Q5T6S3 (PHF19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
PHD finger protein 19

Alternative name(s):
Polycomb-like protein 3
Short name=hPCL3

Gene names

Name:	PHF19
Synonyms:	PCL3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	580 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of histone H3-K27 methylation Inferred from mutant phenotype Ref.12. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	methylated histone residue binding Inferred from direct assay Ref.12Ref.8Ref.10. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 580

580

PHD finger protein 19

PRO_0000318570

Regions

Domain

40 – 93

54

Tudor

Zinc finger

96 – 151

56

PHD-type 1

Zinc finger

195 – 249

55

PHD-type 2

Region

74 – 80

7

Histone H3K36me3 binding

Sites

Binding site

47

1

Histone H3K36me3

Binding site

55

1

Histone H3K36me3

Natural variations

Alternative sequence

122 – 130

9

GYHQQCHIP → VPHPHSGQC in isoform 3.

VSP_031222

Alternative sequence

131 – 580

450

Missing in isoform 3.

VSP_031223

Alternative sequence

155 – 207

53

RKGGA…PGEWY → RVSLPSSPVPASPASSSGAD QRLPSQSLSSKQKGHTWALE TDSASATVLGQDL in isoform 2.

VSP_031224

Alternative sequence

208 – 580

373

Missing in isoform 2.

VSP_031225

Experimental info

Mutagenesis

50

1

W → A in muthPhf19; abolishes histone H3K36me3-binding and impaired activity of the PRC2 complex and subsequent H3K27me3 methylation. Ref.8 Ref.12

Mutagenesis

50

1

W → C: Abolishes histone H3K36me3-binding and recruitment of the PRC2 complex and NO66; when associated with A-56. Ref.8 Ref.12

Mutagenesis

56

1

Y → 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 conflict

181

1

E → G in CAE45832. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

580

Helix Strand Turn

Details...

Beta strand

45 – 49

5

Beta strand

55 – 60

6

Beta strand

68 – 74

7

Beta strand

79 – 83

5

Helix

84 – 86

3

Beta strand

87 – 89

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PCL3L) (hPCL3L) [UniParc]. Last modified December 21, 2004. Version 1. Checksum: 17CCF21BA2827826	FASTA	580	65,591
	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
	Isoform 2 (PCL3S) (hPCL3S) [UniParc]. Checksum: 34F3EF834B17FAF0	FASTA	207	22,512
	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 ALAVRVSLPS SPVPASPASS SGADQRLPSQ 190 200 SLSSKQKGHT WALETDSASA TVLGQDL
	Isoform 3 [UniParc]. Checksum: E10645A3F782774C	FASTA	130	14,386
	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 LVPHPHSGQC

References

	« Hide 'large scale' referencesShow '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. , 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), MASS SPECTROMETRY. 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.
+	Additional computationally mapped references.

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.

IPI

IPI00152220.
IPI00157837.
IPI00743344.

PIR

T17260.

RefSeq

NP_001009936.1. NM_001009936.1.
NP_056466.1. NM_015651.1.

UniGene

Hs.460124.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2E5Q	NMR	-	A	40-95	[»]
4BD3	NMR	-	A	38-95	[»]

ProteinModelPortal

Q5T6S3.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q5T6S3. 1 interaction.

STRING

9606.ENSP00000363003.

PTM databases

PhosphoSite

Q5T6S3.

Polymorphism databases

DMDM

74745265.

Proteomic databases

PaxDb

Q5T6S3.

PRIDE

Q5T6S3.

Protocols and materials databases

DNASU

26147.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000312189; ENSP00000310372; ENSG00000119403.
ENST00000373896; ENSP00000363003; ENSG00000119403.
ENST00000456291; ENSP00000397935; ENSG00000119403.

GeneID

26147.

KEGG

hsa:26147.

UCSC

uc004bks.1. human.
uc004bkt.3. human.

Organism-specific databases

CTD

26147.

GeneCards

GC09M123617.

HGNC

HGNC:24566. PHF19.

HPA

HPA051458.

MIM

609740. gene.

neXtProt

NX_Q5T6S3.

PharmGKB

PA134911501.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG244542.

HOGENOM

HOG000010307.

HOVERGEN

HBG004755.

InParanoid

Q5T6S3.

KO

K11486.

OMA

HHMANIF.

OrthoDB

EOG4ZGPC7.

Gene expression databases

ArrayExpress

Q5T6S3.

Bgee

Q5T6S3.

CleanEx

HS_PHF19.

Genevestigator

Q5T6S3.

Family and domain databases

Gene3D

3.30.40.10. 2 hits.

InterPro

IPR025894. 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]

Pfam

PF14061. Mtf2_C. 1 hit.
PF00628. PHD. 1 hit.
[Graphical view]

SMART

SM00249. PHD. 2 hits.
SM00333. TUDOR. 1 hit.
[Graphical view]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 2 hits.

PROSITE

PS50304. TUDOR. False negative.
PS01359. ZF_PHD_1. 2 hits.
PS50016. ZF_PHD_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

PHF19. human.

EvolutionaryTrace

Q5T6S3.

GenomeRNAi

26147.

NextBio

48205.

SOURCE

Search...

Entry information

Entry name

PHF19_HUMAN

Accession

Primary (citable) accession number: Q5T6S3
Secondary accession number(s): Q32NF2 , Q5T6S4, Q6N038, Q8TBL6, Q9UFS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	December 21, 2004
Last modified:	May 1, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.