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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762628    155 EHTIVVLHLWSEGFSLDDGSLRLYALPENERFLRAILRGDFPEEMLRV---PRVQLSVQDHTNESYRHLSR--KQFMGPG 229
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVakgQPVNVDVEDHRDEDYVAPPGafKPFSGSG 80

                           90
                   ....*....|...
gi 24762628    230 RPLNSPSPQILVV 242
Cdd:smart00553  81 QKLGSPGPQSLST 93

UBA-like domain found in the NXF family of mRNA nuclear export factors and similar proteins; This family includes nuclear RNA export factors (NXF1/NXF2), FAS-associated factors (FAF1/2), tyrosyl-DNA phosphodiesterase 2 (TDP2), OTU domain-containing proteins (OTU7A/OTU7B), NSFL1 cofactor p47, defective in cullin neddylation protein 1 (DCN1)-like protein (DCNL1/DCNL2), yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. 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. FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. Its biological function remains unclear. TDP2 is a 5'-Tyr-DNA phosphodiesterase required for the efficient repair of topoisomerase II-induced DNA double strand breaks. OTU7A and OTU7B are zinc finger proteins that function as deubiquitinating enzymes. p47 is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. DCNL1 plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. The biological function of DCNL2 remains unclear. Yeast DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity.

                        10        20        30
                ....*....|....*....|....*....|
gi 24762628  10 FMKRHGVREEVARQYLSSNNWSLEVASSTY 39
Cdd:cd14273   1 FMEITGADPETARQYLESNNWDLEAAINLY 30

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762628    155 EHTIVVLHLWSEGFSLDDGSLRLYALPENERFLRAILRGDFPEEMLRV---PRVQLSVQDHTNESYRHLSR--KQFMGPG 229
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVakgQPVNVDVEDHRDEDYVAPPGafKPFSGSG 80

                           90
                   ....*....|...
gi 24762628    230 RPLNSPSPQILVV 242
Cdd:smart00553  81 QKLGSPGPQSLST 93

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24762628   161 LHLWSEGFSLDDGSLRLYALPENERFLRAILRGDFPEEMLRVPR---VQLSVQDHTNESYRHLSRKQ--FMGPGR 230
Cdd:pfam08059   1 LTFWRNGFSVDDGPLRRYDDPANAEFLEAINRGEAPLELLNVAPgqgVDVNLEDRRDEDYVPPKKKYkpFSGSGR 75

UBA-like domain found in the NXF family of mRNA nuclear export factors and similar proteins; This family includes nuclear RNA export factors (NXF1/NXF2), FAS-associated factors (FAF1/2), tyrosyl-DNA phosphodiesterase 2 (TDP2), OTU domain-containing proteins (OTU7A/OTU7B), NSFL1 cofactor p47, defective in cullin neddylation protein 1 (DCN1)-like protein (DCNL1/DCNL2), yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. 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. FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. Its biological function remains unclear. TDP2 is a 5'-Tyr-DNA phosphodiesterase required for the efficient repair of topoisomerase II-induced DNA double strand breaks. OTU7A and OTU7B are zinc finger proteins that function as deubiquitinating enzymes. p47 is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. DCNL1 plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. The biological function of DCNL2 remains unclear. Yeast DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity.

                        10        20        30
                ....*....|....*....|....*....|
gi 24762628  10 FMKRHGVREEVARQYLSSNNWSLEVASSTY 39
Cdd:cd14273   1 FMEITGADPETARQYLESNNWDLEAAINLY 30

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24762628    260 TTTVQLRMADGSRVAGRFNLTHNVGDLYQYARlARPEFSDRSFVLMTAFPRQELVESDTRTLVQAN 325
Cdd:smart00166   1 VCRLQIRLPDGSRLVRRFPSSDTLRTVYEFVS-AALGDGNDPFTLNSPFPRRTFTKDDYSKKLLEL 65

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762628    155 EHTIVVLHLWSEGFSLDDGSLRLYALPENERFLRAILRGDFPEEMLRV---PRVQLSVQDHTNESYRHLSR--KQFMGPG 229
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVakgQPVNVDVEDHRDEDYVAPPGafKPFSGSG 80

                           90
                   ....*....|...
gi 24762628    230 RPLNSPSPQILVV 242
Cdd:smart00553  81 QKLGSPGPQSLST 93

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 24762628   161 LHLWSEGFSLDDGSLRLYALPENERFLRAILRGDFPEEMLRVPR---VQLSVQDHTNESYRHLSRKQ--FMGPGR 230
Cdd:pfam08059   1 LTFWRNGFSVDDGPLRRYDDPANAEFLEAINRGEAPLELLNVAPgqgVDVNLEDRRDEDYVPPKKKYkpFSGSGR 75

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762628 254 LNERADTTTVQLRMADGSRVAGRFNLTHNVGDLYQYARLARPEFSDRSFVLMTAFPRQELVESDtRTLVQANLCNVVVIQ 333
Cdd:cd17162   1 INDSEPVTNIQIRLADGGRLVQKFNHSHRIRDIRLFIVDARPAMAATSFVLMTTFPNKELTDEN-QTLKEANLLNAVIVQ 79

                ..
gi 24762628 334 HL 335
Cdd:cd17162  80 RL 81

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24762628 254 LNERADTTTVQLRMADGSRVAGRFNLTHNVGDLYQYarLARPEFSDRS--FVLMTAFPRQELVEsDTRTLVQANLCNVVV 331
Cdd:cd17160   1 LNELEPITNIQIWLADGRRIVQKFNLSHRISHVRDF--VEKIQGSSMSvpFTLATSLPFRELLD-ETLTLQEADLQNAVI 77

                ....
gi 24762628 332 IQHL 335
Cdd:cd17160  78 VQRL 81

UBA-like domain found in the NXF family of mRNA nuclear export factors and similar proteins; This family includes nuclear RNA export factors (NXF1/NXF2), FAS-associated factors (FAF1/2), tyrosyl-DNA phosphodiesterase 2 (TDP2), OTU domain-containing proteins (OTU7A/OTU7B), NSFL1 cofactor p47, defective in cullin neddylation protein 1 (DCN1)-like protein (DCNL1/DCNL2), yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. 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. FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. Its biological function remains unclear. TDP2 is a 5'-Tyr-DNA phosphodiesterase required for the efficient repair of topoisomerase II-induced DNA double strand breaks. OTU7A and OTU7B are zinc finger proteins that function as deubiquitinating enzymes. p47 is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. DCNL1 plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. The biological function of DCNL2 remains unclear. Yeast DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity.

                        10        20        30
                ....*....|....*....|....*....|
gi 24762628  10 FMKRHGVREEVARQYLSSNNWSLEVASSTY 39
Cdd:cd14273   1 FMEITGADPETARQYLESNNWDLEAAINLY 30

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 2 (FAF2, also known as UBXN3B) and similar proteins; UBX domain-containing protein 3B (UBXN3B), also termed protein ETEA, or FAF2, or UBX domain-containing protein 8 (UBXD8), 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. FAF2 functions as a cofactor 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 p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated the RNA-binding protein HuR from messenger ribonucleoprotein (mRNP). Moreover, FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. A yeast two-hybrid assay showed that FAF2 can interact with Fas.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24762628 263 VQLRMADGSRVAGRFNLTHNVGDLYQYArLARPEFSDRsFVLMTAFPRQELV------ESDTRTLVQANLCN 328
Cdd:cd16120   3 ILFKLPNGTRLERRFLKSDSLKVLYDFV-FSHEDSPDK-FQLVTNFPRRVLPcqpteeQPNPPTLEEAGLGK 72

UBA-like domain found in NSFL1 cofactor p47 and similar proteins; p47, also called UBX domain-containing protein 2C, is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. p47, together with p97, forms the p97-p47 complex that plays an important role in regulation of membrane fusion events. p47 contains an N-terminal ubiquitin-associated (UBA)-like domain, a central SEP (named after shp1, eyc and p47) domain, and a ubiquitin-like (UBX) domain. UBA-like domain is responsible for forming a highly stable complex with ubiquitin. SEP domain and UBX domain may involve in p47 trimerization or forms a stable complex with the p97 N-terminal domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 24762628   4 EQKLSTFMKRHGVREEVARQYLSSNNWSLEVASSTY 39
Cdd:cd14348   1 DELIAQFVSVTGADEDRAKFFLESAGWDLEAALSSF 36

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 1 (UBXN1) and similar proteins; UBXN1, also termed SAPK substrate protein 1 (SAKS1), UBA/UBX 33.3 kDa protein (Y33K), or UBXD10, is a widely expressed protein containing an N-terminal ubiquitin-associated (UBA) domain, a coiled-coil region, and a C-terminal ubiquitin-like (Ubl or UBX) domain that has a beta-grasp ubiquitin-like fold without the C-terminal double glycine motif. UBXN1 has been identified as a substrate for stress-activated protein kinases (SAPKs). It binds polyubiquitin and valosin-containing protein (VCP), suggesting a role as an adaptor that directs VCP to polyubiquitinated proteins facilitating its destruction by the proteasome. In addition, UBXN1 specifically binds to Homer2b. It may also interact with ubiquitin (Ub) and be involved in the Ub-proteasome proteolytic pathways. UBXN1 can also associate with autoubiquitinated BRCA1 tumor suppressor and inhibit its enzymatic function through its UBA domains.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24762628 259 DTTTVQLRMADGSRVAGRFNLTHNVGDLYQYARLARPEfSDRSFVLMTAFPRQELVESD 317
Cdd:cd01772   5 DECRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTD-GDGPFSLMTTFPRKVFTEED 62

UBA-like domain found in DCN1-like protein DCNL1, DCNL2 and similar proteins; DCNL1 (defective in cullin neddylation protein 1-like protein 1), also called DCUN1 domain-containing protein 1, is encoded by squamous cell carcinoma-related oncogene SCCRO (DCUN1D1). It interacts with known cullin isoforms as well as ROC1, Ubc12 and CAND1, the components of the neddylation pathway. It plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. DCNL1 contains an N-terminal ubiquitin-associated (UBA)-like domain and a C-terminal cullin binding domain that binds to cullins and Rbx-1, components of an E3 ubiquitin ligase complex for neddylation. DCNL2 (defective in cullin neddylation protein 1-like protein 2), also called DCUN1 domain-containing protein 2, is encoded by gene DCUN1D2. Although its biological function remains unclear, DCNL2 shows high sequence similarity with DCNL1 and may also contribute to neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes. Like DCNL1, DCNL2 contains an N-terminal UBA-like domain and a C-terminal cullin binding domain.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 24762628   5 QKLSTFMKRHGVREEVARQYLSSNNWSLEVASSTY 39
Cdd:cd14350   4 DKVRQFMSITQANEKTAIQCLKDADWNLELAVDAY 38