P., Zhu J.
Gene 343:69-78(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[6]"Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes."
Boulay G., Rosnoblet C., Guerardel C., Angrand P.O., Leprince D.
Biochem. J. 434:333-342(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ALTERNATIVE SPLICING, INTERACTION WITH EZH2.
[7]"PHF19 and Akt control the switch between proliferative and invasive states in melanoma."
Ghislin S., Deshayes F., Middendorp S., Boggetto N., Alcaide-Loridan C.
Cell Cycle 11:1634-1645(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: DOWN-REGULATION IN SPHEROID MELANOMA CELLS.
[8]"Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation."
Brien G.L., Gambero G., O'Connell D.J., Jerman E., Turner S.A., Egan C.M., Dunne E.J., Jurgens M.C., Wynne K., Piao L., Lohan A.J., Ferguson N., Shi X., Sinha K.M., Loftus B.J., Cagney G., Bracken A.P.
Nat. Struct. Mol. Biol. 19:1273-1281(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, H3K36ME3-BINDING, DOMAIN, INTERACTION WITH NO66, MUTAGENESIS OF TRP-50 AND TYR-56.
[9]"Tudor domains of the PRC2 components PHF1 and PHF19 selectively bind to histone H3K36me3."
Qin S., Guo Y., Xu C., Bian C., Fu M., Gong S., Min J.
Biochem. Biophys. Res. Commun. 430:547-553(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: H3K36ME3-BINDING.
[10]"An H3K36 methylation-engaging Tudor motif of Polycomb-like proteins mediates PRC2 complex targeting."
Cai L., Rothbart S.B., Lu R., Xu B., Chen W.Y., Tripathy A., Rockowitz S., Zheng D., Patel D.J., Allis C.D., Strahl B.D., Song J., Wang G.G.
Mol. Cell 49:571-582(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: H3K36ME3-BINDING, MUTAGENESIS OF TYR-56.
[11]"Solution structure of the tudor domain of PHD finger protein 19, isoform B [Homo sapiens]."
RIKEN structural genomics initiative (RSGI)
Submitted (FEB-2009) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 40-95.
[12]"Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity."
Ballare C., Lange M., Lapinaite A., Martin G.M., Morey L., Pascual G., Liefke R., Simon B., Shi Y., Gozani O., Carlomagno T., Benitah S.A., Di Croce L.
Nat. Struct. Mol. Biol. 19:1257-1265(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 38-95, FUNCTION, ASSOCIATION WITH THE PRC2 COMPLEX, H3K36ME3-BINDING, DOMAIN, INTERACTION WITH SUZ12, MUTAGENESIS OF TRP-50.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL117477 mRNA. Translation: CAB55950.1.
BX640713 mRNA. Translation: CAE45832.1. Different initiation.
AL354792 Genomic DNA. Translation: CAI15690.1.
AL354792 Genomic DNA. Translation: CAI15691.1.
AL354792, AL161911 Genomic DNA. Translation: CAI15692.1.
AL161911, AL354792 Genomic DNA. Translation: CAI95112.1.
BC022374 mRNA. Translation: AAH22374.1.
BC108663 mRNA. Translation: AAI08664.1.
BC125076 mRNA. Translation: AAI25077.1.
BC125077 mRNA. Translation: AAI25078.1.
PIRT17260.
RefSeqNP_001009936.1. NM_001009936.2.
NP_001273769.1. NM_001286840.1.
NP_001273772.1. NM_001286843.1.
NP_056466.1. NM_015651.2.
XP_005251963.1. XM_005251906.1.
UniGeneHs.460124.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2E5QNMR-A40-95[»]
4BD3NMR-A38-95[»]
ProteinModelPortalQ5T6S3.
SMRQ5T6S3. Positions 38-156, 194-342.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117578. 7 interactions.
IntActQ5T6S3. 4 interactions.
MINTMINT-8417713.
STRING9606.ENSP00000363003.

PTM databases

PhosphoSiteQ5T6S3.

Polymorphism databases

DMDM74745265.

Proteomic databases

PaxDbQ5T6S3.
PRIDEQ5T6S3.

Protocols and materials databases

DNASU26147.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000312189; ENSP00000310372; ENSG00000119403. [Q5T6S3-2]
ENST00000373896; ENSP00000363003; ENSG00000119403. [Q5T6S3-1]
GeneID26147.
KEGGhsa:26147.
UCSCuc004bks.1. human. [Q5T6S3-1]
uc004bkt.3. human. [Q5T6S3-2]

Organism-specific databases

CTD26147.
GeneCardsGC09M123617.
HGNCHGNC:24566. PHF19.
HPAHPA051458.
MIM609740. gene.
neXtProtNX_Q5T6S3.
PharmGKBPA134911501.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG244542.
HOGENOMHOG000010307.
HOVERGENHBG004755.
InParanoidQ5T6S3.
KOK11486.
OMADWDSPHR.
OrthoDBEOG73V6JJ.
PhylomeDBQ5T6S3.
TreeFamTF106420.

Gene expression databases

ArrayExpressQ5T6S3.
BgeeQ5T6S3.
CleanExHS_PHF19.
GenevestigatorQ5T6S3.

Family and domain databases

Gene3D3.30.40.10. 2 hits.
InterProIPR025894. Mtf2_C_dom.
IPR002999. Tudor.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF14061. Mtf2_C. 1 hit.
PF00628. PHD. 1 hit.
[Graphical view]
SMARTSM00249. PHD. 2 hits.
SM00333. TUDOR. 1 hit.
[Graphical view]
SUPFAMSSF57903. SSF57903. 2 hits.
PROSITEPS01359. ZF_PHD_1. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPHF19. human.
EvolutionaryTraceQ5T6S3.
GenomeRNAi26147.
NextBio48205.
PROQ5T6S3.
SOURCESearch...

Entry information

Entry namePHF19_HUMAN
AccessionPrimary (citable) accession number: Q5T6S3
Secondary accession number(s): Q32NF2 expand/collapse secondary AC list , Q5T6S4, Q6N038, Q8TBL6, Q9UFS9
Entry history
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: December 21, 2004
Last modified: April 16, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM