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Conserved domains on  [gi|17550542|ref|NP_508620|]
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GRAM domain-containing protein [Caenorhabditis elegans]

Protein Classification

GRAM domain-containing protein( domain architecture ID 10192315)

GRAM domain-containing protein is a membrane-associated protein; similar to Homo sapiens WW domain-binding protein 2, which acts as a transcriptional coactivator of estrogen and progesterone receptors (ESR1 and PGR) upon hormone activation

CATH:  2.30.29.30
Gene Ontology:  GO:0003713|GO:0031490
PubMed:  11050430|18201690
SCOP:  4000903

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PH-GRAM_WBP2 cd13214
WW binding protein 2 (WB2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 29-131 2.07e-43

WW binding protein 2 (WB2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; WBP2 plays a number of roles including: acting as a tyrosine kinase substrate, activation of estrogen receptor alpha (ERalpha)/progesterone receptor (PR) transcription, and playing a role in breast cancer. WBP2 contain a N-terminal PH-GRAM domain and a C-terminal WWbp domain. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The WWbp domain is characterized by several short PY and PT-like motifs of the PPPPY form and binds to WW domains. WW domains contain two highly conserved tryptophans that are spaced 20-23 residues apart. They bind proline-rich peptide motifs [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs.


:

Pssm-ID: 275401  Cd Length: 103  Bit Score: 143.85  E-value: 2.07e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542  29 VKLKFEKYNVPAFKSTKSGALYLTSHRIIFMNESKKDEFKSFAMPFNSVRDVKLEQPLLTPNYLKGWVQPMPGGNFDGCP 108
Cdd:cd13214   1 VESVKGKGAPPFFKGSKKGTIYLTNQRLIFVSSKPTDNFQSFSMPLLNIRDVKFEQPVFGANYLKGKVKPVPGGGWPGEA 80

                        90       100
                ....*....|....*....|...
gi 17550542 109 EWRLSFPKGGCIEFGEALLRAAD 131
Cdd:cd13214  81 EFKLTFKDGGAIEFGQAFLRLAE 103
Atrophin-1 super family cl38111
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 204-296 7.73e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


The actual alignment was detected with superfamily member pfam03154:

Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 37.82  E-value: 7.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542   204 QTTPYPAGQFQPVGTVQYQNVGAYPGQPQQPGQYHPyPTNQPPQGGFN-------VGQGAAPHPSTLPDYNNIQQQSSAQ 276
Cdd:pfam03154 177 QSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSP-ATSQPPNQTQStaaphtlIQQTPTLHPQRLPSPHPPLQPMTQP 255

                          90       100
                  ....*....|....*....|
gi 17550542   277 PPAYNAYQEAPPLPSKNGPL 296
Cdd:pfam03154 256 PPPSQVSPQPLPQPSLHGQM 275
 
Name Accession Description Interval E-value
PH-GRAM_WBP2 cd13214
WW binding protein 2 (WB2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 29-131 2.07e-43

WW binding protein 2 (WB2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; WBP2 plays a number of roles including: acting as a tyrosine kinase substrate, activation of estrogen receptor alpha (ERalpha)/progesterone receptor (PR) transcription, and playing a role in breast cancer. WBP2 contain a N-terminal PH-GRAM domain and a C-terminal WWbp domain. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The WWbp domain is characterized by several short PY and PT-like motifs of the PPPPY form and binds to WW domains. WW domains contain two highly conserved tryptophans that are spaced 20-23 residues apart. They bind proline-rich peptide motifs [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs.


Pssm-ID: 275401  Cd Length: 103  Bit Score: 143.85  E-value: 2.07e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542  29 VKLKFEKYNVPAFKSTKSGALYLTSHRIIFMNESKKDEFKSFAMPFNSVRDVKLEQPLLTPNYLKGWVQPMPGGNFDGCP 108
Cdd:cd13214   1 VESVKGKGAPPFFKGSKKGTIYLTNQRLIFVSSKPTDNFQSFSMPLLNIRDVKFEQPVFGANYLKGKVKPVPGGGWPGEA 80

                        90       100
                ....*....|....*....|...
gi 17550542 109 EWRLSFPKGGCIEFGEALLRAAD 131
Cdd:cd13214  81 EFKLTFKDGGAIEFGQAFLRLAE 103
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 44-130 6.07e-06

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.


Pssm-ID: 397160  Cd Length: 112  Bit Score: 44.28  E-value: 6.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542    44 TKSGALYLTSHRIIFMneSKKDEF-KSFAMPFNSVRDVklEQPLLTPNYLKGWVQpmpggNFDGCPE---WRLSFPKGGC 119
Cdd:pfam02893  29 PVQGRLYLTNYRLCFR--SLPKGWsTKVVIPLVDIEEI--EKLKGGANLFPNGIQ-----VETGSNDkfsFAGFVTRDEA 99

                          90
                  ....*....|.
gi 17550542   120 IEFGEALLRAA 130
Cdd:pfam02893 100 IEFILALLKNA 110
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 204-296 7.73e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 37.82  E-value: 7.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542   204 QTTPYPAGQFQPVGTVQYQNVGAYPGQPQQPGQYHPyPTNQPPQGGFN-------VGQGAAPHPSTLPDYNNIQQQSSAQ 276
Cdd:pfam03154 177 QSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSP-ATSQPPNQTQStaaphtlIQQTPTLHPQRLPSPHPPLQPMTQP 255

                          90       100
                  ....*....|....*....|
gi 17550542   277 PPAYNAYQEAPPLPSKNGPL 296
Cdd:pfam03154 256 PPPSQVSPQPLPQPSLHGQM 275
 
Name Accession Description Interval E-value
PH-GRAM_WBP2 cd13214
WW binding protein 2 (WB2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 29-131 2.07e-43

WW binding protein 2 (WB2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; WBP2 plays a number of roles including: acting as a tyrosine kinase substrate, activation of estrogen receptor alpha (ERalpha)/progesterone receptor (PR) transcription, and playing a role in breast cancer. WBP2 contain a N-terminal PH-GRAM domain and a C-terminal WWbp domain. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The WWbp domain is characterized by several short PY and PT-like motifs of the PPPPY form and binds to WW domains. WW domains contain two highly conserved tryptophans that are spaced 20-23 residues apart. They bind proline-rich peptide motifs [AP]-P-P-[AP]-Y, and/or phosphoserine- phosphothreonine-containing motifs.


Pssm-ID: 275401  Cd Length: 103  Bit Score: 143.85  E-value: 2.07e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542  29 VKLKFEKYNVPAFKSTKSGALYLTSHRIIFMNESKKDEFKSFAMPFNSVRDVKLEQPLLTPNYLKGWVQPMPGGNFDGCP 108
Cdd:cd13214   1 VESVKGKGAPPFFKGSKKGTIYLTNQRLIFVSSKPTDNFQSFSMPLLNIRDVKFEQPVFGANYLKGKVKPVPGGGWPGEA 80

                        90       100
                ....*....|....*....|...
gi 17550542 109 EWRLSFPKGGCIEFGEALLRAAD 131
Cdd:cd13214  81 EFKLTFKDGGAIEFGQAFLRLAE 103
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 44-130 6.07e-06

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.


Pssm-ID: 397160  Cd Length: 112  Bit Score: 44.28  E-value: 6.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542    44 TKSGALYLTSHRIIFMneSKKDEF-KSFAMPFNSVRDVklEQPLLTPNYLKGWVQpmpggNFDGCPE---WRLSFPKGGC 119
Cdd:pfam02893  29 PVQGRLYLTNYRLCFR--SLPKGWsTKVVIPLVDIEEI--EKLKGGANLFPNGIQ-----VETGSNDkfsFAGFVTRDEA 99

                          90
                  ....*....|.
gi 17550542   120 IEFGEALLRAA 130
Cdd:pfam02893 100 IEFILALLKNA 110
Vps36_ESCRT-II pfam11605
Vacuolar protein sorting protein 36 Vps36; Vps36 is a subunit of ESCRT-II, a protein involved ...
 8-62 1.42e-04

Vacuolar protein sorting protein 36 Vps36; Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes.


Pssm-ID: 402964  Cd Length: 92  Bit Score: 39.98  E-value: 1.42e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 17550542     8 TPDGQGILIyNGEMILLYTTNVKLKFEKYNVPAFKStksGALYLTSHRIIFMNES 62
Cdd:pfam11605   3 NTSGRPVLR-ENEVDIYVQDNVGLYQGDQKILNRQN---GRLYLTTHRIIYVDSA 53
PH-GRAM-like_Vps36 cd13227
Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Vps36; ...
 8-80 3.76e-04

Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Vps36; ESCRT complexes form the main machinery driving protein sorting from endosomes to lysosomes. Yeast/human ESCRT-I consists of Vps23/Tsg101, Vps28/Vps28, and Vps37/Vps37 homolog. Yeast/human ESCRT-II is composed of Vps25/EAP20, Vps22/EAP30, and Vps36/EAP45. Yeast ESCRT-III consists Vps2, Vps20, Vps24, and Snf7 subunits. In contrast, there are three human paralogs of Snf7 (hSnf7-1/CHMP4A, hSnf7-2/CHMP4B, and hSnf7-3/CHMP4C) and two paralogs of Vps2 (CHMP2A and CHMP2B). Yeast ESCRT-I links directly to ESCRT-II, through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc-finger insertion within the GLUE domain of Vps36. The Vps36 subunit (ESCRT-II) binds ubiquitin using one of its two NZF zinc fingers in its N-terminal region. Human Vps36, EAP45, also binds ubiquitin despite having no NZF domain. Instead, mammalian ESCRT-II interacts with Ub through the Eap45 GLUE domain itself. The yeast Vps36 GLUE has a complete PH domain, wherease Eap45 GLUE only has a PH-like fold since it lacks the secondary structure element corresponding to the 4 strand. ESCRT-II also interacts with ESCRT-III via a Vps25(EAP20)/Vps20(CHMP6) interaction. Structure 2CAY is missing this insertion that contains 2 NZF zinc fingers. It is a split PH domain, with a noncanonical lipid binding pocket that binds PI(3)P. The interactions of ESCRT-II GLUE domain with membranes, ESCRT-I, and ubiquitin are critical for ubiquitinated cargo progression from early to late endosomes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275409 [Multi-domain]  Cd Length: 119  Bit Score: 39.62  E-value: 3.76e-04
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17550542   8 TPDGQGILiYNGEMILLYTTNVKLKFEKYNVPAFKStksGALYLTSHRIIFMNESKKDEfKSFAMPFNSVRDV 80
Cdd:cd13227   7 TRSGQPIL-RENEKDIYVDDNVGLYHGKSKILNRQN---GRIYLTSQRIIYVDDDDPKK-NSVALELDDIKSV 74
Atrophin-1 pfam03154
Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian ...
 204-296 7.73e-03

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.


Pssm-ID: 460830 [Multi-domain]  Cd Length: 991  Bit Score: 37.82  E-value: 7.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17550542   204 QTTPYPAGQFQPVGTVQYQNVGAYPGQPQQPGQYHPyPTNQPPQGGFN-------VGQGAAPHPSTLPDYNNIQQQSSAQ 276
Cdd:pfam03154 177 QSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSP-ATSQPPNQTQStaaphtlIQQTPTLHPQRLPSPHPPLQPMTQP 255

                          90       100
                  ....*....|....*....|
gi 17550542   277 PPAYNAYQEAPPLPSKNGPL 296
Cdd:pfam03154 256 PPPSQVSPQPLPQPSLHGQM 275
 
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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