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Conserved domains on  [gi|1039729838|ref|XP_017177728|]
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UBX domain-containing protein 4 isoform X2 [Mus musculus]

Protein Classification

UBX domain-containing protein( domain architecture ID 1006295)

UBX domain-containing protein with a UAS domain belonging to the thioredoxin superfamily, similar to human UBX domain-containing protein 4 that is involved in endoplasmic reticulum-associated protein degradation (ERAD)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
 317-354 3.09e-17

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.


The actual alignment was detected with superfamily member cd16117:

Pssm-ID: 475130 [Multi-domain]  Cd Length: 77  Bit Score: 76.21  E-value: 3.09e-17
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039729838 317 IARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQAGRPA 354
Cdd:cd16117     1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPA 38
Thioredoxin_like super family cl00388
Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold; The thioredoxin ...
 4-113 2.70e-04

Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold; The thioredoxin (TRX)-like superfamily is a large, diverse group of proteins containing a TRX fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include the families of TRX, protein disulfide isomerase (PDI), tlpA, glutaredoxin, NrdH redoxin, and bacterial Dsb proteins (DsbA, DsbC, DsbG, DsbE, DsbDgamma). Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins, glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.


The actual alignment was detected with superfamily member cd02958:

Pssm-ID: 469754 [Multi-domain]  Cd Length: 114  Bit Score: 40.28  E-value: 2.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039729838   4 FQGAIPAAIASAKRSGAVFVVFVAGDDEQSIQMAAS--WEDEKVTQASSNNFVAIKID-TKSEAcLQFSQIYPVVCVPSS 80
Cdd:cd02958     2 FQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRdlWSNESVKEFIRENFIFWQCDiDSSEG-QRFLQSYKVDKYPHI 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039729838  81 FFIG-DSGIPLEVIAGSVSADELVTRIHKVQQMH 113
Cdd:cd02958    81 AIIDpRTGEVLKVWSGNITPEDLLSQLIEFLEEF 114
 
Name Accession Description Interval E-value
UBX_UBXN4 cd16117
Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; ...
 317-354 3.09e-17

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; UBXN4, also termed ERAD (endoplasmic-reticulum-associated protein degradation) substrate erasing protein (erasin), or UBX domain-containing protein 2 (UBXD2), or UBXDC1, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN4 is an endoplasmic reticulum (ER) localized protein that interacts with p97 (also known as VCP or Cdc48) via its UBX domain. Erasin exists in a complex with other p97/VCP-associated factors involved in endoplasmic-reticulum-associated protein degradation (ERAD). p97 is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The overexpression of UBXN4 increases degradation of a classical ERAD substrate and UBXN4 levels are increased in ER stressed cells. Anti-UBXN4 staining is increased in neuropathological lesions in brains of patients with Alzheimer's disease.


Pssm-ID: 340534 [Multi-domain]  Cd Length: 77  Bit Score: 76.21  E-value: 3.09e-17
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039729838 317 IARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQAGRPA 354
Cdd:cd16117     1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPA 38
UBX smart00166
Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.
 318-350 2.97e-07

Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.


Pssm-ID: 197552 [Multi-domain]  Cd Length: 77  Bit Score: 47.68  E-value: 2.97e-07
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1039729838  318 ARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQA 350
Cdd:smart00166   2 CRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAA 34
UBX pfam00789
UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general ...
 318-355 2.47e-06

UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module.


Pssm-ID: 395637 [Multi-domain]  Cd Length: 80  Bit Score: 45.36  E-value: 2.47e-06
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039729838 318 ARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQAGRPAT 355
Cdd:pfam00789   5 TRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDL 42
UAS cd02958
UAS family; UAS is a domain of unknown function. Most members of this family are ...
 4-113 2.70e-04

UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting domain. FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.


Pssm-ID: 239256 [Multi-domain]  Cd Length: 114  Bit Score: 40.28  E-value: 2.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039729838   4 FQGAIPAAIASAKRSGAVFVVFVAGDDEQSIQMAAS--WEDEKVTQASSNNFVAIKID-TKSEAcLQFSQIYPVVCVPSS 80
Cdd:cd02958     2 FQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRdlWSNESVKEFIRENFIFWQCDiDSSEG-QRFLQSYKVDKYPHI 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039729838  81 FFIG-DSGIPLEVIAGSVSADELVTRIHKVQQMH 113
Cdd:cd02958    81 AIIDpRTGEVLKVWSGNITPEDLLSQLIEFLEEF 114
DsbD COG4232
Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, ...
 2-111 6.15e-03

Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 443376 [Multi-domain]  Cd Length: 416  Bit Score: 38.63  E-value: 6.15e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039729838   2 LWFQGAIPAAIASAKRSG-AVFVVFVAgdD--------EQSIqmaasWEDEKVTQASSNNFVAIKIDT--KSEACLQFSQ 70
Cdd:COG4232   303 LAWQADLEAALAEARAEGkPVFVDFTA--DwcvtckenERTV-----FSDPEVQAALADDVVLLKADVtdNDPEITALLK 375

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039729838  71 IYPVVCVPSSFFIGDSGIPLEVIAGSVSADELVTRIHKVQQ 111
Cdd:COG4232   376 RFGRFGVPTYVFYDPDGEELPRLGFMLTADEFLAALEKAKG 416
 
Name Accession Description Interval E-value
UBX_UBXN4 cd16117
Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; ...
 317-354 3.09e-17

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; UBXN4, also termed ERAD (endoplasmic-reticulum-associated protein degradation) substrate erasing protein (erasin), or UBX domain-containing protein 2 (UBXD2), or UBXDC1, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN4 is an endoplasmic reticulum (ER) localized protein that interacts with p97 (also known as VCP or Cdc48) via its UBX domain. Erasin exists in a complex with other p97/VCP-associated factors involved in endoplasmic-reticulum-associated protein degradation (ERAD). p97 is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. The overexpression of UBXN4 increases degradation of a classical ERAD substrate and UBXN4 levels are increased in ER stressed cells. Anti-UBXN4 staining is increased in neuropathological lesions in brains of patients with Alzheimer's disease.


Pssm-ID: 340534 [Multi-domain]  Cd Length: 77  Bit Score: 76.21  E-value: 3.09e-17
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039729838 317 IARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQAGRPA 354
Cdd:cd16117     1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPA 38
UBX smart00166
Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.
 318-350 2.97e-07

Domain present in ubiquitin-regulatory proteins; Present in FAF1 and Shp1p.


Pssm-ID: 197552 [Multi-domain]  Cd Length: 77  Bit Score: 47.68  E-value: 2.97e-07
                           10        20        30
                   ....*....|....*....|....*....|...
gi 1039729838  318 ARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQA 350
Cdd:smart00166   2 CRLQIRLPDGSRLVRRFPSSDTLRTVYEFVSAA 34
UBX pfam00789
UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general ...
 318-355 2.47e-06

UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module.


Pssm-ID: 395637 [Multi-domain]  Cd Length: 80  Bit Score: 45.36  E-value: 2.47e-06
                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1039729838 318 ARIQFRLPDGSSFTNQFPSDAPLEEARQFAAQAGRPAT 355
Cdd:pfam00789   5 TRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDL 42
UBX cd01767
Ubiquitin regulatory domain X (UBX) structurally similar to a beta-grasp ubiquitin-like fold; ...
 319-353 1.68e-05

Ubiquitin regulatory domain X (UBX) structurally similar to a beta-grasp ubiquitin-like fold; The UBXD family of proteins contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. Members in this family function as cofactors of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. Based on domain composition, UBXD proteins can be divided into two main groups, with and without ubiquitin-associated (UBA) domain.


Pssm-ID: 340466 [Multi-domain]  Cd Length: 74  Bit Score: 42.64  E-value: 1.68e-05
                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1039729838 319 RIQFRLPDGSSFTNQFPSDAPLEEARQFAAQAGRP 353
Cdd:cd01767     1 RIQIRLPDGSRIQRRFSKSDTLQDLYDFVESNLGD 35
UAS cd02958
UAS family; UAS is a domain of unknown function. Most members of this family are ...
 4-113 2.70e-04

UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting domain. FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.


Pssm-ID: 239256 [Multi-domain]  Cd Length: 114  Bit Score: 40.28  E-value: 2.70e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039729838   4 FQGAIPAAIASAKRSGAVFVVFVAGDDEQSIQMAAS--WEDEKVTQASSNNFVAIKID-TKSEAcLQFSQIYPVVCVPSS 80
Cdd:cd02958     2 FQGSFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRdlWSNESVKEFIRENFIFWQCDiDSSEG-QRFLQSYKVDKYPHI 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1039729838  81 FFIG-DSGIPLEVIAGSVSADELVTRIHKVQQMH 113
Cdd:cd02958    81 AIIDpRTGEVLKVWSGNITPEDLLSQLIEFLEEF 114
DsbD COG4232
Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, ...
 2-111 6.15e-03

Thiol:disulfide interchange protein DsbD [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 443376 [Multi-domain]  Cd Length: 416  Bit Score: 38.63  E-value: 6.15e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039729838   2 LWFQGAIPAAIASAKRSG-AVFVVFVAgdD--------EQSIqmaasWEDEKVTQASSNNFVAIKIDT--KSEACLQFSQ 70
Cdd:COG4232   303 LAWQADLEAALAEARAEGkPVFVDFTA--DwcvtckenERTV-----FSDPEVQAALADDVVLLKADVtdNDPEITALLK 375

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039729838  71 IYPVVCVPSSFFIGDSGIPLEVIAGSVSADELVTRIHKVQQ 111
Cdd:COG4232   376 RFGRFGVPTYVFYDPDGEELPRLGFMLTADEFLAALEKAKG 416
 
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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