PRDM9_HUMAN
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 03-AUG-2022, entry version 177.
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};
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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 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; Q9NQV7; -.
DR PeptideAtlas; Q9NQV7; -.
DR PRIDE; Q9NQV7; -.
DR ProteomicsDB; 82198; -.
DR Antibodypedia; 22638; 84 antibodies from 24 providers.
DR DNASU; 56979; -.
DR Ensembl; ENST00000296682.4; ENSP00000296682.4; 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 CTD; 56979; -.
DR DisGeNET; 56979; -.
DR GeneCards; PRDM9; -.
DR HGNC; HGNC:13994; PRDM9.
DR HPA; ENSG00000164256; Tissue enhanced (brain, epididymis, testis).
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; RSCNDKT; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q9NQV7; -.
DR TreeFam; TF338096; -.
DR BioCyc; MetaCyc:HS09047-MON; -.
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; 17 hits in 1068 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 right testis and 59 other 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 methyltransferase activity (H3-K36 specific); IMP:UniProtKB.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IMP:UniProtKB.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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:0097676; P:histone H3-K36 dimethylation; IDA:UniProtKB.
DR GO; GO:0097198; P:histone H3-K36 trimethylation; ISS:UniProtKB.
DR GO; GO:0044648; P:histone H3-K4 dimethylation; ISS:UniProtKB.
DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR GO; GO:0097692; P:histone H3-K4 monomethylation; IDA:UniProtKB.
DR GO; GO:0080182; P:histone H3-K4 trimethylation; IDA:UniProtKB.
DR GO; GO:0051567; P:histone H3-K9 methylation; 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:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1905516; P:positive regulation of fertilization; ISS:UniProtKB.
DR GO; GO:2001255; P:positive regulation of histone H3-K36 trimethylation; IDA:UniProtKB.
DR GO; GO:1905437; P:positive regulation of histone H3-K4 trimethylation; ISS:UniProtKB.
DR GO; GO:0010845; P:positive regulation of reciprocal meiotic recombination; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro.
DR CDD; cd07765; KRAB_A-box; 1.
DR CDD; cd19193; PR-SET_PRDM7_9; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR003655; aKRAB.
DR InterPro; IPR001909; KRAB.
DR InterPro; IPR036051; KRAB_dom_sf.
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 Pfam; PF01352; KRAB; 1.
DR Pfam; PF00856; SET; 1.
DR Pfam; PF09514; SSXRD; 1.
DR Pfam; PF00096; zf-C2H2; 9.
DR SMART; SM00349; KRAB; 1.
DR SMART; SM00355; ZnF_C2H2; 14.
DR SUPFAM; SSF109640; SSF109640; 1.
DR SUPFAM; SSF57667; SSF57667; 7.
DR SUPFAM; SSF82199; SSF82199; 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 (variant of uncertain significance; may be a
FT genetic risk for patients with azoospermia caused by
FT meiotic arrest)"
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
