PRDM8_HUMAN
ID PRDM8_HUMAN Reviewed; 689 AA.
AC Q9NQV8; A8K7X2; Q6IQ36;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 04-NOV-2008, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=PR domain zinc finger protein 8;
DE EC=2.1.1.-;
DE AltName: Full=PR domain-containing protein 8;
GN Name=PRDM8; Synonyms=PFM5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Yang X.-H., Huang S.;
RT "A family of novel PR-domain (PRDM) genes as candidate tumor suppressors.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH EPM2A AND
RP NHLRC1, LACK OF HISTONE METHYLTRANSFERASE ACTIVITY, INVOLVEMENT IN EPM10,
RP VARIANT EPM10 LEU-261, AND CHARACTERIZATION OF VARIANT EPM10 LEU-261.
RX PubMed=22961547; DOI=10.1093/brain/aws205;
RA Turnbull J., Girard J.M., Lohi H., Chan E.M., Wang P., Tiberia E., Omer S.,
RA Ahmed M., Bennett C., Chakrabarty A., Tyagi A., Liu Y., Pencea N., Zhao X.,
RA Scherer S.W., Ackerley C.A., Minassian B.A.;
RT "Early-onset Lafora body disease.";
RL Brain 135:2684-2698(2012).
CC -!- FUNCTION: Probable histone methyltransferase, preferentially acting on
CC 'Lys-9' of histone H3 (By similarity). Involved in the control of
CC steroidogenesis through transcriptional repression of steroidogenesis
CC marker genes such as CYP17A1 and LHCGR (By similarity). Forms with
CC BHLHE22 a transcriptional repressor complex controlling genes involved
CC in neural development and neuronal differentiation (By similarity). In
CC the retina, it is required for rod bipolar and type 2 OFF-cone bipolar
CC cell survival (By similarity). {ECO:0000250|UniProtKB:Q8BZ97}.
CC -!- SUBUNIT: Interacts with EPM2A and NHLRC1. This interaction sequesters
CC EPM2A and NHLRC1 to the nucleus (PubMed:22961547). Interacts with
CC BHLHE22 (By similarity). {ECO:0000250|UniProtKB:Q8BZ97,
CC ECO:0000269|PubMed:22961547}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22961547}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NQV8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQV8-2; Sequence=VSP_035602, VSP_035603;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, skeletal muscle, testes,
CC prostate. {ECO:0000269|PubMed:22961547}.
CC -!- DISEASE: Epilepsy, progressive myoclonic 10 (EPM10) [MIM:616640]: A
CC form of progressive myoclonic epilepsy, a clinically and genetically
CC heterogeneous group of disorders defined by the combination of action
CC and reflex myoclonus, other types of epileptic seizures, and
CC progressive neurodegeneration and neurocognitive impairment. EPM10 is
CC an autosomal recessive form characterized by progressive dysarthria,
CC myoclonus, ataxia, cognitive decline, psychosis, dementia and
CC spasticity, with onset in childhood. There is variability between
CC patients. {ECO:0000269|PubMed:22961547}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- CAUTION: In disagreement with experimental results in mouse,
CC PubMed:22961547 reports lack of histone methyltransferase activity on
CC core histones generally, and on histone H3 specifically.
CC {ECO:0000269|PubMed:22961547}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF87241.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF275815; AAF87241.1; ALT_FRAME; mRNA.
DR EMBL; AK292137; BAF84826.1; -; mRNA.
DR EMBL; CH471057; EAX05851.1; -; Genomic_DNA.
DR EMBL; BC071584; AAH71584.1; -; mRNA.
DR CCDS; CCDS43243.1; -. [Q9NQV8-1]
DR RefSeq; NP_001092873.1; NM_001099403.1. [Q9NQV8-1]
DR RefSeq; NP_064611.3; NM_020226.3. [Q9NQV8-1]
DR RefSeq; XP_005263203.1; XM_005263146.4. [Q9NQV8-1]
DR AlphaFoldDB; Q9NQV8; -.
DR BioGRID; 121296; 3.
DR IntAct; Q9NQV8; 1.
DR STRING; 9606.ENSP00000339764; -.
DR iPTMnet; Q9NQV8; -.
DR PhosphoSitePlus; Q9NQV8; -.
DR BioMuta; PRDM8; -.
DR DMDM; 212276495; -.
DR jPOST; Q9NQV8; -.
DR MassIVE; Q9NQV8; -.
DR PaxDb; Q9NQV8; -.
DR PeptideAtlas; Q9NQV8; -.
DR PRIDE; Q9NQV8; -.
DR ProteomicsDB; 82199; -. [Q9NQV8-1]
DR ProteomicsDB; 82200; -. [Q9NQV8-2]
DR Antibodypedia; 24988; 115 antibodies from 18 providers.
DR DNASU; 56978; -.
DR Ensembl; ENST00000339711.8; ENSP00000339764.4; ENSG00000152784.16. [Q9NQV8-1]
DR Ensembl; ENST00000415738.3; ENSP00000406998.2; ENSG00000152784.16. [Q9NQV8-1]
DR Ensembl; ENST00000504452.5; ENSP00000423985.1; ENSG00000152784.16. [Q9NQV8-1]
DR GeneID; 56978; -.
DR KEGG; hsa:56978; -.
DR MANE-Select; ENST00000415738.3; ENSP00000406998.2; NM_001099403.2; NP_001092873.1.
DR UCSC; uc003hmb.5; human. [Q9NQV8-1]
DR CTD; 56978; -.
DR DisGeNET; 56978; -.
DR GeneCards; PRDM8; -.
DR HGNC; HGNC:13993; PRDM8.
DR HPA; ENSG00000152784; Tissue enhanced (prostate, retina, seminal vesicle).
DR MalaCards; PRDM8; -.
DR MIM; 616639; gene.
DR MIM; 616640; phenotype.
DR neXtProt; NX_Q9NQV8; -.
DR OpenTargets; ENSG00000152784; -.
DR Orphanet; 324290; Early-onset Lafora body disease.
DR PharmGKB; PA33720; -.
DR VEuPathDB; HostDB:ENSG00000152784; -.
DR eggNOG; KOG1721; Eukaryota.
DR eggNOG; KOG2461; Eukaryota.
DR GeneTree; ENSGT00890000139463; -.
DR HOGENOM; CLU_034617_1_0_1; -.
DR InParanoid; Q9NQV8; -.
DR OMA; KHHSGNK; -.
DR OrthoDB; 1327331at2759; -.
DR PhylomeDB; Q9NQV8; -.
DR TreeFam; TF327090; -.
DR PathwayCommons; Q9NQV8; -.
DR SignaLink; Q9NQV8; -.
DR BioGRID-ORCS; 56978; 9 hits in 1104 CRISPR screens.
DR ChiTaRS; PRDM8; human.
DR GenomeRNAi; 56978; -.
DR Pharos; Q9NQV8; Tbio.
DR PRO; PR:Q9NQV8; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9NQV8; protein.
DR Bgee; ENSG00000152784; Expressed in cortical plate and 94 other tissues.
DR ExpressionAtlas; Q9NQV8; baseline and differential.
DR Genevisible; Q9NQV8; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0014003; P:oligodendrocyte development; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR CDD; cd19192; PR-SET_PRDM8; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR044402; PRDM8_PR/SET.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 1.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Disease variant; DNA-binding; Epilepsy;
KW Metal-binding; Methyltransferase; Neurodegeneration; Neurogenesis; Nucleus;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..689
FT /note="PR domain zinc finger protein 8"
FT /id="PRO_0000047764"
FT DOMAIN 16..131
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 155..183
FT /note="C2H2-type 1; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 625..648
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 666..688
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 185..333
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 397..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 238..260
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 458..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 332..334
FT /note="GRG -> AAL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_035602"
FT VAR_SEQ 335..689
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_035603"
FT VARIANT 261
FT /note="F -> L (in EPM10; does not affect interaction with
FT EPM2A and NHLRC1; dbSNP:rs863225286)"
FT /evidence="ECO:0000269|PubMed:22961547"
FT /id="VAR_075044"
FT CONFLICT 323
FT /note="G -> A (in Ref. 1; AAF87241)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="Q -> R (in Ref. 4; AAH71584)"
FT /evidence="ECO:0000305"
FT CONFLICT 640
FT /note="L -> M (in Ref. 4; AAH71584)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 689 AA; 71663 MW; 4D8E3EA8B463682A CRC64;
MEDTGIQRGI WDGDAKAVQQ CLTDIFTSVY TTCDIPENAI FGPCVLSHTS LYDSIAFIAL
KSTDKRTVPY IFRVDTSAAN GSSEGLMWLR LVQSARDKEE QNLEAYIKNG QLFYRSLRRI
AKDEELLVWY GKELTELLLL CPSRSHNKMN GSSPYTCLEC SQRFQFEFPY VAHLRFRCPK
RLHSADISPQ DEQGGGVGTK DHGGGGGGGK DQQQQQQEAP LGPGPKFCKA GPLHHYPSPS
PESSNPSAAA GGSSAKPSTD FHNLARELEN SRGGSSCSPA QSLSSGSGSG GGGGHQEAEL
SPDGIATGGG KGKRKFPEEA AEGGGGAGLV GGRGRFVERP LPASKEDLVC TPQQYRASGS
YFGLEENGRL FAPPSPETGE AKRSAFVEVK KAARAASLQE EGTADGAGVA SEDQDAGGGG
GSSTPAAASP VGAEKLLAPR PGGPLPSRLE GGSPARGSAF TSVPQLGSAG STSGGGGTGA
GAAGGAGGGQ GAASDERKSA FSQPARSFSQ LSPLVLGQKL GALEPCHPAD GVGPTRLYPA
AADPLAVKLQ GAADLNGGCG SLPSGGGGLP KQSPFLYATA FWPKSSAAAA AAAAAAAAGP
LQLQLPSALT LLPPSFTSLC LPAQNWCAKC NASFRMTSDL VYHMRSHHKK EYAMEPLVKR
RREEKLKCPI CNESFRERHH LSRHMTSHN
