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Conserved domains on  [gi|2462570809|ref|XP_054196846|]
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UBX domain-containing protein 2A isoform X2 [Homo sapiens]

Protein Classification

SEP and UBX domain-containing protein( domain architecture ID 13742902)

SEP and UBX domain-containing protein, similar to UBX domain-containing proteins 2A and 2B

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
SEP pfam08059
SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila ...
 65-138 3.27e-32

SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47. In p47, the SEP domain has been shown to bind to and inhibit the cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain.


:

Pssm-ID: 462348  Cd Length: 75  Bit Score: 112.57  E-value: 3.27e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462570809  65 IKLWKNGFTVND-DFRSYSDGASQQFLNSIKKGELPSELQGIFDKEEVDVKVEDKKNEICLSTKPVFQPFSGQGH 138
Cdd:pfam08059   1 LTFWRNGFSVDDgPLRRYDDPANAEFLEAINRGEAPLELLNVAPGQGVDVNLEDRRDEDYVPPKKKYKPFSGSGR 75
Ubl1_cv_Nsp3_N-like super family cl28922
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ...
 167-194 4.19e-13

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 cd17160:

Pssm-ID: 475130  Cd Length: 84  Bit Score: 62.95  E-value: 4.19e-13
                          10        20
                  ....*....|....*....|....*...
gi 2462570809 167 LNNLEPITNIQIWLANGKRIVQKFNITH 194
Cdd:cd17160     1 LNELEPITNIQIWLADGRRIVQKFNLSH 28
 
Name Accession Description Interval E-value
SEP pfam08059
SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila ...
 65-138 3.27e-32

SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47. In p47, the SEP domain has been shown to bind to and inhibit the cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain.


Pssm-ID: 462348  Cd Length: 75  Bit Score: 112.57  E-value: 3.27e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462570809  65 IKLWKNGFTVND-DFRSYSDGASQQFLNSIKKGELPSELQGIFDKEEVDVKVEDKKNEICLSTKPVFQPFSGQGH 138
Cdd:pfam08059   1 LTFWRNGFSVDDgPLRRYDDPANAEFLEAINRGEAPLELLNVAPGQGVDVNLEDRRDEDYVPPKKKYKPFSGSGR 75
SEP smart00553
Domain present in Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc) ...
 59-149 3.89e-28

Domain present in Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47;


Pssm-ID: 197786  Cd Length: 93  Bit Score: 102.48  E-value: 3.89e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570809   59 KQVDVNIKLWKNGFTVND-DFRSYSDGASQQFLNSIKKGELPSELQGIFDKEEVDVKVEDKKNEICLSTKPVFQPFSGQG 137
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDgPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|..
gi 2462570809  138 HRLGSATPKIVS 149
Cdd:smart00553  81 QKLGSPGPQSLS 92
UBX_UBXN2A cd17160
Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar ...
 167-194 4.19e-13

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar proteins; UBXN2A, also termed UBX domain-containing protein 4 (UBXD4), 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. UBXN2A functions as a p97 (also known as VCP or Cdc48) adaptor protein facilitating the regulation of the cell surface number and stability of alpha3-containing neuronal nicotinic acetylcholine receptors (nAChRs). It also regulates nicotinic receptor degradation by modulating the E3 ligase activity of carboxyl terminus of Hsc70 interacting protein (CHIP) that is involved in the degradation of several disease-related proteins. In addition, UBXN2A is an important anticancer factor that contributes to p53 localization and activation as a host defense mechanism against cancerous growth. It acts as a potential mortalin inhibitor, as well as a potential chemotherapy sensitizer for clinical application. It binds to the oncoprotein mortalin-2 (mot-2), and further unsequesters p53 from mot-2 in the cytoplasm, resulting in translocation of p53 to the nucleus where p53 proteins activate their downstream biological effects, including apoptosis.


Pssm-ID: 340680  Cd Length: 84  Bit Score: 62.95  E-value: 4.19e-13
                          10        20
                  ....*....|....*....|....*...
gi 2462570809 167 LNNLEPITNIQIWLANGKRIVQKFNITH 194
Cdd:cd17160     1 LNELEPITNIQIWLADGRRIVQKFNLSH 28
 
Name Accession Description Interval E-value
SEP pfam08059
SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila ...
 65-138 3.27e-32

SEP domain; The SEP domain is named after Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47. In p47, the SEP domain has been shown to bind to and inhibit the cysteine protease cathepsin L. Most SEP domains are succeeded closely by a UBX domain.


Pssm-ID: 462348  Cd Length: 75  Bit Score: 112.57  E-value: 3.27e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462570809  65 IKLWKNGFTVND-DFRSYSDGASQQFLNSIKKGELPSELQGIFDKEEVDVKVEDKKNEICLSTKPVFQPFSGQGH 138
Cdd:pfam08059   1 LTFWRNGFSVDDgPLRRYDDPANAEFLEAINRGEAPLELLNVAPGQGVDVNLEDRRDEDYVPPKKKYKPFSGSGR 75
SEP smart00553
Domain present in Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc) ...
 59-149 3.89e-28

Domain present in Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47;


Pssm-ID: 197786  Cd Length: 93  Bit Score: 102.48  E-value: 3.89e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462570809   59 KQVDVNIKLWKNGFTVND-DFRSYSDGASQQFLNSIKKGELPSELQGIFDKEEVDVKVEDKKNEICLSTKPVFQPFSGQG 137
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDgPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|..
gi 2462570809  138 HRLGSATPKIVS 149
Cdd:smart00553  81 QKLGSPGPQSLS 92
UBX_UBXN2A cd17160
Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar ...
 167-194 4.19e-13

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2A (UBXN2A) and similar proteins; UBXN2A, also termed UBX domain-containing protein 4 (UBXD4), 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. UBXN2A functions as a p97 (also known as VCP or Cdc48) adaptor protein facilitating the regulation of the cell surface number and stability of alpha3-containing neuronal nicotinic acetylcholine receptors (nAChRs). It also regulates nicotinic receptor degradation by modulating the E3 ligase activity of carboxyl terminus of Hsc70 interacting protein (CHIP) that is involved in the degradation of several disease-related proteins. In addition, UBXN2A is an important anticancer factor that contributes to p53 localization and activation as a host defense mechanism against cancerous growth. It acts as a potential mortalin inhibitor, as well as a potential chemotherapy sensitizer for clinical application. It binds to the oncoprotein mortalin-2 (mot-2), and further unsequesters p53 from mot-2 in the cytoplasm, resulting in translocation of p53 to the nucleus where p53 proteins activate their downstream biological effects, including apoptosis.


Pssm-ID: 340680  Cd Length: 84  Bit Score: 62.95  E-value: 4.19e-13
                          10        20
                  ....*....|....*....|....*...
gi 2462570809 167 LNNLEPITNIQIWLANGKRIVQKFNITH 194
Cdd:cd17160     1 LNELEPITNIQIWLADGRRIVQKFNLSH 28
UBX_UBXN2C cd17162
Ubiquitin regulatory domain X (UBX) found in NSFL1 cofactor (also known as UBX ...
 167-195 2.86e-07

Ubiquitin regulatory domain X (UBX) found in NSFL1 cofactor (also known as UBX domain-containing protein 2C (UBXN2C) and similar proteins; UBXN2C, also termed NSFL1C, or NSFL1 cofactor p47, or p97 cofactor p47, UBX1, or UBXD10, 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. UBXN2C is a major adaptor 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. The main role of the UBXN2C/p97 complex is in regulation of membrane fusion events. It plays an essential role in the reassembly of Golgi stacks at the end of mitosis. UBXN2C also functions as an essential factor for Golgi membrane fusion, which associates with the nuclear factor-kappaB essential modulator (NEMO) subunit of the IkappaB kinase (IKK) complex upon tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 stimulation, induces the lysosome-dependent degradation of polyubiquitinated NEMO without p97, and thus inhibits IKK activation. Moreover, UBXN2C regulates a membrane fusion process, which is required by the maintenance of the endoplasmic reticulum (ER) network, through phosphorylation by Cdc2 kinase.


Pssm-ID: 340682  Cd Length: 82  Bit Score: 46.85  E-value: 2.86e-07
                          10        20
                  ....*....|....*....|....*....
gi 2462570809 167 LNNLEPITNIQIWLANGKRIVQKFNITHS 195
Cdd:cd17162     1 INDSEPVTNIQIRLADGGRLVQKFNHSHR 29
UBX_UBXN2 cd01770
Ubiquitin regulatory domain X (UBX) found in UBX domain-containing proteins UBXN2A, UBXN2B, ...
 175-194 1.35e-06

Ubiquitin regulatory domain X (UBX) found in UBX domain-containing proteins UBXN2A, UBXN2B, NSFL1C/UBXN2C, and similar proteins; This family includes UBX domain-containing proteins UBXN2A, UBXN2B, and NSFL1C/UBXN2C, which contain a SEP (Saccharomyces cerevisiae Shp1, Drosophila melanogaster eyes closed gene (eyc), and vertebrate p47) domain, and a ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold at the C-terminus. UBX domain participates broadly in the regulation of protein degradation. UBXN2A, UBXN2B, and UBXN2C function as the adaptor proteins 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.


Pssm-ID: 340468  Cd Length: 71  Bit Score: 44.86  E-value: 1.35e-06
                          10        20
                  ....*....|....*....|
gi 2462570809 175 NIQIWLANGKRIVQKFNITH 194
Cdd:cd01770     1 SIQIRLADGSRLVARFNLTH 20
UBX_UBXN2B cd17161
Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2B (UBXN2B) and similar ...
 172-194 8.75e-05

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 2B (UBXN2B) and similar proteins; UBXN2B, also termed NSFL1 cofactor p37, or p97 cofactor p37, 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. UBXN2B is an adaptor protein 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. UBXN2B forms a tight complex with p97 in the cytosol and localizes to the Golgi and endoplasmic reticulum (ER).


Pssm-ID: 340681  Cd Length: 82  Bit Score: 39.87  E-value: 8.75e-05
                          10        20
                  ....*....|....*....|...
gi 2462570809 172 PITNIQIWLANGKRIVQKFNITH 194
Cdd:cd17161     6 PTTKIQIRLADGSRLIQRFNQSH 28
 
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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