PWWP domain found in glyoxylate reductase 1 (GLYR1) and similar proteins; GLYR1, also called 3-hydroxyisobutyrate dehydrogenase-like protein, cytokine-like nuclear factor N-PAC, nuclear protein NP60, or nuclear protein of 60 kDa, is a putative oxidoreductase that is recruited on chromatin and promotes KDM1B demethylase activity. It recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3). GLYR1 enhances the activity of MAP2K4 and MAP2K6 kinases to phosphorylate p38-alpha. In addition to the PWWP domain, GLYR1 also contains an AT-hook and a C-terminal NAD-binding domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   6 LRLGDLVWGKLGRYPPWPGKIVNPPKDLKKPRGKK-CFFVKFFGTEDHAWIKVEQLKPYHAHKEEMIKINKGKRFQQAVD 84
Cdd:cd05836     1 FKIGDLVWAKMKGFPPWPGKIVNPPPDLKKPPRKKkMHCVYFFGSENYAWIEDENIKPYEEFKEEMLKSKKSAGFKDAVE 80

                  ....*.
gi 1635577269  85 AVEEFL 90
Cdd:cd05836    81 AIEEYI 86

tartronate semialdehyde reductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 187 KKIGFLGLGLMGSGIVSNLLKMGHTVTVWNRTAE------KEGARLGRTPAEVVSTCDITFACVSDPKAAKDLVLGPSGV 260
Cdd:PRK11559    3 MKVGFIGLGIMGKPMSKNLLKAGYSLVVYDRNPEavaeviAAGAETASTAKAVAEQCDVIITMLPNSPHVKEVALGENGI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 261 LQGIRPGKCYVDMSTVDADTVTELAQVIVSRGGRFLEAPVSGNQQLSNDGMLVILAAGDRGLYEDCSSCFQAMGKTSFFL 340
Cdd:PRK11559   83 IEGAKPGTVVIDMSSIAPLASREIAAALKAKGIEMLDAPVSGGEPKAIDGTLSVMVGGDKAIFDKYYDLMKAMAGSVVHT 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 341 GEV--GNAAKM--MLIVNMVqgsfMATIAEGLTLAQVTGQSQQTLLDILNQGQLASIFLDQKCQNILQGNFKPDFYLKYI 416
Cdd:PRK11559  163 GDIgaGNVTKLanQVIVALN----IAAMSEALVLATKAGVNPDLVYQAIRGGLAGSTVLDAKAPMVMDRNFKPGFRIDLH 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1635577269 417 QKDLRLAIALGDAVNHPTPMAAAANEVYKRAKALDQSDNDMSAVYRAY 464
Cdd:PRK11559  239 IKDLANALDTSHGVGAPLPLTAAVMEMMQALKADGLGTADHSALACYY 286

NAD binding domain of 6-phosphogluconate dehydrogenase; The NAD binding domain of 6-phosphogluconate dehydrogenase adopts a Rossmann fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 188 KIGFLGLGLMGSGIVSNLLKMGHTVTVWNRTAEK------EGARLGRTPAEVVSTCDITFACVSDPKAAKDLVLGPsGVL 261
Cdd:pfam03446   1 KIGFIGLGVMGSPMALNLLKAGYTVTVYNRTPEKveelvaAGAIAAASPAEFVAGLDVVITMVPAGAAVDAVIFGE-GLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 262 QGIRPGKCYVDMSTVDADTVTELAQVIVSRGGRFLEAPVSGNQQLSNDGMLVILAAGDRGLYEDCSSCFQAMGKTSFFLG 341
Cdd:pfam03446  80 PGLKPGDIIIDGSTSSPEDARRRAKELKEKGLHFLDAPVSGGEAGAENGTLSIMVGGDEEAFERVKPILEAMGACVTYIG 159

PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   9 GDLVWGKLGRYPPWPGKIVNPPKD----LKKPRGKKCFFVKFFGTEDHAWIKVEQLKPYHAHKE-EMIKINKGK----RF 79
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPEELpenvLKPKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEfEYLKKKKKKkkkkAF 80

                          90
                  ....*....|..
gi 1635577269  80 QQAVDAVEEFLR 91
Cdd:pfam00855  81 KKALEEAEEALK 92

NADP-binding domain of glutamyl-tRNA reductase; Glutamyl-tRNA reductase catalyzes the conversion of glutamyl-tRNA to glutamate-1-semialdehyde, initiating the synthesis of tetrapyrrole. Whereas tRNAs are generally associated with peptide bond formation in protein translation, here the tRNA activates glutamate in the initiation of tetrapyrrole biosynthesis in archaea, plants and many bacteria. In the first step, activated glutamate is reduced to glutamate-1-semi-aldehyde via the NADPH dependent glutamyl-tRNA reductase. Glutamyl-tRNA reductase forms a V-shaped dimer. Each monomer has 3 domains: an N-terminal catalytic domain, a classic nucleotide binding domain, and a C-terminal dimerization domain. Although the representative structure 1GPJ lacks a bound NADPH, a theoretical binding pocket has been described. (PMID 11172694). Amino acid dehydrogenase (DH)-like NAD(P)-binding domains are members of the Rossmann fold superfamily and include glutamate, leucine, and phenylalanine DHs, methylene tetrahydrofolate DH, methylene-tetrahydromethanopterin DH, methylene-tetrahydropholate DH/cyclohydrolase, Shikimate DH-like proteins, malate oxidoreductases, and glutamyl tRNA reductase. Amino acid DHs catalyze the deamination of amino acids to keto acids with NAD(P)+ as a cofactor. The NAD(P)-binding Rossmann fold superfamily includes a wide variety of protein families including NAD(P)- binding domains of alcohol DHs, tyrosine-dependent oxidoreductases, glyceraldehyde-3-phosphate DH, lactate/malate DHs, formate/glycerate DHs, siroheme synthases, 6-phosphogluconate DH, amino acid DHs, repressor rex, NAD-binding potassium channel domain, CoA-binding, and ornithine cyclodeaminase-like domains. These domains have an alpha-beta-alpha configuration. NAD binding involves numerous hydrogen and van der Waals contacts.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 129 VKDAdphfhhFLLSQTEKPA------VCYQAIT--KKLKiceEET----GSTSI-QAADSTAVNGSITPTDKKIGFLGLG 195
Cdd:cd05213   117 VKNA------YKLAKEAGTSgkllnrLFQKAIKvgKRVR---TETgisrGAVSIsSAAVELAEKIFGNLKGKKVLVIGAG 187

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1635577269 196 LMGSGIVSNLLKMGHT-VTVWNRTAEKEGARLGRTPAEVVS---------TCDITFACVSDPKAAKD 252
Cdd:cd05213   188 EMGELAAKHLAAKGVAeITIANRTYERAEELAKELGGNAVPldellellnEADVVISATGAPHYAKI 254

tartronate semialdehyde reductase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 187 KKIGFLGLGLMGSGIVSNLLKMGHTVTVWNRTAE------KEGARLGRTPAEVVSTCDITFACVSDPKAAKDLVLGPSGV 260
Cdd:PRK11559    3 MKVGFIGLGIMGKPMSKNLLKAGYSLVVYDRNPEavaeviAAGAETASTAKAVAEQCDVIITMLPNSPHVKEVALGENGI 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 261 LQGIRPGKCYVDMSTVDADTVTELAQVIVSRGGRFLEAPVSGNQQLSNDGMLVILAAGDRGLYEDCSSCFQAMGKTSFFL 340
Cdd:PRK11559   83 IEGAKPGTVVIDMSSIAPLASREIAAALKAKGIEMLDAPVSGGEPKAIDGTLSVMVGGDKAIFDKYYDLMKAMAGSVVHT 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 341 GEV--GNAAKM--MLIVNMVqgsfMATIAEGLTLAQVTGQSQQTLLDILNQGQLASIFLDQKCQNILQGNFKPDFYLKYI 416
Cdd:PRK11559  163 GDIgaGNVTKLanQVIVALN----IAAMSEALVLATKAGVNPDLVYQAIRGGLAGSTVLDAKAPMVMDRNFKPGFRIDLH 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1635577269 417 QKDLRLAIALGDAVNHPTPMAAAANEVYKRAKALDQSDNDMSAVYRAY 464
Cdd:PRK11559  239 IKDLANALDTSHGVGAPLPLTAAVMEMMQALKADGLGTADHSALACYY 286

NAD binding domain of 6-phosphogluconate dehydrogenase; The NAD binding domain of 6-phosphogluconate dehydrogenase adopts a Rossmann fold.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 188 KIGFLGLGLMGSGIVSNLLKMGHTVTVWNRTAEK------EGARLGRTPAEVVSTCDITFACVSDPKAAKDLVLGPsGVL 261
Cdd:pfam03446   1 KIGFIGLGVMGSPMALNLLKAGYTVTVYNRTPEKveelvaAGAIAAASPAEFVAGLDVVITMVPAGAAVDAVIFGE-GLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 262 QGIRPGKCYVDMSTVDADTVTELAQVIVSRGGRFLEAPVSGNQQLSNDGMLVILAAGDRGLYEDCSSCFQAMGKTSFFLG 341
Cdd:pfam03446  80 PGLKPGDIIIDGSTSSPEDARRRAKELKEKGLHFLDAPVSGGEAGAENGTLSIMVGGDEEAFERVKPILEAMGACVTYIG 159

sulfolactaldehyde 3-reductase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 188 KIGFLGLGLMGSGIVSNLLKMGHTVTVWN------RTAEKEGARLGRTPAEVVSTCDITFACVSDPKAAKDLVLGPSGVL 261
Cdd:PRK15461    3 AIAFIGLGQMGSPMASNLLKQGHQLQVFDvnpqavDALVDKGATPAASPAQAAAGAEFVITMLPNGDLVRSVLFGENGVC 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 262 QGIRPGKCYVDMSTVDADTVTELAQVIVSRGGRFLEAPVSGNQQLSNDGMLVILAAGDRGLYEDCSSCFQAMGKTSFFLG 341
Cdd:PRK15461   83 EGLSRDALVIDMSTIHPLQTDKLIADMQAKGFSMMDVPVGRTSDNAITGTLLLLAGGTAEQVERATPILMAMGNELINAG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269 342 EVGNAAKMMLIVNMVQGSFMATIAEGLTLAQVTGQSQQTLLDILNqGQLASI--FLDQKCQNILQGNFKPDFYLKYIQKD 419
Cdd:PRK15461  163 GPGMGIRVKLINNYMSIALNALSAEAAVLCEALGLSFDVALKVMS-GTAAGKghFTTTWPNKVLKGDLSPAFMIDLAHKD 241

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 1635577269 420 LRLAIALGDAVNHPTPMAAAANEVYKRAKALDQSDNDMSAVY 461
Cdd:PRK15461  242 LGIALDVANQLHVPMPLGAASREVYSQARAAGRGRQDWSAIL 283

PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, is a small domain consisting of 100-150 amino acids and is composed of a five-stranded antiparallel beta-barrel followed by a helical region. It is found in numerous proteins that are involved in cell division, growth, and differentiation. Most PWWP-domain proteins seem to be nuclear, often DNA-binding, proteins that function as transcription factors regulating a variety of developmental processes. PWWP domains specifically recognize DNA and histone methylated lysines at the level of the nucleosome. Based on the fact that other regions of PWWP-domain proteins are responsible for nuclear localization and DNA-binding, is likely that the PWWP domain acts as a site for protein-protein binding interactions, influencing chromatin remodeling and thereby regulating transcriptional processes. Some PWWP-domain proteins have been linked to cancer or other diseases; some are known to function as growth factors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   9 GDLVWGKLGRYPPWPGKIVNP---PKDLKKPRGKKCFFVKFFGTEDHAWIKVEQLKPYHAHKEEMIKINK--GKRFQQAV 83
Cdd:cd05162     1 GDLVWAKLKGYPWWPARVVDPeelPEEVGKKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKkkSKKFKKAV 80

                  ....*.
gi 1635577269  84 DAVEEF 89
Cdd:cd05162    81 EEAEEA 86

fructose-bisphosphate aldolase

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269  185 TDKKIGFLGLGLMGSGIVSNLLKMGHTVT---VWNRTA---EKEGARLGRTPAEVVSTCDITFACVSDPKAAKDLVLGPS 258
Cdd:PLN02858   323 PVKRIGFIGLGAMGFGMASHLLKSNFSVCgydVYKPTLvrfENAGGLAGNSPAEVAKDVDVLVIMVANEVQAENVLFGDL 402

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269  259 GVLQGIRPGKCYVDMSTVDADTVTELAQVI--VSRGGRFLEAPVSGNQQLSNDGMLVILAAG-DRGLyEDCSSCFQAMGK 335
Cdd:PLN02858   403 GAVSALPAGASIVLSSTVSPGFVIQLERRLenEGRDIKLVDAPVSGGVKRAAMGTLTIMASGtDEAL-KSAGSVLSALSE 481

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269  336 TSFFLGEVGNAAKMMLIVN-MVQGSFMATIAEGLTLAQVTGQSQQTLLDILNQGQLASIFLDQKCQNILQGNFKPDFYLK 414
Cdd:PLN02858   482 KLYVIKGGCGAGSGVKMVNqLLAGVHIASAAEAMAFGARLGLNTRKLFDIISNAGGTSWMFENRVPHMLDNDYTPYSALD 561

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1635577269  415 YIQKDLRLAIALGDAVNHPTPMAAAANEVYKRAKALDQSDNDMSAVYRAY 464
Cdd:PLN02858   562 IFVKDLGIVSREGSSRKIPLHLSTVAHQLFLAGSASGWGRIDDAAVVKVY 611

fructose-bisphosphate aldolase

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269  185 TDKKIGFLGLGLMGSGIVSNLLKMGHTVTVW-------NRTAEKEGARLGrTPAEVVSTCDITFACVSDPKAAKDLVLGP 257
Cdd:PLN02858     3 SAGVVGFVGLDSLSFELASSLLRSGFKVQAFeistplmEKFCELGGHRCD-SPAEAAKDAAALVVVLSHPDQVDDVFFGD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269  258 SGVLQGIRPGKCYVDMSTVDADTVTELAQVIVSRGGR--FLEAPVSGNQQLSNDGMLVILAAGDRGLYEDCSSCFQAMGK 335
Cdd:PLN02858    82 EGAAKGLQKGAVILIRSTILPLQLQKLEKKLTERKEQifLVDAYVSKGMSDLLNGKLMIIASGRSDAITRAQPFLSAMCQ 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269  336 TSFFL-GEVGNAAKMMLIVNMVQGSFMATIAEGLTLAQVTGQSQQTLLDILNQGQLASIFLDQKCQNILQGNFKPDFYLK 414
Cdd:PLN02858   162 KLYTFeGEIGAGSKVKMVNELLEGIHLVASAEAMALGVRAGIHPWIIYDIISNAAGSSWIFKNHVPLLLKDDYIEGRFLN 241

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1635577269  415 YIQKDLRLAIALGDAVNHPTPMAAAANEVYKRAKALDQSDNDMSAVYRAY 464
Cdd:PLN02858   242 VLVQNLGIVLDMAKSLPFPLPLLAVAHQQLISGSSSMQGDDTATSLAKVW 291

second PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein family consists of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising in suppressing cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play nonredundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). This model corresponds to the second PWWP domain. The family also includes Drosophila melanogaster maternal-effect sterile 4 (dMes4) that may act as a histone-lysine N-methyltransferase required for wing morphogenesis. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   9 GDLVWGKLGRYPPWPGKIVN----PPKDLKKPRGKKCFFVKFFGTEDHAWIKVEQLKPYHAHKEEMIKINK---GKRFQQ 81
Cdd:cd05838     3 GDIVWVKLGNYRWWPAEILHprevPDNIQSLPHPPGEFPVRFFGSHDYYWVHRGRVFLFEEGDKGSKEKSKkslDKSFKR 82

                  ....*....
gi 1635577269  82 AV-DAVEEF 89
Cdd:cd05838    83 ALkEANEAF 91

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana ATX3 (also called protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also called protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also called protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. They show distinct phylogenetic origins from the family of ATX1 and ATX2. They are multi-domain containing protein that consists of an N-terminal PWWP domain, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   9 GDLVWGKLGRYPPWPGKIVNP---PKDLKKPRGKKCFFVKFFGTE---DHAWIKVEQLKPY----HAHKEEMIKINKG-K 77
Cdd:cd20143     3 GDLVWAKVGTHPFWPARVVEPaeqAEEVRRRCVPGSLCVYFFGPGgsrDYGWVRRSMIFPFtddlARFQTQKIKNKKRpQ 82

                          90
                  ....*....|....*.
gi 1635577269  78 RFQQAVD----AVEEF 89
Cdd:cd20143    83 EFQEALEeaklADAGF 98

PWWP domain found in Arabidopsis thaliana histone-lysine N-methyltransferase trithorax-like proteins ATX1, ATX2, and similar proteins; This family includes A. thaliana ATX1 and ATX2, which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also called protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1 regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also called protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical plant homeodomain (PHD) domain, a non-canonical extended PHD (ePHD) domain, and a C-terminal SET domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   7 RLGDLVWGKLGRYPPWPGKIVN---------PPKDLKKPRGkkcFFVKFFGTEDHAWIKVEQL--------KPYHAHKee 69
Cdd:cd20142     1 SPGDVVWAKVKGYPMWPALVIDeehaercglEANRPGKKGT---VPVQFFGTYEVARLNPKKVvgfskgldLKYHSKC-- 75

                          90       100
                  ....*....|....*....|....*
gi 1635577269  70 mikinKGKRFQQAVDAVEEFLRRAK 94
Cdd:cd20142    76 -----KAPVFRQALEEAERYLKEGK 95

PWWP domain found in DNA mismatch repair protein MSH6 and similar proteins; MSH6, also called G/T mismatch-binding protein (GTBP or GTMBP), MutS protein homolog 6, or MutS-alpha 160 kDa subunit (p160), is a mismatch repair protein homologous to bacterial MutS. It is a component of the post-replicative DNA mismatch repair system (MMR). It heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, it forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Mutations in MSH6 have been linked to increased cancer susceptibility, particularly in hereditary nonpolyposis colorectal cancer in humans. MSH6 contains a PWWP domain, but its role in MSH6 remains unclear. MSH6 orthologs found in Saccharomyces cerevisiae, Caenorhabditis elegans, and Arabidopsis thaliana lack the PWWP domain. PWWP domains typically recognize DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   8 LGDLVWGKLGRYPPWPGKIVNPPKDLKKPRGKKC--FFVKFFG-TEDHAWIKVEQLKPY------HAHKEEMIKINKGKR 78
Cdd:cd05837     3 PGDLVWAKLEGYPWWPSLVCNHPTTGFHKKFGKKgeVHVQFFDdPPSRAWVKAKNVKPFtgsddkEFQKGGMFFSKDPKW 82

                          90
                  ....*....|..
gi 1635577269  79 ---FQQAVDAVE 87
Cdd:cd05837    83 kkaVKEADKALK 94

PWWP domain found in Saccharomyces cerevisiae ISWI one complex protein 4 (ScIOC4) and similar proteins; ScIOC4 functions as a component of the ISW1B complex, which acts in remodeling the chromatin by catalyzing an ATP-dependent alteration in the structure of nucleosomal DNA. The ISW1B complex acts within coding regions to control the amount of RNA polymerase II released into productive elongation and to coordinate elongation with termination and pre-mRNA processing. The family also includes Schizosaccharomyces pombe PWWP domain-containing proteins 1 and 2 (SpPDP1 and SpPDP2). SpPDP1 associates with Set9 to regulate its chromatin localization and methyltransferase activity towards H4K20. Members of this family contain a PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   9 GDLVWGKLGRYPPWPGKIVNP---------PKDLKKPRGKKCFFVKFFGTEDHAWIKVEQLKPYhahKEEMIK--INKGK 77
Cdd:cd05840     1 GDLVLAKVKGYPPWPAMVLPEellpknvlkAKKRKPKSKKTVYPVQFFPDNEYYWVSPSSLKPL---TKEEIDkfLSKSK 77

                          90
                  ....*....|..
gi 1635577269  78 RFQQA-VDAVEE 88
Cdd:cd05840    78 RKNKDlIEAYEV 89

PWWP domain found in Arabidopsis thaliana protein HUA2-LIKE (HULK) family; The HULK family includes HUA2-like proteins 1-3 (HULK1-3), which are probable transcription factors that act with partial redundancy with each other. They may play diverse and essential roles in the control of plant development, physiology and flowering time. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   9 GDLVWGKLGRYPPWPGKiVNPPKDLKKPRGKKCFFVKFFGTEDHAWIKVEQLKPY-----HAHKEEMIKINKGKRFQQAV 83
Cdd:cd20147     1 GDLVLAKVKGFPAWPAQ-VSEPEDWGSAPDPKKVFVHFFGTQQIGFCNPGELSEFteeikQSLLARTLKKKKGSDFSRAV 79

                          90
                  ....*....|..
gi 1635577269  84 DAVEEFLRRAKG 95
Cdd:cd20147    80 KEICELYEERKG 91

first PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein family consists of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 that are critical in maintaining the chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising in suppressing cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and play nonredundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, through mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). This model corresponds to the first PWWP domain. This family also includes Drosophila melanogaster maternal-effect sterile 4 (dMes4) that may act as a histone-lysine N-methyltransferase required for wing morphogenesis. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   8 LGDLVWGKLGRYPPWPGKIVNPPK-DL---KKPRGKKC---FFVKFFGTED-HAWIKVEQLKPYH------AHKEEMIK- 72
Cdd:cd20144     1 VGDLVWAKVSGHPWWPCMVTYDPEsGLytkIKGSGGRTyrqYHVQFFGDNGeRGWVSEKSLMPFEgkekfeELVKELKKk 80

                          90
                  ....*....|..
gi 1635577269  73 -INKGKRFQQAV 83
Cdd:cd20144    81 aKKKSKKAKLEK 92

PWWP domain found in Hepatoma-derived growth factor-related protein 2 (HDGFL2); HDGFL2, also called HDGF-related protein 2 (HRP-2), or Hepatoma-derived growth factor 2 (HDGF-2), is involved in cellular growth control, through the regulation of cyclin D1 expression. It contains a PWWP domain, which is necessary for DNA binding.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   6 LRLGDLVWGKLGRYPPWPGKIVNPPKDLKKPRGKKCfFVKFFGTEDHAWIKVEQLKPYHAHKEEMIKINKGKRFQQAVDA 85
Cdd:cd20149     1 FKPGDLVFAKMKGYPHWPARIDDIADGAVKPPPNKY-PIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWE 79

                  ..
gi 1635577269  86 VE 87
Cdd:cd20149    80 IQ 81

first PWWP domain found in nuclear SET domain-containing protein 3 (NSD3) and similar proteins; NSD3, also called histone-lysine N-methyltransferase NSD3, protein whistle, WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions. This model corresponds to the first PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1635577269   7 RLGDLVWGKLGRYPPWPGKIVNPPK----DLKKPRGKKCFFVKFFGTE-DHAWIKVEQLKPYHAHKE 68
Cdd:cd20163     2 QVGDLVWSKVGTYPWWPCMVSSDPQlevhTKINTRGAREYHVQFFSSQpERAWVHEKRVREYKGHKQ 68

PWWP domain found in the PWWP domain-containing protein 2 (PWWP2) family; The PWWP2 family includes PWWP2A and its paralog PWWP2B. PWWP2A is a H2A.Z-specific chromatin binding protein which may play an important role in the neural crest stem cell migration and differentiation during early development. It is also required for proper mitosis progression. PWWP2A and PWWP2B form a stable complex with NuRD subunits MTA1/2/3:HDAC1/2:RBBP4/7, but not with MBD2/3, p66alpha/beta, and CHD3/4. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1635577269   6 LRLGDLVWGKLGRYPPWPGKIV------NPPKDLKKPRGKkcffVKFFGTEDHAWIKVEQLKPYhahkEEMIKI--NKGK 77
Cdd:cd20140     4 LRVGDIVWGKIHGFPWWPGRILsitvsrDDNGELSTQEAH----VSWFGSSTTSYMPCSQLYPF----LEDFKLryNKKK 75

                  ....*...
gi 1635577269  78 R--FQQAV 83
Cdd:cd20140    76 RgpYKEAV 83

first PWWP domain found in nuclear receptor-binding SET domain-containing protein 1 (NSD1) and similar proteins; NSD1, also called H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, androgen receptor coactivator 267 kDa protein, androgen receptor-associated protein of 267 kDa, H3-K36-HMTase H4-K20-HMTase, Lysine N-methyltransferase 3B (KMT3B), or NR-binding SET domain-containing protein, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription. It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD domains are involved in protein-protein interactions. The model corresponds to the first PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1635577269   4 VSLRLGDLVWGKLGRYPPWPGKIVNPP-----KDLKKPRGKKC--FFVKFFGT-EDHAWIKVEQLKPY 63
Cdd:cd20161     2 VKYEVGDLVWAKFSRRPWWPCRICADPlldthSKMKVPSRRPCrqYYVETLGElTEKAWVAAKAVVPF 69

NADP-dependent phosphogluconate dehydrogenase;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1635577269 188 KIGFLGLGLMGSGIVSNLLKMGHTVTVWNR------TAEKEGARLGRTPAEVVS 235
Cdd:PRK09599    2 QLGMIGLGRMGGNMARRLLRGGHEVVGYDRnpeaveALAEEGATGADSLEELVA 55

PWWP domain found in the bromodomain and PHD finger-containing (BRPF) protein family; The BRPF family of proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, C2HC5HC2H, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. The PHD finger binds to lysine 4 of histone H3 (K4H3), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties.