PRDM9
Histone-lysine N-methyltransferase PRDM9
Also known as: KMT8B, Meisetz, MSBP3, PFM6, PRDM9_HUMAN, ZNF899
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q9NQV7
- Gene
- PRDM9
- Ensembl
- ENSG00000164256
- Chromosome
- 5
- Canonical length
- 894 aa
- Protein class
- Enzymes, Predicted intracellular proteins, Transcription factors
- Quaternary structure
- Homodimer
OverviewNCBI Gene
The protein encoded by this gene is a zinc finger protein with histone methyltransferase activity that catalyzes histone H3 lysine 4 trimethylation (H3K4me3) during meiotic prophase. This protein contains multiple domains, including a Kruppel-associated box (KRAB) domain, an SSX repression domain (SSXRD), a PRD1-BF1 and RIZ homologous region, a subclass of SET (PR/SET) domain, and a tandem array of C2H2 zinc fingers. The zinc finger array recognizes a short sequence motif, leading to local H3K4me3, and meiotic recombination hotspot activity. The observed allelic variation alters the DNA-binding sequence specificity of the protein, resulting in distinct meiotic recombination hotspots amongst individuals and populations. Multiple alternate alleles of this gene have been described. [provided by RefSeq, Jul 2015]
Canonical amino-acid sequenceUniProt
894 residues, UniProt reviewed canonical sequence.
>Q9NQV7|PRDM9
1 MSPEKSQEES PEEDTERTER KPMVKDAFKD ISIYFTKEEW AEMGDWEKTR YRNVKRNYNA
61 LITIGLRATR PAFMCHRRQA IKLQVDDTED SDEEWTPRQQ VKPPWMALRV EQRKHQKGMP
121 KASFSNESSL KELSRTANLL NASGSEQAQK PVSPSGEAST SGQHSRLKLE LRKKETERKM
181 YSLRERKGHA YKEVSEPQDD DYLYCEMCQN FFIDSCAAHG PPTFVKDSAV DKGHPNRSAL
241 SLPPGLRIGP SGIPQAGLGV WNEASDLPLG LHFGPYEGRI TEDEEAANNG YSWLITKGRN
301 CYEYVDGKDK SWANWMRYVN CARDDEEQNL VAFQYHRQIF YRTCRVIRPG CELLVWYGDE
361 YGQELGIKWG SKWKKELMAG REPKPEIHPC PSCCLAFSSQ KFLSQHVERN HSSQNFPGPS
421 ARKLLQPENP CPGDQNQEQQ YPDPHSRNDK TKGQEIKERS KLLNKRTWQR EISRAFSSPP
481 KGQMGSCRVG KRIMEEESRT GQKVNPGNTG KLFVGVGISR IAKVKYGECG QGFSVKSDVI
541 THQRTHTGEK LYVCRECGRG FSWKSHLLIH QRIHTGEKPY VCRECGRGFS WQSVLLTHQR
601 THTGEKPYVC RECGRGFSRQ SVLLTHQRRH TGEKPYVCRE CGRGFSRQSV LLTHQRRHTG
661 EKPYVCRECG RGFSWQSVLL THQRTHTGEK PYVCRECGRG FSWQSVLLTH QRTHTGEKPY
721 VCRECGRGFS NKSHLLRHQR THTGEKPYVC RECGRGFRDK SHLLRHQRTH TGEKPYVCRE
781 CGRGFRDKSN LLSHQRTHTG EKPYVCRECG RGFSNKSHLL RHQRTHTGEK PYVCRECGRG
841 FRNKSHLLRH QRTHTGEKPY VCRECGRGFS DRSSLCYHQR THTGEKPYVC REDELocalizationUniProt · AlphaFold · HPA
Whether an antibody against PRDM9 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.45
- Highest tissue expression
- 4.1 nTPM
Expression across tissuesHPA
Tissue
- testis: 4.1 nTPM
- epididymis: 1.5 nTPM
- skin: 0.2 nTPM
- bone marrow: 0.1 nTPM
- adipose tissue: 0 nTPM
- adrenal gland: 0 nTPM
Single-cell type
- early primary spermatocytes: 73 nCPM
- epididymal principal cells: 15 nCPM
- late primary spermatocytes: 3.5 nCPM
- late spermatids: 3.2 nCPM
- early spermatids: 2.7 nCPM
- undifferentiated spermatogonia: 2.4 nCPM
Immune cell
- neutrophil: 1.1 nTPM
- basophil: 0.7 nTPM
- NK-cell: 0.5 nTPM
- classical monocyte: 0.2 nTPM
- naive B-cell: 0.2 nTPM
- gdT-cell: 0.1 nTPM
Brain region
- white matter: 2.6 nTPM
- choroid plexus: 2.2 nTPM
- medulla oblongata: 2 nTPM
- pons: 1.9 nTPM
- basal ganglia: 1.8 nTPM
- hypothalamus: 1.8 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about PRDM9.
Disease | GeneticClinVar
3 pathogenic / likely-pathogenic of 176 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.32
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.75
- DepMap mean gene effect
- 0.17
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- double-strand break repair involved in meiotic recombination
- female gamete generation
- homologous chromosome pairing at meiosis
- male gamete generation
- meiotic gene conversion
- methylation
- negative regulation of apoptotic process
- positive regulation of fertilization
- positive regulation of reciprocal meiotic recombination
- regulation of DNA-templated transcription
- regulation of gene expression
Molecular functions
- histone H3K36 methyltransferase activity
- histone H3K36 trimethyltransferase activity
- histone H3K4 methyltransferase activity
- histone H3K4 trimethyltransferase activity
- histone H3K9 trimethyltransferase activity
- histone H4K20 monomethyltransferase activity
- histone H4K20me methyltransferase activity
- protein homodimerization activity
- transcription cis-regulatory region binding
- zinc ion binding
- recombination hotspot binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- SET domain
- Krueppel-associated box
- Ancestral KRAB domain
- Zinc finger C2H2-type
- SSXRD motif
- Krueppel-associated box domain superfamily
- Zinc finger C2H2 superfamily
- PRDM7/PRDM9, PR/SET domain
- SET domain superfamily
- Histone-lysine N-methyltransferase PRDM9-like, C2H2 zinc finger-like
- Zinc finger, C2H2 type
- KRAB box
- SSXRD motif
- C2H2-type zinc finger
- PR domain zinc finger protein 2, PR domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of PRDM9 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PRDM9 as an antibody target. Whether an autoantibody or antibody against PRDM9 could matter depends on whether native PRDM9 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PRDM9 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label PRDM9 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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