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Conserved domains on  [gi|984290516|ref|NP_001306115|]
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hepatoma-derived growth factor isoform d [Homo sapiens]

Protein Classification

PWWP domain-containing protein( domain architecture ID 2155)

PWWP domain-containing protein similar to Homo sapiens hepatoma-derived growth factor that may act as a transcriptional repressor

Gene Ontology:  GO:0003677|GO:0000166|GO:0005515
PubMed:  28510146|10802047|25277115

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PWWP super family cl02554
PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, ...
 43-112 2.54e-41

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.


The actual alignment was detected with superfamily member cd20148:

Pssm-ID: 470613 [Multi-domain]  Cd Length: 87  Bit Score: 137.08  E-value: 2.54e-41
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516  43 PHTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 112
Cdd:cd20148   18 PARIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 87
 
Name Accession Description Interval E-value
PWWP_HDGF cd20148
PWWP domain found in Hepatoma-derived growth factor (HDGF); HDGF, also called high mobility ...
 43-112 2.54e-41

PWWP domain found in Hepatoma-derived growth factor (HDGF); HDGF, also called high mobility group protein 1-like 2 (HMG-1L2), is a heparin-binding protein that acts as a transcriptional repressor with mitogenic activity for fibroblasts. It contains a PWWP domain, which is necessary for DNA binding.


Pssm-ID: 438976 [Multi-domain]  Cd Length: 87  Bit Score: 137.08  E-value: 2.54e-41
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516  43 PHTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 112
Cdd:cd20148   18 PARIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 87
PWWP pfam00855
PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain ...
 55-109 4.85e-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: 49.73  E-value: 4.85e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516   55 KSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKR-----KGFSEGLWEIENNP 109
Cdd:pfam00855  32 KKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKkkkkkKAFKKALEEAEEAL 91
PWWP smart00293
domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues
 43-83 5.05e-06

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


Pssm-ID: 214603 [Multi-domain]  Cd Length: 63  Bit Score: 43.10  E-value: 5.05e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 984290516    43 PHTIDEMPEAAV-----KSTANKYQVFFFGTHETAFLGPKDLFPYE 83
Cdd:smart00293  18 PALVISPKMTPDnimkrKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63
 
Name Accession Description Interval E-value
PWWP_HDGF cd20148
PWWP domain found in Hepatoma-derived growth factor (HDGF); HDGF, also called high mobility ...
 43-112 2.54e-41

PWWP domain found in Hepatoma-derived growth factor (HDGF); HDGF, also called high mobility group protein 1-like 2 (HMG-1L2), is a heparin-binding protein that acts as a transcriptional repressor with mitogenic activity for fibroblasts. It contains a PWWP domain, which is necessary for DNA binding.


Pssm-ID: 438976 [Multi-domain]  Cd Length: 87  Bit Score: 137.08  E-value: 2.54e-41
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516  43 PHTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 112
Cdd:cd20148   18 PARIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 87
PWWP_PSIP cd20151
PWWP domain found in PC4 and SFRS1-interacting protein (PSIP); PSIP, also called ...
 43-112 9.22e-36

PWWP domain found in PC4 and SFRS1-interacting protein (PSIP); PSIP, also called CLL-associated antigen KW-7, dense fine speckles 70 kDa protein (DFS 70), lens epithelium-derived growth factor (LEDGF), or transcriptional coactivator p75/p52, acts as a transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. It contains a PWWP domain, which is necessary for DNA binding.


Pssm-ID: 438979 [Multi-domain]  Cd Length: 88  Bit Score: 122.79  E-value: 9.22e-36
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516  43 PHTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 112
Cdd:cd20151   18 PARVDEVPDGAVKPPTNKLPIFFFGTHETAFLGPKDIFPYSENKEKYGKPNKRKGFNEGLWEIDNNPKVK 87
PWWP_HRP cd05834
PWWP domain found in hepatoma-derived growth factor (HDGF)-related protein (HRP) family; The ...
 46-108 5.21e-33

PWWP domain found in hepatoma-derived growth factor (HDGF)-related protein (HRP) family; The HRP family includes hepatoma-derived growth factor (HDGF), and HDGF-related proteins (HRPs). HDGF, also called high mobility group protein 1-like 2 (HMG-1L2), is a heparin-binding protein that acts as a transcriptional repressor with mitogenic activity for fibroblasts. It is a prognostic factor in several types of cancer. HDGFL1 is also called PWWP domain-containing protein 1 (PWWP1). Its biological function remains unclear. HDGFL2, also called HDGF-related protein 2 (HRP-2), or hepatoma-derived growth factor 2 (HDGF-2), is involved in cellular growth control, through the regulation of cyclin D1 expression. HDGFL3, also called HDGF-related protein 3 (HRP-3), enhances DNA synthesis and may play a role in cell proliferation. The family also includes PC4 and SFRS1-interacting protein (PSIP) and similar proteins. PSIP, also called CLL-associated antigen KW-7, dense fine speckles 70 kDa protein (DFS 70), lens epithelium-derived growth factor (LEDGF), or transcriptional coactivator p75/p52, acts as a transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Members of the HRP family contains a PWWP domain, which is necessary for DNA binding.


Pssm-ID: 438959 [Multi-domain]  Cd Length: 82  Bit Score: 115.34  E-value: 5.21e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 984290516  46 IDEMPEAAvKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENN 108
Cdd:cd05834   21 IDEIPEGA-KIPKNKYPVFFYGTHETAFLKPKDLFPYEENKEKYGKPRKRKGFNEGLWEIENN 82
PWWP_HDGFL2 cd20149
PWWP domain found in Hepatoma-derived growth factor-related protein 2 (HDGFL2); HDGFL2, also ...
 43-109 6.87e-33

PWWP domain found in Hepatoma-derived growth factor-related protein 2 (HDGFL2); HDGFL2, also called HDGF-related protein 2 (HRP-2), or Hepatoma-derived growth factor 2 (HDGF-2), is involved in cellular growth control, through the regulation of cyclin D1 expression. It contains a PWWP domain, which is necessary for DNA binding.


Pssm-ID: 438977 [Multi-domain]  Cd Length: 84  Bit Score: 115.38  E-value: 6.87e-33
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 984290516  43 PHTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNP 109
Cdd:cd20149   18 PARIDDIADGAVKPPPNKYPIFFFGTHETAFLGPKDLFPYDKYKDKYGKPNKRKGFNEGLWEIQNNP 84
PWWP_HDGFL3 cd20150
PWWP domain found in Hepatoma-derived growth factor-related protein 3 (HDGFL3); HDGFL3, also ...
 43-112 2.55e-32

PWWP domain found in Hepatoma-derived growth factor-related protein 3 (HDGFL3); HDGFL3, also called HDGF-related protein 3 (HRP-3), is the only hepatoma-derived growth factor (HDGF)-related protein (HRP) family member whose expression is almost restricted to the nervous tissue. It enhances DNA synthesis and may play a role in cell proliferation. It contains a PWWP domain, which is necessary for DNA binding.


Pssm-ID: 438978 [Multi-domain]  Cd Length: 93  Bit Score: 114.00  E-value: 2.55e-32
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516  43 PHTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIENNPTVK 112
Cdd:cd20150   23 PARIDELPEGAVKPPANKYPIFFFGTHETAFLGPKDLFPYKEYKDKFGKSNKRKGFNEGLWEIENNPGVK 92
PWWP_GLYR1 cd05836
PWWP domain found in glyoxylate reductase 1 (GLYR1) and similar proteins; GLYR1, also called ...
 50-106 2.60e-09

PWWP domain found in glyoxylate reductase 1 (GLYR1) and similar proteins; GLYR1, also called 3-hydroxyisobutyrate dehydrogenase-like protein, cytokine-like nuclear factor N-PAC, nuclear protein NP60, or nuclear protein of 60 kDa, is a putative oxidoreductase that is recruited on chromatin and promotes KDM1B demethylase activity. It recognizes and binds trimethylated 'Lys-36' of histone H3 (H3K36me3). GLYR1 enhances the activity of MAP2K4 and MAP2K6 kinases to phosphorylate p38-alpha. In addition to the PWWP domain, GLYR1 also contains an AT-hook and a C-terminal NAD-binding domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438961 [Multi-domain]  Cd Length: 86  Bit Score: 52.99  E-value: 2.60e-09
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516  50 PEAAVKSTANK---YQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKGFSEGLWEIE 106
Cdd:cd05836   24 PPPDLKKPPRKkkmHCVYFFGSENYAWIEDENIKPYEEFKEEMLKSKKSAGFKDAVEAIE 83
PWWP pfam00855
PWWP domain; The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. The domain ...
 55-109 4.85e-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: 49.73  E-value: 4.85e-08
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 984290516   55 KSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKR-----KGFSEGLWEIENNP 109
Cdd:pfam00855  32 KKKDGEYLVRFFGDSEFAWVKPKDLKPFDEGDEFEYLKKKKkkkkkKAFKKALEEAEEAL 91
PWWP cd05162
PWWP (Pro-Trp-Trp-Pro) domain; The PWWP domain, named for a conserved Pro-Trp-Trp-Pro motif, ...
 44-106 1.73e-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: 47.88  E-value: 1.73e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 984290516  44 HTIDEMPEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYEESKEKFGKPNK--RKGFSEGLWEIE 106
Cdd:cd05162   20 DPEELPEEVGKKKKKGGVLVQFFGDNDYAWVKSKNIKPFEEGFKKEFKKKKkkSKKFKKAVEEAE 84
PWWP smart00293
domain with conserved PWWP motif; conservation of Pro-Trp-Trp-Pro residues
 43-83 5.05e-06

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


Pssm-ID: 214603 [Multi-domain]  Cd Length: 63  Bit Score: 43.10  E-value: 5.05e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 984290516    43 PHTIDEMPEAAV-----KSTANKYQVFFFGTHETAFLGPKDLFPYE 83
Cdd:smart00293  18 PALVISPKMTPDnimkrKSDENLYPVLFFGDKDTAWIPSSKLFPLT 63
PWWP_PRKCBP1 cd20160
PWWP domain found in protein kinase C-binding protein 1 (PRKCBP1) and similar proteins; ...
 50-106 2.59e-04

PWWP domain found in protein kinase C-binding protein 1 (PRKCBP1) and similar proteins; PRKCBP1, also called cutaneous T-cell lymphoma-associated antigen se14-3 (CTCL-associated antigen se14-3), Rack7, or zinc finger MYND domain-containing protein 8 (ZMYND8), is a novel receptor for activated C-kinase (RACK)-like protein that may play an important role in the activation and regulation of PKC-beta I, and the PKC signaling cascade. It also has been identified as a formin homology-2-domain containing protein 1 (FHOD1)-binding protein that may be involved in FHOD1-regulated actin polymerization and transcription. Moreover, PRKCBP1 may function as a REST co-repressor 2 (RCOR2) interacting factor. They form a RCOR2/ZMYND8 complex which might be involved in the regulation of neural differentiation. PRKCBP1 contains a plant homeodomain (PHD) finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. The PWWP domain specifically recognizes DNA and histone methylated lysines.


Pssm-ID: 438988  Cd Length: 91  Bit Score: 39.09  E-value: 2.59e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 984290516  50 PEAAVKSTANKYQVFFFGTHETAFLGPKDLFPYeeSKE-KFGKPNKRKGFSEGLWEIE 106
Cdd:cd20160   21 PAKALRVNNGQVDVRFFGAHDRAWVPVKDCYLY--SKEpPTSVKKKKSGLDEAMEELE 76
PWWP_NSD_rpt2 cd05838
second PWWP domain found in nuclear receptor-binding SET domain-containing (NSD) proteins; The ...
 35-104 2.62e-04

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.


Pssm-ID: 438963 [Multi-domain]  Cd Length: 96  Bit Score: 39.15  E-value: 2.62e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 984290516  35 IPDVSRATPHTIDEMPeaavkstankyqVFFFGTHETAFLGPKDLFPYEESKEKFGKPNKRKG---FSEGLWE 104
Cdd:cd05838   26 VPDNIQSLPHPPGEFP------------VRFFGSHDYYWVHRGRVFLFEEGDKGSKEKSKKSLdksFKRALKE 86
 
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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