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Q9UPP1 (PHF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Histone lysine demethylase PHF8

EC=1.14.11.27
Alternative name(s):
PHD finger protein 8
Gene names
Name:PHF8
Synonyms:KIAA1111, ZNF422
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1060 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.23 Ref.25

Catalytic activity

Protein N6,N(6)-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO2. Ref.14 Ref.25

Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2. Ref.14 Ref.25

Cofactor

Binds 1 Fe2+ ion per subunit Probable. Ref.14 Ref.25

Subunit structure

Interacts with POLR1B, UBTF, SETD1A, HCFC1, E2F1 and ZNF711. Ref.15 Ref.17 Ref.19

Subcellular location

Nucleus. Nucleusnucleolus. Note: Recruited to H3K4me3 sites on chromatin during interphase. Dissociates from chromatin when cells enter mitosis. Ref.12 Ref.14 Ref.17 Ref.19

Domain

The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2. Ref.15 Ref.16 Ref.18 Ref.19 Ref.25

The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3. Ref.15 Ref.16 Ref.18 Ref.19 Ref.25

Post-translational modification

Phosphorylation at Ser-69 and Ser-120 are required for dissociation from chromatin and accumulation of H4K20Me1 levels during prophase.

Involvement in disease

Mental retardation, X-linked, syndromic, Siderius type (MRXSSD) [MIM:300263]: A syndrome characterized by mild to borderline mental retardation with or without cleft lip/cleft palate.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.23 Ref.26

Sequence similarities

Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.

Contains 1 JmjC domain.

Contains 1 PHD-type zinc finger.

Biophysicochemical properties

Kinetic parameters:

KM=134 µM for histone H3 H3K9Me2 Ref.25

KM=8 µM for histone H3 H3K4me3 and H3K9Me2

Sequence caution

The sequence BAA83063.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence BAB13877.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence CAI45929.1 differs from that shown. Reason: Erroneous termination at position 419. Translated as Arg.

Ontologies

Keywords
   Biological processCell cycle
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Mental retardation
   DomainZinc-finger
   LigandIron
Metal-binding
Zinc
   Molecular functionActivator
Chromatin regulator
Dioxygenase
Oxidoreductase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG1/S transition of mitotic cell cycle

Inferred from mutant phenotype Ref.19. Source: UniProtKB

brain development

Inferred from sequence or structural similarity. Source: UniProtKB

histone H3-K27 demethylation

Inferred from direct assay Ref.18Ref.19. Source: UniProtKB

histone H3-K36 demethylation

Inferred from direct assay Ref.17Ref.18. Source: UniProtKB

histone H3-K9 demethylation

Inferred from direct assay Ref.25Ref.17Ref.15Ref.18Ref.19. Source: UniProtKB

histone H4-K20 demethylation

Inferred from direct assay Ref.18Ref.19. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

negative regulation of chromatin silencing at rDNA

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of transcription from RNA polymerase I promoter

Inferred from direct assay Ref.17. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.18. Source: UniProtKB

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentmicrotubule cytoskeleton

Inferred from direct assay. Source: HPA

nucleolus

Inferred from direct assay Ref.17. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.14. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from direct assay Ref.19. Source: UniProtKB

histone demethylase activity

Inferred from direct assay Ref.14. Source: UniProtKB

histone demethylase activity (H3-K27 specific)

Inferred from direct assay Ref.18Ref.19. Source: UniProtKB

histone demethylase activity (H3-K36 specific)

Inferred from direct assay Ref.17Ref.18. Source: UniProtKB

histone demethylase activity (H3-K9 specific)

Inferred from direct assay Ref.25Ref.17Ref.15Ref.18Ref.19. Source: UniProtKB

histone demethylase activity (H4-K20 specific)

Inferred from direct assay Ref.18Ref.19. Source: UniProtKB

iron ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

methylated histone binding

Inferred from direct assay Ref.25Ref.17Ref.15Ref.18Ref.19PubMed 21029866. Source: UniProtKB

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors

Inferred from direct assay Ref.25. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 23518351. Source: IntAct

zinc ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PML-RARQ151566EBI-6601215,EBI-867256
RARAP102762EBI-6601215,EBI-413374

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UPP1-1)

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.
Isoform 2 (identifier: Q9UPP1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
Isoform 3 (identifier: Q9UPP1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     478-578: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9UPP1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     478-578: Missing.
     1060-1060: L → LRQVIVQAECRQAIHEPKLKRRDAHP
Note: No experimental confirmation available.
Isoform 5 (identifier: Q9UPP1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     717-746: KLGNGSGAGGILDLLKASRQVGGPDYAALT → YQTATPAPAQGAS
     920-931: ELQKAQKKKYIK → VKKMKLSLTDSG
     932-1060: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10601060Histone lysine demethylase PHF8
PRO_0000059295

Regions

Domain231 – 387157JmjC
Zinc finger41 – 9252PHD-type
Region101 – 11515Linker
Compositional bias769 – 80739Ser-rich

Sites

Metal binding2831Iron; catalytic
Metal binding2851Iron; catalytic
Metal binding3551Iron; catalytic
Binding site2801Substrate
Binding site3001Substrate

Amino acid modifications

Modified residue691Phosphoserine; by CDK1 Ref.19
Modified residue1201Phosphoserine; by CDK1 Ref.19
Modified residue6511Phosphoserine Ref.11
Modified residue7051Phosphothreonine Ref.9 Ref.11
Modified residue7061Phosphothreonine Ref.9 Ref.11
Modified residue8041Phosphoserine Ref.20
Modified residue8541Phosphoserine Ref.9 Ref.11 Ref.22
Modified residue8571Phosphoserine Ref.8 Ref.9 Ref.11 Ref.20 Ref.22
Modified residue8801Phosphoserine Ref.9 Ref.20 Ref.22

Natural variations

Alternative sequence1 – 3636Missing in isoform 2, isoform 4 and isoform 5.
VSP_014964
Alternative sequence478 – 578101Missing in isoform 3 and isoform 4.
VSP_014965
Alternative sequence717 – 74630KLGNG…YAALT → YQTATPAPAQGAS in isoform 5.
VSP_054019
Alternative sequence920 – 93112ELQKA…KKYIK → VKKMKLSLTDSG in isoform 5.
VSP_054020
Alternative sequence932 – 1060129Missing in isoform 5.
VSP_054021
Alternative sequence10601L → LRQVIVQAECRQAIHEPKLK RRDAHP in isoform 4.
VSP_043640
Natural variant3151F → S in MRXSSD; abolishes histone methyltransferase activity. Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.23 Ref.26
VAR_062250

Experimental info

Mutagenesis431Y → A: Abolishes binding to H3K4me3; when associated with A-50. Ref.17 Ref.18
Mutagenesis501Y → A: Abolishes binding to H3K4me3; when associated with A-43. Abolishes binding to H3K4me3; when associated with A-65. Ref.18
Mutagenesis651W → A: Abolishes binding to H3K4me3; when associated with A-50. Ref.18
Mutagenesis691S → A: Impairs phosphorylation by CDK1 and dissociation from chromatin when cells enter mitosis; when associated with A-120. Ref.19
Mutagenesis1201S → A: Impairs phosphorylation by CDK1 and dissociation from chromatin when cells enter mitosis; when associated with A-69. Ref.19
Mutagenesis283 – 2853HID → AAA: Abolishes histone methyltransferase activity. Ref.12 Ref.15 Ref.17 Ref.19
Mutagenesis2831H → A: Abolishes histone methyltransferase activity. Ref.12 Ref.15 Ref.19
Sequence conflict2321S → P in BAB13877. Ref.2

Secondary structure

................................................................................ 1060
Helix Strand Turn

Details...

Sequences

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

Last modified August 16, 2005. Version 3.
Checksum: 04C83D7C5E9E56B8

FASTA1,060117,864
        10         20         30         40         50         60 
MNRSRAIVQR GRVLPPPAPL DTTNLAGRRT LQGRAKMASV PVYCLCRLPY DVTRFMIECD 

        70         80         90        100        110        120 
MCQDWFHGSC VGVEEEKAAD IDLYHCPNCE VLHGPSIMKK RRGSSKGHDT HKGKPVKTGS 

       130        140        150        160        170        180 
PTFVRELRSR TFDSSDEVIL KPTGNQLTVE FLEENSFSVP ILVLKKDGLG MTLPSPSFTV 

       190        200        210        220        230        240 
RDVEHYVGSD KEIDVIDVTR QADCKMKLGD FVKYYYSGKR EKVLNVISLE FSDTRLSNLV 

       250        260        270        280        290        300 
ETPKIVRKLS WVENLWPEEC VFERPNVQKY CLMSVRDSYT DFHIDFGGTS VWYHVLKGEK 

       310        320        330        340        350        360 
IFYLIRPTNA NLTLFECWSS SSNQNEMFFG DQVDKCYKCS VKQGQTLFIP TGWIHAVLTP 

       370        380        390        400        410        420 
VDCLAFGGNF LHSLNIEMQL KAYEIEKRLS TADLFRFPNF ETICWYVGKH ILDIFRGLRE 

       430        440        450        460        470        480 
NRRHPASYLV HGGKALNLAF RAWTRKEALP DHEDEIPETV RTVQLIKDLA REIRLVEDIF 

       490        500        510        520        530        540 
QQNVGKTSNI FGLQRIFPAG SIPLTRPAHS TSVSMSRLSL PSKNGSKKKG LKPKELFKKA 

       550        560        570        580        590        600 
ERKGKESSAL GPAGQLSYNL MDTYSHQALK TGSFQKAKFN ITGACLNDSD DDSPDLDLDG 

       610        620        630        640        650        660 
NESPLALLMS NGSTKRVKSL SKSRRTKIAK KVDKARLMAE QVMEDEFDLD SDDELQIDER 

       670        680        690        700        710        720 
LGKEKATLII RPKFPRKLPR AKPCSDPNRV REPGEVEFDI EEDYTTDEDM VEGVEGKLGN 

       730        740        750        760        770        780 
GSGAGGILDL LKASRQVGGP DYAALTEAPA SPSTQEAIQG MLCMANLQSS SSSPATSSLQ 

       790        800        810        820        830        840 
AWWTGGQDRS SGSSSSGLGT VSNSPASQRT PGKRPIKRPA YWRTESEEEE ENASLDEQDS 

       850        860        870        880        890        900 
LGACFKDAEY IYPSLESDDD DPALKSRPKK KKNSDDAPWS PKARVTPTLP KQDRPVREGT 

       910        920        930        940        950        960 
RVASIETGLA AAAAKLAQQE LQKAQKKKYI KKKPLLKEVE QPRPQDSNLS LTVPAPTVAA 

       970        980        990       1000       1010       1020 
TPQLVTSSSP LPPPEPKQEA LSGSLADHEY TARPNAFGMA QANRSTTPMA PGVFLTQRRP 

      1030       1040       1050       1060 
SVGSQSNQAG QGKRPKKGLA TAKQRLGRIL KIHRNGKLLL 

« Hide

Isoform 2 [UniParc].

Checksum: 75773C0918578FB0
Show »

FASTA1,024113,913
Isoform 3 [UniParc].

Checksum: F54BE8A814BF1701
Show »

FASTA959106,902
Isoform 4 [UniParc].

Checksum: F32740CB7A2CE3F6
Show »

FASTA948105,913
Isoform 5 [UniParc].

Checksum: 690CE764C0C28D28
Show »

FASTA87898,290

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-927 (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 515-1060 (ISOFORM 1).
Tissue: Embryo, Teratocarcinoma and Trachea.
[4]"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 2).
Tissue: Endometrial tumor.
[5]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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 2 AND 5).
Tissue: Brain and Cervix.
[7]"Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate."
Laumonnier F., Holbert S., Ronce N., Faravelli F., Lenzner S., Schwartz C.E., Lespinasse J., Van Esch H., Lacombe D., Goizet C., Phan-Dinh Tuy F., van Bokhoven H., Fryns J.-P., Chelly J., Ropers H.-H., Moraine C., Hamel B.C.J., Briault S.
J. Med. Genet. 42:780-786(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRXSSD.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-857, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-705; THR-706; SER-854; SER-857 AND SER-880, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-651; THR-705; THR-706; SER-854 AND SER-857, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis."
Zhu Z., Wang Y., Li X., Wang Y., Xu L., Wang X., Sun T., Dong X., Chen L., Mao H., Yu Y., Li J., Chen P.A., Chen C.D.
Cell Res. 20:794-801(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-283.
[13]"The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation."
Qiu J., Shi G., Jia Y., Li J., Wu M., Li J., Dong S., Wong J.
Cell Res. 20:908-918(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANT MRXSSD SER-315.
[14]"PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an Nepsilon-dimethyl lysine demethylase."
Loenarz C., Ge W., Coleman M.L., Rose N.R., Cooper C.D.O., Klose R.J., Ratcliffe P.J., Schofield C.J.
Hum. Mol. Genet. 19:217-222(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION.
[15]"A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation."
Kleine-Kohlbrecher D., Christensen J., Vandamme J., Abarrategui I., Bak M., Tommerup N., Shi X., Gozani O., Rappsilber J., Salcini A.E., Helin K.
Mol. Cell 38:165-178(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN PHD-FINGER, INTERACTION WITH ZNF711, CHARACTERIZATION OF VARIANT MRXSSD SER-315, MUTAGENESIS OF HIS-283.
[16]"PHF8 targets histone methylation and RNA polymerase II to activate transcription."
Fortschegger K., de Graaf P., Outchkourov N.S., van Schaik F.M., Timmers H.T., Shiekhattar R.
Mol. Cell. Biol. 30:3286-3298(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN PHD-FINGER, CHARACTERIZATION OF VARIANT MRXSSD SER-315.
[17]"PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation."
Feng W., Yonezawa M., Ye J., Jenuwein T., Grummt I.
Nat. Struct. Mol. Biol. 17:445-450(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH POLR1B AND UBTF, CHARACTERIZATION OF VARIANT MRXSSD SER-315, MUTAGENESIS OF TYR-43 AND 283-HIS--ASP-285.
[18]"Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development."
Qi H.H., Sarkissian M., Hu G.Q., Wang Z., Bhattacharjee A., Gordon D.B., Gonzales M., Lan F., Ongusaha P.P., Huarte M., Yaghi N.K., Lim H., Garcia B.A., Brizuela L., Zhao K., Roberts T.M., Shi Y.
Nature 466:503-507(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN PHD-FINGER, CHARACTERIZATION OF VARIANT MRXSSD SER-315, MUTAGENESIS OF TYR-43; TYR-50 AND TRP-65.
[19]"PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression."
Liu W., Tanasa B., Tyurina O.V., Zhou T.Y., Gassmann R., Liu W.T., Ohgi K.A., Benner C., Garcia-Bassets I., Aggarwal A.K., Desai A., Dorrestein P.C., Glass C.K., Rosenfeld M.G.
Nature 466:508-512(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN PHD-FINGER, INTERACTION WITH SETD1A; HCFC1 AND E2F1, CHARACTERIZATION OF VARIANT MRXSSD SER-315, PHOSPHORYLATION AT SER-69 AND SER-120, MUTAGENESIS OF SER-69; SER-120 AND HIS-283.
[20]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-804; SER-857 AND SER-880, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-854; SER-857 AND SER-880, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Structural insights into a novel histone demethylase PHF8."
Yu L., Wang Y., Huang S., Wang J., Deng Z., Zhang Q., Wu W., Zhang X., Liu Z., Gong W., Chen Z.
Cell Res. 20:166-173(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 122-483 IN COMPLEX WITH IRON AND ALPHA-KETOGLUTARATE, FUNCTION, CHARACTERIZATION OF VARIANT MRXSSD SER-315.
[24]"Crystal structure of the PHF8 Jumonji domain, an N(epsilon)-methyl lysine demethylase."
Yue W.W., Hozjan V., Ge W., Loenarz C., Cooper C.D., Schofield C.J., Kavanagh K.L., Oppermann U., McDonough M.A.
FEBS Lett. 584:825-830(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 115-483.
[25]"Enzymatic and structural insights for substrate specificity of a family of jumonji histone lysine demethylases."
Horton J.R., Upadhyay A.K., Qi H.H., Zhang X., Shi Y., Cheng X.
Nat. Struct. Mol. Biol. 17:38-43(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-447 IN COMPLEX WITH IRON AND N-OXALYLGLYCINE, ZINC-BINDING, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, DOMAIN LINKER AND PHD-FINGER.
[26]"Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate."
Koivisto A.M., Ala-Mello S., Lemmelae S., Komu H.A., Rautio J., Jaervelae I.
Clin. Genet. 72:145-149(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MRXSSD SER-315.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB029034 mRNA. Translation: BAA83063.1. Different initiation.
CR933612 mRNA. Translation: CAI45929.1. Sequence problems.
AK021696 mRNA. Translation: BAB13877.1. Different initiation.
AK022788 mRNA. Translation: BAG51116.1.
AK304272 mRNA. Translation: BAH14147.1.
AL589872 Genomic DNA. No translation available.
AL732374 Genomic DNA. No translation available.
Z98051 Genomic DNA. No translation available.
BC042108 mRNA. No translation available.
BC053861 mRNA. Translation: AAH53861.1.
CCDSCCDS14355.1. [Q9UPP1-2]
CCDS55418.1. [Q9UPP1-4]
CCDS55420.1. [Q9UPP1-1]
RefSeqNP_001171825.1. NM_001184896.1. [Q9UPP1-1]
NP_001171826.1. NM_001184897.1. [Q9UPP1-4]
NP_055922.1. NM_015107.2. [Q9UPP1-2]
UniGeneHs.133352.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2WWUX-ray2.15A115-483[»]
3K3NX-ray2.40A122-483[»]
3K3OX-ray2.10A122-483[»]
3KV4X-ray2.19A37-483[»]
4DO0X-ray2.55A115-483[»]
ProteinModelPortalQ9UPP1.
SMRQ9UPP1. Positions 39-483.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116751. 32 interactions.
DIPDIP-38913N.
IntActQ9UPP1. 3 interactions.
MINTMINT-4651164.
STRING9606.ENSP00000338868.

Chemistry

BindingDBQ9UPP1.
ChEMBLCHEMBL1938212.
GuidetoPHARMACOLOGY2698.

PTM databases

PhosphoSiteQ9UPP1.

Polymorphism databases

DMDM73620986.

Proteomic databases

MaxQBQ9UPP1.
PaxDbQ9UPP1.
PRIDEQ9UPP1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338154; ENSP00000338868; ENSG00000172943. [Q9UPP1-2]
ENST00000338946; ENSP00000340051; ENSG00000172943. [Q9UPP1-4]
ENST00000357988; ENSP00000350676; ENSG00000172943. [Q9UPP1-1]
ENST00000595978; ENSP00000469335; ENSG00000268312. [Q9UPP1-2]
ENST00000596621; ENSP00000473074; ENSG00000268312. [Q9UPP1-1]
ENST00000601647; ENSP00000472063; ENSG00000268312. [Q9UPP1-4]
GeneID23133.
KEGGhsa:23133.
UCSCuc004dst.3. human. [Q9UPP1-1]
uc004dsw.3. human. [Q9UPP1-4]

Organism-specific databases

CTD23133.
GeneCardsGC0XM053979.
HGNCHGNC:20672. PHF8.
HPAHPA038779.
MIM300263. phenotype.
300560. gene.
neXtProtNX_Q9UPP1.
Orphanet85287. intellectual disability, X-linked, Siderius type.
PharmGKBPA134889361.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG290496.
HOGENOMHOG000231232.
HOVERGENHBG045631.
InParanoidQ9UPP1.
KOK11445.
OMAEIDLYHC.
PhylomeDBQ9UPP1.
TreeFamTF106480.

Enzyme and pathway databases

ReactomeREACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.

Gene expression databases

ArrayExpressQ9UPP1.
BgeeQ9UPP1.
CleanExHS_PHF8.
GenevestigatorQ9UPP1.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR003347. JmjC_dom.
IPR019786. Zinc_finger_PHD-type_CS.
IPR011011. Znf_FYVE_PHD.
IPR001965. Znf_PHD.
IPR019787. Znf_PHD-finger.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF02373. JmjC. 1 hit.
PF00628. PHD. 1 hit.
[Graphical view]
SMARTSM00558. JmjC. 1 hit.
SM00249. PHD. 1 hit.
[Graphical view]
SUPFAMSSF57903. SSF57903. 1 hit.
PROSITEPS51184. JMJC. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPHF8. human.
EvolutionaryTraceQ9UPP1.
GeneWikiPHF8.
GenomeRNAi23133.
NextBio35468941.
PROQ9UPP1.
SOURCESearch...

Entry information

Entry namePHF8_HUMAN
AccessionPrimary (citable) accession number: Q9UPP1
Secondary accession number(s): B3KMV4 expand/collapse secondary AC list , B7Z911, Q5H9U5, Q5JPR9, Q5JPS0, Q5JPS2, Q5JPS3, Q5VUJ4, Q7Z6D4, Q9HAH2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: August 16, 2005
Last modified: July 9, 2014
This is version 117 of the entry and version 3 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

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