PRD12_HUMAN
ID PRD12_HUMAN Reviewed; 367 AA.
AC Q9H4Q4; A3KFK9;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=PR domain zinc finger protein 12;
DE EC=2.1.1.-;
DE AltName: Full=PR domain-containing protein 12;
GN Name=PRDM12; Synonyms=PFM9;
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].
RA Yang X.-H., Huang S.;
RT "A family of novel PR-domain (PRDM) genes as candidate tumor suppressors.";
RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(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 X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 60-229.
RG Structural genomics consortium (SGC);
RT "The crystal structure of methyltransferase domain of human PR domain-
RT containing protein 12.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, POLYMORPHISM,
RP INVOLVEMENT IN HSAN8, VARIANTS HSAN8 TYR-31; ASN-102; CYS-160; CYS-168;
RP ASP-172; LEU-289 AND POLY-ALA-352 INS, AND CHARACTERIZATION OF VARIANTS
RP HSAN8 TYR-31; ASN-102; CYS-160; CYS-168; ASP-172; LEU-289 AND POLY-ALA-352
RP INS.
RX PubMed=26005867; DOI=10.1038/ng.3308;
RA Chen Y.C., Auer-Grumbach M., Matsukawa S., Zitzelsberger M.,
RA Themistocleous A.C., Strom T.M., Samara C., Moore A.W., Cho L.T.,
RA Young G.T., Weiss C., Schabhuettl M., Stucka R., Schmid A.B., Parman Y.,
RA Graul-Neumann L., Heinritz W., Passarge E., Watson R.M., Hertz J.M.,
RA Moog U., Baumgartner M., Valente E.M., Pereira D., Restrepo C.M.,
RA Katona I., Dusl M., Stendel C., Wieland T., Stafford F., Reimann F.,
RA von Au K., Finke C., Willems P.J., Nahorski M.S., Shaikh S.S.,
RA Carvalho O.P., Nicholas A.K., Karbani G., McAleer M.A., Cilio M.R.,
RA McHugh J.C., Murphy S.M., Irvine A.D., Jensen U.B., Windhager R., Weis J.,
RA Bergmann C., Rautenstrauss B., Baets J., De Jonghe P., Reilly M.M.,
RA Kropatsch R., Kurth I., Chrast R., Michiue T., Bennett D.L., Woods C.G.,
RA Senderek J.;
RT "Transcriptional regulator PRDM12 is essential for human pain perception.";
RL Nat. Genet. 47:803-808(2015).
CC -!- FUNCTION: Involved in the positive regulation of histone H3-K9
CC dimethylation. {ECO:0000269|PubMed:26005867}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26005867}.
CC -!- TISSUE SPECIFICITY: Not found in adult tissues except in dorsal root
CC ganglia. {ECO:0000269|PubMed:26005867}.
CC -!- POLYMORPHISM: The poly-alanine tract is polymorphic in the general
CC population and contains a maximum of 14 alanines.
CC {ECO:0000269|PubMed:26005867}.
CC -!- DISEASE: Neuropathy, hereditary sensory and autonomic, 8 (HSAN8)
CC [MIM:616488]: A form of hereditary sensory and autonomic neuropathy, a
CC genetically and clinically heterogeneous group of disorders
CC characterized by degeneration of dorsal root and autonomic ganglion
CC cells, and by sensory and/or autonomic abnormalities. HSAN8 patients
CC manifest congenital insensitivity to pain resulting in ulceration to
CC the fingers, tongue, lips, and other distal appendages. Some patients
CC may also have decreased sweating and tear production.
CC {ECO:0000269|PubMed:26005867}. Note=The disease is caused by variants
CC 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}.
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DR EMBL; AY004252; AAG13447.2; -; mRNA.
DR EMBL; AL359092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW87940.1; -; Genomic_DNA.
DR CCDS; CCDS6934.1; -.
DR RefSeq; NP_067632.2; NM_021619.2.
DR PDB; 3EP0; X-ray; 2.10 A; A/B=60-229.
DR PDBsum; 3EP0; -.
DR AlphaFoldDB; Q9H4Q4; -.
DR SMR; Q9H4Q4; -.
DR BioGRID; 121878; 8.
DR STRING; 9606.ENSP00000253008; -.
DR iPTMnet; Q9H4Q4; -.
DR PhosphoSitePlus; Q9H4Q4; -.
DR BioMuta; PRDM12; -.
DR DMDM; 25008955; -.
DR EPD; Q9H4Q4; -.
DR MassIVE; Q9H4Q4; -.
DR PaxDb; Q9H4Q4; -.
DR PeptideAtlas; Q9H4Q4; -.
DR PRIDE; Q9H4Q4; -.
DR ProteomicsDB; 80872; -.
DR Antibodypedia; 17995; 135 antibodies from 26 providers.
DR DNASU; 59335; -.
DR Ensembl; ENST00000253008.3; ENSP00000253008.2; ENSG00000130711.5.
DR GeneID; 59335; -.
DR KEGG; hsa:59335; -.
DR MANE-Select; ENST00000253008.3; ENSP00000253008.2; NM_021619.3; NP_067632.2.
DR UCSC; uc004bzt.2; human.
DR CTD; 59335; -.
DR DisGeNET; 59335; -.
DR GeneCards; PRDM12; -.
DR GeneReviews; PRDM12; -.
DR HGNC; HGNC:13997; PRDM12.
DR HPA; ENSG00000130711; Tissue enriched (brain).
DR MalaCards; PRDM12; -.
DR MIM; 616458; gene.
DR MIM; 616488; phenotype.
DR neXtProt; NX_Q9H4Q4; -.
DR OpenTargets; ENSG00000130711; -.
DR Orphanet; 478664; Hereditary sensory and autonomic neuropathy type 8.
DR PharmGKB; PA33710; -.
DR VEuPathDB; HostDB:ENSG00000130711; -.
DR eggNOG; KOG2461; Eukaryota.
DR GeneTree; ENSGT00940000161616; -.
DR HOGENOM; CLU_064013_0_1_1; -.
DR InParanoid; Q9H4Q4; -.
DR OMA; HHANPKT; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q9H4Q4; -.
DR TreeFam; TF332260; -.
DR PathwayCommons; Q9H4Q4; -.
DR BioGRID-ORCS; 59335; 19 hits in 1092 CRISPR screens.
DR ChiTaRS; PRDM12; human.
DR EvolutionaryTrace; Q9H4Q4; -.
DR GenomeRNAi; 59335; -.
DR Pharos; Q9H4Q4; Tbio.
DR PRO; PR:Q9H4Q4; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9H4Q4; protein.
DR Bgee; ENSG00000130711; Expressed in buccal mucosa cell and 29 other tissues.
DR ExpressionAtlas; Q9H4Q4; baseline and differential.
DR Genevisible; Q9H4Q4; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:1990226; F:histone methyltransferase binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:MGI.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:ARUK-UCL.
DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR GO; GO:0031175; P:neuron projection development; IMP:MGI.
DR GO; GO:1900111; P:positive regulation of histone H3-K9 dimethylation; IMP:UniProtKB.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0019233; P:sensory perception of pain; IMP:MGI.
DR CDD; cd19196; PR-SET_PRDM12; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR044406; PRDM12_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 InterPro; IPR017126; Znf_PRDM12.
DR Pfam; PF00096; zf-C2H2; 2.
DR PIRSF; PIRSF037163; PRDM12; 1.
DR SMART; SM00317; SET; 1.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; DNA-binding; Metal-binding;
KW Methyltransferase; Neurodegeneration; Neuropathy; Nucleus;
KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Triplet repeat expansion; Zinc;
KW Zinc-finger.
FT CHAIN 1..367
FT /note="PR domain zinc finger protein 12"
FT /id="PRO_0000047769"
FT DOMAIN 86..203
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT ZN_FING 243..265
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 271..293
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 299..323
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 318..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 31
FT /note="D -> Y (in HSAN8; no effect on nuclear localization;
FT not able to induce histone H3-K9 dimethylation;
FT dbSNP:rs879255637)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074617"
FT VARIANT 102
FT /note="I -> N (in HSAN8; no effect on nuclear localization;
FT not able to induce histone H3-K9 dimethylation;
FT dbSNP:rs879255636)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074618"
FT VARIANT 160
FT /note="W -> C (in HSAN8; no effect on nuclear localization;
FT not able to induce histone H3-K9 dimethylation)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074619"
FT VARIANT 168
FT /note="R -> C (in HSAN8; no effect on nuclear localization;
FT not able to induce histone H3-K9 dimethylation;
FT dbSNP:rs767397937)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074620"
FT VARIANT 172
FT /note="E -> D (in HSAN8; no effect on nuclear localization;
FT not able to induce histone H3-K9 dimethylation;
FT dbSNP:rs755205487)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074621"
FT VARIANT 289
FT /note="H -> L (in HSAN8; no effect on nuclear localization;
FT not able to induce histone H3-K9 dimethylation;
FT dbSNP:rs879255638)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074622"
FT VARIANT 352
FT /note="A -> AAAAAAAA (in HSAN8; reduced protein amount;
FT results in protein aggregation)"
FT /evidence="ECO:0000269|PubMed:26005867"
FT /id="VAR_074623"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 99..106
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 136..140
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 144..151
FT /evidence="ECO:0007829|PDB:3EP0"
FT HELIX 160..163
FT /evidence="ECO:0007829|PDB:3EP0"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 175..180
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 183..190
FT /evidence="ECO:0007829|PDB:3EP0"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:3EP0"
SQ SEQUENCE 367 AA; 40403 MW; F2C665E3AE076C76 CRC64;
MMGSVLPAEA LVLKTGLKAP GLALAEVITS DILHSFLYGR WRNVLGEQLF EDKSHHASPK
TAFTAEVLAQ SFSGEVQKLS SLVLPAEVII AQSSIPGEGL GIFSKTWIKA GTEMGPFTGR
VIAPEHVDIC KNNNLMWEVF NEDGTVRYFI DASQEDHRSW MTYIKCARNE QEQNLEVVQI
GTSIFYKAIE MIPPDQELLV WYGNSHNTFL GIPGVPGLEE DQKKNKHEDF HPADSAAGPA
GRMRCVICHR GFNSRSNLRS HMRIHTLDKP FVCRFCNRRF SQSSTLRNHV RLHTGERPYK
CQVCQSAYSQ LAGLRAHQKS ARHRPPSTAL QAHSPALPAP HAHAPALAAA AAAAAAAAAH
HLPAMVL
