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Conserved domains on  [gi|1773401176|ref|NP_001362891|]
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histone-lysine N-methyltransferase SMYD3 isoform 3 [Homo sapiens]

Protein Classification

SET and MYND domain-containing protein( domain architecture ID 15749132)

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) and MYND (myeloid, Nervy, and DEAF-1) domain-containing protein may function as a protein-lysine N-methyltransferase, catalyzing the S-adenosyl-L-methionine (SAM)-dependent methylation at specific lysine residues of target proteins such as histones

CATH:  2.170.270.10
Gene Ontology:  GO:0032259|GO:0042054|GO:0046872|GO:1904047
PubMed:  16086857|25580534|25125178|34555372|24710145
SCOP:  4000530

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SET super family cl40432
SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily; The Su(var)3-9, ...
 5-234 3.50e-95

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily; The Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain superfamily corresponds to SET domain-containing lysine methyltransferases, which catalyze site and state-specific methylation of lysine residues in histones that are fundamental in epigenetic regulation of gene activation and silencing in eukaryotic organisms. 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 has 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 N-SET and C-SET. C-SET forms an unusual and conserved knot-like structure of probable functional importance. In addition to N-SET and C-SET, an insert region (I-SET) and flanking regions of high structural variability form part of the overall structure. Some family members contain a pre-SET domain, which is found in a number of histone methyltransferases (HMTase), and a post-SET domain, which harbors a zinc-binding site.


The actual alignment was detected with superfamily member cd19203:

Pssm-ID: 394802 [Multi-domain]  Cd Length: 210  Bit Score: 283.49  E-value: 3.50e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176   5 KVEKFATAKRGNGLRAVTPLRPGELLFRSDPLAYTVCKgsrgvvcdrcllgkeklmrcsqcrvakycsakcqkkawpdhk 84
Cdd:cd19203     2 KVEKFETAEKGRGLRAVTPLKPGELVLKADPFAYTVCN------------------------------------------ 39

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  85 reckclksckpryPPDSVRLLGRVVFKLMDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTFQHFMREEIQDASQ 164
Cdd:cd19203    40 -------------PPDSVRLEGRIIFKLLDKAPSESEKLYSFYDLQSNINKLSEDRKEGLRQLAMVLQHYLREEIQDASQ 106

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176 165 LPPAFDLFEAFAKVICNSFTICNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd19203   107 LPPAFDIFELFAKVTCNSFTICDAEMQEVGVGLYPSASLLNHSCDPNCVIVFNGPHLLLRAIREIEVGEE 176
zf-MYND pfam01753
MYND finger;
49-87 2.16e-14

MYND finger;


:

Pssm-ID: 460312  Cd Length: 39  Bit Score: 66.67  E-value: 2.16e-14
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1773401176  49 CDRCLLGKEKLMRCSQCRVAKYCSAKCQKKAWPDHKREC 87
Cdd:pfam01753   1 CAVCGKEALKLLRCSRCKSVYYCSKECQKADWPYHKKEC 39
 
Name Accession Description Interval E-value
SET_SMYD3 cd19203
SET domain (including post-SET domain) found in SET and MYND domain-containing protein 3 ...
 5-234 3.50e-95

SET domain (including post-SET domain) found in SET and MYND domain-containing protein 3 (SMYD3) and similar proteins; SMYD3 (also termed zinc finger MYND domain-containing protein 1) functions as a histone methyltransferase that specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It also methylates 'Lys-5' of histone H4. SMYD3 plays an important role in transcriptional activation as a member of an RNA polymerase complex. It is overexpressed in colorectal, breast, prostate, and hepatocellular tumors, and has been implicated as an oncogene in human malignancies. Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers.


Pssm-ID: 380980 [Multi-domain]  Cd Length: 210  Bit Score: 283.49  E-value: 3.50e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176   5 KVEKFATAKRGNGLRAVTPLRPGELLFRSDPLAYTVCKgsrgvvcdrcllgkeklmrcsqcrvakycsakcqkkawpdhk 84
Cdd:cd19203     2 KVEKFETAEKGRGLRAVTPLKPGELVLKADPFAYTVCN------------------------------------------ 39

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  85 reckclksckpryPPDSVRLLGRVVFKLMDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTFQHFMREEIQDASQ 164
Cdd:cd19203    40 -------------PPDSVRLEGRIIFKLLDKAPSESEKLYSFYDLQSNINKLSEDRKEGLRQLAMVLQHYLREEIQDASQ 106

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176 165 LPPAFDLFEAFAKVICNSFTICNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd19203   107 LPPAFDIFELFAKVTCNSFTICDAEMQEVGVGLYPSASLLNHSCDPNCVIVFNGPHLLLRAIREIEVGEE 176
zf-MYND pfam01753
MYND finger;
49-87 2.16e-14

MYND finger;


Pssm-ID: 460312  Cd Length: 39  Bit Score: 66.67  E-value: 2.16e-14
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1773401176  49 CDRCLLGKEKLMRCSQCRVAKYCSAKCQKKAWPDHKREC 87
Cdd:pfam01753   1 CAVCGKEALKLLRCSRCKSVYYCSKECQKADWPYHKKEC 39
SET pfam00856
SET domain; SET domains are protein lysine methyltransferase enzymes. SET domains appear to be ...
 203-234 1.23e-08

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.


Pssm-ID: 459965 [Multi-domain]  Cd Length: 115  Bit Score: 52.53  E-value: 1.23e-08
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1773401176 203 LLNHSCDPNCSIVF----NGPHLLLRAVRDIEVGEE 234
Cdd:pfam00856  74 FINHSCDPNCEVRVvyvnGGPRIVIFALRDIKPGEE 109
SET COG2940
SET domain-containing protein (function unknown) [General function prediction only];
202-234 1.69e-08

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


Pssm-ID: 442183 [Multi-domain]  Cd Length: 134  Bit Score: 52.66  E-value: 1.69e-08
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1773401176 202 SLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:COG2940    78 RFINHSCDPNCEADEEDGRIFIVALRDIAAGEE 110
SET smart00317
SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain; Putative methyl transferase, based on ...
 148-234 7.06e-08

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


Pssm-ID: 214614 [Multi-domain]  Cd Length: 124  Bit Score: 50.80  E-value: 7.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  148 VMTFQHFMREEIQDASQLPPAFDLFEAFAKVICNsfticnaemqevGVGLYPSISLLNHSCDPNCSIVF----NGPHLLL 223
Cdd:smart00317  34 IITSEEAEERPKAYDTDGAKAFYLFDIDSDLCID------------ARRKGNLARFINHSCEPNCELLFvevnGDDRIVI 101

                           90
                   ....*....|.
gi 1773401176  224 RAVRDIEVGEE 234
Cdd:smart00317 102 FALRDIKPGEE 112
 
Name Accession Description Interval E-value
SET_SMYD3 cd19203
SET domain (including post-SET domain) found in SET and MYND domain-containing protein 3 ...
 5-234 3.50e-95

SET domain (including post-SET domain) found in SET and MYND domain-containing protein 3 (SMYD3) and similar proteins; SMYD3 (also termed zinc finger MYND domain-containing protein 1) functions as a histone methyltransferase that specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It also methylates 'Lys-5' of histone H4. SMYD3 plays an important role in transcriptional activation as a member of an RNA polymerase complex. It is overexpressed in colorectal, breast, prostate, and hepatocellular tumors, and has been implicated as an oncogene in human malignancies. Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers.


Pssm-ID: 380980 [Multi-domain]  Cd Length: 210  Bit Score: 283.49  E-value: 3.50e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176   5 KVEKFATAKRGNGLRAVTPLRPGELLFRSDPLAYTVCKgsrgvvcdrcllgkeklmrcsqcrvakycsakcqkkawpdhk 84
Cdd:cd19203     2 KVEKFETAEKGRGLRAVTPLKPGELVLKADPFAYTVCN------------------------------------------ 39

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  85 reckclksckpryPPDSVRLLGRVVFKLMDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTFQHFMREEIQDASQ 164
Cdd:cd19203    40 -------------PPDSVRLEGRIIFKLLDKAPSESEKLYSFYDLQSNINKLSEDRKEGLRQLAMVLQHYLREEIQDASQ 106

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176 165 LPPAFDLFEAFAKVICNSFTICNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd19203   107 LPPAFDIFELFAKVTCNSFTICDAEMQEVGVGLYPSASLLNHSCDPNCVIVFNGPHLLLRAIREIEVGEE 176
SET_SMYD1_2_3-like cd19167
SET domain (including post-SET domain) found in SET and MYND domain-containing proteins, SMYD1, ...
 4-234 6.28e-82

SET domain (including post-SET domain) found in SET and MYND domain-containing proteins, SMYD1, SMYD2, SMYD3 and similar proteins; The family includes SET and MYND domain-containing proteins, SMYD1, SMYD2 and SMYD3. SMYD1 (EC 2.1.1.43; also termed BOP) is a heart and muscle specific SET-MYND domain containing protein, which functions as a histone methyltransferase and regulates downstream gene transcription. It methylates histone H3 at 'Lys-4' (H3K4me), seems able to perform both mono-, di-, and trimethylation. SMYD2 (also termed HSKM-B, or lysine N-methyltransferase 3C (KMT3C)) functions as a histone methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. It specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). SMYD3 (also termed zinc finger MYND domain-containing protein 1) functions as a histone methyltransferase that specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It also methylates 'Lys-5' of histone H4. SMYD3 plays an important role in transcriptional activation as a member of an RNA polymerase complex.


Pssm-ID: 380944 [Multi-domain]  Cd Length: 205  Bit Score: 249.27  E-value: 6.28e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176   4 LKVEKFATAKRGNGLRAVTPLRPGELLFRSDPLAYTVCkgsrgvvcdrcllgkeklmrcsqcrvakycsakcqkkawpdh 83
Cdd:cd19167     1 GQVERFCSPGKGRGLRALKPFEPGDLIFSERPYAYVLT------------------------------------------ 38

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  84 kreckclksckpryPPDSVRLLGRVVFKLMDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTFQHFMREEIQdas 163
Cdd:cd19167    39 --------------PPEHVRLTGRILYKQHIRKTRTSGKLLSVYDLESHVEKLDEEKKDGLRSDVATLHQFMSKDLQ--- 101

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1773401176 164 qLPPAFDLFEAFAKVICNSFTICNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd19167   102 -LPDAAYLVELFGKVNCNGFTISDEELQHVGVGIYPQAALLNHSCCPNCIVTFNGPNIEVRAVQEIEPGEE 171
SET_SMYD1 cd10526
SET domain (including post-SET domain) found in SET and MYND domain-containing protein 1 ...
 4-234 5.73e-26

SET domain (including post-SET domain) found in SET and MYND domain-containing protein 1 (SMYD1) and similar proteins; SMYD1 (EC 2.1.1.43), also termed BOP, is a heart and muscle specific SET-MYND domain containing protein, which functions as a histone methyltransferase and regulates downstream gene transcription. It methylates histone H3 at 'Lys-4' (H3K4me), seems able to perform both mono-, di-, and trimethylation. SMYD1 plays a critical role in cardiomyocyte differentiation, cardiac morphogenesis and myofibril organization, as well as in the regulation of endothelial cells (ECs). It is expressed in vascular endothelial cells, it has beenshown that knockdown of SMYD1 in endothelial cells impairs EC migration and tube formation.


Pssm-ID: 380924 [Multi-domain]  Cd Length: 210  Bit Score: 103.65  E-value: 5.73e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176   4 LKVEKFATAKRGNGLRAVTPLRPGELLFRSDPLAYTVCkgsrgvvcdrcllgkeklmrcsqcrvakycsakcqkkawpdh 83
Cdd:cd10526     1 EGVEVFTSEGKGRGLKATKEFWAGDVIFAEPPYAAVVF------------------------------------------ 38

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  84 kreckclksckPRYPPDSVRLLGRVVFKL-MDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTF-QHFMREEIQD 161
Cdd:cd10526    39 -----------GKAPNENIRLAARILWRIeREGGGLKEGELVSIEDLQDHLEDFSEEEKKDLREDVHSFlDYWPYQSQQF 107

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1773401176 162 ASQlppafDLFEAFAKVICNSFTICNAE-MQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd10526   108 SME-----YISHIFGVINCNGFTLSDQRgLQAVGVGIFPNLCLVNHDCWPNCTVIFNNGRIELRALGKISEGDE 176
SET_SMYD2 cd19202
SET domain (including post-SET domain) found in SET and MYND domain-containing protein 2 ...
 90-234 1.62e-20

SET domain (including post-SET domain) found in SET and MYND domain-containing protein 2 (SMYD2) and similar proteins; SMYD2 (also termed HSKM-B, lysine N-methyltransferase 3C (KMT3C)) functions as a histone methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. It specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). It plays a role in myofilament organization in both skeletal and cardiac muscles via Hsp90 methylation. SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. It regulates leukemia cell growth such that diminished SMYD2 expression upregulates SET7/9, thereby possibly shifting leukemia cells from growth to quiescence state associated with resistance to DNA damage associated with Acute Myeloid Leukemia (AML).


Pssm-ID: 380979 [Multi-domain]  Cd Length: 206  Bit Score: 88.73  E-value: 1.62e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  90 LKSCkPRY-----PPDSVRLLGRVVFKL-MDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMTFQHFMREEIQdas 163
Cdd:cd19202    27 LFSC-PAYayvltPSETVRLTARILAKQkIHPERTPSEKLLAVKEFESHLDKLDNEKKDLIQSDIAALHHFYSKHLE--- 102

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1773401176 164 qLPPAFDLFEAFAKVICNSFTICNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd19202   103 -FPDNDSLVVLFAQVNCNGFTIEDEELSHLGSAIFPDVALMNHSCCPNVIVTYKGTLAEVRAVQEIKPGEE 172
SET_SMYD cd20071
SET domain (including SET domain and post-SET domain) found in SET and MYND domain-containing ...
 172-255 1.52e-17

SET domain (including SET domain and post-SET domain) found in SET and MYND domain-containing protein, and similar proteins; The family includes SET and MYND domain-containing proteins, SMYD1-SYMD5. SMYD1 (EC 2.1.1.43; also termed BOP) is a heart and muscle specific SET-MYND domain containing protein, which functions as a histone methyltransferase and regulates downstream gene transcription. It methylates histone H3 at 'Lys-4' (H3K4me), seems able to perform both mono-, di-, and trimethylation. SMYD2 (also termed HSKM-B, or lysine N-methyltransferase 3C (KMT3C)) functions as a histone methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. It specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). SMYD3 (also termed zinc finger MYND domain-containing protein 1) functions as a histone methyltransferase that specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation. It also methylates 'Lys-5' of histone H4. SMYD3 plays an important role in transcriptional activation as a member of an RNA polymerase complex. SMYD4 functions as a potential tumor suppressor that plays a critical role in breast carcinogenesis at least partly through inhibiting the expression of PDGFR-alpha. SMYD5 (also termed protein NN8-4AG, or retinoic acid-induced protein 15) functions as histone lysine methyltransferase that mediates H4K20me3 at heterochromatin regions.


Pssm-ID: 380997 [Multi-domain]  Cd Length: 122  Bit Score: 78.19  E-value: 1.52e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176 172 FEAFAKVICNSFTICNaEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLL-LRAVRDIEVGEEdadmLT----GDEQVW 246
Cdd:cd20071    28 EKPLVSVPSNSFSLTD-GLNEIGVGLFPLASLLNHSCDPNAVVVFDGNGTLrVRALRDIKAGEE----LTisyiDPLLPR 102


                  ....*....
gi 1773401176 247 KEVQESLKK 255
Cdd:cd20071   103 TERRRELLE 111
zf-MYND pfam01753
MYND finger;
49-87 2.16e-14

MYND finger;


Pssm-ID: 460312  Cd Length: 39  Bit Score: 66.67  E-value: 2.16e-14
                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1773401176  49 CDRCLLGKEKLMRCSQCRVAKYCSAKCQKKAWPDHKREC 87
Cdd:pfam01753   1 CAVCGKEALKLLRCSRCKSVYYCSKECQKADWPYHKKEC 39
SET_SMYD4 cd10536
SET domain (including iSET domain and post-SET domain) found in SET and MYND domain-containing ...
 180-234 1.24e-13

SET domain (including iSET domain and post-SET domain) found in SET and MYND domain-containing protein 4 (SMYD4) and similar proteins; SMYD4 functions as a potential tumor suppressor that plays a critical role in breast carcinogenesis at least partly through inhibiting the expression of PDGFR-alpha. In zebrafish, SMYD4 is ubiquitously expressed in early embryos and becomes enriched in the developing heart; mutants show a strong defect in cardiomyocyte proliferation, which lead to a severe cardiac malformation.


Pssm-ID: 380934 [Multi-domain]  Cd Length: 218  Bit Score: 69.63  E-value: 1.24e-13
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1773401176 180 CNSFTI------------CNAEMQEVGVGLYPSISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd10536   118 CNAHAItelqttssgsqvDTSKQVRIATAIYPTLSLLNHSCDPNTIRSFYGNTIVVRATRPIKKGEE 184
SET pfam00856
SET domain; SET domains are protein lysine methyltransferase enzymes. SET domains appear to be ...
 203-234 1.23e-08

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.


Pssm-ID: 459965 [Multi-domain]  Cd Length: 115  Bit Score: 52.53  E-value: 1.23e-08
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1773401176 203 LLNHSCDPNCSIVF----NGPHLLLRAVRDIEVGEE 234
Cdd:pfam00856  74 FINHSCDPNCEVRVvyvnGGPRIVIFALRDIKPGEE 109
SET COG2940
SET domain-containing protein (function unknown) [General function prediction only];
202-234 1.69e-08

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


Pssm-ID: 442183 [Multi-domain]  Cd Length: 134  Bit Score: 52.66  E-value: 1.69e-08
                          10        20        30
                  ....*....|....*....|....*....|...
gi 1773401176 202 SLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEE 234
Cdd:COG2940    78 RFINHSCDPNCEADEEDGRIFIVALRDIAAGEE 110
SET smart00317
SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain; Putative methyl transferase, based on ...
 148-234 7.06e-08

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


Pssm-ID: 214614 [Multi-domain]  Cd Length: 124  Bit Score: 50.80  E-value: 7.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  148 VMTFQHFMREEIQDASQLPPAFDLFEAFAKVICNsfticnaemqevGVGLYPSISLLNHSCDPNCSIVF----NGPHLLL 223
Cdd:smart00317  34 IITSEEAEERPKAYDTDGAKAFYLFDIDSDLCID------------ARRKGNLARFINHSCEPNCELLFvevnGDDRIVI 101

                           90
                   ....*....|.
gi 1773401176  224 RAVRDIEVGEE 234
Cdd:smart00317 102 FALRDIKPGEE 112
SET cd08161
SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily; The Su(var)3-9, ...
 205-234 8.13e-08

SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain superfamily; The Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain superfamily corresponds to SET domain-containing lysine methyltransferases, which catalyze site and state-specific methylation of lysine residues in histones that are fundamental in epigenetic regulation of gene activation and silencing in eukaryotic organisms. 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 has 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 N-SET and C-SET. C-SET forms an unusual and conserved knot-like structure of probable functional importance. In addition to N-SET and C-SET, an insert region (I-SET) and flanking regions of high structural variability form part of the overall structure. Some family members contain a pre-SET domain, which is found in a number of histone methyltransferases (HMTase), and a post-SET domain, which harbors a zinc-binding site.


Pssm-ID: 380914 [Multi-domain]  Cd Length: 72  Bit Score: 49.17  E-value: 8.13e-08
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1773401176 205 NHSCDPNCSIVF----NGPHLLLRAVRDIEVGEE 234
Cdd:cd08161    33 NHSCEPNCEFEEvyvgGKPRVFIVALRDIKAGEE 66
SET_Suv4-20-like cd10524
SET domain (including post-SET domain) found in Drosophila melanogaster suppressor of ...
 201-234 4.66e-06

SET domain (including post-SET domain) found in Drosophila melanogaster suppressor of variegation 4-20 (Suv4-20) and similar proteins; Suv4-20 (also termed Su(var)4-20) is a histone-lysine N-methyltransferase that specifically trimethylates 'Lys-20' of histone H4. It acts as a dominant suppressor of position-effect variegation. The family also includes Suv4-20 homologs, lysine N-methyltransferase 5B (KMT5B) and lysine N-methyltransferase 5C (KMT5C). Both KMT5B (also termed lysine-specific methyltransferase 5B, or suppressor of variegation 4-20 homolog 1, or Su(var)4-20 homolog 1, or Suv4-20h1) and KMT5C (also termed lysine-specific methyltransferase 5C, or suppressor of variegation 4-20 homolog 2, or Su(var)4-20 homolog 2, or Suv4-20h2) are histone methyltransferases that specifically trimethylate 'Lys-20' of histone H4 (H4K20me3). They play central roles in the establishment of constitutive heterochromatin in pericentric heterochromatin regions.


Pssm-ID: 380922 [Multi-domain]  Cd Length: 141  Bit Score: 45.73  E-value: 4.66e-06
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1773401176 201 ISLLNHSCDPNCSIVFNGPHL-LLRAVRDIEVGEE 234
Cdd:cd10524    77 AAFINHDCRPNCKFVPTGKSTaCVKVLRDIEPGEE 111
SET_SMYD5 cd10521
SET domain (including iSET domain and post-SET domain) found in SET and MYND domain-containing ...
 194-234 7.78e-06

SET domain (including iSET domain and post-SET domain) found in SET and MYND domain-containing protein 5 (SMYD5) and similar proteins; SMYD5 (also termed protein NN8-4AG, or retinoic acid-induced protein 15) functions as histone lysine methyltransferase that mediates H4K20me3 at heterochromatin regions. It plays an important role in chromosome integrity by regulating heterochromatin and repressing endogenous repetitive DNA elements during differentiation. In zebrafish embryogenesis, it plays pivotal roles in both primitive and definitive hematopoiesis.


Pssm-ID: 380919 [Multi-domain]  Cd Length: 282  Bit Score: 46.92  E-value: 7.78e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1773401176 194 GVGLYPSISLLNHSCDPNCSIVF--NGPHLLLRAVRDIEVGEE 234
Cdd:cd10521   202 GSGLYLLQSCCNHSCVPNAEITFpeNNFTLSLKALRDIQEGEE 244
SET_SETD8 cd10528
SET domain found in SET domain-containing protein 8 (SETD8) and similar proteins; SETD8 (EC 2. ...
 203-234 4.73e-05

SET domain found in SET domain-containing protein 8 (SETD8) and similar proteins; SETD8 (EC 2.1.1.43; also termed N-lysine methyltransferase KMT5A, H4-K20-HMTase KMT5A, lysine N-methyltransferase 5A, lysine-specific methylase 5A, PR/SET domain-containing protein 07, PR-Set7 or PR/SET07) is a nucleosomal histone-lysine N-methyltransferase that specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). It plays a central role in the silencing of euchromatic genes.


Pssm-ID: 380926 [Multi-domain]  Cd Length: 141  Bit Score: 42.95  E-value: 4.73e-05
                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1773401176 203 LLNHSC-DPNC---SIVFNG-PHLLLRAVRDIEVGEE 234
Cdd:cd10528    97 LINHSKkKPNLktkLLVIDGvPHLILVAKRDIKPGEE 133
SET_SETD1-like cd10518
SET domain (including post-SET domain) found in SET domain-containing proteins (SETD1A/SETD1B), ...
 203-234 1.06e-04

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).


Pssm-ID: 380916  Cd Length: 150  Bit Score: 42.20  E-value: 1.06e-04
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1773401176 203 LLNHSCDPNC---SIVFNGP-HLLLRAVRDIEVGEE 234
Cdd:cd10518    90 FINHSCDPNCyakIITVDGEkHIVIFAKRDIAPGEE 125
SET_SETMAR cd10544
SET domain (including pre-SET and post-SET domains) found in SET domain and mariner ...
 204-234 1.35e-04

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.


Pssm-ID: 380942 [Multi-domain]  Cd Length: 254  Bit Score: 43.06  E-value: 1.35e-04
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1773401176 204 LNHSCDPNCSIV---FNG--PHLLLRAVRDIEVGEE 234
Cdd:cd10544   173 LNHSCEPNLFMVpvrVDSmvPKLALFAARDIVAGEE 208
SET_LSMT cd10527
SET domain found in Rubisco large subunit methyltransferase (LSMT) and similar proteins; ...
 11-234 3.88e-04

SET domain found in Rubisco large subunit methyltransferase (LSMT) and similar proteins; Rubisco LSMT is a non-histone protein methyl transferase responsible for the trimethylation of lysine14 in the large subunit of Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase). The family also includes SET domain-containing proteins, SETD3, SETD4 and SETD6, which belong to methyltransferase class VII that represents classical non-histone SET domain methyltransferases. Members in this family contain a SET domain and a C-terminal RubisCO LSMT substrate-binding (Rubis-subs-bind) domain.


Pssm-ID: 380925 [Multi-domain]  Cd Length: 236  Bit Score: 41.67  E-value: 3.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  11 TAKRGNGLRAVTPLRPGELLFRSdPLaytvckgsrgvvcdRCLLGKEKLMRCSQCRVAKYCSAKCQKKAWpdhkreckcl 90
Cdd:cd10527     7 SPDGGRGLFATRDIAAGEVLLSV-PR--------------SLLLTVETARESPLGGAALALLELDPELSW---------- 61

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176  91 ksckpryppdSVRLLGRVVFKLMDGA-----------PSESEKLYSFYDLE-------SNINKLTEDKKEGLRQLVMTFQ 152
Cdd:cd10527    62 ----------DVALALFLLYERARGPdsfwapyldslPRPFEDTPLFWSEEeldalqgTPLLEAAAAQRRRLREEYEALV 131

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176 153 HFMREEIQDASQLPPAFDLFE-AFAKVICNSFTIcNAEMQEVGVGLYPSISLLNHSCD-PNCSIVF--NGPHLLLRAVRD 228
Cdd:cd10527   132 EALPEALPAEPGEAFTLEEFLwALALVLSRAFSL-PVPDGGGGLALVPLADMLNHSPDaPNVRYEYdeDEGSFVLVATRD 210


                  ....*.
gi 1773401176 229 IEVGEE 234
Cdd:cd10527   211 IAAGEE 216
SET_SETD2-like cd10531
SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2), ...
 204-234 5.75e-04

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.


Pssm-ID: 380929  Cd Length: 136  Bit Score: 39.55  E-value: 5.75e-04
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1773401176 204 LNHSCDPNCS----IVFNGPHLLLRAVRDIEVGEE 234
Cdd:cd10531    77 INHSCEPNCEtqkwIVNGEYRIGIFALRDIPAGEE 111
SET_SpSet7-like cd10540
SET domain found in Schizossacharomyces pombe Set7 and similar proteins; Schizosaccharomyces ...
 202-234 7.04e-04

SET domain found in Schizossacharomyces pombe Set7 and similar proteins; Schizosaccharomyces pombe Set7 is a novel histone-lysine N-methyltransferase. The family also includes a viral histone H3 lysine 27 methyltransferase from Paramecium bursaria Chlorella virus 1 (PBCV-1).


Pssm-ID: 380938  Cd Length: 112  Bit Score: 38.77  E-value: 7.04e-04
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1773401176 202 SLLNHSCDPNCSIVFNGPHLLLR--AVRDIEVGEE 234
Cdd:cd10540    67 SMFNHSYTPNAEYEIDFENQTIVfyALRDIEAGEE 101
SET_ASH1L cd19174
SET domain (including post-SET domain) found in ASH1-like protein (ASH1L) and similar proteins; ...
 205-234 1.57e-03

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).


Pssm-ID: 380951 [Multi-domain]  Cd Length: 141  Bit Score: 38.43  E-value: 1.57e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1773401176 205 NHSCDPNCSIV---FNG-PHLLLRAVRDIEVGEE 234
Cdd:cd19174    77 NHSCDPNCEMQkwsVNGvYRIGLFALKDIPAGEE 110
SET_EZH cd10519
SET domain found in enhancer of zeste homolog 1 (EZH1), zeste homolog 2 (EZH2) and similar ...
 205-234 1.72e-03

SET domain found in enhancer of zeste homolog 1 (EZH1), zeste homolog 2 (EZH2) and similar proteins; The family includes EZH1 and EZH2. EZH1 (EC 2.1.1.43; also termed ENX-2, or histone-lysine N-methyltransferase EZH1) is a catalytic subunit of the PRC2/EED-EZH1 complex, which methylates 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. EZH2 (EC 2.1.1.43; also termed lysine N-methyltransferase 6, ENX-1, or histone-lysine N-methyltransferase EZH2) is a catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Both, EZH1 and EZH2, can mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively.


Pssm-ID: 380917  Cd Length: 117  Bit Score: 37.99  E-value: 1.72e-03
                          10        20        30
                  ....*....|....*....|....*....|....
gi 1773401176 205 NHSCDPNCS---IVFNGPHLL-LRAVRDIEVGEE 234
Cdd:cd10519    77 NHSSNPNCYakvMMVNGDHRIgIFAKRDIEAGEE 110
SET_NSD cd19173
SET domain (including post-SET domain) found in nuclear SET domain-containing proteins, NSD1, ...
 204-234 1.89e-03

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.


Pssm-ID: 380950 [Multi-domain]  Cd Length: 142  Bit Score: 38.45  E-value: 1.89e-03
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1773401176 204 LNHSCDPNCSI---VFNGPHLL-LRAVRDIEVGEE 234
Cdd:cd19173    79 MNHSCQPNCETqkwTVNGDTRVgLFAVRDIPAGEE 113
SET_SETD2 cd19172
SET domain (including post-SET domain) found in SET domain-containing protein 2 (SETD2) and ...
 204-245 3.33e-03

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.


Pssm-ID: 380949 [Multi-domain]  Cd Length: 142  Bit Score: 37.56  E-value: 3.33e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1773401176 204 LNHSCDPNCSI---VFNGphlLLR----AVRDIEVGEEdadmLTGDEQV 245
Cdd:cd19172    79 INHSCEPNCETqkwTVNG---ELRvgffAKRDIPAGEE----LTFDYQF 120
SET_SUV39H cd10542
SET domain (including pre-SET and post-SET domains) found in suppressor of variegation 3-9 ...
 192-242 4.26e-03

SET domain (including pre-SET and post-SET domains) found in suppressor of variegation 3-9 homologs, SUV39H1, SUV39H2 and similar proteins; This family includes 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. Also included are Schizosaccharomyces pombe H3K9 methyltransferase Clr4 (SUV39H homolog) and Neurospora crassa DIM-5, both of which also methylate 'Lys-9' of histone H3.


Pssm-ID: 380940 [Multi-domain]  Cd Length: 245  Bit Score: 38.43  E-value: 4.26e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401176 192 EVGVGLYPSIS-LLNHSCDPNCSI--VFNG------PHLLLRAVRDIEVGEEdadmLTGD 242
Cdd:cd10542   155 TVDAAYYGNIShFINHSCDPNLAVyaVWINhldprlPRIAFFAKRDIKAGEE----LTFD 210
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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