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 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLALRGG 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 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLALRGG 76
Cdd:cd01806  1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

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 15221154     1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLA 72
Cdd:smart00213  1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

ubiquitin; Provisional

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15221154   1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLALRGG 76
Cdd:PTZ00044  1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRGG 76

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 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLALRGG 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 15221154    3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLALR 74
Cdd:pfam00240  1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15221154   1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVL 71
Cdd:COG5272   1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVT 71

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 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLV 70
Cdd:cd17039  1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

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        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15221154  1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLV 70
Cdd:cd16106  1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLV 70

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
               ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15221154  1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEG-IPPVHQRIVYTGKQLADDLTAKHYNLE 62
Cdd:cd01805  1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGdFPASGQKLIYSGKVLKDDKTLSEYNIK 63

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 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLV 70
Cdd:cd00196  1 VKVETPSLKKIVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 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        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15221154  1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLErGSVLHLV 70
Cdd:cd01809  1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVD-GKVIHLV 69

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15221154 13 IDIEIELTDTIERIKERIEEKEGIPPVHQRIVY-TGKQLADDLTAKHYNLERGSVLHLVL 71
Cdd:cd01800 24 LELTLPLTDTISVLKEKIHEELGMPANKQKLQVeGGGFLKDSNSLAFYNLGSGTVLTLSL 83

ubiquitin-like (Ubl) domain 2 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the second Ubl domain of FAT10. Some family members contain only one Ubl domain.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15221154  1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDL-TAKHYNLERGSVLHLV 70
Cdd:cd17053  1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGDkTLGEYGIKTGDTLYLL 71

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 15221154    1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQ-RIVYTGKQLADDLTAKHYNLERGSVLHLVL 71
Cdd:pfam11976  1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

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 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVL 71
Cdd:cd01794  1 LKLRLSTGKDLKLSVRSTDTVLQAKRRLQALEGIEPSRQRWFFSGKLLTDKTRIEDAKIPKGFVVQVIV 69

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 15221154  1 MEIKVKTLTEKQIDIEIELTDTIERIKERIEEKEG---IPPVHQRIVYTGKQLADDLTAKHYNLE 62
Cdd:cd16126  1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKID 65

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        60
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVL 71
Cdd:cd17120  1 LKVRLSTGKDVRLSASMSDTIGQLKKQLHAQEGIEPSWQRWFFSGKLLTDKTRLQETKIQKDFVIQVIV 69

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein 2 (UBTD2); UBTD2, also termed dendritic cell-derived ubiquitin-like protein (DC-UbP), or ubiquitin-like protein SB72, is a potential ubiquitin shuttle protein firstly identified in dendritic cells and implicated in apoptosis. It binds proteins involved in the ubiquitination pathway and may play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells. UBTD2 is expressed in tumor cells but not in normal human adult tissue suggesting a role in tumorogenesis. It can potentially regulate the stability of proteins involved in various physiological processes relevant to many disease phenotypes, such as ageing and cancer. UBTD2 reconciles protein ubiquitination and deubiquitination via linking UbE1 and USP5 enzymes.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15221154  2 EIKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVLHLVLA 72
Cdd:cd17121  3 QLRLRLSTGKDLKLAVRSTDTVYHMKRRLHTAEGVEPGSQRWFFSGRPLTDKMKLEELKIPKDYVVQVIVS 73

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
               ....*....|....*....|....*....|....*....|....*...
gi 15221154 11 KQIDIEIELTDTIERIKERIEEKEGIPPVHQRIV---YTGKQLADDLT 55
Cdd:cd01813 10 KEYPVTVLSSDTVLDLKQRIFELTGVLPKRQKLLglkVKGKPADDDVK 57

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein UBFD1 and similar proteins; UBFD1, also termed ubiquitin-binding protein homolog (UBPH), is a polyubiquitin binding protein containing a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. It may play a role as nuclear factor-kappaB (NF-kappaB) regulator.

                       10        20        30        40        50        60
               ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15221154 11 KQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGkQLADDLTAKHYNLERGSVLHLV 70
Cdd:cd17047 10 EKYDVKFPLDSTIAELKEHIETLTGVPPAMQKLMYKG-LLKDDKTLRELKVTKGAKVMVV 68

ubiquitin-like (Ubl) domain found in ubiquitin carboxyl-terminal hydrolase 14 (USP14) and similar proteins; USP14 (EC 3.4.19.12), also termed deubiquitinating enzyme 14, or ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, or ubiquitin carboxyl-terminal hydrolase 14, is a component of proteasome regulatory subunit 19S that regulates deubiquitinated proteins entering inside the proteasome core 20S, which plays an inhibitory role in protein degradation. USP14 is also associated with various signal transduction pathways and tumorigenesis, and thus plays an essential role in the development of various types of cancer. Moreover, USP14 mediates the development of cardiac hypertrophy by promoting GSK-3beta phosphorylation, suggesting a role in cardiac hypertrophy treatment. USP14 contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and a C-terminal ubiquitin-specific protease (USP) domain.

                       10        20        30        40        50
               ....*....|....*....|....*....|....*....|....*....|.
gi 15221154  3 IKVKTLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADD 53
Cdd:cd16104  4 VNVKWGKEKFDDVELDTDEPPLVFKAQLFALTGVPPERQKIMVKGGVLKDD 54

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.

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gi 15221154 10 EKQIDIEIELTDTIERIKERIEEKEGIPPVHQRI 43
Cdd:cd17129 10 DRTIDVVLPDTETVGDIKQILENELGIPPCKQIL 43

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier 1 (SUMO-1) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. Four SUMO paralogs exist in mammals, SUMO1 through SUMO4. SUMO2-SUMO4 are more closely related to each other than they are to SUMO1. SUMO1 is a binding partner of the RAD51/52 nucleoprotein filament proteins, which mediate DNA strand exchange. SUMO1 conjugation to cellular proteins has been implicated in multiple important cellular processes, such as nuclear transport, cell cycle control, oncogenesis, inflammation, and the response to virus infection.

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gi 15221154  3 IKVKTLTE--KQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVL 67
Cdd:cd16114  2 IKLKVIGQdsSEIHFKVKMTTHLKKLKESYCQRQGVPMNSLRFLFEGQRINDNHTPKELGMEEEDVI 68

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.

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gi 15221154 16 EIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADD 53
Cdd:cd17049 18 EVPPSAAVRDIKELIYEETDFPVSEQQLWHNGKELSDW 55

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier (SUMO) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins, and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4, which all regulate different cellular functions by conjugating to different proteins. SUMO2-4 are more closely related to each other than to SUMO1.

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gi 15221154  1 MEIKVK-TLTEKQIDIEIELTDTIERIKERIEEKEGIPPVHQRIVYTGKQLADDLTAKHYNLERGSVL 67
Cdd:cd01763  2 ITIKVRgQDGGKKVRFKVKKTTKLKKLFDAYAEKKGLDPDSLRFTFDGERISPNDTPESLGLEDGDII 69