UBA domain-like superfamily; The ubiquitin-associated (UBA) domain-like superfamily contains alpha-helical structural homology ubiquitin-binding domains, including UBA domains and coupling of ubiquitin conjugation to endoplasmic reticulum degradation (CUE) domains which share a common three-helical bundle architecture. UBA domains are commonly occurring sequence motifs found in proteins involved in ubiquitin-mediated proteolysis. They contribute to ubiquitin (Ub) binding or ubiquitin-like (UbL) domain binding. However, some kinds of UBA domains can only bind the UbL domain, but not the Ub domain. UBA domains are normally comprised of compact three-helix bundles which contain a conserved GF/Y-loop. They can bind polyubiquitin with high affinity. They also bind monoubiquitin and other proteins. Most UBA domain-containing proteins have one UBA domain, but some harbor two or three UBA domains. CUE domain containing proteins are characterized by an FP and a di-leucine-like sequence and bind to monoubiquitin with varying affinities. Some higher eukaryotic CUE domain proteins do not bind monoubiquitin efficiently, since they carry LP, rather than FP among CUE domains. This superfamily also includes many UBA-like domains found in AMP-activated protein kinase (AMPK) related kinases, the NXF family of mRNA nuclear export factors, elongation factor Ts (EF-Ts), nascent polypeptide-associated complex subunit alpha (NACA) and similar proteins. Although many UBA-like domains may have a conserved TG but not GF/Y-loop, they still show a high level of structural and sequence similarity with three-helical ubiquitin binding domains.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 17506767   1 MSIAQQLMDMGFPADKAEAAAGNNRN--LDQALDWIEK 36
Cdd:cd14295   2 QELVAQLMEMGFPKVRAEKALFFTQNkgLEEAMEWLEE 39

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 17506767   219 DYSTTTLQFRLLDGQTVRQQFEANEPLAMVRAWVETN-HANGVPFTLMTPFPRKVFTEDDMGTPLKVLNLVPSANVIL 295
Cdd:pfam00789   1 AEDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNrYDDLEPFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTLVL 78

UBA1 domain found in Arabidopsis thaliana ubiquitin carboxyl-terminal hydrolase 14 (atUBP14) and similar proteins; atUBP14, also called deubiquitinating enzyme 14, TITAN-6 protein, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is related to the isopeptidase T class of deubiquitinating enzymes that recycle polyubiquitin chains following protein degradation. atUBP14 is essential for early plant development. It can disassemble multi-ubiquitin chains linked internally via epsilon-amino isopeptide bonds using Lys48 and can process some, but not all, translational fusions of ubiquitin linked via alpha-amino peptide bonds. atUBP14 contains two ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 17506767   1 MSIAQQLMDMGFPADKAEAAAGNNRN--LDQALDWIEK 36
Cdd:cd14295   2 QELVAQLMEMGFPKVRAEKALFFTQNkgLEEAMEWLEE 39

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17506767   108 EKAAKVLEIREKIKVHQAKKAKLEAE--ENR----EKEKKRREDGKAMISHKEAARDREIREAAQDRRREKNEDEiARKR 181
Cdd:pfam17380 475 KKLELEKEKRDRKRAEEQRRKILEKEleERKqamiEEERKRKLLEKEMEERQKAIYEEERRREAEEERRKQQEME-ERRR 553

                          90
                  ....*....|..
gi 17506767   182 VLEQIRLDKEAR 193
Cdd:pfam17380 554 IQEQMRKATEER 565

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 17506767   219 DYSTTTLQFRLLDGQTVRQQFEANEPLAMVRAWVETN-HANGVPFTLMTPFPRKVFTEDDMGTPLKVLNLVPSANVIL 295
Cdd:pfam00789   1 AEDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNrYDDLEPFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTLVL 78

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17506767 222 TTTLQFRLLDGQTVRQQFEANEPLAMVRAWVETNHAN-GVPFTLMTPFPRKVFTEDDMGTPLKVLNLVPSANVIL 295
Cdd:cd16117   1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTVGPaYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVV 75

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 1 (FAF1, also known as UBXN3A) and similar proteins; UBX domain-containing protein 3A (UBXN3A),also termed UBX domain-containing protein 12 (UBXD12), or FAF1, 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. In addition, FAF1 contains two tandem ubiquitin-like (Ubl) domains, which shows high structural similarity with UBX domain. FAF1 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 FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, 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. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to UBX domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 17506767 220 YSTTTLQFRLLDGQTVRQQFEANEPLAMVRAWVETnhaNGVP---FTLMTPFPRKVFTEDDMGTPLKVLNLVPSANVIL 295
Cdd:cd01771   2 EPISKLRFRLPGGEFLTRRFLASEPLQVLLNFVAS---KGYPpdeYKLLTTFPRRDLTQLDPSKTLEELKLFPQETLFL 77

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 6 (UBXN6) and similar proteins; UBXN6, also termed UBX domain-containing protein 1 (UBXD1), and UBXDC2, 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. UBXN6 acts 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. Unlike other p97 cofactors that binds the N-domain of p97 through their UBX domain, UBXN6 binds p97 in two regions, at the p97 C terminus via a PUB domain and at the p97 N-domain with a short linear interaction motif termed VIM. Its UBX domain is not functional for the binding of p97. The UBXN6-p97 complex regulates the endolysosomal sorting of ubiquitylated plasma membrane protein caveolin-1 (CAV1), as well as the trafficking of ERGIC-53-containing vesicles by controlling the interaction of transport factors with the cytoplasmic tail of ERGIC-53. In addition, UBXN6 is a regulatory component of endoplasmic reticulum-associated degradation (ERAD) that may modulate the adaptor binding to p97.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 17506767 239 FEANEPLAMVRAWVETNHANG-VPFTLMTPFPRKVftEDDMGTpLKVLNLVPSAnvILN 296
Cdd:cd16119  18 FYAREKLSAVREFVREALANDwLPFELVTPGGQKL--TDEDAT-LAELGLVPAA--LLN 71

UBA1 domain found in Arabidopsis thaliana ubiquitin carboxyl-terminal hydrolase 14 (atUBP14) and similar proteins; atUBP14, also called deubiquitinating enzyme 14, TITAN-6 protein, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is related to the isopeptidase T class of deubiquitinating enzymes that recycle polyubiquitin chains following protein degradation. atUBP14 is essential for early plant development. It can disassemble multi-ubiquitin chains linked internally via epsilon-amino isopeptide bonds using Lys48 and can process some, but not all, translational fusions of ubiquitin linked via alpha-amino peptide bonds. atUBP14 contains two ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 17506767   1 MSIAQQLMDMGFPADKAEAAAGNNRN--LDQALDWIEK 36
Cdd:cd14295   2 QELVAQLMEMGFPKVRAEKALFFTQNkgLEEAMEWLEE 39

Ubiquitin regulatory domain X (UBX) 2 found in UBX domain protein 9 (UBXN9, UBXD9, or ASPSCR1) and similar proteins; UBXN9, also termed tether containing UBX domain for GLUT4 (TUG), or alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1), or alveolar soft part sarcoma locus (ASPL), or renal papillary cell carcinoma protein 17 (RCC17), belongs to the UBXD family of proteins that contains two ubiquitin regulatory domains 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. In addition, UBXN9 contains an N-terminal ubiquitin-like (Ubl) domain. UBXN9 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. However, high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers; the extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers.UBXN9 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4, assembly of the Golgi apparatus. In addition to GLUT4, UBXN9 also controls vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. UBXN9 and its budding yeast ortholog, Ubx4p, are multifunctional proteins that share some, but not all functions. Yeast Ubx4p is important for endoplasmic reticulum-associated protein degradation (ERAD) but UBXN9 appears not to share this function.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17506767 223 TTLQFRLLDGQTVRQQFEANEPLAMVRAWVETNHAN-GVPFTL-MTPfPRKVFteDDMGTPLKVLNLVPSANV 293
Cdd:cd16118   1 AVIRVQFPDRLVLQAFFRPLETVRALYDFVKSHLADpDLPFYLyTTP-PKRVL--KDKNKTLYQAGLVPAALV 70

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17506767    86 ASKTKHENFSESSEAIKPLTAEEKAAKVLEIREKIKVHQAKKA--KLEAEENREKEKKRREDgkAMISHKEAARDREIRE 163
Cdd:PTZ00121 1488 AKKKAEEAKKKADEAKKAAEAKKKADEAKKAEEAKKADEAKKAeeAKKADEAKKAEEKKKAD--ELKKAEELKKAEEKKK 1565

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 17506767   164 AAQDRRREKNED------EIARK----RVLEQIRLDKEARKAKA 197
Cdd:PTZ00121 1566 AEEAKKAEEDKNmalrkaEEAKKaeeaRIEEVMKLYEEEKKMKA 1609

UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins; HUWE1, also called ARF-binding protein 1 (ARF-BP1), HECT, UBA and WWE domain-containing protein 1, homologous to E6AP carboxyl terminus homologs protein 9 (HectH9), large structure of UREB1 (LASU1), Mcl-1 ubiquitin ligase E3 (Mule), upstream regulatory element-binding protein 1 (URE-B1), or URE-binding protein 1, may function as a ubiquitin-protein ligase that involves in the ubiquitination cascade that targets specific substrate proteins in proteolysis. It can ubiquitylate DNA polymerase beta (Pol beta), the major BER DNA polymerase and modulates base excision repair (BER). HUWE1 also acts as a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF tumor suppressor in p53 regulation. Moreover, HUWE1 is both required and sufficient for the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involving in DNA damage-induced apoptosis. Furthermore, HUWE1 plays an important role in the regulation of Cdc6 stability after DNA damage. In addition, HUWE1 works as a partner of N-Myc oncoprotein in neural cells. It ubiquitinates N-Myc and primes it for proteasomal-mediated degradation. HUWE1 contains a ubiquitin-associated (UBA) domain, a WWE domain, and a Bcl-2 homology region 3 (BH3) domain at the N-terminus and a HECT domain at the C-terminus. WWE domain plays a role in the regulation of specific protein-protein interactions in a ubiquitin conjugation system. BH3 domain is responsible for the specific binding to Mcl-1. HECT domain involves in the inhibition of the transcriptional activity of p53 via a ubiquitin-dependent degradation pathway. It also controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.

                        10        20        30
                ....*....|....*....|....*....|
gi 17506767   5 QQLMDMGFPADKAEAAAGNNRNLDQALDWI 34
Cdd:cd14288   7 QQLMDMGFTREHALEALLHTSTLEQATEYL 36

UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also called negative regulator of ubiquitin-like proteins 1, renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) which may function in the regulation of cell cycle progression. NUB1 contains three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif. This model corresponds to UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|..
gi 17506767   5 QQLMDMGFPADKAEAA--AGNNrNLDQALDWI 34
Cdd:cd14291   6 QQLMEMGFSEAEARLAlrACNG-NVERAVDYI 36

UBA1 domain found in Saccharomyces cerevisiae ubiquitin carboxyl-terminal hydrolase 14 (scUBP14) and similar proteins; scUBP14, also called deubiquitinating enzyme 14, glucose-induced degradation protein 6, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is the yeast ortholog of human Isopeptidase T (USP5), a deubiquitinating enzyme known to bind the 29-linked polyubiquitin chains. scUBP14 has been identified as a K29-linked polyubiquitin binding protein as well. It is involved in K29-linked polyubiquitin metabolism by binding to the 29-linked Ub4 resin and serving as an internal positive control in budding yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 17506767   1 MSIAQQLMDMGFPADKAEAA--AGNNRNLDQALDWI 34
Cdd:cd14296   1 EEAVSQLMSMGFSENAAKRAlyYTGNSSVEAAMNWL 36

UBA2 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA2 domain.

                        10        20        30
                ....*....|....*....|....*....|.
gi 17506767   5 QQLMDMGFPADKAEAA-AGNNRNLDQALDWI 34
Cdd:cd14297   5 KQLVDMGFTEAQARKAlRKTNNNVERAVDWL 35

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17506767    90 KHENFSESSEAIKPLTAEEKAAKVLEIREKIKVHQAKKAKLEAEENR---EKEKKRREDG--KAMISHKEAARDREIREA 164
Cdd:PTZ00121 1614 KAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAEEENKikaAEEAKKAEEDkkKAEEAKKAEEDEKKAAEA 1693

                          90       100       110
                  ....*....|....*....|....*....|..
gi 17506767   165 AQDRRREKNEDEIARKRVLEQIRLDKEARKAK 196
Cdd:PTZ00121 1694 LKKEAEEAKKAEELKKKEAEEKKKAEELKKAE 1725

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17506767    86 ASKTKHENFSESSEAIKplTAEEKAAKVLEIREK------IKVHQAKK----AKLEAEENR---EKEKKRREDGKAMISH 152
Cdd:PTZ00121 1333 AAKKKAEEAKKAAEAAK--AEAEAAADEAEAAEEkaeaaeKKKEEAKKkadaAKKKAEEKKkadEAKKKAEEDKKKADEL 1410

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 17506767   153 KEAARDREIREAAQDRRREKNEDEIARKRVLEQIRLDKEARKAK 196
Cdd:PTZ00121 1411 KKAAAAKKKADEAKKKAEEKKKADEAKKKAEEAKKADEAKKKAE 1454

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17506767    86 ASKTKHENFSESSEAIKPLTAEEKAAKVLEIREKIKVHQAKKAK-------LEAEENREKEKKRREDGKAMISHKEAARD 158
Cdd:PTZ00121 1530 AEEAKKADEAKKAEEKKKADELKKAEELKKAEEKKKAEEAKKAEedknmalRKAEEAKKAEEARIEEVMKLYEEEKKMKA 1609

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 17506767   159 REIREAAQDRRRE---KNEDEIARKRVLEQIRLDKEARKAK 196
Cdd:PTZ00121 1610 EEAKKAEEAKIKAeelKKAEEEKKKVEQLKKKEAEEKKKAE 1650

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17506767    99 EAIKPLTAEEKAAKVLEIR----EKIKVHQAKKA-----------KLEAEENREKEKKRREDGKAMISHKEAARD----- 158
Cdd:PTZ00121 1595 EEVMKLYEEEKKMKAEEAKkaeeAKIKAEELKKAeeekkkveqlkKKEAEEKKKAEELKKAEEENKIKAAEEAKKaeedk 1674

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 17506767   159 ---REIREAAQDRRR--EKNEDEIARKRVLEQIRLDKEARKAKA 197
Cdd:PTZ00121 1675 kkaEEAKKAEEDEKKaaEALKKEAEEAKKAEELKKKEAEEKKKA 1718