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Conserved domains on  [gi|28373192|ref|NP_008933|]
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proteasomal ubiquitin receptor ADRM1 isoform 1 [Homo sapiens]

Protein Classification

proteasomal ubiquitin receptor ADRM1 family protein( domain architecture ID 10882094)

proteasomal ubiquitin receptor ADRM1 family protein is a regulatory component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins

CATH:  2.30.29.70
Gene Ontology:  GO:0070628|GO:0043248
PubMed:  22350895|18497817|15493994
SCOP:  4004665|4005018

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PH_Rpn13 cd13314
Pleckstrin homology-like domain of Regulatory Particle Non-ATPase 13; Targeted protein ...
 24-128 8.16e-76

Pleckstrin homology-like domain of Regulatory Particle Non-ATPase 13; Targeted protein degradation is performed to a great extent by the ubiquitin-proteasome pathway, in which substrate proteins are marked by covalently attached ubiquitin chains that mediate recognition by the proteasome. Rpn13(also called ADRM1/ARM1) is one of the two major ubiquitin receptors of the proteasome, the other being S5a/Rpn10 which is not essential for ubiquitin-mediated protein degradation in budding yeast2. S5a has two ubiquitin interacting motifs (UIMs) that bind simultaneously to ubiquitin moieties to increase affinity while Rpn13 binds ubiquitin with a single, high affinity surface within its N-terminal PH domain. Rpn13 also binds and activates deubiquitinating enzyme Uch37, one of the proteasome's three deubiquitinating enzymes. Recently it was discovered that the ubiquitin-binding domain (BD) and Uch37 BD of human (h) Rpn13 pack against each other when it is not incorporated into the proteasome reducing hRpn13's affinity for ubiquitin. However when hRpn13 binds to hRpn2/S1 this abrogates its interdomain interactions, thus activating hRpn13 for ubiquitin binding. 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: 270124  Cd Length: 105  Bit Score: 230.62  E-value: 8.16e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192  24 VEFRAGKMSLKGTTVTPDKRKGLVYIQQTDDSLIHFCWKDRTSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSK 103
Cdd:cd13314   1 VEFKAGKMTLKGTTVTPDPRKGLVYLQQGDDGLIHFCWKDRTSGAVEDDLIIFPDDAEFEKVPQCTTGRVYVLKFKSSSQ 80

                        90       100
                ....*....|....*....|....*
gi 28373192 104 RLFFWMQEPKTDQDEEHCRKVNEYL 128
Cdd:cd13314  81 KHFFWMQEPSTDKDEEICKKVNELL 105
RPN13_C pfam16550
UCH-binding domain; RPN13_C is a family of all-helical domains that forms the binding-surface ...
 274-381 6.71e-44

UCH-binding domain; RPN13_C is a family of all-helical domains that forms the binding-surface for the proteasome-ubiquitn-receptor protein Rpn13 to UCH37, one of the three de-ubiquitinating enzymes of the proteasome.


:

Pssm-ID: 465170  Cd Length: 106  Bit Score: 148.17  E-value: 6.71e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192   274 MNVPAGPAGGQQVDLASVLTPEIMAPILANADVQERLLPYLPsgESLPQTADEIQNTLTSPQFQQALGMFSAALASGQLG 353
Cdd:pfam16550   1 LQQAGAAGGGPGVDLTDILTPENLSPLLNDPELVEALAPHLP--PPGPPTPEELRETLRSPQFRQALSSFSQALQSGQLG 78

                          90       100
                  ....*....|....*....|....*...
gi 28373192   354 PLMCQFGLPAEAVEAANKGDVEAFAKAM 381
Cdd:pfam16550  79 PVLSQFGLDPEAVAAANGGGVEAFLKAL 106
 
Name Accession Description Interval E-value
PH_Rpn13 cd13314
Pleckstrin homology-like domain of Regulatory Particle Non-ATPase 13; Targeted protein ...
 24-128 8.16e-76

Pleckstrin homology-like domain of Regulatory Particle Non-ATPase 13; Targeted protein degradation is performed to a great extent by the ubiquitin-proteasome pathway, in which substrate proteins are marked by covalently attached ubiquitin chains that mediate recognition by the proteasome. Rpn13(also called ADRM1/ARM1) is one of the two major ubiquitin receptors of the proteasome, the other being S5a/Rpn10 which is not essential for ubiquitin-mediated protein degradation in budding yeast2. S5a has two ubiquitin interacting motifs (UIMs) that bind simultaneously to ubiquitin moieties to increase affinity while Rpn13 binds ubiquitin with a single, high affinity surface within its N-terminal PH domain. Rpn13 also binds and activates deubiquitinating enzyme Uch37, one of the proteasome's three deubiquitinating enzymes. Recently it was discovered that the ubiquitin-binding domain (BD) and Uch37 BD of human (h) Rpn13 pack against each other when it is not incorporated into the proteasome reducing hRpn13's affinity for ubiquitin. However when hRpn13 binds to hRpn2/S1 this abrogates its interdomain interactions, thus activating hRpn13 for ubiquitin binding. 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: 270124  Cd Length: 105  Bit Score: 230.62  E-value: 8.16e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192  24 VEFRAGKMSLKGTTVTPDKRKGLVYIQQTDDSLIHFCWKDRTSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSK 103
Cdd:cd13314   1 VEFKAGKMTLKGTTVTPDPRKGLVYLQQGDDGLIHFCWKDRTSGAVEDDLIIFPDDAEFEKVPQCTTGRVYVLKFKSSSQ 80

                        90       100
                ....*....|....*....|....*
gi 28373192 104 RLFFWMQEPKTDQDEEHCRKVNEYL 128
Cdd:cd13314  81 KHFFWMQEPSTDKDEEICKKVNELL 105
Proteasom_Rpn13 pfam04683
Proteasome complex subunit Rpn13 ubiquitin receptor; This family was thought originally to be ...
 29-111 2.41e-47

Proteasome complex subunit Rpn13 ubiquitin receptor; This family was thought originally to be involved in cell-adhesion, but the members are now known to be proteasome subunit Rpn13, a novel ubiquitin receptor. The 26S proteasome is a huge macromolecular protein-degradation machine consisting of a proteolytically active 20S core, in the form of four disc-like proteins, and one or two 19S regulatory particles. The regulatory particle(s) sit on the top and or bottom of the core, de-ubiquitinate the substrate peptides, unfold them and guide them into the narrow channel through the centre of the core. Rpn13 and its homologs dock onto the regulatory particle through the N-terminal region which binds Rpn2. The C-terminal part of the domain binds de-ubiquitinating enzyme Uch37/UCHL5 and enhances its isopeptidase activity. Rpn13 binds ubiquitin via a conserved amino-terminal region called the pleckstrin-like receptor for ubiquitin, termed Pru, domain. The domain forms two contiguous anti-parallel beta-sheets with a configuration similar to the pleckstrin-homology domain (PHD) fold. Rpn13's ability to bind ubiquitin and the proteasome subunit Rpn2/S1 simultaneously supports evidence of its role as a ubiquitin receptor. Finally, when complexed to di-ubiquitin, via the Pru, and Uch37 via the C-terminal part, it frees up the distal ubiquitin for de-ubiquitination by the Uch37.


Pssm-ID: 461390  Cd Length: 87  Bit Score: 156.56  E-value: 2.41e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192    29 GKMSLKGTT--VTPDKRKGLVYIQQTDDSLIHFCWKDR--TSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSKR 104
Cdd:pfam04683   1 GKCDLDGETkkVTPDPRKGLIYLYSSEDGLLHFCWKPRdaPTGEVEDDLIIFPGDATFKKVKSCTTGRVFVLKFSSSSQR 80


                  ....*..
gi 28373192   105 LFFWMQE 111
Cdd:pfam04683  81 HFFWMQE 87
RPN13_C pfam16550
UCH-binding domain; RPN13_C is a family of all-helical domains that forms the binding-surface ...
 274-381 6.71e-44

UCH-binding domain; RPN13_C is a family of all-helical domains that forms the binding-surface for the proteasome-ubiquitn-receptor protein Rpn13 to UCH37, one of the three de-ubiquitinating enzymes of the proteasome.


Pssm-ID: 465170  Cd Length: 106  Bit Score: 148.17  E-value: 6.71e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192   274 MNVPAGPAGGQQVDLASVLTPEIMAPILANADVQERLLPYLPsgESLPQTADEIQNTLTSPQFQQALGMFSAALASGQLG 353
Cdd:pfam16550   1 LQQAGAAGGGPGVDLTDILTPENLSPLLNDPELVEALAPHLP--PPGPPTPEELRETLRSPQFRQALSSFSQALQSGQLG 78

                          90       100
                  ....*....|....*....|....*...
gi 28373192   354 PLMCQFGLPAEAVEAANKGDVEAFAKAM 381
Cdd:pfam16550  79 PVLSQFGLDPEAVAAANGGGVEAFLKAL 106
 
Name Accession Description Interval E-value
PH_Rpn13 cd13314
Pleckstrin homology-like domain of Regulatory Particle Non-ATPase 13; Targeted protein ...
 24-128 8.16e-76

Pleckstrin homology-like domain of Regulatory Particle Non-ATPase 13; Targeted protein degradation is performed to a great extent by the ubiquitin-proteasome pathway, in which substrate proteins are marked by covalently attached ubiquitin chains that mediate recognition by the proteasome. Rpn13(also called ADRM1/ARM1) is one of the two major ubiquitin receptors of the proteasome, the other being S5a/Rpn10 which is not essential for ubiquitin-mediated protein degradation in budding yeast2. S5a has two ubiquitin interacting motifs (UIMs) that bind simultaneously to ubiquitin moieties to increase affinity while Rpn13 binds ubiquitin with a single, high affinity surface within its N-terminal PH domain. Rpn13 also binds and activates deubiquitinating enzyme Uch37, one of the proteasome's three deubiquitinating enzymes. Recently it was discovered that the ubiquitin-binding domain (BD) and Uch37 BD of human (h) Rpn13 pack against each other when it is not incorporated into the proteasome reducing hRpn13's affinity for ubiquitin. However when hRpn13 binds to hRpn2/S1 this abrogates its interdomain interactions, thus activating hRpn13 for ubiquitin binding. 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: 270124  Cd Length: 105  Bit Score: 230.62  E-value: 8.16e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192  24 VEFRAGKMSLKGTTVTPDKRKGLVYIQQTDDSLIHFCWKDRTSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSK 103
Cdd:cd13314   1 VEFKAGKMTLKGTTVTPDPRKGLVYLQQGDDGLIHFCWKDRTSGAVEDDLIIFPDDAEFEKVPQCTTGRVYVLKFKSSSQ 80

                        90       100
                ....*....|....*....|....*
gi 28373192 104 RLFFWMQEPKTDQDEEHCRKVNEYL 128
Cdd:cd13314  81 KHFFWMQEPSTDKDEEICKKVNELL 105
Proteasom_Rpn13 pfam04683
Proteasome complex subunit Rpn13 ubiquitin receptor; This family was thought originally to be ...
 29-111 2.41e-47

Proteasome complex subunit Rpn13 ubiquitin receptor; This family was thought originally to be involved in cell-adhesion, but the members are now known to be proteasome subunit Rpn13, a novel ubiquitin receptor. The 26S proteasome is a huge macromolecular protein-degradation machine consisting of a proteolytically active 20S core, in the form of four disc-like proteins, and one or two 19S regulatory particles. The regulatory particle(s) sit on the top and or bottom of the core, de-ubiquitinate the substrate peptides, unfold them and guide them into the narrow channel through the centre of the core. Rpn13 and its homologs dock onto the regulatory particle through the N-terminal region which binds Rpn2. The C-terminal part of the domain binds de-ubiquitinating enzyme Uch37/UCHL5 and enhances its isopeptidase activity. Rpn13 binds ubiquitin via a conserved amino-terminal region called the pleckstrin-like receptor for ubiquitin, termed Pru, domain. The domain forms two contiguous anti-parallel beta-sheets with a configuration similar to the pleckstrin-homology domain (PHD) fold. Rpn13's ability to bind ubiquitin and the proteasome subunit Rpn2/S1 simultaneously supports evidence of its role as a ubiquitin receptor. Finally, when complexed to di-ubiquitin, via the Pru, and Uch37 via the C-terminal part, it frees up the distal ubiquitin for de-ubiquitination by the Uch37.


Pssm-ID: 461390  Cd Length: 87  Bit Score: 156.56  E-value: 2.41e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192    29 GKMSLKGTT--VTPDKRKGLVYIQQTDDSLIHFCWKDR--TSGNVEDDLIIFPDDCEFKRVPQCPSGRVYVLKFKAGSKR 104
Cdd:pfam04683   1 GKCDLDGETkkVTPDPRKGLIYLYSSEDGLLHFCWKPRdaPTGEVEDDLIIFPGDATFKKVKSCTTGRVFVLKFSSSSQR 80


                  ....*..
gi 28373192   105 LFFWMQE 111
Cdd:pfam04683  81 HFFWMQE 87
RPN13_C pfam16550
UCH-binding domain; RPN13_C is a family of all-helical domains that forms the binding-surface ...
 274-381 6.71e-44

UCH-binding domain; RPN13_C is a family of all-helical domains that forms the binding-surface for the proteasome-ubiquitn-receptor protein Rpn13 to UCH37, one of the three de-ubiquitinating enzymes of the proteasome.


Pssm-ID: 465170  Cd Length: 106  Bit Score: 148.17  E-value: 6.71e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192   274 MNVPAGPAGGQQVDLASVLTPEIMAPILANADVQERLLPYLPsgESLPQTADEIQNTLTSPQFQQALGMFSAALASGQLG 353
Cdd:pfam16550   1 LQQAGAAGGGPGVDLTDILTPENLSPLLNDPELVEALAPHLP--PPGPPTPEELRETLRSPQFRQALSSFSQALQSGQLG 78

                          90       100
                  ....*....|....*....|....*...
gi 28373192   354 PLMCQFGLPAEAVEAANKGDVEAFAKAM 381
Cdd:pfam16550  79 PVLSQFGLDPEAVAAANGGGVEAFLKAL 106
PH-like cd00900
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 24-124 2.91e-10

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


Pssm-ID: 275390  Cd Length: 89  Bit Score: 56.64  E-value: 2.91e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 28373192  24 VEFRAGKMSLKgttvTPDKRKGLVYIQQtddslIHFCWKDRTSGNVEDDLIIFpDDCEFKRVPQCPSGRVYVLKFKAGSK 103
Cdd:cd00900   1 LKFRAVRVYRE----PTKRVEGTLYITS-----DRLILRDKNDGGLELSIPIS-DIVNVNVSPQGPSSRYLVLVLKDRGE 70

                        90       100
                ....*....|....*....|.
gi 28373192 104 RLFFWMQEPKtdQDEEHCRKV 124
Cdd:cd00900  71 FVGFSFPKEE--DAIEISDAL 89
 
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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