PWWP domain found in mutated melanoma-associated antigen 1 (MUM-1) and similar proteins; MUM-1, also called PWWP domain-containing DNA repair factor 3A (PWWP3A), or protein expandere (EXPAND1), is a melanoma-associated antigen (MAA) that belongs to the mutated or aberrantly expressed type of MAAs, along with antigens such as CDK4, beta-catenin, gp100-in4, p15, and N-acetylglucosaminyltransferase V. It is highly expressed in several types of human cancers and involved in the DNA damage response pathway by contributing to the maintenance of chromatin architecture. MUM-1 is recruited to the vicinity of DNA breaks by TP53BP1 and plays an accessory role to facilitate damage-induced chromatin changes and promoting chromatin relaxation. It is required for efficient DNA repair and cell survival following DNA damage. This subfamily also includes mutated melanoma-associated antigen 1-like protein 1 (MUM1L1), also called MUM1-like protein 1, or PWWP domain-containing DNA repair factor 3B (PWWP3B). Its biological function remains unclear. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564358248 397 FEVGMLVWLKYQKYPFWPAVVKSVRRRDKKASVLFIEGnmNPKGRGITVSLRRLKHFDCKEKHALLDRAKED-FAQAIGW 475
Cdd:cd06080    1 FSKGDIVWAKYRKYPYWPAVVKSVYKKPKKASVLFLEL--PPEKKGIKVSLKKLKPFDCKEKEELLEEGKESpYSEDFKE 78

                         90
                 ....*....|..
gi 564358248 476 CVSLITDYRVRL 487
Cdd:cd06080   79 AVELAEDYLIKK 90

PWWP domain found in mutated melanoma-associated antigen 1 (MUM-1) and similar proteins; MUM-1, also called PWWP domain-containing DNA repair factor 3A (PWWP3A), or protein expandere (EXPAND1), is a melanoma-associated antigen (MAA) that belongs to the mutated or aberrantly expressed type of MAAs, along with antigens such as CDK4, beta-catenin, gp100-in4, p15, and N-acetylglucosaminyltransferase V. It is highly expressed in several types of human cancers and involved in the DNA damage response pathway by contributing to the maintenance of chromatin architecture. MUM-1 is recruited to the vicinity of DNA breaks by TP53BP1 and plays an accessory role to facilitate damage-induced chromatin changes and promoting chromatin relaxation. It is required for efficient DNA repair and cell survival following DNA damage. This subfamily also includes mutated melanoma-associated antigen 1-like protein 1 (MUM1L1), also called MUM1-like protein 1, or PWWP domain-containing DNA repair factor 3B (PWWP3B). Its biological function remains unclear. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564358248 397 FEVGMLVWLKYQKYPFWPAVVKSVRRRDKKASVLFIEGnmNPKGRGITVSLRRLKHFDCKEKHALLDRAKED-FAQAIGW 475
Cdd:cd06080    1 FSKGDIVWAKYRKYPYWPAVVKSVYKKPKKASVLFLEL--PPEKKGIKVSLKKLKPFDCKEKEELLEEGKESpYSEDFKE 78

                         90
                 ....*....|..
gi 564358248 476 CVSLITDYRVRL 487
Cdd:cd06080   79 AVELAEDYLIKK 90

domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 564358248   397 FEVGMLVWLKYQKYPFWPAVV------KSVRRRDKKASVLF 431
Cdd:smart00293   1 FKPGDLVWAKMKGFPWWPALVispkmtPDNIMKRKSDENLY 41

PWWP domain found in mutated melanoma-associated antigen 1 (MUM-1) and similar proteins; MUM-1, also called PWWP domain-containing DNA repair factor 3A (PWWP3A), or protein expandere (EXPAND1), is a melanoma-associated antigen (MAA) that belongs to the mutated or aberrantly expressed type of MAAs, along with antigens such as CDK4, beta-catenin, gp100-in4, p15, and N-acetylglucosaminyltransferase V. It is highly expressed in several types of human cancers and involved in the DNA damage response pathway by contributing to the maintenance of chromatin architecture. MUM-1 is recruited to the vicinity of DNA breaks by TP53BP1 and plays an accessory role to facilitate damage-induced chromatin changes and promoting chromatin relaxation. It is required for efficient DNA repair and cell survival following DNA damage. This subfamily also includes mutated melanoma-associated antigen 1-like protein 1 (MUM1L1), also called MUM1-like protein 1, or PWWP domain-containing DNA repair factor 3B (PWWP3B). Its biological function remains unclear. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564358248 397 FEVGMLVWLKYQKYPFWPAVVKSVRRRDKKASVLFIEGnmNPKGRGITVSLRRLKHFDCKEKHALLDRAKED-FAQAIGW 475
Cdd:cd06080    1 FSKGDIVWAKYRKYPYWPAVVKSVYKKPKKASVLFLEL--PPEKKGIKVSLKKLKPFDCKEKEELLEEGKESpYSEDFKE 78

                         90
                 ....*....|..
gi 564358248 476 CVSLITDYRVRL 487
Cdd:cd06080   79 AVELAEDYLIKK 90

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 564358248  400 GMLVWLKYQKYPFWPAVV-------KSVRRRDKKAS---VLFIegnmnPKGRGITVSLRRLKHFDCKEKHALLDRAK--- 466
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVvdpeelpENVLKPKKKDGeylVRFF-----GDSEFAWVKPKDLKPFDEGDEFEYLKKKKkkk 75

                  ....*....
gi 564358248  467 --EDFAQAI 473
Cdd:pfam00855  76 kkKAFKKAL 84

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
                 ....*....|....*....|....*....|....*....
gi 564358248 397 FEVGMLVWLKYQKYPFWPAVV------KSVRRRDKKASV 429
Cdd:cd05837    1 FSPGDLVWAKLEGYPWWPSLVcnhpttGFHKKFGKKGEV 39