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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543252604   193 QDVQILLKLWRNGFSLDDGELRSYSDPTNAQFLESVKRGEIPLELQRLVHGGQVNLDMEDHQEQEYVKPRLRFKAFSGEG 272
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|...
gi 543252604   273 QKLGSLTPEIVST 285
Cdd:smart00553  81 QKLGSPGPQSLST 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543252604   193 QDVQILLKLWRNGFSLDDGELRSYSDPTNAQFLESVKRGEIPLELQRLVHGGQVNLDMEDHQEQEYVKPRLRFKAFSGEG 272
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|...
gi 543252604   273 QKLGSLTPEIVST 285
Cdd:smart00553  81 QKLGSPGPQSLST 93

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 543252604  308 PATKIQIRLADGSRLIQRFNQTHRIKHIRDFIIQSRPAFATTdFVLVTTFPNKELT--DESLTLQEADIL-NTVILQQL 383
Cdd:pfam00789   3 DVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDLEP-FSLNTPFPRRPLTdlDYSKTLKEAGLLpNSTLVLEP 80

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 543252604   193 QDVQILLKLWRNGFSLDDGELRSYSDPTNAQFLESVKRGEIPLELQRLVHGGQVNLDMEDHQEQEYVKPRLRFKAFSGEG 272
Cdd:smart00553   1 QKVIHTLTFWSNGFSVDDGPLRTYDDPENAEFLESIRRGEAPLELLRVAKGQPVNVDVEDHRDEDYVAPPGAFKPFSGSG 80

                           90
                   ....*....|...
gi 543252604   273 QKLGSLTPEIVST 285
Cdd:smart00553  81 QKLGSPGPQSLST 93

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 543252604 303 IDDSMPATKIQIRLADGSRLIQRFNQTHRIKHIRDFIIQSRPAFATTDFVLVTTFPNKELTDESLTLQEADILNTVILQQ 382
Cdd:cd17162    1 INDSEPVTNIQIRLADGGRLVQKFNHSHRIRDIRLFIVDARPAMAATSFVLMTTFPNKELTDENQTLKEANLLNAVIVQR 80

                 ..
gi 543252604 383 LK 384
Cdd:cd17162   81 LK 82

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 543252604 303 IDDSMPATKIQIRLADGSRLIQRFNQTHRIKHIRDFIIQSRPAFATTDFVLVTTFPNKELTDESLTLQEADILNTVILQQ 382
Cdd:cd17160    1 LNELEPITNIQIWLADGRRIVQKFNLSHRISHVRDFVEKIQGSSMSVPFTLATSLPFRELLDETLTLQEADLQNAVIVQR 80

                 ..
gi 543252604 383 LK 384
Cdd:cd17160   81 LQ 82

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 543252604 311 KIQIRLADGSRLIQRFNQTHRIKHIRDFIIQSRPaFATTDFVLVTTFPNKELTDE--SLTLQEADIL-NTVILQQ 382
Cdd:cd01767    1 RIQIRLPDGSRIQRRFSKSDTLQDLYDFVESNLG-DSPSSFSLVTSFPRRVLTDEdsDKTLEELGLTpNAVLFVE 74

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 543252604 310 TKIQIRLADGSRLIQRFNQTHRIKHIRDFIIqSRPAfATTDFVLVTTFPNKEL----TDES---LTLQEADILNTVIL 380
Cdd:cd16120    1 VKILFKLPNGTRLERRFLKSDSLKVLYDFVF-SHED-SPDKFQLVTNFPRRVLpcqpTEEQpnpPTLEEAGLGKSEVL 76

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 543252604 310 TKIQIRLADGSRLIQRFNQTHRIKHIRDFIIQSRPAfATTDFVLVTTFPNKELTDESL--TLQEADILNTVIL 380
Cdd:cd01772    7 CRLQVRLTNGSTLTQTFGAKEQLAAVRLYVELNRTD-GDGPFSLMTTFPRKVFTEEDMekPLKELGLVPSAVL 78

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 11 (UBXN11) and similar proteins; UBXN11, also termed colorectal tumor-associated antigen COA-1, or socius, or UBX domain-containing protein 5 (UBXD5), 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. UBXN11 may function 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. UBXN11 also acts as a novel interacting partner of Rnd proteins (Rnd1, Rnd2, and Rnd3/RhoE), new members of Rho family of small GTPases. It directly binds to Rnd GTPases through its C-terminal region, and further participates in disassembly of actin stress fibers. UBXN11 also binds directly to Galpha12 and Galpha13 through its N-terminal region. As a novel activator of the Galpha12 family, UBXN11 promotes the Galpha12-induced RhoA activation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 543252604 310 TKIQIRLADGSR---LIQRFNQThrIKHIRDFIIQSRPAFATtDFVLVTTFPNKELTDESLTLQEAD 373
Cdd:cd17077    3 TTLRIKSENGEQtyiLKMRFSDT--IGDLRRYLDKHRSKDAA-SYEIVTTFPNKVYDDDSATLEELG 66

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 7 (UBXN7) and similar proteins; UBXN7, also termed UBX domain-containing protein 7 (UBXD7), 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. UBXN7 functions as a ubiquitin-binding adaptor that mediates the interaction between the AAA+ ATPase p97 (also known as VCP or Cdc48) and the transcription factor HIF1-alpha. It binds only to the active, NEDD8- or Rub1-modified form of cullins. In addition to having a UBX domain, UBXD7 contains a ubiquitin-associated (UBA), ubiquitin-associating (UAS), and ubiquitin-interacting motif (UIM) domains. Either UBA or UIM could serve as a docking site for neddylated-cullins. UBA domain is required for binding ubiquitylated-protein substrates, while the UIM motif is responsible for the binding to cullin RING ligases (CRLs), and the UBX domain is essential for p97 binding.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 543252604 309 ATKIQIRLADGSRLIQRFNQTHRIKHIRDFIiqSRPAFATTDFVLVTTFPNKELT--DESLTLQEA 372
Cdd:cd01773    1 KSKLMLRFPDGKREQLSLPASAKLKALVKYV--SSKGYPNERYELVTNFPRRKLShlDYDITLKEA 64