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Conserved domains on  [gi|32564211|ref|NP_871849|]
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Histone-lysine N-methyltransferase set-18 [Caenorhabditis elegans]

Protein Classification

SET and MYND domain-containing protein( domain architecture ID 15872007)

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, ...
 82-274 3.94e-23

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: 97.05  E-value: 3.94e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211  82 AWLVHKPECKRLKASFPNLPlTEVLFLSKvidriqflekngdklgieaerkFSSLVDHKVDIrdDEEKMAHFEKIFEKMG 161
Cdd:cd19203  40 PPDSVRLEGRIIFKLLDKAP-SESEKLYS----------------------FYDLQSNINKL--SEDRKEGLRQLAMVLQ 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 162 AFRGEEMIEK------GEFFDVFCKATINSHSIHTNAGNEVGMALDLGVSKYNHSCRPTCSMVFDGYRVCLR---PLVPG 232
Cdd:cd19203  95 HYLREEIQDAsqlppaFDIFELFAKVTCNSFTICDAEMQEVGVGLYPSASLLNHSCDPNCVIVFNGPHLLLRairEIEVG 174

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 32564211 233 vdaentEEAFISYIDVGRSKYIRRRDLNSRWYFNCECTRCMD 274
Cdd:cd19203 175 ------EELTISYIDMLMPSEERRKQLRDQYCFECDCFRCQD 210
zf-MYND pfam01753
MYND finger;
49-90 7.75e-13

MYND finger;


:

Pssm-ID: 460312  Cd Length: 39  Bit Score: 62.44  E-value: 7.75e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 32564211    49 CANCLRGPapgEKLLRCGGCNFSMYCSKECQATAWLVHKPEC 90
Cdd:pfam01753   1 CAVCGKEA---LKLLRCSRCKSVYYCSKECQKADWPYHKKEC 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 ...
 82-274 3.94e-23

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: 97.05  E-value: 3.94e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211  82 AWLVHKPECKRLKASFPNLPlTEVLFLSKvidriqflekngdklgieaerkFSSLVDHKVDIrdDEEKMAHFEKIFEKMG 161
Cdd:cd19203  40 PPDSVRLEGRIIFKLLDKAP-SESEKLYS----------------------FYDLQSNINKL--SEDRKEGLRQLAMVLQ 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 162 AFRGEEMIEK------GEFFDVFCKATINSHSIHTNAGNEVGMALDLGVSKYNHSCRPTCSMVFDGYRVCLR---PLVPG 232
Cdd:cd19203  95 HYLREEIQDAsqlppaFDIFELFAKVTCNSFTICDAEMQEVGVGLYPSASLLNHSCDPNCVIVFNGPHLLLRairEIEVG 174

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 32564211 233 vdaentEEAFISYIDVGRSKYIRRRDLNSRWYFNCECTRCMD 274
Cdd:cd19203 175 ------EELTISYIDMLMPSEERRKQLRDQYCFECDCFRCQD 210
zf-MYND pfam01753
MYND finger;
49-90 7.75e-13

MYND finger;


Pssm-ID: 460312  Cd Length: 39  Bit Score: 62.44  E-value: 7.75e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 32564211    49 CANCLRGPapgEKLLRCGGCNFSMYCSKECQATAWLVHKPEC 90
Cdd:pfam01753   1 CAVCGKEA---LKLLRCSRCKSVYYCSKECQKADWPYHKKEC 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 ...
 82-274 3.94e-23

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: 97.05  E-value: 3.94e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211  82 AWLVHKPECKRLKASFPNLPlTEVLFLSKvidriqflekngdklgieaerkFSSLVDHKVDIrdDEEKMAHFEKIFEKMG 161
Cdd:cd19203  40 PPDSVRLEGRIIFKLLDKAP-SESEKLYS----------------------FYDLQSNINKL--SEDRKEGLRQLAMVLQ 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 162 AFRGEEMIEK------GEFFDVFCKATINSHSIHTNAGNEVGMALDLGVSKYNHSCRPTCSMVFDGYRVCLR---PLVPG 232
Cdd:cd19203  95 HYLREEIQDAsqlppaFDIFELFAKVTCNSFTICDAEMQEVGVGLYPSASLLNHSCDPNCVIVFNGPHLLLRairEIEVG 174

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 32564211 233 vdaentEEAFISYIDVGRSKYIRRRDLNSRWYFNCECTRCMD 274
Cdd:cd19203 175 ------EELTISYIDMLMPSEERRKQLRDQYCFECDCFRCQD 210
SET_SMYD cd20071
SET domain (including SET domain and post-SET domain) found in SET and MYND domain-containing ...
 181-272 5.66e-21

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: 88.20  E-value: 5.66e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 181 ATINSHSIHTNaGNEVGMALDLGVSKYNHSCRPTCSMVFDGYR----VCLRPLVPGvdaentEEAFISYIDVGRSKYIRR 256
Cdd:cd20071  34 VPSNSFSLTDG-LNEIGVGLFPLASLLNHSCDPNAVVVFDGNGtlrvRALRDIKAG------EELTISYIDPLLPRTERR 106

                        90
                ....*....|....*.
gi 32564211 257 RDLNSRWYFNCECTRC 272
Cdd:cd20071 107 RELLEKYGFTCSCPRC 122
SET_SMYD1_2_3-like cd19167
SET domain (including post-SET domain) found in SET and MYND domain-containing proteins, SMYD1, ...
 101-272 6.53e-15

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: 73.61  E-value: 6.53e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 101 PLTEVLFLS---KVIDRIQFLEKNGDKLGIEAERKFSSLVDHkVDIRDDEEKmahfEKIFEKMGAFRgEEMIEKGEFFD- 176
Cdd:cd19167  32 PYAYVLTPPehvRLTGRILYKQHIRKTRTSGKLLSVYDLESH-VEKLDEEKK----DGLRSDVATLH-QFMSKDLQLPDa 105

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 177 -----VFCKATINSHSIHTNAGNEVGMALDLGVSKYNHSCRPTCSMVFDGYRVCLRPLVpgvDAENTEEAFISYIDVGRS 251
Cdd:cd19167 106 aylveLFGKVNCNGFTISDEELQHVGVGIYPQAALLNHSCCPNCIVTFNGPNIEVRAVQ---EIEPGEEVFHSYIDLLYP 182

                       170       180
                ....*....|....*....|.
gi 32564211 252 KYIRRRDLNSRWYFNCECTRC 272
Cdd:cd19167 183 TEERRDQLRDQYFFLCQCADC 203
zf-MYND pfam01753
MYND finger;
49-90 7.75e-13

MYND finger;


Pssm-ID: 460312  Cd Length: 39  Bit Score: 62.44  E-value: 7.75e-13
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 32564211    49 CANCLRGPapgEKLLRCGGCNFSMYCSKECQATAWLVHKPEC 90
Cdd:pfam01753   1 CAVCGKEA---LKLLRCSRCKSVYYCSKECQKADWPYHKKEC 39
SET_SMYD1 cd10526
SET domain (including post-SET domain) found in SET and MYND domain-containing protein 1 ...
 97-272 9.49e-13

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: 67.44  E-value: 9.49e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211  97 FPNLPLTEVLFLSKVIDRIqflEKNGDKLGIEAERKFSSLVDHkVDIRDDEEKMAHFEKIFEKMGAFRGEEMIEKGEFFD 176
Cdd:cd10526  38 FGKAPNENIRLAARILWRI---EREGGGLKEGELVSIEDLQDH-LEDFSEEEKKDLREDVHSFLDYWPYQSQQFSMEYIS 113

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 177 -VFCKATINSHSIHTNAG-NEVGMALDLGVSKYNHSCRPTCSMVFDGYRVCLRPLVPgvdAENTEEAFISYIDVGRSKYI 254
Cdd:cd10526 114 hIFGVINCNGFTLSDQRGlQAVGVGIFPNLCLVNHDCWPNCTVIFNNGRIELRALGK---ISEGDELTVSYIDFLNTSED 190

                       170
                ....*....|....*...
gi 32564211 255 RRRDLNSRWYFNCECTRC 272
Cdd:cd10526 191 RKEQLKKQYYFDCTCEHC 208
SET_SMYD4 cd10536
SET domain (including iSET domain and post-SET domain) found in SET and MYND domain-containing ...
 179-272 9.66e-08

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: 52.69  E-value: 9.66e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 179 CKATINSHSIHTNAGNEVGMALDLGVSKYNHSCRPTCSMVFDG---YRVCLRPLVPGvdaentEEAFISY----IDVGRS 251
Cdd:cd10536 126 LQTTSSGSQVDTSKQVRIATAIYPTLSLLNHSCDPNTIRSFYGntiVVRATRPIKKG------EEITICYgphfSRMKRS 199

                        90       100
                ....*....|....*....|.
gi 32564211 252 KyiRRRDLNSRWYFNCECTRC 272
Cdd:cd10536 200 E--RQRLLKEQYFFDCSCEAC 218
SET_SMYD5 cd10521
SET domain (including iSET domain and post-SET domain) found in SET and MYND domain-containing ...
 197-273 1.32e-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: 50.00  E-value: 1.32e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 197 GMALDLGVSKYNHSCRPTCSMVFDG--YRVCLRPLVpgvDAENTEEAFISYID---VGRSKYIRRRDLNSRWYFNCECTR 271
Cdd:cd10521 202 GSGLYLLQSCCNHSCVPNAEITFPEnnFTLSLKALR---DIQEGEEICISYLDecqRERSRHSRQKILRENYLFICNCPK 278


                ..
gi 32564211 272 CM 273
Cdd:cd10521 279 CE 280
SET_SMYD2 cd19202
SET domain (including post-SET domain) found in SET and MYND domain-containing protein 2 ...
 177-272 9.57e-04

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: 40.58  E-value: 9.57e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 32564211 177 VFCKATINSHSIHTNAGNEVGMALDLGVSKYNHSCRPTCSMVFDGYRVCLRPLvpgVDAENTEEAFISYIDVGRSKYIRR 256
Cdd:cd19202 112 LFAQVNCNGFTIEDEELSHLGSAIFPDVALMNHSCCPNVIVTYKGTLAEVRAV---QEIKPGEEVFTSYIDLLYPTEDRN 188

                        90
                ....*....|....*.
gi 32564211 257 RDLNSRWYFNCECTRC 272
Cdd:cd19202 189 DRLRDSYFFTCECQEC 204
 
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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