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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096  318 PLKYEVGDLIWAKFKRRPWWPCRICSDPLINTHSKMKVSNRRPYRQYYVEAFGDPSERAWVAGKAIVMFEGRHQFEELPV 397
Cdd:cd20161     1 PVKYEVGDLVWAKFSRRPWWPCRICADPLLDTHSKMKVPSRRPCRQYYVETLGELTEKAWVAAKAVVPFEGRHQFEELPV 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 966950096  398 LRRRGKQKEKGYRHKVPQKILSKWEASVGLAEQYDV 433
Cdd:cd20161    81 LRRRGKQKEKDYKHKIPQKLLSLWEASVAHAEDFLS 116

PHD finger 3 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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 (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the third PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966950096 1638 ICITCHAANPANVSASKGRLMRCVRCPVAYHANDFCLAAGSKILASNSIICPNH 1691
Cdd:cd15653     1 ICLTCHATNPSNPSASKGRLMRCVRCPVAYHANDFCLAAGSVILASNSIICPNH 54

PHD finger 5 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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 (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fifth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 966950096 2119 ECFSCGDAGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 2161
Cdd:cd15659     1 ECFSCGDGGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 43

PHD finger 4 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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 (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fourth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 966950096 1708 WCFVCSEGGSLLCCDSCPAAFHRECLNIDIPEGNWYCNDC 1747
Cdd:cd15656     1 WCFVCSEGGSLLCCESCPAAFHRECLNIDMPEGSWYCNDC 40

AWS domain; This entry represents the AWS (associated with SET domain) domain. This is a zinc binding domain. The full AWS domain contains 8 cysteines. This entry represents the N-terminal part of the domain, with the C-terminal part interwoven with the SET domain.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 966950096  1900 DENPCGIDSECINRMLLYECHPTVCPAGGRCQNQCFSKR 1938
Cdd:pfam17907    1 DDPPCGCGSDCINRMLFVECTPKTCPCGESCQNQRFQRK 39

Chromatin remodeling protein, contains PhD zinc finger [Chromatin structure and dynamics];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1430 LSKKCYEAGHLENGITESCATSYSKDFGGGTSKIFDRPRKRKRQRHAAAKMQCKKVKnddSSKEIP-SLEGELMPhRTAA 1508
Cdd:COG5034   120 ENCHDAVSRLERNSYSSAARRSSGEHRSAASSQGSRHTKLKKRKNIHNLKRRSPELS---SKREVSfTLESPSVP-DTAT 195

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1509 SPKETVEEGVEHDSGMPASKKMQGERgggaalKENVCQNCEkLGELLLCEAQCCGA--FHLECLGLTEMPRGKFICNECR 1586
Cdd:COG5034   196 RVKEGNNGGSTKSRGVSSEDNSEGEE------LYCFCQQVS-YGQMVACDNANCKRewFHLECVGLKEPPKGKWYCPECK 268

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096  318 PLKYEVGDLIWAKFKRRPWWPCRICSDPLINTHSKMKVSNRRPYRQYYVEAFGDPSERAWVAGKAIVMFEGRHQFEELPV 397
Cdd:cd20161     1 PVKYEVGDLVWAKFSRRPWWPCRICADPLLDTHSKMKVPSRRPCRQYYVETLGELTEKAWVAAKAVVPFEGRHQFEELPV 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 966950096  398 LRRRGKQKEKGYRHKVPQKILSKWEASVGLAEQYDV 433
Cdd:cd20161    81 LRRRGKQKEKDYKHKIPQKLLSLWEASVAHAEDFLS 116

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain; Putative methyl transferase, based on outlier plant homologues

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096   1941 PEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNH 2020
Cdd:smart00317    1 NKLEVFKSPGKGWGVRATEDIPKGEFIGEYVGEIITSEEAEERPKAYDTDGAKAFYLFDIDSDLCIDARRKGNLARFINH 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....
gi 966950096   2021 CCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGN 2064
Cdd:smart00317   81 SCEPNCELLFVEVNGDDRIVIFALRDIKPGEELTIDYGSDYANE 124

PHD finger 3 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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 (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the third PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966950096 1638 ICITCHAANPANVSASKGRLMRCVRCPVAYHANDFCLAAGSKILASNSIICPNH 1691
Cdd:cd15653     1 ICLTCHATNPSNPSASKGRLMRCVRCPVAYHANDFCLAAGSVILASNSIICPNH 54

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 966950096  1757 EIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDV--SSKDKMGKGVDGTYK 1834
Cdd:pfam00855    2 DLVWAKLKGYPWWPARVVDPEELPENVLKPKKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEfeYLKKKKKKKKKKAFK 81

                           90
                   ....*....|.
gi 966950096  1835 KALQEAAARFE 1845
Cdd:pfam00855   82 KALEEAEEALK 92

PHD finger 5 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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 (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fifth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 966950096 2119 ECFSCGDAGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 2161
Cdd:cd15659     1 ECFSCGDGGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 43

PHD finger 1 found in nuclear receptor-binding SET domain-containing protein NSD1 and NSD2; NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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). NSD2, also termed histone-lysine N-methyltransferase NSD2, or multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). Both NSD1 and NSD2 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 (Cys5HisCysHis). In addition, NSD2 harbors a high mobility group (HMG) box. The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 966950096 1544 VCQNCEKLGELLLCEAQCCGAFHLECLGLTEMPRGKFICNECR 1586
Cdd:cd15648     1 VCQVCEKPGELLLCEGQCCGAFHLDCIGLSEMPSGKFICDECI 43

NSD Cys-His rich domain; This is an NSD-specific Cys-His rich region (C5HCH) domain. Family members include NSD3 (nuclear receptor SET domain-containing) proteins. This domain is located on the C-terminal of NSD1, 2 and 3 proteins. C5HCH domain lies adjacent to the fifth plant homeodomain (PHD5). The PHD5-C5HCH module of NSD3 (PHD5-C5HCHNSD3) recognizes the H3 N-terminal peptide containing unmodified K4 and trimethylated K9. Moreover, it has been reported that the PHD5-C5HCH module of NSD1 (PHD5-C5HCH) was the sole region required for tight binding of the NUP98-NSD1 fusion protein to the HoxA9 gene promoter, implicating that PHD5-C5HCH might have chromatin targeting ability.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 966950096  2160 WHQCDICGKEAASFCEMCPSSFCKQHREGMLFISKLDGRLSCTEHDPCGP 2209
Cdd:pfam17982    1 WHQCSVCGSPATSFCEFCPSSFCKDHEKGALVPSALEGRLCCSEHDPESP 50

AWS domain; This entry represents the AWS (associated with SET domain) domain. This is a zinc binding domain. The full AWS domain contains 8 cysteines. This entry represents the N-terminal part of the domain, with the C-terminal part interwoven with the SET domain.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 966950096  1900 DENPCGIDSECINRMLLYECHPTVCPAGGRCQNQCFSKR 1938
Cdd:pfam17907    1 DDPPCGCGSDCINRMLFVECTPKTCPCGESCQNQRFQRK 39

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*..
gi 966950096   1708 WCFVCSE---GGSLLCCDSCPAAFHRECLNI----DIPEGNWYCNDC 1747
Cdd:smart00249    1 YCSVCGKpddGGELLQCDGCDRWYHQTCLGPplleEEPDGKWYCPKC 47

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

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 966950096    321 YEVGDLIWAKFKRRPWWPCRICSDPLINThSKMKvsNRRPYRQYYVEAFGDPsERAWV 378
Cdd:smart00293    1 FKPGDLVWAKMKGFPWWPALVISPKMTPD-NIMK--RKSDENLYPVLFFGDK-DTAWI 54

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2207 CGPNPLEPG-EIREYVPPPVPLPPGPSTHLAEQ--STGMAAQAPKMSDKPPADTNQTLSLSKKALAGTCQRPLLPERPLE 2283
Cdd:PHA03247 2573 PAPRPSEPAvTSRARRPDAPPQSARPRAPVDDRgdPRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERP 2652

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2284 RTDSRSQPLDKVRDLAGSGTKSQSLVSSQRPLDRQ-PAVAGPRPQLSDKPSPVTSPSSSPSVRSQPLERPLGTADPRLDK 2362
Cdd:PHA03247 2653 RDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAaRPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQAS 2732

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2363 SIGAASPRPQSLEKTPVPTGLRLPPPDRLLITSSPKPQtsdrPPDKPHASLSQRLPPPekvlsAVVQTLVAKEKALRPVD 2442
Cdd:PHA03247 2733 PALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPA----PPAAPAAGPPRRLTRP-----AVASLSESRESLPSPWD 2803

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2443 qntQSKNRAALVMDLIDLTPRQkeRAASPHEVTPQADEKMPVLESSSWPASKGLGhmpravekGSVSDPLQTSGKVAAHS 2522
Cdd:PHA03247 2804 ---PADPPAAVLAPAAALPPAA--SPAGPLPPPTSAQPTAPPPPPGPPPPSLPLG--------GSVAPGGDVRRRPPSRS 2870

                         330       340       350       360       370       380       390
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966950096 2523 EDPWQAVKSFTQARLLSQP----PAKAFLYEPTTQASGRAPAGTEQ-TPGPLSQVPGLVKQAKQMIGGQQLPA 2590
Cdd:PHA03247 2871 PAAKPAAPARPPVRRLARPavsrSTESFALPPDQPERPPQPQAPPPpQPQPQPPPPPQPQPPPPPPPRPQPPL 2943

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 966950096  1544 VCQNCEKLGELLLCEaQCCGAFHLECLGLT----EMPRGKFICNECR 1586
Cdd:pfam00628    4 VCGKSDDGGELVQCD-GCDDWFHLACLGPPldpaEIPSGEWLCPECK 49

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2399 PQTSDRPPDKPHASLSQRLPPPEKV-------LSAVVQTLVAKEKALRPvdqntQSknrAALVMDLIDLTPRQKERAASP 2471
Cdd:COG0515   207 PFDGDSPAELLRAHLREPPPPPSELrpdlppaLDAIVLRALAKDPEERY-----QS---AAELAAALRAVLRSLAAAAAA 278

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2472 HEVTPQADEKMPVLESSSWPASKGLGHMPRAVEKGSVSDPlqtsgkVAAHSEDPWQAVKSFTQARLLSQPPAKAFLYEPT 2551
Cdd:COG0515   279 AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA------AAAAPAAAAAAAAAAAALAAAAAAAAAAAAAALL 352

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2552 TQASGRAPAGTEQTPGPLSQVPGLVKQAKQMIGGQQLPALAARSGQSFRSLGKAPASLPTEEKKLVTTEQSPWALGKASS 2631
Cdd:COG0515   353 AAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAA 432

                         250
                  ....*....|....*
gi 966950096 2632 RAGLWPIVAGQTLAQ 2646
Cdd:COG0515   433 AAAAAAAAAARLLAA 447

SET domain (including post-SET domain) found in nuclear SET domain-containing proteins, NSD1, NSD2, NSD3 and similar proteins; The nuclear receptor-binding SET Domain (NSD) family of histone H3 lysine 36 methyltransferases is comprised of NSD1, NSD2, and NSD3, which are primarily known to be involved in chromatin integrity and gene expression through mono-, di-, or tri-methylating lysine 36 of histone H3 (H3K36), respectively. NSD1 (EC 2.1.1.43; also termed histone-lysine N-methyltransferase H3 lysine-36 and H4 lysine-20 specific, androgen receptor coactivator 267 kDa protein (ARA267), 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 1) functions as a histone-lysine N-methyltransferase that preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4. NSD2 (EC 2.1.1.43; also termed multiple myeloma SET domain-containing protein (MMSET), protein trithorax-5 (TRX5), or wolf-Hirschhorn syndrome candidate 1 protein (WHSC1)) acts as histone-lysine N-methyltransferase with histone H3 'Lys-27' (H3K27me) methyltransferase activity. NSD3 (EC 2.1.1.43; also termed protein whistle, WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1L1), or WHSC1-like protein 1) functions as a histone-lysine N-methyltransferase that preferentially methylates 'Lys-4' and 'Lys-27' of histone H3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1940 YPEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMN 2019
Cdd:cd19173     1 YPPTEPFKTGDRGWGLRTKRDIKKGDFVIEYVGELIDEEECRRRLKKAHENNITNFYMLTLDKDRIIDAGPKGNLSRFMN 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966950096 2020 HCCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCSGFLG 2081
Cdd:cd19173    81 HSCQPNCETQKWTVNGDTRVGLFAVRDIPAGEELTFNYNLDCLGNEKKVCRCGAPNCSGFLG 142

SET domain (including post-SET domain) found in nuclear receptor-binding SET domain-containing protein 3 (NSD3) and similar proteins; NSD3 (EC 2.1.1.43; also termed protein whistle, WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1L1), or WHSC1-like protein 1) functions as a histone-lysine N-methyltransferase that preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. NSD3 is amplified and overexpressed in multiple cancer types, including acute myeloid leukemia (AML), breast, lung, pancreatic and bladder cancers, as well as squamous cell carcinoma of the head and neck (SCCHN). NSD3 contributes to tumorigenesis by interacting with bromodomain-containing protein 4 (BRD4), the bromodomain and extraterminal (BET) protein, which is a potential therapeutic target in acute myeloid leukemia (AML). NSD3 is amplified in primary tumors and cell lines from breast carcinoma, and can promote the cell viability of small-cell lung cancer and pancreatic ductal adenocarcinoma. High NSD3 expression is implicated in poor grade and heavy smoking history in SCCHN. Thus, NSD3 may serve as a potential druggable target for selective cancer therapy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1940 YPEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMN 2019
Cdd:cd19212     1 YPDAEIIKTERRGWGLRTKRSIKKGEFVNEYVGELIDEEECRLRIKRAHENSVTNFYMLTVTKDRIIDAGPKGNYSRFMN 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966950096 2020 HCCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCSGFLG 2081
Cdd:cd19212    81 HSCNPNCETQKWTVNGDVRVGLFALCDIPAGMELTFNYNLDCLGNGRTECHCGADNCSGFLG 142

SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2), nuclear SETD2 (NSD2), ASH1-like protein (ASH1L) and similar proteins; This family includes SET domain-containing protein 2 (SETD2), nuclear SETD2 (NSD2) and ASH1-like protein (ASH1L), which function as histone-lysine N-methyltransferases. SETD2 specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate. NSD2 shows histone H3 'Lys-27' (H3K27me) methyltransferase activity. ASH1L specifically methylates 'Lys-36' of histone H3 (H3K36me). The family also includes Arabidopsis thaliana ASH1-related protein 3 (ASHR3) and similar proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1942 EVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHC 2021
Cdd:cd10531     1 KLELFRTEKKGWGVKAKEDIQKGEFIIEYVGEVIDKKEFKERLDEYEELGKSNFYILSLSDDVVIDATRKGNLSRFINHS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 966950096 2022 CQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCS 2077
Cdd:cd10531    81 CEPNCETQKWIVNGEYRIGIFALRDIPAGEELTFDYNFVNYNEAKQVCLCGAQNCR 136

SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2) and similar proteins; SETD2 (also termed HIF-1, huntingtin yeast partner B, huntingtin-interacting protein 1 (HIP-1), huntingtin-interacting protein B, lysine N-methyltransferase 3A or protein-lysine N-methyltransferase SETD2) acts as histone-lysine N-methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using demethylated 'Lys-36' (H3K36me2) as substrate. It has been shown that methylation is a posttranslational modification of dynamic microtubules and that SETD2 methylates alpha-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1940 YPEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMN 2019
Cdd:cd19172     1 YAKVEVFRTEKKGWGLRAAEDLPKGTFVIEYVGEVLDEKEFKRRMKEYAREGNRHYYFMALKSDEIIDATKKGNLSRFIN 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966950096 2020 HCCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCSGFLG 2081
Cdd:cd19172    81 HSCEPNCETQKWTVNGELRVGFFAKRDIPAGEELTFDYQFERYGKEAQKCYCGSPNCRGYIG 142

SET domain (including post-SET domain) found in Arabidopsis thaliana ASH1-related protein 3 (ASHR3) and similar proteins; This family includes Arabidopsis thaliana ASH1-related protein 3 (ASHR3, also termed protein SET DOMAIN GROUP 4 or protein stamen loss), ASH1 homolog 3 (ASHH3, also termed protein SET DOMAIN GROUP 7) and homolog 4 (ASHH4, also termed protein SET DOMAIN GROUP 24). They all function as histone-lysine N-methyltransferases (EC 2.1.1.43).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1943 VEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHCC 2022
Cdd:cd19175     2 MKLVKTEKCGWGLVADEDINAGEFIIEYVGEVIDDKTCEERLWDMKHKGEKNFYMCEIDKDMVIDATFKGNLSRFINHSC 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 966950096 2023 QPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNgKTVCKCGAPNCSGFLG 2081
Cdd:cd19175    82 DPNCELQKWQVDGETRIGVFAIRDIKKGEELTYDYQFVQFGA-DQDCHCGSKNCRGKLG 139

second PWWP domain found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins; NSD2, also called histone-lysine N-methyltransferase NSD2, multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, through mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, an high mobility group (HMG) box, five PHD (plant-homeodomain) zinc finger motifs, and an NSD-specific Cys-His rich domain (C5HCH). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD domains mediate chromatin interaction and recognition of histone marks. This model corresponds to the second PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1754 HYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 1833
Cdd:cd20165     1 RFQDIIWVKLGNYRWWPAEVCHPKNVPPNIQKMKHEIGEFPVFFFGSKDYYWTHQARVFPYMEGDRGSKYQGGKGIGKVF 80

                          90
                  ....*....|....*
gi 966950096 1834 KKALQEAAARFEELK 1848
Cdd:cd20165    81 KNALQEAEARFREIK 95

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain; Putative methyl transferase, based on outlier plant homologues

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096   1941 PEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNH 2020
Cdd:smart00317    1 NKLEVFKSPGKGWGVRATEDIPKGEFIGEYVGEIITSEEAEERPKAYDTDGAKAFYLFDIDSDLCIDARRKGNLARFINH 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....
gi 966950096   2021 CCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGN 2064
Cdd:smart00317   81 SCEPNCELLFVEVNGDDRIVIFALRDIKPGEELTIDYGSDYANE 124

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 966950096  323 VGDLIWAKFKRRPWWPCRICSDPLINTHSKMKVSNRRPYRQYYVEAFGDPSERAWVAGKAIVMFEGRHQFEELPVLRRRG 402
Cdd:cd20144     1 VGDLVWAKVSGHPWWPCMVTYDPESGLYTKIKGSGGRTYRQYHVQFFGDNGERGWVSEKSLMPFEGKEKFEELVKELKKK 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 966950096  403 ----KQKEKgYRHKVPQKILSKWEASVGLAEQ 430
Cdd:cd20144    81 akkkSKKAK-LEKKVKPSRRKKWEIAVEEAEE 111

SET domain (including pre-SET and post-SET domains) found in SET domain bifurcated 1 (SETDB1) and 2 (SETDB2), suppressor of variegation 3-9 homologs, SUV39H1 and SUV39H2, euchromatic histone-lysine N-methyltransferase EHMT1 and EHMT2, and similar proteins; The family includes SET domain bifurcated 1 (SETDB1) and 2 (SETDB2), suppressor of variegation 3-9 homologs, SUV39H1 and SUV39H2, euchromatic histone-lysine N-methyltransferase EHMT1 and EHMT2. SETDB1 (EC 2.1.1.43; also termed ERG-associated protein with SET domain (ESET), histone H3-K9 methyltransferase 4, H3-K9-HMTase 4, or lysine N-methyltransferase 1E (KMT1E)) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). It mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. SETDB2 (EC 2.1.1.43; also termed chronic lymphocytic leukemia deletion region gene 8 protein (CLLD8), or lysine N-methyltransferase 1F (KMT1F)) acts as a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). It is involved in left-right axis specification in early development and mitosis. SUV39H1 (also termed histone H3-K9 methyltransferase 1, H3-K9-HMTase 1, lysine N-methyltransferase 1A, KMT1A, position-effect variegation 3-9 homolog, SUV39H, or Su(var)3-9 homolog 1) and SUV39H2 (also termed histone H3-K9 methyltransferase 2, H3-K9-HMTase 2, lysine N-methyltransferase 1B, KMT1B, or Su(var)3-9 homolog 2), both act as histone-lysine N-methyltransferases that specifically trimethylate 'Lys-9' of histone H3 (H3K9me3) using monomethylated H3 'Lys-9' as substrate. They mainly function in heterochromatin regions, thereby playing central roles in the establishment of constitutive heterochromatin at pericentric and telomere regions. EHMT1 (also termed Eu-HMTase1, G9a-like protein 1, GLP, GLP1, histone H3-K9 methyltransferase 5, H3-K9-HMTase 5, lysine N-methyltransferase 1D, or KMT1D) and EHMT2 (also termed Eu-HMTase2, HLA-B-associated transcript 8, histone H3-K9 methyltransferase 3, H3-K9-HMTase 3, lysine N-methyltransferase 1C, KMT1C, or protein G9a), both act as histone-lysine N-methyltransferases that specifically mono- and dimethylate 'Lys-9' of histone H3 (H3K9me1 and H3K9me2, respectively) in euchromatin. This family also includes the pre-SET domain, which is found in a number of histone methyltransferases (HMTase), N-terminal to the SET domain. Pre-SET domain is a zinc binding motif which contains 9 conserved cysteines that coordinate three zinc ions. It is thought that this region plays a structural role in stabilizing SET domains. Most family members, except for Arabidopsis thaliana SUVH9, contain a post-SET domain which harbors a zinc-binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1867 PPYKHIKVNRPIGRVQIFTADLSE-----IPRC---NCKATDENP--CGIDSECINRM-----LLYECHPTvCPAGGRCQ 1931
Cdd:cd10538     1 PSFTYIKDNIVGKNVQPFSNIIDSvgckcKDDCldsKCACAAESDgiFAYTKNGLLRLnnsppPIFECNSK-CSCDDDCK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1932 NQCFSKRQYPEVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITnfYMLTLDKDR------- 2004
Cdd:cd10538    80 NRVVQRGLQARLQVFRTSKKGWGVRSLEFIPKGSFVCEYVGEVITTSEADRRGKIYDKSGGS--YLFDLDEFSdsdgdge 157

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 2005 --IIDAGPKGNYARFMNHCCQPNCETQK-WSVNGDT---RVGLFALSDIKAGTELTFNYN 2058
Cdd:cd10538   158 elCVDATFCGNVSRFINHSCDPNLFPFNvVIDHDDLrypRIALFATRDILPGEELTFDYG 217

SET domain (including pre-SET and post-SET domains) found in SET domain and mariner transposase fusion protein (SETMAR) and similar proteins; SETMAR (also termed metnase) is a DNA-binding protein that is indirectly recruited to sites of DNA damage through protein-protein interactions. It has a sequence-specific DNA-binding activity recognizing the 19-mer core of the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element and displays a DNA nicking and end joining activity. SETMAR also acts as a histone-lysine N-methyltransferase that methylates 'Lys-4' and 'Lys-36' of histone H3. It specifically mediates dimethylation of H3 'Lys-36' at sites of DNA double-strand break and may recruit proteins required for efficient DSB repair through non-homologous end-joining.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1891 IPRCNCKatdENPCGIDSE-CI---------NRMLL----------YECHpTVCPAGGRCQNQCFSKRQYPEVEIFRTLQ 1950
Cdd:cd10544    24 FPGCDCK---TSSCEPETCsCLrkygpnyddDGCLLdfdgkysgpvFECN-SMCKCSESCQNRVVQNGLQFKLQVFKTPK 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966950096 1951 RGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRyAQEHDITNfYMLTLDKDR--------IIDAGPKGNYARFMNHCC 2022
Cdd:cd10544   100 KGWGLRTLEFIPKGRFVCEYAGEVIGFEEARRRTK-SQTKGDMN-YIIVLREHLssgkvletFVDPTYIGNIGRFLNHSC 177

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966950096 2023 QPNCETQKWSVNGDT-RVGLFALSDIKAGTELTFNY-----NLECLGN--------GKTVCKCGAPNCSGFL 2080
Cdd:cd10544   178 EPNLFMVPVRVDSMVpKLALFAARDIVAGEELSFDYsgefsNSVESVTlarqdeskSRKPCLCGAENCRGFL 249

PHD finger 3 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or 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 (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the third PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 966950096 1638 ICITCHAANPANVSASKGRLMRCVRCPVAYHANDFCLAAGSKILASNSIICPNH 1691
Cdd:cd15653     1 ICLTCHATNPSNPSASKGRLMRCVRCPVAYHANDFCLAAGSVILASNSIICPNH 54