ID PRDM9_HUMAN Reviewed; 894 AA. AC Q9NQV7; B4DX22; Q27Q50; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 04-NOV-2008, sequence version 2. DT 24-JAN-2024, entry version 185. DE RecName: Full=Histone-lysine N-methyltransferase PRDM9 {ECO:0000305}; DE AltName: Full=PR domain zinc finger protein 9; DE AltName: Full=PR domain-containing protein 9; DE AltName: Full=Protein-lysine N-methyltransferase PRDM9 {ECO:0000250|UniProtKB:Q96EQ9}; DE EC=2.1.1.- {ECO:0000250|UniProtKB:Q96EQ9}; DE AltName: Full=[histone H3]-lysine36 N-trimethyltransferase PRDM9 {ECO:0000305}; DE EC=2.1.1.359 {ECO:0000269|PubMed:24634223}; DE AltName: Full=[histone H3]-lysine4 N-trimethyltransferase PRDM9 {ECO:0000305}; DE EC=2.1.1.354 {ECO:0000269|PubMed:24095733, ECO:0000269|PubMed:24634223, ECO:0000269|PubMed:26833727}; DE AltName: Full=[histone H3]-lysine9 N-trimethyltransferase PRDM9 {ECO:0000250|UniProtKB:Q96EQ9}; DE EC=2.1.1.355 {ECO:0000250|UniProtKB:Q96EQ9}; DE AltName: Full=[histone H4]-N-methyl-L-lysine20 N-methyltransferase PRDM9 {ECO:0000250|UniProtKB:Q96EQ9}; DE EC=2.1.1.362 {ECO:0000250|UniProtKB:Q96EQ9}; DE AltName: Full=[histone H4]-lysine20 N-methyltransferase PRDM9 {ECO:0000250|UniProtKB:Q96EQ9}; DE EC=2.1.1.361 {ECO:0000250|UniProtKB:Q96EQ9}; GN Name=PRDM9 {ECO:0000312|HGNC:HGNC:13994}; Synonyms=PFM6; 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 Ying J., Wong A.H.Y., Li H., Wang Y., Tao Q.; RT "Cloning and characterization of PR domain-containing 9 (PRDM9)."; RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE A). RC TISSUE=Testis; 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] (ALLELE B). RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 205-894 (ALLELE B). RX PubMed=10668202; DOI=10.14670/hh-15.109; RA Jiang G.L., Huang S.; RT "The yin-yang of PR-domain family genes in tumorigenesis."; RL Histol. Histopathol. 15:109-117(2000). RN [5] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY RP REGULATION. RX PubMed=24634223; DOI=10.1074/jbc.m113.523183; RA Eram M.S., Bustos S.P., Lima-Fernandes E., Siarheyeva A., Senisterra G., RA Hajian T., Chau I., Duan S., Wu H., Dombrovski L., Schapira M., RA Arrowsmith C.H., Vedadi M.; RT "Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 RT protein."; RL J. Biol. Chem. 289:12177-12188(2014). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-357. RX PubMed=27129774; DOI=10.1074/jbc.m116.721472; RA Blazer L.L., Lima-Fernandes E., Gibson E., Eram M.S., Loppnau P., RA Arrowsmith C.H., Schapira M., Vedadi M.; RT "PR Domain-containing Protein 7 (PRDM7) Is a Histone 3 Lysine 4 RT Trimethyltransferase."; RL J. Biol. Chem. 291:13509-13519(2016). RN [7] RP VARIANT HIS-335. RX PubMed=18941885; DOI=10.1007/s10815-008-9270-x; RA Miyamoto T., Koh E., Sakugawa N., Sato H., Hayashi H., Namiki M., RA Sengoku K.; RT "Two single nucleotide polymorphisms in PRDM9 (MEISETZ) gene may be a RT genetic risk factor for Japanese patients with azoospermia by meiotic RT arrest."; RL J. Assist. Reprod. Genet. 25:553-557(2008). RN [8] {ECO:0007744|PDB:4IJD} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 195-415 IN COMPLEX WITH ZINC, RP MUTAGENESIS OF ASP-199 AND LYS-374, FUNCTION, CATALYTIC ACTIVITY, AND RP SUBUNIT. RX PubMed=24095733; DOI=10.1016/j.celrep.2013.08.035; RA Wu H., Mathioudakis N., Diagouraga B., Dong A., Dombrovski L., Baudat F., RA Cusack S., de Massy B., Kadlec J.; RT "Molecular basis for the regulation of the H3K4 methyltransferase activity RT of PRDM9."; RL Cell Rep. 5:13-20(2013). RN [9] {ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, ECO:0007744|PDB:5EI9} RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 717-858 (ALLELE B) IN COMPLEX RP WITH ZINC AND DNA, DNA-BINDING, SUBUNIT, CATALYTIC ACTIVITY, REGION, RP FUNCTION, CHARACTERIZATION OF ALLELES L20; L13 AND L9/24, AND POLYMORPHISM. RX PubMed=26833727; DOI=10.1101/gad.274928.115; RA Patel A., Horton J.R., Wilson G.G., Zhang X., Cheng X.; RT "Structural basis for human PRDM9 action at recombination hot spots."; RL Genes Dev. 30:257-265(2016). RN [10] {ECO:0007744|PDB:6NM4} RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 195-385 IN COMPLEX WITH RP INHIBITOR; ZINC AND S-ADENOSYL-L-METHIONINE, AND SUBUNIT. RA Ivanochko D., Halabelian L., Fischer C., Sanders J.M., Kattar S.D., RA Brown P.J., Edwards A.M., Bountra C., Arrowsmith C.H.; RT "Crystal structure of SAM-bound PRDM9 in complex with MRK-740 inhibitor."; RL Submitted (JAN-2019) to the PDB data bank. CC -!- FUNCTION: Histone methyltransferase that sequentially mono-, di-, and CC tri-methylates both 'Lys-4' (H3K4) and 'Lys-36' (H3K36) of histone H3 CC to produce respectively trimethylated 'Lys-4' (H3K4me3) and CC trimethylated 'Lys-36' (H3K36me3) histone H3 and plays a key role in CC meiotic prophase by determining hotspot localization thereby promoting CC meiotic recombination (PubMed:24634223, PubMed:24095733, CC PubMed:26833727, PubMed:27129774). Can also methylate all four core CC histones with H3 being the best substrate and the most highly modified CC (PubMed:24095733, PubMed:24634223, PubMed:26833727). Is also able, on CC one hand, to mono and di-methylate H4K20 and on other hand to CC trimethylate H3K9 with the di-methylated H3K9 as the best substrate (By CC similarity). During meiotic prophase, binds specific DNA sequences CC through its zinc finger domains thereby determining hotspot CC localization where it promotes local H3K4me3 and H3K36me3 enrichment on CC the same nucleosomes through its histone methyltransferase activity CC (PubMed:26833727). Thereby promotes double-stranded breaks (DSB) CC formation, at this subset of PRDM9-binding sites, that initiates CC meiotic recombination for the proper meiotic progression (By CC similarity). During meiotic progression hotspot-bound PRDM9 interacts CC with several complexes; in early leptonema binds CDYL and EHMT2 CC followed by EWSR1 and CXXC1 by the end of leptonema. EWSR1 joins PRDM9 CC with the chromosomal axis through REC8 (By similarity). In this way, CC controls the DSB repair pathway, pairing of homologous chromosomes and CC sex body formation (By similarity). Moreover plays a central role in CC the transcriptional activation of genes during early meiotic prophase CC thanks to H3K4me3 and H3K36me3 enrichment that represents a specific CC tag for epigenetic transcriptional activation (By similarity). In CC addition performs automethylation (By similarity). Acetylation and CC phosphorylation of histone H3 attenuate or prevent histone H3 CC methylation (By similarity). {ECO:0000250|UniProtKB:Q96EQ9, CC ECO:0000269|PubMed:24095733, ECO:0000269|PubMed:24634223, CC ECO:0000269|PubMed:26833727}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) + N(6)- CC methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:51736, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13053, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51737; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-methionine = H(+) CC + N(6),N(6)-dimethyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:54196, Rhea:RHEA-COMP:13053, Rhea:RHEA-COMP:13827, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54197; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + CC N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:60260, Rhea:RHEA-COMP:15537, Rhea:RHEA- CC COMP:15547, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.354; CC Evidence={ECO:0000269|PubMed:24095733, ECO:0000269|PubMed:24634223, CC ECO:0000269|PubMed:26833727, ECO:0000269|PubMed:27129774}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60261; CC Evidence={ECO:0000269|PubMed:24634223, ECO:0000269|PubMed:27129774}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(36)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) CC + N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 3 S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:60324, Rhea:RHEA-COMP:9785, Rhea:RHEA- CC COMP:15536, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.359; CC Evidence={ECO:0000269|PubMed:24634223, ECO:0000269|PubMed:27129774}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60325; CC Evidence={ECO:0000269|PubMed:24634223, ECO:0000269|PubMed:27129774}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + CC N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:60276, Rhea:RHEA-COMP:15538, Rhea:RHEA- CC COMP:15546, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.355; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60277; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) + CC N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine; CC Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60345; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L- CC homocysteine; Xref=Rhea:RHEA:60348, Rhea:RHEA-COMP:15555, Rhea:RHEA- CC COMP:15556, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; EC=2.1.1.362; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60349; CC Evidence={ECO:0000250|UniProtKB:Q96EQ9}; CC -!- ACTIVITY REGULATION: Inhibited by suramin with an IC(50) of 4.1 uM. CC {ECO:0000269|PubMed:24634223}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1 uM for H3K4me0 {ECO:0000269|PubMed:24634223}; CC KM=1 uM for H3K4me1 {ECO:0000269|PubMed:24634223}; CC KM=3 uM for H3K4me2 {ECO:0000269|PubMed:24634223}; CC KM=1.5 uM for H3K36me0 {ECO:0000269|PubMed:24634223}; CC KM=2.4 uM for H3K36me1 {ECO:0000269|PubMed:24634223}; CC KM=2.5 uM for H3K36me2 {ECO:0000269|PubMed:24634223}; CC KM=0.7 uM for native H3-H4 tetramer {ECO:0000269|PubMed:24634223}; CC KM=120 uM for S-adenosyl-L-methionine (with H3K4me0 as substrate) CC {ECO:0000269|PubMed:24634223}; CC KM=170 uM for S-adenosyl-L-methionine (with H3K4me1 as substrate) CC {ECO:0000269|PubMed:24634223}; CC KM=140 uM for S-adenosyl-L-methionine (with H3K4me2 as substrate) CC {ECO:0000269|PubMed:24634223}; CC KM=87 uM for S-adenosyl-L-methionine (with H3K36me0 as substrate) CC {ECO:0000269|PubMed:24634223}; CC KM=130 uM for S-adenosyl-L-methionine (with H3K36me1 as substrate) CC {ECO:0000269|PubMed:24634223}; CC KM=62 uM for S-adenosyl-L-methionine (with H3K36me2 as substrate) CC {ECO:0000269|PubMed:24634223}; CC KM=240 uM for S-adenosyl-L-methionine (with native H3-H4 tetramer as CC substrate) {ECO:0000269|PubMed:24634223}; CC Note=All kinetic experiments are done with 10 mm Tris-HCl, 0.01% CC Triton X-100, and 10 mm DTT and at pH 8.5. CC {ECO:0000269|PubMed:24634223}; CC pH dependence: CC Optimum pH is 8.5. {ECO:0000269|PubMed:24634223}; CC -!- SUBUNIT: Homodimer (PubMed:26833727, PubMed:24095733, Ref.10). CC Interacts with EHMT2 and CDYL; interaction only takes place when PRDM9 CC is bound to hotspot DNA. Interacts with CXXC1; this interaction does CC not link PRDM9-activated recombination hotspot sites with DSB machinery CC and is not required for the hotspot recognition pathway. Forms a CC complex with EWSR1, REC8, SYCP3 and SYCP1; complex formation is CC dependent of phosphorylated form of REC8 and requires PRDM9 bound to CC hotspot DNA; EWSR1 joins PRDM9 with the chromosomal axis through REC8 CC (By similarity). {ECO:0000250|UniProtKB:Q96EQ9, CC ECO:0000269|PubMed:24095733, ECO:0000269|PubMed:26833727, CC ECO:0000269|Ref.10}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96EQ9}. CC Chromosome {ECO:0000250|UniProtKB:Q96EQ9}. Note=Localizes in nuclei of CC pre-leptotene, leptotene, and early to mid-zygotene spermatocytes. CC {ECO:0000250|UniProtKB:Q96EQ9}. CC -!- DOMAIN: The C2H2-type zinc fingers determine the hotspot localization CC through its binding to specific DNA sequences. Variations in their CC sequence affect affinity towards DNA-binding motif. CC {ECO:0000250|UniProtKB:Q96EQ9}. CC -!- PTM: Mono-methylated; automethylated. Tri-methylated; automethylated. CC Mono-methylation is predominant; automethylation is lower and slower CC than H3 peptide methylation and is in a highest S-adenosyl-L-methionine CC concentration-dependent. There are two major sites for automethylation CC at Lys-368 and Lys-374. Lysines can be simultaneously methylated, such CC as Lys-368(me3)/Lys-372(me1), Lys-368(me1)/Lys-374(me1) and Lys- CC 368(me1)/Lys-372(me1)/Lys-374(me1). Automethylation is an CC intramolecular (cis) process. {ECO:0000250|UniProtKB:Q96EQ9}. CC -!- POLYMORPHISM: Several alleles exist depending on both the number of CC zinc finger C2H2 type domains and their identity (PubMed:26833727). CC Each allele binds to a specific hotspot set (PubMed:26833727). CC Variations in the zinc finger C2H2 type domains are associated with CC significant differences in affinity towards DNA-binding motif CC (PubMed:26833727). The sequence shown is that of allele B. CC {ECO:0000269|PubMed:26833727}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF87242.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; DQ388610; ABD47939.1; -; mRNA. DR EMBL; AK301776; BAG63234.1; -; mRNA. DR EMBL; AC025451; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF275816; AAF87242.1; ALT_INIT; mRNA. DR CCDS; CCDS43307.1; -. DR RefSeq; NP_001297143.1; NM_001310214.1. DR RefSeq; NP_064612.2; NM_020227.3. DR PDB; 4IJD; X-ray; 2.15 A; A/B=195-415. DR PDB; 5EGB; X-ray; 1.98 A; A=717-858. DR PDB; 5EH2; X-ray; 2.05 A; E/F=717-858. DR PDB; 5EI9; X-ray; 1.92 A; E/F=717-858. DR PDB; 6NM4; X-ray; 2.58 A; A/B=195-385. DR PDBsum; 4IJD; -. DR PDBsum; 5EGB; -. DR PDBsum; 5EH2; -. DR PDBsum; 5EI9; -. DR PDBsum; 6NM4; -. DR AlphaFoldDB; Q9NQV7; -. DR SMR; Q9NQV7; -. DR BioGRID; 121297; 7. DR IntAct; Q9NQV7; 6. DR MINT; Q9NQV7; -. DR STRING; 9606.ENSP00000296682; -. DR BindingDB; Q9NQV7; -. DR ChEMBL; CHEMBL3588737; -. DR GlyGen; Q9NQV7; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NQV7; -. DR PhosphoSitePlus; Q9NQV7; -. DR BioMuta; PRDM9; -. DR DMDM; 212276459; -. DR MassIVE; Q9NQV7; -. DR PaxDb; 9606-ENSP00000296682; -. DR PeptideAtlas; Q9NQV7; -. DR ProteomicsDB; 82198; -. DR Antibodypedia; 22638; 95 antibodies from 24 providers. DR DNASU; 56979; -. DR Ensembl; ENST00000296682.4; ENSP00000296682.4; ENSG00000164256.11. DR Ensembl; ENST00000502755.6; ENSP00000425471.2; ENSG00000164256.11. DR GeneID; 56979; -. DR KEGG; hsa:56979; -. DR MANE-Select; ENST00000296682.4; ENSP00000296682.4; NM_020227.4; NP_064612.2. DR UCSC; uc003jgo.3; human. DR AGR; HGNC:13994; -. DR CTD; 56979; -. DR DisGeNET; 56979; -. DR GeneCards; PRDM9; -. DR HGNC; HGNC:13994; PRDM9. DR HPA; ENSG00000164256; Group enriched (epididymis, testis). DR MalaCards; PRDM9; -. DR MIM; 609760; gene. DR neXtProt; NX_Q9NQV7; -. DR OpenTargets; ENSG00000164256; -. DR PharmGKB; PA33721; -. DR VEuPathDB; HostDB:ENSG00000164256; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; KOG2461; Eukaryota. DR GeneTree; ENSGT00940000163405; -. DR HOGENOM; CLU_002678_32_0_1; -. DR InParanoid; Q9NQV7; -. DR OMA; KRTWQRE; -. DR OrthoDB; 3470369at2759; -. DR PhylomeDB; Q9NQV7; -. DR TreeFam; TF338096; -. DR BioCyc; MetaCyc:HS09047-MONOMER; -. DR BRENDA; 2.1.1.359; 2681. DR PathwayCommons; Q9NQV7; -. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-912446; Meiotic recombination. DR SignaLink; Q9NQV7; -. DR BioGRID-ORCS; 56979; 18 hits in 1146 CRISPR screens. DR GeneWiki; PRDM9; -. DR GenomeRNAi; 56979; -. DR Pharos; Q9NQV7; Tbio. DR PRO; PR:Q9NQV7; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q9NQV7; Protein. DR Bgee; ENSG00000164256; Expressed in male germ line stem cell (sensu Vertebrata) in testis and 61 other cell types or tissues. DR ExpressionAtlas; Q9NQV7; baseline and differential. DR Genevisible; Q9NQV7; HS. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; IMP:UniProtKB. DR GO; GO:0140955; F:histone H3K36 trimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0042800; F:histone H3K4 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0140999; F:histone H3K4 trimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0140949; F:histone H3K9 trimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0140944; F:histone H4K20 monomethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0140941; F:histone H4K20me methyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0010844; F:recombination hotspot binding; IDA:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:UniProtKB. DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; ISS:UniProtKB. DR GO; GO:0007292; P:female gamete generation; ISS:UniProtKB. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; ISS:UniProtKB. DR GO; GO:0048232; P:male gamete generation; ISS:UniProtKB. DR GO; GO:0006311; P:meiotic gene conversion; IDA:MGI. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:1905516; P:positive regulation of fertilization; ISS:UniProtKB. DR GO; GO:0010845; P:positive regulation of reciprocal meiotic recombination; IMP:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IEA:InterPro. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR CDD; cd07765; KRAB_A-box; 1. DR CDD; cd19193; PR-SET_PRDM7_9; 1. DR Gene3D; 6.10.140.140; -; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 14. DR Gene3D; 2.170.270.10; SET domain; 1. DR InterPro; IPR003655; aKRAB. DR InterPro; IPR001909; KRAB. DR InterPro; IPR036051; KRAB_dom_sf. DR InterPro; IPR048414; PDRM9-like_Znf-C2H2. DR InterPro; IPR044417; PRDM7_9_PR-SET. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR019041; SSXRD_motif. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR16515:SF10; HISTONE-LYSINE N-METHYLTRANSFERASE PRDM9; 1. DR PANTHER; PTHR16515; PR DOMAIN ZINC FINGER PROTEIN; 1. DR Pfam; PF01352; KRAB; 1. DR Pfam; PF21549; PRDM2_PR; 1. DR Pfam; PF09514; SSXRD; 1. DR Pfam; PF00096; zf-C2H2; 12. DR Pfam; PF21225; zf-C2H2_5; 1. DR SMART; SM00349; KRAB; 1. DR SMART; SM00355; ZnF_C2H2; 14. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 7. DR SUPFAM; SSF109640; KRAB domain (Kruppel-associated box); 1. DR SUPFAM; SSF82199; SET domain; 1. DR PROSITE; PS50806; KRAB_RELATED; 1. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 13. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 14. PE 1: Evidence at protein level; KW 3D-structure; Activator; Chromatin regulator; Chromosome; DNA-binding; KW Meiosis; Metal-binding; Methylation; Methyltransferase; Nucleus; KW Reference proteome; Repeat; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase; Zinc; Zinc-finger. FT CHAIN 1..894 FT /note="Histone-lysine N-methyltransferase PRDM9" FT /id="PRO_0000047766" FT DOMAIN 23..86 FT /note="KRAB-related" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00120" FT DOMAIN 244..358 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT ZN_FING 388..411 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 524..546 FT /note="C2H2-type 2; degenerate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 552..574 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 580..602 FT /note="C2H2-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 608..630 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 636..658 FT /note="C2H2-type 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 664..686 FT /note="C2H2-type 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 692..714 FT /note="C2H2-type 8" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 720..742 FT /note="C2H2-type 9" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 748..770 FT /note="C2H2-type 10" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 776..798 FT /note="C2H2-type 11" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 804..826 FT /note="C2H2-type 12" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 832..854 FT /note="C2H2-type 13" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 860..882 FT /note="C2H2-type 14" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 143..174 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 408..469 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 730..820 FT /note="DNA-binding" FT /evidence="ECO:0000269|PubMed:26833727" FT COMPBIAS 143..165 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 443..468 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 205 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24095733, ECO:0000269|Ref.10, FT ECO:0007744|PDB:4IJD, ECO:0007744|PDB:6NM4" FT BINDING 208 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24095733, ECO:0000269|Ref.10, FT ECO:0007744|PDB:4IJD, ECO:0007744|PDB:6NM4" FT BINDING 216 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24095733, ECO:0000269|Ref.10, FT ECO:0007744|PDB:4IJD, ECO:0007744|PDB:6NM4" FT BINDING 219 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:24095733, ECO:0000269|Ref.10, FT ECO:0007744|PDB:4IJD, ECO:0007744|PDB:6NM4" FT BINDING 256..258 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.10" FT BINDING 288..294 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96EQ9" FT BINDING 291 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.10" FT BINDING 320..321 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000269|Ref.10" FT BINDING 357 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q96EQ9" FT BINDING 390 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24095733, FT ECO:0007744|PDB:4IJD" FT BINDING 393 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24095733, FT ECO:0007744|PDB:4IJD" FT BINDING 406 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24095733, FT ECO:0007744|PDB:4IJD" FT BINDING 411 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000269|PubMed:24095733, FT ECO:0007744|PDB:4IJD" FT BINDING 722 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 725 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 738 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 742 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 750 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 753 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 766 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 770 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 778 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 781 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 794 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 798 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="5" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 806 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 809 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 822 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT BINDING 826 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="6" FT /evidence="ECO:0000269|PubMed:26833727, FT ECO:0007744|PDB:5EGB, ECO:0007744|PDB:5EH2, FT ECO:0007744|PDB:5EI9" FT MOD_RES 368 FT /note="N6,N6,N6-trimethyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q96EQ9" FT MOD_RES 368 FT /note="N6-methyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q96EQ9" FT MOD_RES 372 FT /note="N6-methyllysine" FT /evidence="ECO:0000250|UniProtKB:Q96EQ9" FT MOD_RES 374 FT /note="N6-methyllysine" FT /evidence="ECO:0000250|UniProtKB:Q96EQ9" FT VARIANT 335 FT /note="Y -> H (found in patients with azoospermia caused by FT meiotic arrest; uncertain significance)" FT /evidence="ECO:0000269|PubMed:18941885" FT /id="VAR_054417" FT VARIANT 681 FT /note="T -> S (in allele A; dbSNP:rs6875787)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_082281" FT VARIANT 788 FT /note="K -> E (in allele L9/24; significantly reduces FT affinity for the DNA-binding motif 5'-GCCTCCCTAGCCACG-3'; FT dbSNP:rs146505774)" FT /evidence="ECO:0000269|PubMed:26833727" FT /id="VAR_082282" FT VARIANT 790 FT /note="N -> H (in allele L20; reduces affinity for the DNA- FT binding motif 5?-GCCTCCCTAGCCACG-3'; dbSNP:rs77287813)" FT /evidence="ECO:0000269|PubMed:26833727" FT /id="VAR_082283" FT VARIANT 814 FT /note="S -> R (in allele L13; Increases affinity for the FT DNA-binding motif 5'-GCCTCCCTAGCCACG-3'; dbSNP:rs1445421439 FT and dbSNP:rs61051796)" FT /evidence="ECO:0000269|PubMed:26833727" FT /id="VAR_082284" FT MUTAGEN 199 FT /note="D->Y: Increases histone-lysine N-methyltransferase FT activity; when associated with D-374." FT /evidence="ECO:0000269|PubMed:24095733" FT MUTAGEN 357 FT /note="Y->S: Loss of histone-lysine N-methyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27129774" FT MUTAGEN 374 FT /note="K->D: Increases histone-lysine N-methyltransferase FT activity; when associated with Y-199." FT /evidence="ECO:0000269|PubMed:24095733" FT CONFLICT 295 FT /note="I -> VRRACHF (in Ref. 4; AAF87242)" FT /evidence="ECO:0000305" FT CONFLICT 377..381 FT /note="Missing (in Ref. 4; AAF87242)" FT /evidence="ECO:0000305" FT HELIX 199..201 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 203..205 FT /evidence="ECO:0007829|PDB:4IJD" FT TURN 206..209 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 210..216 FT /evidence="ECO:0007829|PDB:4IJD" FT TURN 217..219 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:6NM4" FT HELIX 237..240 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 246..250 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 258..262 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:6NM4" FT STRAND 278..281 FT /evidence="ECO:0007829|PDB:4IJD" FT HELIX 284..286 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 289..298 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 301..306 FT /evidence="ECO:0007829|PDB:4IJD" FT TURN 310..312 FT /evidence="ECO:0007829|PDB:4IJD" FT HELIX 315..318 FT /evidence="ECO:0007829|PDB:4IJD" FT TURN 325..327 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 338..345 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 354..356 FT /evidence="ECO:0007829|PDB:4IJD" FT HELIX 362..367 FT /evidence="ECO:0007829|PDB:4IJD" FT TURN 368..370 FT /evidence="ECO:0007829|PDB:4IJD" FT HELIX 373..377 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 391..394 FT /evidence="ECO:0007829|PDB:4IJD" FT STRAND 396..399 FT /evidence="ECO:0007829|PDB:4IJD" FT HELIX 400..410 FT /evidence="ECO:0007829|PDB:4IJD" FT TURN 723..725 FT /evidence="ECO:0007829|PDB:5EI9" FT STRAND 728..731 FT /evidence="ECO:0007829|PDB:5EI9" FT HELIX 732..743 FT /evidence="ECO:0007829|PDB:5EI9" FT TURN 751..753 FT /evidence="ECO:0007829|PDB:5EI9" FT STRAND 756..759 FT /evidence="ECO:0007829|PDB:5EI9" FT HELIX 760..765 FT /evidence="ECO:0007829|PDB:5EI9" FT HELIX 768..771 FT /evidence="ECO:0007829|PDB:5EI9" FT TURN 779..781 FT /evidence="ECO:0007829|PDB:5EI9" FT STRAND 784..787 FT /evidence="ECO:0007829|PDB:5EI9" FT HELIX 788..799 FT /evidence="ECO:0007829|PDB:5EI9" FT TURN 807..809 FT /evidence="ECO:0007829|PDB:5EI9" FT STRAND 812..815 FT /evidence="ECO:0007829|PDB:5EI9" FT HELIX 816..823 FT /evidence="ECO:0007829|PDB:5EI9" FT TURN 824..826 FT /evidence="ECO:0007829|PDB:5EI9" SQ SEQUENCE 894 AA; 103376 MW; DE53094C32EFF83B CRC64; MSPEKSQEES PEEDTERTER KPMVKDAFKD ISIYFTKEEW AEMGDWEKTR YRNVKRNYNA LITIGLRATR PAFMCHRRQA IKLQVDDTED SDEEWTPRQQ VKPPWMALRV EQRKHQKGMP KASFSNESSL KELSRTANLL NASGSEQAQK PVSPSGEAST SGQHSRLKLE LRKKETERKM YSLRERKGHA YKEVSEPQDD DYLYCEMCQN FFIDSCAAHG PPTFVKDSAV DKGHPNRSAL SLPPGLRIGP SGIPQAGLGV WNEASDLPLG LHFGPYEGRI TEDEEAANNG YSWLITKGRN CYEYVDGKDK SWANWMRYVN CARDDEEQNL VAFQYHRQIF YRTCRVIRPG CELLVWYGDE YGQELGIKWG SKWKKELMAG REPKPEIHPC PSCCLAFSSQ KFLSQHVERN HSSQNFPGPS ARKLLQPENP CPGDQNQEQQ YPDPHSRNDK TKGQEIKERS KLLNKRTWQR EISRAFSSPP KGQMGSCRVG KRIMEEESRT GQKVNPGNTG KLFVGVGISR IAKVKYGECG QGFSVKSDVI THQRTHTGEK LYVCRECGRG FSWKSHLLIH QRIHTGEKPY VCRECGRGFS WQSVLLTHQR THTGEKPYVC RECGRGFSRQ SVLLTHQRRH TGEKPYVCRE CGRGFSRQSV LLTHQRRHTG EKPYVCRECG RGFSWQSVLL THQRTHTGEK PYVCRECGRG FSWQSVLLTH QRTHTGEKPY VCRECGRGFS NKSHLLRHQR THTGEKPYVC RECGRGFRDK SHLLRHQRTH TGEKPYVCRE CGRGFRDKSN LLSHQRTHTG EKPYVCRECG RGFSNKSHLL RHQRTHTGEK PYVCRECGRG FRNKSHLLRH QRTHTGEKPY VCRECGRGFS DRSSLCYHQR THTGEKPYVC REDE //