ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILSDDTALKEYKIDEKNFVVVMVTKPK 78
Cdd:cd16126    1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPK 78

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 171906578     1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKdafPVAGQKLIYAGKILSDDTALKEYKIDEKNFVVVMVT 75
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGI---PPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

Cell division protein DedD (periplasmic protein involved in septation) [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 171906578 121 STPASTAPASTTASSEPAPAGATQPEKPAEKPAQTPVLTSPAPADS 166
Cdd:COG3147   19 AAAAAPAPAAAAAAAAPKPAAKPAAPKPAAAAAAAPAAKAAAPAGG 64

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILSDDTALKEYKIDEKNFVVVMVTKPK 78
Cdd:cd16126    1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPK 78

ubiquitin-like (Ubl) domain found in the Rad23 protein family; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry an ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. The Ubl domain is responsible for the binding to proteasome. The UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates, which suggests Rad23 proteins might be involved in certain pathways of Ub metabolism. Both the Ubl domain and the XPC-binding domain are necessary for efficient NER function of Rad23 proteins.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdAFPVAGQKLIYAGKILSDDTALKEYKIDEKNFVVVMV 74
Cdd:cd01805    1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQG--DFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFVVVMV 72

UBA2 domain of UV excision repair protein RAD23 homolog B (HR23B) found in vertebrates; HR23B, also called xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26 S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (UBL) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function. This model corresponds to the UBA2 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 171906578 372 QEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQNFDED 416
Cdd:cd14428    1 QEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQNFDDD 45

UBA1 domain of UV excision repair protein RAD23 homolog B (HR23B) found in vertebrates; HR23B, also called xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26 S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (UBL) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function. This model corresponds to the UBA1 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 171906578 185 VTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIP 230
Cdd:cd14426    1 VTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIP 46

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 171906578     1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKdafPVAGQKLIYAGKILSDDTALKEYKIDEKNFVVVMVT 75
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGI---PPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 171906578    3 VTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDTALKEYKIDEKNFVVVMVTKP 77
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEG---VPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

UBA1 domain of Schizosaccharomyces pombe UV excision repair protein Rhp23p and its homologs; The subfamily contains several fungal multi-ubiquitin receptors, including Schizosaccharomyces pombe Rhp23p and Saccharomyces cerevisiae Rad23p, both of which are orthologs of human HR23A. They play roles in nucleotide excision repair (NER) and in cell cycle regulation. They also function as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. For instance, S. pombe Rhp23p forms a complex with Rhp41p to recognize photolesions and help initiate DNA repair, and it also protects ubiquitin chains against disassembly by deubiquitinating enzymes. Like human HR23A, members in this subfamily interact with the proteasome through their N-terminal ubiquitin-like domain (UBL), and with ubiquitin (Ub), or multi-ubiquitinated substrates, through their two ubiquitin-associated domains (UBA), termed internal UBA1 and C-terminal UBA2. In addition, they contain a xeroderma pigmentosum group C (XPC) protein-binding domain that might be necessary for its efficient NER function. This model corresponds to the UBA1 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 171906578 184 LVTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIP 230
Cdd:cd14378    1 LVVGLDYNQTVQNIMEMGYEREQVERALRASFNNPDRAVEYLLTGIP 47

UBA2 domain of Rad23 proteins found in eukaryotes; The Rad23 family includes the yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe), their mammalian orthologs HR23A and HR23B, and putative DNA repair proteins from plants. Rad23 proteins play dual roles in DNA repair as well as in proteosomal degradation. They have affinity for both the proteasome and ubiquitinylated proteins and participate in translocating polyubiquitinated proteins to the proteasome. Rad23 proteins carry a ubiquitin-like (UBL) and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. UBL domain is responsible for the binding to proteasome. UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates which suggests Rad23 proteins might be involved in certain pathways of ubiquitin metabolism. Both UBL domain and XPC-binding domain are necessary for efficient NER function of Rad23 proteins. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 171906578 372 QEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLL 409
Cdd:cd14281    1 EEREAIERLVALGFSRDQAIEAYLACDKNEELAANYLF 38

UBA1 domain of putative DNA repair proteins Rad23 found in plant; The radiation sensitive 23 (Rad23) subfamily consists of four isoforms of putative DNA repair proteins from Arabidopsis thaliana and similar proteins from other plants. The nuclear-enriched Rad23 proteins function in the cell cycle, morphology, and fertility of plants through their delivery of ubiquitin (Ub)/26S proteasome system (UPS) substrates to the 26S proteasome. Rad23 proteins contain an N-terminal ubiquitin-like (UBL) domain that associates with the 26S proteasome Ub receptor RPN10, and two C-terminal ubiquitin-associated (UBA) domains that bind Ub conjugates. This model corresponds to the UBA1 domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 171906578 184 LVTGQSYENMVTEIMSMG---YEREQVIAALRASFNNPDRAVEYLLMGIP 230
Cdd:cd14379    1 LVAGSSLEQTVQQIMDMGggsWDRDTVVRALRAAYNNPERAVEYLYSGIP 50

ubiquitin-like (Ubl) domain found in Saccharomyces cerevisiae proteasome interacting protein Dsk2p and similar proteins; The family contains several fungal multiubiquitin receptors, including Saccharomyces cerevisiae Dsk2p and Schizosaccharomyces pombe Dph1p, both of which have been characterized as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. They interact with the proteasome through their N-terminal ubiquitin-like domain (Ubl) and with ubiquitin (Ub) through their C-terminal Ub-associated domain (UBA). S. cerevisiae Dsk2p is a nuclear-enriched protein that may involve in the ubiquitin-proteasome proteolytic pathway through interacting with K48-linked polyubiquitin and the proteasome. Moreover, it has been implicated in spindle pole duplication through assisting in Cdc31 assembly into the new spindle pole body (SPB). S. pombe Dph1p is an ubiquitin (Ub0 receptor working in concert with the class V myosin, Myo52, to target the degradation of the S. pombe CLIP-170 homolog, Tip1. It also can protect Ub chains against disassembly by deubiquitinating enzymes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDTALKEYKI 64
Cdd:cd16106    1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSD---IPAEQQRLIYKGKILKDEETLSSYKI 61

UBA2 domain of Schizosaccharomyces pombe UV excision repair protein Rhp23p and its fungal homologs; The subfamily contains several fungal multiubiquitin receptors, including Schizosaccharomyces pombe Rhp23p and Saccharomyces cerevisiae Rad23p, both of which are orthologs of human HR23A. They play roles in nucleotide excision repair (NER) and in cell cycle regulation. They also function as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. For instance, S. pombe Rhp23p forms a complex with Rhp41p to recognize photolesions and help initiate DNA repair, and it also protects ubiquitin chains against disassembly by deubiquitinating enzymes. Like human HR23A, members in this subfamily interact with the proteasome through their N-terminal ubiquitin-like domain (UBL), and with ubiquitin (Ub), or multi-ubiquitinated substrates, through their two ubiquitin-associated domains (UBA), termed internal UBA1 and C-terminal UBA2. In addition, they contain a xeroderma pigmentosum group C (XPC) protein-binding domain that might be necessary for its efficient NER function. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 171906578 372 QEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQ 410
Cdd:cd14381    1 EEDQAIDRLCELGFDRDLVIQAYLACDKNEEMAANFLFE 39

ubiquitin-like (Ubl) domain found in neural precursor cell expressed developmentally down-regulated protein 8 (NEDD8) and similar proteins; NEDD8, also termed Neddylin, or RELATED TO UBIQUITIN (RUB/Rub1p) in plant and yeast, is a ubiquitin-like protein that conjugates to nuclear proteins in a manner analogous to ubiquitination and sentrinization. It modifies a family of molecular scaffold proteins called cullins that are responsible for assembling the ROC1/Rbx1 RING-based E3 ubiquitin ligases, of which several play a direct role in tumorigenesis. NEDD8 deamidation and its inhibition of Cullin-RING ubiquitin ligases (CRLs) activity are responsible for Cycle-inhibiting factor (Cif)/Cif homolog in Burkholderia pseudomallei (CHBP)-induced cytopathic effect. NEDD8 contains a single conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Polyubiquitination, signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. Ubl NEDD8, contains many of the same lysines (K6, K11, K27, K33, K48) as Ub, where K27 has an role (other than conjugation) in the mechanism of protein neddylation.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171906578   3 VTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDTALKEYKIDE 66
Cdd:cd01806    1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEG---IPPQQQRLIFSGKQMNDEKTAADYKIEG 61

Ubiquitin associated domain; Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 171906578   190 YENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLL 226
Cdd:smart00165   1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYLL 37

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDTALKEYKIDE 66
Cdd:cd01802    1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEG---IPVSQQHLIWSGRELEDDYCLHDYNITD 63

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 171906578 191 ENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYL 225
Cdd:cd14291    2 EDKLQQLMEMGFSEAEARLALRACNGNVERAVDYI 36

UBA2 domain found in ubiquitin carboxyl-terminal hydrolase 5 (UBP5); UBP5, also called deubiquitinating enzyme 5, Isopeptidase T (IsoT), ubiquitin thioesterase 5, or ubiquitin-specific-processing protease 5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell. Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. ZnF domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 171906578 191 ENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGI 229
Cdd:cd14386    3 EEAVAMLVSMGFTRDQAIKALKATDNNVERAADWIFSHP 41

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVagqKLIYAGKILSDDTALKEYKI 64
Cdd:PTZ00044   1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQI---RLIYSGKQMSDDLKLSDYKV 61

UBA2 domain found in Kip1 ubiquitination-promoting complex protein 2 (KPC2) and similar proteins; KPC2, also called ubiquitin-associated domain-containing protein 1 (UBAC1), or glialblastoma cell differentiation-related protein 1, is one of two subunits of Kip1 ubiquitination-promoting complex (KPC), a novel E3 ubiquitin-protein ligase that also contains KPC1 subunit and regulates the ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p27 at G1 phase. KPC2 contains a ubiquitin-like (UBL) domain and two ubiquitin-associated (UBA) domains. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 171906578 191 ENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLL 226
Cdd:cd14304    3 PRAVQSLMEMGFEEEDVLEALRVTRNNQNAACEWLL 38

UBA domain found in proteins involved in ubiquitin-mediated proteolysis; The ubiquitin-associated (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 the bind 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.

                         10        20        30
                 ....*....|....*....|....*....|
gi 171906578 194 VTEIMSMGYEREQVIAALRASFNNPDRAVE 223
Cdd:cd14270    1 LAQLVEMGFSREQARRALRATNGDVEAAVE 30

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-Ubl shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 171906578   1 MQVTLKTL-QQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDT-ALKEYKIDEKNFVVVMV 74
Cdd:cd01796    1 MKLTVTTEdDDRLFSLEVSPDMTLEDLKALCEAETG---IPAAEQVLLHNGQPLTDDKkTLEALGLKDGDLLLLRP 73

DNA polymerase III subunits gamma and tau; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578  85 PATTQPSSTPSPTAVSSSPAVAAAQAPAPTPALPPTSTPASTAPASTTASSEPAPAGATQPEKPAEKPAQtpvltSPAPA 164
Cdd:PRK07764 430 QPAPAPAPAPAPPSPAGNAPAGGAPSPPPAAAPSAQPAPAPAAAPEPTAAPAPAPPAAPAPAAAPAAPAA-----PAAPA 504

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578 165 DSTPGDSSRSNLfeDATSALVTGQSY---ENMVTEIMSMGYEREQVI-----AALRASFNNPDRA---VEYLLMGIPGDR 233
Cdd:PRK07764 505 GADDAATLRERW--PEILAAVPKRSRktwAILLPEATVLGVRGDTLVlgfstGGLARRFASPGNAevlVTALAEELGGDW 582

                        170       180
                 ....*....|....*....|..
gi 171906578 234 ESQAVVDPPPQAVSTGTPQSPA 255
Cdd:PRK07764 583 QVEAVVGPAPGAAGGEGPPAPA 604

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 171906578   2 QVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDTALKEYKIDE 66
Cdd:cd16103    3 QIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGG---PPVEDQILLFQGQELRDKKSLKYYGIKD 64

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 171906578 191 ENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLL 226
Cdd:cd14297    1 EDLVKQLVDMGFTEAQARKALRKTNNNVERAVDWLF 36

UBA domain found in Arabidopsis thaliana E3 ubiquitin-protein ligase UPL1 (atUPL1), UPL2 (atUPL2) and similar proteins; The family includes two highly similar 405-kDa HECT E3 ubiquitin-protein ligases (UPLs), UPL1 and UPL2, from Arabidopsis thaliana. The HECT E3 UPL family plays a prominent role in the ubiquitination of plant proteins. The biological functions of UPL1 and UPL2 remain unclear. Both of them contain a ubiquitin-associated (UBA) domain and a C-terminal HECT domain. UBA domain may be involved in ubiquitin metabolism. HECT domain is necessary and sufficient for their E3 catalytic activity, but requires ATP, E1 and an E2 of the Arabidopsis UBC8 family to ubiquitinate proteins.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 171906578 192 NMVTEIMSMGYEREQVIAALRA-SFNNPDRAVEYLL 226
Cdd:cd14327    1 EAVAQLVEMGFSRERAEEALRAvGTNSVELAMEWLF 36

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or 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 a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171906578  13 FKIDIDPEETVKALKEKIESEKGKDAFPVagqKLIYAGKILSDDTALKEYKIdeKNFVVVMVTK 76
Cdd:cd17062   19 ITLETSLDITGSELREKIAEELGVPEDRI---KLISNGKVLKDEKTLAEQGV--KNNSQVMVLV 77

ubiquitin-like (Ubl) domain found in BAG family molecular chaperone regulator 1 (BAG1) and similar proteins; BAG1, also termed Bcl-2-associated athanogene 1, or HAP, is a multifunctional protein involved in a variety of cellular functions such as apoptosis, transcription, and proliferative pathways, as well as in cell signaling and differentiation. It delivers chaperone-recognized unfolded substrates to the proteasome for degradation. BAG1 functions as a co-chaperone for Hsp70/Hsc70 to increase Hsp70 foldase activity. It also suppresses apoptosis and enhances neuronal differentiation. As an anti-apoptotic factor, BAG1 interacts with tau and regulates its proteasomal degradation. It also binds to BCR-ABL with a high affinity, and directly routes immature BCR-ABL for proteasomal degradation. It acts as a potential therapeutic target in Parkinson's disease. It also modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution, suggesting a role in Huntington's disease. There are at least four isoforms of Bag1 protein that are formed by alternative initiation of translation within a common mRNA. BAG1 contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and a C-terminal BAG domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 171906578   1 MQVTLkTLQQQTFKIDI----DPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDTA-LKEYKIdeKNFVVVMV 74
Cdd:cd01812    1 LTVTV-IHGSNKHTIELpsqdEDEPTLQDLAEAIEEVTG---VPVENQKLIFKGKSLKDPEQpLSALGV--KNGSKIML 73

UBA domain found in vacuolar protein sorting-associated protein 13D (VP13D) and similar proteins; VP13D is a chorea-acanthocytosis (CHAC)-similar protein encoded by gene VPS13D. it contains two putative domains, ubiquitin-associated (UBA) domain and lectin domain of ricin B chain profile (ricin-B-lectin), suggesting it may interact with, and be involved in the trafficking of, proteins modified with ubiquitin and/or carbohydrate molecules. Further investigation is required.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 171906578 377 IERLKALGFPEGLVIQAYFACEKNENLAANFLLQQ 411
Cdd:cd14306    1 VAKLMELGFPEEDCIRALRACGGNVEEAANWLLEN 35

ubiquitin-like (Ubl) domain found in plant TBP-associated factors (TAFs) and similar proteins; TAFs, also termed transcription initiation factor TFIID subunits, or TAFII250 subunits, are components of the TFIID complex, a multisubunit protein complex involved in promoter recognition and essential for mediating regulation of RNA polymerase transcription. TAFs is the core scaffold of the TFIID complex, which is comprised of the TATA binding protein (TBP) and 12-15 TAFs. TAFs contain a ubiquitin-like (Ubl) domain and a Bromo domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIeSEKGKDAfPVAGQKLIYAGKILSDDTALKE 61
Cdd:cd17064    1 MKVIVKSLGGKGSLLRVDASETLESLKGKA-SKKLDDK-PSEKVKLFYSGKELEDGKSLAE 59

Ubiquitin-2 like Rad60 SUMO-like;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578   18 DPEETVKALKEKIESEKGKDAFPVAGQ----KLIYAGKILSDDTALKEYKIDEKNFvvvmvtkPKAVTT----AVPATTQ 89
Cdd:pfam13881  21 SPATTVADLKEKVIAQWPKDKENGPKTvndvKLINAGKILENNKTLGECRLPVGET-------PGGVTTmhvvVRPNLPE 93

                  ....
gi 171906578   90 PSST 93
Cdd:pfam13881  94 PNSE 97

ubiquitin-like (Ubl) domain found in eukaryotic protein linking integrin-associated protein (IAP, also known as CD47) with cytoskeleton (PLIC) proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like (Ubl) Dsk2 protein, PLIC-1 (also termed ubiquilin-1), PLIC-2 (also termed ubiquilin-2, or Chap1), PLIC-3 (also termed ubiquilin-3) and PLIC-4 (also termed ubiquilin-4, ataxin-1 interacting ubiquitin-like protein, A1Up, connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin (Ub)-binding adaptor proteins involved in all protein degradation pathways through delivering ubiquitinated substrates to proteasomes. They also promote autophagy-dependent cell survival during nutrient starvation. PLIC-1 regulates the function of the thrombospondin receptor CD47 and G protein signaling. It plays a role in TLR4-mediated signaling through interacting with the Toll/interleukin-1 receptor (TIR) domain of TLR4. It also inhibits the TLR3-Trif antiviral pathway by reducing the abundance of Trif. Moreover, PLIC-1 binds to gamma-aminobutyric acid receptors (GABAARs) and modulates the Ub-dependent, proteasomal degradation of GABAARs. Furthermore, PLIC-1 acts as a molecular chaperone regulating amyloid precursor protein (APP) biosynthesis, trafficking, and degradation by stimulating K63-linked polyubiquitination of lysine 688 in the APP intracellular domain. In addition, PLIC-1 is involved in the protein aggregation-stress pathway via associating with the Ub-interacting motif (UIM) proteins ataxin 3, HSJ1a, and epidermal growth factor substrate 15 (EPS15). PLIC-2 is a protein that binds the ATPase domain of the HSP70-like Stch protein. It functions as a negative regulator of G protein-coupled receptor (GPCR) endocytosis. It also involved in amyotrophic lateral sclerosis (ALS)-related dementia. PLIC-3 is encoded by UbiquilinN3, a testis-specific gene. It shows high sequence similarity with the Xenopus protein XDRP1, a nuclear phosphoprotein that binds to the N-terminus of cyclin A and inhibits Ca2+-induced degradation of cyclin A, but not cyclin B. PLIC-4 is an ubiquitin-like (Ubl) nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and Ub-proteasome pathways. It also binds to the non-ubiquitinated gap junction protein connexin43 (Cx43) and regulates the turnover of Cx43 through the proteasomal pathway. PLIC proteins contain an N-terminal Ubl domain that is responsible for the binding of Ub-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal Ub-associated (UBA) domain that interacts with Ub chains present on proteins destined for proteasomal degradation. In addition, mammalian PLIC2 proteins have an extra collagen-like motif region, which is absent in other PLIC proteins and the yeast Dsk2 protein.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 171906578   3 VTLKTLQQQTfKIDIDPEETVKALKEKIeSEKGKDafPVAGQKLIYAGKILSDDTALKEYKIDEkNFVVVMVTK 76
Cdd:cd01808    5 VTVKTPKEKE-DFEVPEDSSVKEFKEEI-SKKFKA--PVEQLVLIFAGKILKDQDTLSQHGIKD-GLTVHLVIK 73

ubiquitin-like (Ubl) domain found in Sacsin and similar proteins; Sacsin, also termed DnaJ homolog subfamily C member 29 (DNAJC29), is encoded by SACS gene that is highly expressed in the brain. Mutations in SACS can cause the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) which is characterized by early-onset spastic ataxia. Sacsin is a modular protein that is localized on the mitochondrial surface and possibaly required for normal mitochondrial network organization. Sacsin knockdown resulted in a reduction in cells expressing plyglutamine-expanded ataxin-1, which correlated with a loss of cells with large nuclear ataxin-1 incusions. At the N-terminus, sacsin contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which can interact with the proteasome. At the C-terminus, sacsin harbors a protein-protein interaction J-domain followed by an higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain. The J-domain is typically associated with DnaJ-like co-chaperones involved in regulation of the Hsp70 heat shock system.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 171906578  19 PEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILSDDT 57
Cdd:cd17049   21 PSAAVRDIKELIYEETD---FPVSEQQLWHNGKELSDWV 56

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578   86 ATTQPSSTPSPTAVSSSPAVAAAQApAPTPALPPTSTPASTAPASTTASSEPAPAGATQPEKPAEKPAQTPVLTSPAPAD 165
Cdd:PRK12270   34 ADYGPGSTAAPTAAAAAAAAAASAP-AAAPAAKAPAAPAPAPPAAAAPAAPPKPAAAAAAAAAPAAPPAAAAAAAPAAAA 112

                  ....
gi 171906578  166 STPG 169
Cdd:PRK12270  113 VEDE 116

Crinkler effector protein N-terminal domain; Phytophthora sojae encodes hundreds of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling- and necrosis-inducing proteins (CRN) or Crinkler. Their functions and mechanisms in pathogenesis are mostly unknown. This N-terminal domain contains a ubiquitin-like fold.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 171906578   12 TFKIDIDPEETVKALKEKIESEKGKD-AFPVAGQKLIYAGKILSDDTA--LKEYKIDEKNF 69
Cdd:pfam20147  14 AFSVKIDESETVGDLKKAIKEKKPNDfKDVAADLKLWKVGSWLDDDDLeeLKELDLDGEEE 74

ubiquitin-like (Ubl) domain 1 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which is required for its antiviral activity. This family corresponds to the first Ubl domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKD------AFPVAGQKLiyagKILSDDTALKEYKI 64
Cdd:cd01811    1 IQVTVKQLGGKSLTLWVNPYDPIWQLKEEIEKEWCIPiyqqrlSFQEPGGER----QVLRNDKTLADYGI 66

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578   75 TKPKAVTT--AVPATTQ--PSSTPSPTAVssspavaaaqapaptpalpptSTPASTAPASTTAS-SEPAPAGATQ---PE 146
Cdd:pfam05109 430 TSPTLNTTgfAAPNTTTglPSSTHVPTNL---------------------TAPASTGPTVSTADvTSPTPAGTTSgasPV 488

                          90       100       110
                  ....*....|....*....|....*....|....
gi 171906578  147 KPAEKP------AQTPVLTSPAPADSTPGDSSRS 174
Cdd:pfam05109 489 TPSPSPrdngteSKAPDMTSPTSAVTTPTPNATS 522

cytoskeleton protein RodZ;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 171906578  81 TTAVPATTQPSSTPSPTAVSSSPAVAAAQAPAPTPALpptSTPASTAPASTTASSEPAPAGATQPEKPAEKPAQTPVLTS 160
Cdd:PRK10856 159 GQSVPLDTSTTTDPATTPAPAAPVDTTPTNSQTPAVA---TAPAPAVDPQQNAVVAPSQANVDTAATPAPAAPATPDGAA 235

                 ....*.
gi 171906578 161 PAPADS 166
Cdd:PRK10856 236 PLPTDQ 241