second 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. 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 1907092814 1371 HYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 1450
Cdd:cd20164      1 HYKEVVWVKVGRYRWWPAEVCHPKSIPTNIQKMKHDIGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 80

                           90
                   ....*....|....*.
gi 1907092814 1451 KKALQEAAARFEELKA 1466
Cdd:cd20164     81 KKALQEAAVRFEELKA 96

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 1907092814 1736 ECFSCGDAGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 1778
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 1907092814 1325 WCFVCSEGGSLLCCDSCPAAFHRECLNIDIPEGNWYCNDC 1364
Cdd:cd15656      1 WCFVCSEGGSLLCCESCPAAFHRECLNIDMPEGSWYCNDC 40

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
                   ....*....|....*....|....*....|....*....|....*....
gi 1907092814    1 MFEGRHQFEELPVLRKRGKQKEKGYRHKVPQKILSKWEASVGLAEQYDV 49
Cdd:cd20161     68 PFEGRHQFEELPVLRRRGKQKEKDYKHKIPQKLLSLWEASVAHAEDFLS 116

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 1907092814 1517 DENPCGIDSECINRMLLYECHPTVCPAGVRCQNQCFSKR 1555
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 1907092814 1068 SHLKEFSGGTTKIFDKPRKRKRQRLVTARVHYKKVKKedlTKDTPSSEGELLIHRTAASPKEILEEGVEHDPGMSASKKL 1147
Cdd:COG5034    141 SSGEHRSAASSQGSRHTKLKKRKNIHNLKRRSPELSS---KREVSFTLESPSVPDTATRVKEGNNGGSTKSRGVSSEDNS 217

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907092814 1148 QVERgggaalKENVCQNCEkLGELLLCEAQCCGA--FHLECLGLPEMPRGKFICNEC 1202
Cdd:COG5034    218 EGEE------LYCFCQQVS-YGQMVACDNANCKRewFHLECVGLKEPPKGKWYCPEC 267

second 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. 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 1907092814 1371 HYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 1450
Cdd:cd20164      1 HYKEVVWVKVGRYRWWPAEVCHPKSIPTNIQKMKHDIGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 80

                           90
                   ....*....|....*.
gi 1907092814 1451 KKALQEAAARFEELKA 1466
Cdd:cd20164     81 KKALQEAAVRFEELKA 96

SET domain-containing protein (function unknown) [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1558 PDVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDItnfYMLTLDKDRIIDAGPKGNYARFMNH 1637
Cdd:COG2940      6 PRIEVRPSPIHGRGVFATRDIPKGTLIGEYPGEVITWAEAERREPHKEPLHT---YLFELDDDGVIDGALGGNPARFINH 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907092814 1638 CCQPNCETqkwsVNGDTRVGLFALSDIKAGTELTFNYNLEClGNGKTVCKCgaPNCSG 1695
Cdd:COG2940     83 SCDPNCEA----DEEDGRIFIVALRDIAAGEELTYDYGLDY-DEEEYPCRC--PNCRG 133

SET domain; SET domains are protein lysine methyltransferase enzymes. SET domains appear to be protein-protein interaction domains. It has been demonstrated that SET domains mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). A subset of SET domains have been called PR domains. These domains are divergent in sequence from other SET domains, but also appear to mediate protein-protein interaction. The SET domain consists of two regions known as SET-N and SET-C. SET-C forms an unusual and conserved knot-like structure of probably functional importance. Additionally to SET-N and SET-C, an insert region (SET-I) and flanking regions of high structural variability form part of the overall structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1569 GWGLRTKTDIKKGEFVNEYVGE-LIDEEECRARIRYAQEHDIT---NFYMLTLDKD--RIID--AGPKGNYARFMNHCCQ 1640
Cdd:pfam00856    1 GRGLFATEDIPKGEFIGEYVEVlLITKEEADKRELLYYDKLELrlwGPYLFTLDEDseYCIDarALYYGNWARFINHSCD 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1907092814 1641 PNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYN 1675
Cdd:pfam00856   81 PNCEVRVVYVNGGPRIVIFALRDIKPGEELTIDYG 115

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 1907092814 1736 ECFSCGDAGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 1778
Cdd:cd15659      1 ECFSCGDGGQLVSCKKPGCPKVYHADCLNLTKRPAGKWECPWH 43

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

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907092814  1370 PHYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYM 1432
Cdd:smart00293    1 FKPGDLVWAKMKGFPWWPALVISPKMTPDNIMKRKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63

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 1907092814 1161 VCQNCEKLGELLLCEAQCCGAFHLECLGLPEMPRGKFICNEC 1202
Cdd:cd15648      1 VCQVCEKPGELLLCEGQCCGAFHLDCIGLSEMPSGKFICDEC 42

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 1907092814 1777 WHQCDVCGKEAASFCEMCPSSFCKQHREGMLFISKLDGRLSCTEHDPCGP 1826
Cdd:pfam17982    1 WHQCSVCGSPATSFCEFCPSSFCKDHEKGALVPSALEGRLCCSEHDPESP 50

associated with SET domains; subdomain of PRESET

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|...
gi 1907092814  1507 EIPRCNCKAT--DENPCGidSECINRMLLYEChPTVCPAGVRCQNQCFSKRQY 1557
Cdd:smart00570    1 DIMTCECKPTddDETACG--SDCLNRMLFIEC-SSSCPCGSYCSNQRFQKRQY 50

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 1907092814  1325 WCFVCSE---GGSLLCCDSCPAAFHRECLNI----DIPEGNWYCNDC 1364
Cdd:smart00249    1 YCSVCGKpddGGELLQCDGCDRWYHQTCLGPplleEEPDGKWYCPKC 47

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 1907092814  1161 VCQNCEKLGELLLCEaQCCGAFHLECLGLP---EMPRGKFICNEC 1202
Cdd:smart00249    4 VCGKPDDGGELLQCD-GCDRWYHQTCLGPPlleEEPDGKWYCPKC 47

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 1907092814  1737 CFSCG---DAGQLVSCKkpGCPKVYHADCLNLTKR---PAGKWECPWH 1778
Cdd:smart00249    2 CSVCGkpdDGGELLQCD--GCDRWYHQTCLGPPLLeeePDGKWYCPKC 47

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 1907092814  1208 TCFVCKQSGEDVK--RCLLplCGKFYHEECVQKYPPTVTQNKGFRCPLH 1254
Cdd:smart00249    1 YCSVCGKPDDGGEllQCDG--CDRWYHQTCLGPPLLEEEPDGKWYCPKC 47

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1907092814 1325 WCFvCSEG--GSLLCCDS--CPAA-FHRECLNI-DIPEGNWYCNDCK 1365
Cdd:COG5034    223 YCF-CQQVsyGQMVACDNanCKREwFHLECVGLkEPPKGKWYCPECK 268

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 1907092814 1557 YPDVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMN 1636
Cdd:cd19173      1 YPPTEPFKTGDRGWGLRTKRDIKKGDFVIEYVGELIDEEECRRRLKKAHENNITNFYMLTLDKDRIIDAGPKGNLSRFMN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907092814 1637 HCCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCSGFLG 1698
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 1907092814 1557 YPDVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMN 1636
Cdd:cd19212      1 YPDAEIIKTERRGWGLRTKRSIKKGEFVNEYVGELIDEEECRLRIKRAHENSVTNFYMLTVTKDRIIDAGPKGNYSRFMN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907092814 1637 HCCQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNCSGFLG 1698
Cdd:cd19212     81 HSCNPNCETQKWTVNGDVRVGLFALCDIPAGMELTFNYNLDCLGNGRTECHCGADNCSGFLG 142

second 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. 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 1907092814 1371 HYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 1450
Cdd:cd20164      1 HYKEVVWVKVGRYRWWPAEVCHPKSIPTNIQKMKHDIGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 80

                           90
                   ....*....|....*.
gi 1907092814 1451 KKALQEAAARFEELKA 1466
Cdd:cd20164     81 KKALQEAAVRFEELKA 96

SET domain (including post-SET domain) found in ASH1-like protein (ASH1L) and similar proteins; ASH1L (EC 2.1.1.43; also termed absent small and homeotic disks protein 1 homolog, KMT2H, or lysine N-methyltransferase 2H) acts as histone-lysine N-methyltransferase that specifically methylates 'Lys-36' of histone H3 (H3K36me). It plays important roles in development; heterozygous mutation of ASH1L is associated with severe intellectual disability (ID) and multiple congenital anomaly (MCA).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1559 DVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRyAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHC 1638
Cdd:cd19174      1 GLERFRTEDKGWGVRTKEPIKAGQFIIEYVGEVVSEQEFRRRMI-EQYHNHSHHYCLNLDSGMVIDGYRMGNEARFVNHS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907092814 1639 CQPNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYNLECLG-NGKTVCKCGAPNCSGFLG 1698
Cdd:cd19174     80 CDPNCEMQKWSVNGVYRIGLFALKDIPAGEELTYDYNFHSFNvEKQQPCKCGSPNCRGVIG 140

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 1907092814 1371 HYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGVDGTY 1450
Cdd:cd05838      1 LYGDIVWVKLGNYRWWPAEILHPREVPDNIQSLPHPPGEFPVRFFGSHDYYWVHRGRVFLFEEGDKGSKEKSKKSLDKSF 80

                           90
                   ....*....|....*.
gi 1907092814 1451 KKALQEAAARFEELKA 1466
Cdd:cd05838     81 KRALKEANEAFRELKA 96

second 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 second PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1371 HYREIVWVKVGRYRWWPAEICHPRAVPSNIDKMRHDVGEFPVLFFGSNDYLWTHQARVFPYMEGDVSSKDKMGKGvDGTY 1450
Cdd:cd20166      1 HYKQIVWVKLGNYRWWPAEICNPRSVPLNIQGLKHDIGDFPVFFFGSHDYYWVHQGRVFPYVEGDKSFAEGQTSI-NKTF 79

                           90
                   ....*....|....*.
gi 1907092814 1451 KKALQEAAARFEELKA 1466
Cdd:cd20166     80 KKALEEAAKRFQELKA 95

SET domain (including post-SET domain) found in SET domain-containing proteins (SETD1A/SETD1B), histone-lysine N-methyltransferases (KMT2A/KMT2B/KMT2C/KMT2D) and similar proteins; This family includes SET domain-containing protein 1A (SETD1A), 1B (SETD1B), as well as histone-lysine N-methyltransferase 2A (KMT2A), 2B (KMT2B), 2C (KMT2C), 2D (KMT2D). These proteins are histone-lysine N-methyltransferases (EC 2.1.1.43) that specifically methylate 'Lys-4' of histone H3 (H3K4me).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1569 GWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITNFYMLTLDKDRIIDAGPKGNYARFMNHCCQPNCETQKW 1648
Cdd:cd10518     25 GWGLFAKRPIAAGEMVIEYVGEVIRPIVADKREKRYDEEGGGGTYMFRIDEDLVIDATKKGNIARFINHSCDPNCYAKII 104

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1907092814 1649 SVNGDTRVGLFALSDIKAGTELTFNYNLECLGNGKTVCKCGAPNC 1693
Cdd:cd10518    105 TVDGEKHIVIFAKRDIAPGEELTYDYKFPIEDEEKIPCLCGAPNC 149

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 1907092814 1484 PPYKHIKVNRPIGRVQIFTADLSE-----IPRC---NCKATDENP--CGIDSECINRM-----LLYECHPTvCPAGVRCQ 1548
Cdd:cd10538      1 PSFTYIKDNIVGKNVQPFSNIIDSvgckcKDDCldsKCACAAESDgiFAYTKNGLLRLnnsppPIFECNSK-CSCDDDCK 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1549 NQCFSKRQYPDVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDITnfYMLTLDKDR------- 1621
Cdd:cd10538     80 NRVVQRGLQARLQVFRTSKKGWGVRSLEFIPKGSFVCEYVGEVITTSEADRRGKIYDKSGGS--YLFDLDEFSdsdgdge 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1622 --IIDAGPKGNYARFMNHCCQPNCETQK-WSVNGDT---RVGLFALSDIKAGTELTFNYN 1675
Cdd:cd10538    158 elCVDATFCGNVSRFINHSCDPNLFPFNvVIDHDDLrypRIALFATRDILPGEELTFDYG 217

SET domain-containing protein (function unknown) [General function prediction only];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1558 PDVEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDItnfYMLTLDKDRIIDAGPKGNYARFMNH 1637
Cdd:COG2940      6 PRIEVRPSPIHGRGVFATRDIPKGTLIGEYPGEVITWAEAERREPHKEPLHT---YLFELDDDGVIDGALGGNPARFINH 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1907092814 1638 CCQPNCETqkwsVNGDTRVGLFALSDIKAGTELTFNYNLEClGNGKTVCKCgaPNCSG 1695
Cdd:COG2940     83 SCDPNCEA----DEEDGRIFIVALRDIAAGEELTYDYGLDY-DEEEYPCRC--PNCRG 133

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 1907092814 1508 IPRCNCKatdENPCGIDSE-CI---------NRMLL----------YECHpTVCPAGVRCQNQCFSKRQYPDVEIFRTLQ 1567
Cdd:cd10544     24 FPGCDCK---TSSCEPETCsCLrkygpnyddDGCLLdfdgkysgpvFECN-SMCKCSESCQNRVVQNGLQFKLQVFKTPK 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1568 RGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRyAQEHDITNfYMLTLDKDR--------IIDAGPKGNYARFMNHCC 1639
Cdd:cd10544    100 KGWGLRTLEFIPKGRFVCEYAGEVIGFEEARRRTK-SQTKGDMN-YIIVLREHLssgkvletFVDPTYIGNIGRFLNHSC 177

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907092814 1640 QPNCETQKWSVNGDT-RVGLFALSDIKAGTELTFNY-----NLECLGN--------GKTVCKCGAPNCSGFL 1697
Cdd:cd10544    178 EPNLFMVPVRVDSMVpKLALFAARDIVAGEELSFDYsgefsNSVESVTlarqdeskSRKPCLCGAENCRGFL 249

SET domain; SET domains are protein lysine methyltransferase enzymes. SET domains appear to be protein-protein interaction domains. It has been demonstrated that SET domains mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). A subset of SET domains have been called PR domains. These domains are divergent in sequence from other SET domains, but also appear to mediate protein-protein interaction. The SET domain consists of two regions known as SET-N and SET-C. SET-C forms an unusual and conserved knot-like structure of probably functional importance. Additionally to SET-N and SET-C, an insert region (SET-I) and flanking regions of high structural variability form part of the overall structure.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1569 GWGLRTKTDIKKGEFVNEYVGE-LIDEEECRARIRYAQEHDIT---NFYMLTLDKD--RIID--AGPKGNYARFMNHCCQ 1640
Cdd:pfam00856    1 GRGLFATEDIPKGEFIGEYVEVlLITKEEADKRELLYYDKLELrlwGPYLFTLDEDseYCIDarALYYGNWARFINHSCD 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1907092814 1641 PNCETQKWSVNGDTRVGLFALSDIKAGTELTFNYN 1675
Cdd:pfam00856   81 PNCEVRVVYVNGGPRIVIFALRDIKPGEELTIDYG 115

SET domain (including post-SET domain) found in histone-lysine N-methyltransferase 2A (KMT2A), 2B (KMT2B) and similar proteins; This family includes KMT2A and KMT2B. Both KMT2A (also termed ALL-1 or CXXC7 or MLL or MLL1 or TRX1 or HRX) and KMT2B (also termed MLL4 or TRX2) act as histone methyltransferases that methylate 'Lys-4' of histone H3 (H3K4me).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907092814 1560 VEIFRTLQRGWGLRTKTDIKKGEFVNEYVGELIDEEECRARIRYAQEHDItNFYMLTLDKDRIIDAGPKGNYARFMNHCC 1639
Cdd:cd19170     16 VGVYRSPIHGRGLFCKRNIDAGEMVIEYAGEVIRSVLTDKREKYYESKGI-GCYMFRIDDDEVVDATMHGNAARFINHSC 94