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Conserved domains on  [gi|94536776|ref|NP_001035522|]
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zinc finger CW-type PWWP domain protein 2 isoform a [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PWWP_ZCWPW2 cd20146
PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ...
 88-195 1.65e-47

PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ZCWPW2 is a histone H3K4me3 reader. In addition to the PWWP domain, ZCWPW2 contains a zinc finger CW (zf-CW) domain that is a histone modification reader for the histone H3 tail with trimethylated K4. The PWWP domain specifically recognizes DNA and histone methylated lysines.


:

Pssm-ID: 438974  Cd Length: 113  Bit Score: 156.69  E-value: 1.65e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94536776  88 GFKIVYSQLPLGSLVLVKLQNWPSWPGILCPDRFKGKYVTYDPDGNVEEYHIEFLGDPHSRSWIKATFVGHYSITLKPEK 167
Cdd:cd20146   1 GLKYVYSQLPLGSLVWAKMTGYPRWPAILTPDPICGEYVDYDEDGEVEKYHVEFLGKPHSHAWISAKSVEPYNSNTKTPK 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 94536776 168 CKNKKKWY-----KSALQEACLLYGYSHEQRLE 195
Cdd:cd20146  81 CKTKKSKKrkksyESALEEAERLLKLTCEERLE 113
zf-CW pfam07496
CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four ...
 29-77 5.40e-15

CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four conserved cysteine residues and a conserved tryptophan. It was first identified by, and is predicted to be a "highly specialized mononuclear four-cysteine zinc finger...that plays a role in DNA binding and/or promoting protein-protein interactions in complicated eukaryotic processes including...chromatin methylation status and early embryonic development." Weak homology to pfam00628 further evidences these predictions (personal obs: C Yeats). Twelve different CW-domain-containing protein subfamilies are described, with different subfamilies being characteriztic of vertebrates, higher plants and other animals in which these domain is found.


:

Pssm-ID: 462181  Cd Length: 46  Bit Score: 68.10  E-value: 5.40e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 94536776    29 VWVQCENenCLKWRLLSSEDsAKVDHDEPWYCFMNTDSRYNNCSISEED 77
Cdd:pfam07496   1 YWVQCDS--CLKWRRLPTEI-DPYELPEPWYCSMNPDPKYNSCDAPEEI 46
 
Name Accession Description Interval E-value
PWWP_ZCWPW2 cd20146
PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ...
 88-195 1.65e-47

PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ZCWPW2 is a histone H3K4me3 reader. In addition to the PWWP domain, ZCWPW2 contains a zinc finger CW (zf-CW) domain that is a histone modification reader for the histone H3 tail with trimethylated K4. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438974  Cd Length: 113  Bit Score: 156.69  E-value: 1.65e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94536776  88 GFKIVYSQLPLGSLVLVKLQNWPSWPGILCPDRFKGKYVTYDPDGNVEEYHIEFLGDPHSRSWIKATFVGHYSITLKPEK 167
Cdd:cd20146   1 GLKYVYSQLPLGSLVWAKMTGYPRWPAILTPDPICGEYVDYDEDGEVEKYHVEFLGKPHSHAWISAKSVEPYNSNTKTPK 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 94536776 168 CKNKKKWY-----KSALQEACLLYGYSHEQRLE 195
Cdd:cd20146  81 CKTKKSKKrkksyESALEEAERLLKLTCEERLE 113
zf-CW pfam07496
CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four ...
 29-77 5.40e-15

CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four conserved cysteine residues and a conserved tryptophan. It was first identified by, and is predicted to be a "highly specialized mononuclear four-cysteine zinc finger...that plays a role in DNA binding and/or promoting protein-protein interactions in complicated eukaryotic processes including...chromatin methylation status and early embryonic development." Weak homology to pfam00628 further evidences these predictions (personal obs: C Yeats). Twelve different CW-domain-containing protein subfamilies are described, with different subfamilies being characteriztic of vertebrates, higher plants and other animals in which these domain is found.


Pssm-ID: 462181  Cd Length: 46  Bit Score: 68.10  E-value: 5.40e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 94536776    29 VWVQCENenCLKWRLLSSEDsAKVDHDEPWYCFMNTDSRYNNCSISEED 77
Cdd:pfam07496   1 YWVQCDS--CLKWRRLPTEI-DPYELPEPWYCSMNPDPKYNSCDAPEEI 46
PWWP pfam00855
PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain ...
 99-152 9.69e-08

PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.


Pssm-ID: 459964 [Multi-domain]  Cd Length: 92  Bit Score: 49.35  E-value: 9.69e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 94536776    99 GSLVLVKLQNWPSWPGILCPDRFKGKYVtYDPDGNVEEYHIEFLGDPHSrSWIK 152
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPEELPENV-LKPKKKDGEYLVRFFGDSEF-AWVK 52
 
Name Accession Description Interval E-value
PWWP_ZCWPW2 cd20146
PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ...
 88-195 1.65e-47

PWWP domain found in zinc finger CW-type PWWP domain protein 2 (ZCWPW2) and similar proteins; ZCWPW2 is a histone H3K4me3 reader. In addition to the PWWP domain, ZCWPW2 contains a zinc finger CW (zf-CW) domain that is a histone modification reader for the histone H3 tail with trimethylated K4. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438974  Cd Length: 113  Bit Score: 156.69  E-value: 1.65e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94536776  88 GFKIVYSQLPLGSLVLVKLQNWPSWPGILCPDRFKGKYVTYDPDGNVEEYHIEFLGDPHSRSWIKATFVGHYSITLKPEK 167
Cdd:cd20146   1 GLKYVYSQLPLGSLVWAKMTGYPRWPAILTPDPICGEYVDYDEDGEVEKYHVEFLGKPHSHAWISAKSVEPYNSNTKTPK 80

                        90       100       110
                ....*....|....*....|....*....|...
gi 94536776 168 CKNKKKWY-----KSALQEACLLYGYSHEQRLE 195
Cdd:cd20146  81 CKTKKSKKrkksyESALEEAERLLKLTCEERLE 113
zf-CW pfam07496
CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four ...
 29-77 5.40e-15

CW-type Zinc Finger; This domain appears to be a zinc finger. The alignment shows four conserved cysteine residues and a conserved tryptophan. It was first identified by, and is predicted to be a "highly specialized mononuclear four-cysteine zinc finger...that plays a role in DNA binding and/or promoting protein-protein interactions in complicated eukaryotic processes including...chromatin methylation status and early embryonic development." Weak homology to pfam00628 further evidences these predictions (personal obs: C Yeats). Twelve different CW-domain-containing protein subfamilies are described, with different subfamilies being characteriztic of vertebrates, higher plants and other animals in which these domain is found.


Pssm-ID: 462181  Cd Length: 46  Bit Score: 68.10  E-value: 5.40e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 94536776    29 VWVQCENenCLKWRLLSSEDsAKVDHDEPWYCFMNTDSRYNNCSISEED 77
Cdd:pfam07496   1 YWVQCDS--CLKWRRLPTEI-DPYELPEPWYCSMNPDPKYNSCDAPEEI 46
PWWP_ZCWPW1 cd20145
PWWP domain found in zinc finger CW-type PWWP domain protein 1 (ZCWPW1) and similar proteins; ...
 91-159 3.15e-11

PWWP domain found in zinc finger CW-type PWWP domain protein 1 (ZCWPW1) and similar proteins; ZCWPW1 is a histone H3K4me3 reader. It is associated with late-onset Alzheimer's disease (LOAD). In addition to the PWWP domain, ZCWPW1 contains a zinc finger CW (zf-CW) domain that is a histone modification reader for the histone H3 tail with trimethylated K4. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438973  Cd Length: 115  Bit Score: 59.87  E-value: 3.15e-11
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94536776  91 IVYSQLPLGSLVLVKLQNWPSWPGIL--CPDR--FkgkYVTYDPDGNVEEYHIEFLGDPHSRSWIKATFVGHY 159
Cdd:cd20145   1 LIYTKYTPGSLVWAKMPGYPWWPAMVedDPDTeeF---FWLDEESDIPTKYHVTFFDKPVSRAWVRASSIKPF 70
PWWP_MSH6 cd05837
PWWP domain found in DNA mismatch repair protein MSH6 and similar proteins; MSH6, also called ...
 98-160 6.07e-11

PWWP domain found in DNA mismatch repair protein MSH6 and similar proteins; MSH6, also called G/T mismatch-binding protein (GTBP or GTMBP), MutS protein homolog 6, or MutS-alpha 160 kDa subunit (p160), is a mismatch repair protein homologous to bacterial MutS. It is a component of the post-replicative DNA mismatch repair system (MMR). It heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, it forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Mutations in MSH6 have been linked to increased cancer susceptibility, particularly in hereditary nonpolyposis colorectal cancer in humans. MSH6 contains a PWWP domain, but its role in MSH6 remains unclear. MSH6 orthologs found in Saccharomyces cerevisiae, Caenorhabditis elegans, and Arabidopsis thaliana lack the PWWP domain. PWWP domains typically recognize DNA and histone methylated lysines.


Pssm-ID: 438962  Cd Length: 103  Bit Score: 58.84  E-value: 6.07e-11
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 94536776  98 LGSLVLVKLQNWPSWPGILCPDRFKGKYVTYDPDGnveEYHIEFLGDPHSRSWIKATFVGHYS 160
Cdd:cd05837   3 PGDLVWAKLEGYPWWPSLVCNHPTTGFHKKFGKKG---EVHVQFFDDPPSRAWVKAKNVKPFT 62
PWWP pfam00855
PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain ...
 99-152 9.69e-08

PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyzes all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organizing higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression.


Pssm-ID: 459964 [Multi-domain]  Cd Length: 92  Bit Score: 49.35  E-value: 9.69e-08
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 94536776    99 GSLVLVKLQNWPSWPGILCPDRFKGKYVtYDPDGNVEEYHIEFLGDPHSrSWIK 152
Cdd:pfam00855   1 GDLVWAKLKGYPWWPARVVDPEELPENV-LKPKKKDGEYLVRFFGDSEF-AWVK 52
PWWP cd05162
PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, ...
 99-160 3.14e-07

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.


Pssm-ID: 438958 [Multi-domain]  Cd Length: 86  Bit Score: 47.49  E-value: 3.14e-07
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 94536776  99 GSLVLVKLQNWPSWPGILCPDRFKGKYVTYDPDGNveEYHIEFLGDpHSRSWIKATFVGHYS 160
Cdd:cd05162   1 GDLVWAKLKGYPWWPARVVDPEELPEEVGKKKKKG--GVLVQFFGD-NDYAWVKSKNIKPFE 59
PWWP_NSD_rpt1 cd20144
first PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The ...
 98-154 9.92e-06

first PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein family consists of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 that are critical in maintaining the chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising in suppressing cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and play nonredundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, through mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (C5HCH). This model corresponds to the first PWWP domain. This family also includes Drosophila melanogaster maternal-effect sterile 4 (dMes4) that may act as a histone-lysine N-methyltransferase required for wing morphogenesis. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438972  Cd Length: 114  Bit Score: 44.23  E-value: 9.92e-06
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 94536776  98 LGSLVLVKLQNWPSWPGILCPDRFKGKYVTYDPDGNVE--EYHIEFLGDPHSRSWIKAT 154
Cdd:cd20144   1 VGDLVWAKVSGHPWWPCMVTYDPESGLYTKIKGSGGRTyrQYHVQFFGDNGERGWVSEK 59
PWWP_ScIOC4-like cd05840
PWWP domain found in Saccharomyces cerevisiae ISWI one complex protein 4 (ScIOC4) and similar ...
 99-154 3.66e-04

PWWP domain found in Saccharomyces cerevisiae ISWI one complex protein 4 (ScIOC4) and similar proteins; ScIOC4 functions as a component of the ISW1B complex, which acts in remodeling the chromatin by catalyzing an ATP-dependent alteration in the structure of nucleosomal DNA. The ISW1B complex acts within coding regions to control the amount of RNA polymerase II released into productive elongation and to coordinate elongation with termination and pre-mRNA processing. The family also includes Schizosaccharomyces pombe PWWP domain-containing proteins 1 and 2 (SpPDP1 and SpPDP2). SpPDP1 associates with Set9 to regulate its chromatin localization and methyltransferase activity towards H4K20. Members of this family contain a PWWP domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438965  Cd Length: 94  Bit Score: 39.21  E-value: 3.66e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 94536776  99 GSLVLVKLQNWPSWPGILCPDRFKGKYV----TYDPDGNVEEYHIEFLGDPhSRSWIKAT 154
Cdd:cd05840   1 GDLVLAKVKGYPPWPAMVLPEELLPKNVlkakKRKPKSKKTVYPVQFFPDN-EYYWVSPS 59
PWWP_NSD2_rpt1 cd20162
first PWWP domain found in nuclear SET domain-containing protein 2 (NSD2) and similar proteins; ...
 98-151 2.53e-03

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


Pssm-ID: 438990  Cd Length: 128  Bit Score: 37.58  E-value: 2.53e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94536776  98 LGSLVLVKLQNWPSWPGILCPD-------RFKGKyvtydpDGNVEEYHIEFLGDPHSRSWI 151
Cdd:cd20162   3 VGDLVWSKVSGYPWWPCMVSADpllhshtKLKGQ------KKSARQYHVQFFGDAPERAWI 57
 
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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