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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVLTLRGG 76
Cdd:cd01806   1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVLTLRGG 76
Cdd:cd01806   1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

ubiquitin; Provisional

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 398365789  1 MIVKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVLTLRGG 76
Cdd:PTZ00044  1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRGG 76

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 398365789   1 MIVKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVL 71
Cdd:COG5272    1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVT 71

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVLTLRGG 76
Cdd:cd01806   1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

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 398365789   3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVLTLR 74
Cdd:pfam00240  1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

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 398365789    1 MIVKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLVLT 72
Cdd:smart00213  1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. 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. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLV 70
Cdd:cd17039   1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing proteins UBTD1, UBTD2, and similar proteins; This family represents a group of ubiquitin-like (Ubl) domain-containing proteins evolutionarily conserved and found in metazoa, fungi, and plants. They may regulate the activity and/or specificity of E2 ubiquitin conjugating enzymes belonging to the UBE2D family. Members in this family contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEG 64
Cdd:cd01794   1 LKLRLSTGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPKG 62

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 398365789  5 VKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLV 70
Cdd:cd16107   4 VRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of ubiquitin and the epsilon-amino group of a substrate lysine. Ubiquitin-like proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLV 70
Cdd:cd00196   1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 398365789   1 MIVKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQ-RLIFQGKQIDDKLTVTDAHLVEGMQLHLVL 71
Cdd:pfam11976  1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLV 70
Cdd:cd01798   1 VFVRFNSSHGFPVEVDSDWSILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAV 68

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHlVEGMQLHLV 70
Cdd:cd01809   3 VTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYD-VDGKVIHLV 69

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 1 (UBTD1); UBTD1 is the mammalian homolog of the mitochondrial Dc-UbP/UBTD2 protein, both of which contain an N-terminal ubiquitin binding domain (UBD) and a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. UBTD1 stably interacts with the UBE2D family of E2 ubiquitin conjugating enzymes. As a tumor suppressor, UBTD1 plays a pivotal role in in regulating cellular senescence that mediates p53 function. It is also involved in MDM2 ubiquitination and degradation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHL 61
Cdd:cd17120   1 LKVRLSTGKDVRLSASMSDTIGQLKKQLHAQEGIEPSWQRWFFSGKLLTDKTRLQETKI 59

ubiquitin-like (Ubl) domain 1 found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin (Ub) regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) fold, but without the C-terminal double glycine motif. The 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 Ubl domains, which show high structural similarity with the 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. The family corresponds to the first Ubl domain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 398365789 11 KEISVELKESDLVYHIKELLEEKEGIPPSQQRLI-FQGKQIDDKLTVTDAHLVEGMQLHLVLT 72
Cdd:cd17129  11 RTIDVVLPDTETVGDIKQILENELGIPPCKQILKgWKARTVSDSTVLRSLHLPKENSLYLLTP 73

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 398365789  9 TGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQI-DDKLTVTDAHLVEGMQLHLV 70
Cdd:cd01795   4 RGERKSLTVSSTTTLKELKLQIMEKFSVAPFDQHLYFNGRELtDDSATLADLGILPGDVLYLK 66

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 398365789  2 IVKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTD 58
Cdd:cd16103   3 QIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKY 59

ubiquitin-like (Ubl) domain found in ubiquitin-like domain-containing CTD phosphatase 1 (UBLCP1) and similar proteins; UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity. It is localized in the nucleus and it contains conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which directly interacts with the proteasome. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. UBLCP1 may also play a role in the regulation of phosphorylation state of RNA polymerase II C-terminal domain, a key event during mRNA metabolism.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 398365789 10 GKEISVELKESDLVYHIKELLEEKEGIPPSQQRLI---FQGKQIDDKLTVTDAHLVEGMQLHLV 70
Cdd:cd01813   9 GKEYPVTVLSSDTVLDLKQRIFELTGVLPKRQKLLglkVKGKPADDDVKLSSLKLKPNTKIMMM 72

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398365789  3 VKVKTLTGKEiSVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDAHLVEGMQLHLV 70
Cdd:cd01808   5 VTVKTPKEKE-DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLV 71

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
                ....*....|....*....|....*....|....*....|....
gi 398365789  3 VKVKTLTGKEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQ 46
Cdd:cd01811   3 VTVKQLGGKSLTLWVNPYDPIWQLKEEIEKEWCIPIYQQRLSFQ 46

ubiquitin-like (Ubl) domain found in transcription elongation factor B (Elongin B) and similar proteins; Elongin B, also termed Elongin 18 kDa subunit, or EloB, or RNA polymerase II transcription factor SIII subunit B (SIII p18), is part of an E3 ubiquitin ligase complex called VEC that activates ubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5. VEC is composed of von Hippel-Lindau tumor suppressor protein (pVHL), elongin C, cullin 2, NEDD8, and Rbx1. ElonginB binds elonginC to form the elonginBC complex which is a positive regulator of RNA polymerase II elongation factor Elongin A. The BC complex then binds VHL (von Hippel-Lindau) tumor suppressor protein to form a VCB ternary complex. Elongin B has a ubiquitin-like (Ubl) domain. Ub has a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 398365789   1 MIVKVKTltgkEISVELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTDA 59
Cdd:cd01788    5 MIRRKKT----TIFTDAKESTTVFELKKIIEGILKRPPEDQRLYKDDQLLDDTKTLGDC 59

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 398365789  1 MIVKVKTLTGKEISV--ELKESDLVYHIKELLEEKEGIPPSQQRLIFQGKQIDDKLTVTD 58
Cdd:cd17122   1 MWIQVRTMDGKETHRidSLSKLTKVEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFD 60

ubiquitin-like (Ubl) domain found in homocysteine-inducible endoplasmic reticulum stress protein HERP; HERP is an endoplasmic reticulum (ER) integral membrane protein containing an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. The Ubl domain is required for the degradation of HERP itself as well as for HERP-mediated anti-apoptotic effects. HERP is induced by the ER stress response pathway and is involved in improving the balance of folding capacity and protein loads in the ER. There are two types of HERP, HERP1 and HERP2, which are encoded by the HERPUD1 and HERPUD2 genes, respectively.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 398365789 12 EISVELKESdlVYHIKELLEEK-EGIP-PSQQRLIFQGKQIDDKLTVTDAHLVEGMQ----LHLV 70
Cdd:cd01790  16 TVNCTLGWT--VLKLKEHLSEVyPSKPlPEDQKLIYSGKLLEDHQTLKDVLREDDPEqvhtVHLV 78

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana Bcl-2-associated athanogenes AtBAG1, AtBAG2, AtBAG3, AtBAG4, and similar proteins; The family includes four Arabidopsis BAG family proteins (AtBAG1, AtBAG2, AtBAG3, AtBAG4) that have very similar domain organizations with a ubiquitin-like (Ubl) domain in the N-terminus and a BAG domain in the C-terminus. They may function as co-chaperones that regulate diverse cellular pathways, such as programmed cell death and stress responses. AtBAG1, AtBAG3, and AtBAG4 are predicted to localize in the cytoplasm, but the localization of AtBAG2 is the microbody. AtBAG4 can interact with Hsc70. The overexpression of AtBAG4 in tobacco plants confers tolerance to a wide range of abiotic stresses such as UV light, cold, oxidants, and salt treatments.

                        10        20
                ....*....|....*....|....*...
gi 398365789 26 IKELLEEKEGIPPSQQRLIFQGKQIDDK 53
Cdd:cd17054  26 LKKLLVQDTGLQPQEQKLLFRGKEKDDK 53