Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
3OJ3_E        4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRG 78
Cdd:COG5272   1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRTLG 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
3OJ3_E         6 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLR 77
Cdd:pfam00240  1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
3OJ3_E          4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEG---IPPDQQRLIFAGKQLEDGRTLSDYNI 64
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGkdaYPVAQQKLIYSGKILSDDKTVKEYKI 64

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
3OJ3_E        4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRG 78
Cdd:COG5272   1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRTLG 75

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
3OJ3_E       6 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 79
Cdd:cd01806  1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*...
3OJ3_E       6 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLV 73
Cdd:cd17039  1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

ubiquitin; Provisional

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
3OJ3_E        4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 79
Cdd:PTZ00044  1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQLRGG 76

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....
3OJ3_E       5 QIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLV 73
Cdd:cd16107  1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFLV 69

ubiquitin-like (Ubl) domain found in ubiquitin-like proteins UBL4A and similar proteins; UBL4A, also termed GdX, is a ubiquitously expressed ubiquitin-like (Ubl) protein that forms a complex with partner proteins and participates in the protein processing through endoplasmic reticulum (ER), acting as a chaperone. As a key component of the BCL2-associated athanogene 6 (BAG6) chaperone complex, UBL4A plays a role in mediating DNA damage signaling and cell death. UBL4A also regulates insulin-induced Akt plasma membrane translocation through promotion of Arp2/3-dependent actin branching. Moreover, UBL4A specifically stabilizes the TC45/STAT3 association and promotes dephosphorylation of STAT3 to repress tumorigenesis. UBL4B is testis-specific, and encoded by an X-derived retrogene Ubl4b, which is specifically expressed in post-meiotic germ cells in mammals. As a germ cell-specific cytoplasmic protein, UBL4B is not present in somatic cells. Moreover, UBL4B is present in elongated spermatids, but not in spermatocytes and round spermatids, suggesting its function is restricted to late spermiogenesis. The function of UBL4A may be compensated by either UBL4B or other Ubl proteins in normal conditions. Both UBL4A and UBL4B contain a conserved Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
3OJ3_E       4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd01807  1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3OJ3_E       4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLV 73
Cdd:cd16106  1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLV 70

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....*...
3OJ3_E       6 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLV 73
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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
3OJ3_E         4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQ-RLIFAGKQLEDGRTLSDYNIQKESTLHLVL 74
Cdd:pfam11976  1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

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        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
3OJ3_E       4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQ-RLIFAGKQLEDGRTLSDYNIQKESTLHLV 73
Cdd:cd17064  1 MKVIVKSLGGKGSLLRVDASETLESLKGKASKKLDDKPSEKvKLFYSGKELEDGKSLAEQNVPPNSLVHLV 71

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
3OJ3_E       4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIF--AGKQLEDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd01792  1 WDLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQQRLAVqpSGVELQDGVRLASQGLGPSSTVLLVVK 74

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
               ....*....|....*....|....*....|....*....|....*....|....*....|....
3OJ3_E       4 MQIFVKTL-TGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQL-EDGRTLSDYNIQ 65
Cdd:cd01796  1 MKLTVTTEdDDRLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLtDDKKTLEALGLK 64

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; 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 of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-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. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

                       10        20        30        40        50        60        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
3OJ3_E       4 MQIFVKTLTGK--TITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd01797  1 MWIQVRTMDGKkeARVDGLSKLTKIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVGLNDIIQLMVR 74

ubiquitin-like (Ubl) domain 1 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 first Ubl domain of FAT10. Some family members contain only one Ubl domain.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....
3OJ3_E       8 VKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRL 76
Cdd:cd17052  4 VQSEEWDLMTFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLKV 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        70
               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3OJ3_E       6 IFVKTLTGKTiTLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd01808  5 VTVKTPKEKE-DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
3OJ3_E       4 MQIFVKTLTGK-TITLEVEPSDT-IENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd17122  1 MWIQVRTMDGKeTHRIDSLSKLTkVEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLLVR 74

ubiquitin-like (Ubl) domain 1 found in Ankyrin repeat and ubiquitin domain-containing 1 (ANKUB1) and similar proteins; ANKUB1 is an uncharacterized protein with two tandem ubiquitin-like (Ubl) domains located at the N-terminal of Ankyrin repeats (ANK). The Ubl domain may have an adaptor role in ubiquitin (Ub)-signaling by mediating protein-protein interaction. Ubl proteins have a beta-grasp Ubl fold and attach to other proteins in a Ubl manner with biochemically distinct roles. The ankyrin repeats have been identified in numerous proteins with diverse functions. The family corresponds to the first Ubl domain.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
3OJ3_E       4 MQIFVkTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQR-------LIFAGKQLEDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd17050  1 MRIFV-AFEGEREPLDVSPGQTVGDVKEMIRDKFHIDLSDGKqgrkflvLTYAGADLQDSWVLSDIGIPPGSTIRCLLR 78

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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               ....*....|....*....|....*....|....*....|....*....|....*....|.
3OJ3_E      14 KTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLI-FAGKQLEDGRTLSDYNIQKESTLHLV 73
Cdd:cd17129 11 RTIDVVLPDTETVGDIKQILENELGIPPCKQILKgWKARTVSDSTVLRSLHLPKENSLYLL 71

ubiquitin-like (Ubl) domain found in midnolin and similar proteins; Midnolin, also termed midbrain nucleolar protein, is a nucleolar protein that may be involved in regulation of genes related to neurogenesis in the nucleolus. It is strongly expressed at the mesencephalon (midbrain) of the embryo in day 12.5 (E12.5) mice and its expression is developmentally regulated. Midnolin plays a role in cellular signaling of adult tissues and regulates glucokinase enzyme activity in pancreatic beta cells. It can also control development via regulation of mRNA transport in cells. Midnolin contains an N-terminal conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3OJ3_E       4 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGrTLSDYNIQKESTLHLV 73
Cdd:cd01804  1 INLYIHPTTGGRFELSVPPNETVEGLKRRISKKLKVPKERITLLHKEKQLKDG-TLRENGIGDGSKLTLL 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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3OJ3_E       5 QIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVL 74
Cdd:cd17121  3 QLRLRLSTGKDLKLAVRSTDTVYHMKRRLHTAEGVEPGSQRWFFSGRPLTDKMKLEELKIPKDYVVQVIV 72

ubiquitin-like (Ubl) domain found in plant membrane-anchored ubiquitin-fold proteins (MUBs); The plant MUBs belong to a family of ubiquitin-fold proteins that are plasma membrane-anchored by prenylation. They may serve as docking site to facilitate the association of specific E2s to the plasma membrane. MUBs contain a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold.

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               ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
3OJ3_E      21 EPSDTIENVKAKI-----QDKEGIP--PDQQRLIFAGKQLEDGRTLSDYN-IQKES-----TLHLVLRLR 77
Cdd:cd01814 20 SSATTVATLKEKViaewpKDKENGPksINDVKLIYAGKVLENGKTLADSRtPGKVPpggviTMHVVVRPP 89

ubiquitin-like (Ubl) domain found in transmembrane and ubiquitin-like domain-containing proteins TMUB1, TMUB2, and similar proteins; TMUB1, also termed dendritic cell-derived ubiquitin-like protein (DULP), or hepatocyte odd protein shuttling protein, or ubiquitin-like protein SB144, or HOPS, is highly expressed in the nervous system. It is involved in the termination of liver regeneration and plays a negative role in interleukin-6-induced hepatocyte proliferation. The overexpression of Tmub1 has been shown to play a role in the inhibition of cell proliferation. TMUB1 has been implicated in the regulation of locomotor activity and wakefulness in mice, perhaps acting through its interaction with CAMLG. It also facilitates the recycling of AMPA receptors into synaptic membrane in cultured primary neurons. TMUB1 contains transmembrane domains and a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. TMUB2 is an uncharacterized transmembrane domain and Ubl domain-containing protein that shows high sequence similarity to TMUB1.

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               ....*....|....*....|....*....|....*....|....*....|....*...
3OJ3_E      19 EVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQL-EDGRTLSDYNIQKESTLHLVLR 75
Cdd:cd17057 17 YARPEDTVGDFKRRHFPDELAQGKRVRLIYQGQLLrDDSRTLSSYGIQDGSVIHCHIS 74

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.

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3OJ3_E       14 KTITLEVEPSDTIENVKAKIqdkEGI---PPDQQRLIFAGKQLEDGRTLSDYNI-------QKESTLHLVLRLRGG 79
Cdd:cd01788  11 TTIFTDAKESTTVFELKKII---EGIlkrPPEDQRLYKDDQLLDDTKTLGDCGFtsqtaraQAPATLGLAFRADGE 83

Ubiquitin-like domain; This entry contains ubiquitin-like domains.

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                 ....*....|....*....|....*....|....*....|....*....|....*....
3OJ3_E        22 PSDTIENVKAKIQDKEGIPPDQQRL-------IFAGKQLEDGRTLSDYNIQKESTLHLV 73
Cdd:pfam14560 21 KSLTIEELKEKLELITGTPPSSMRLqlyddddNLVAKLDDDDALLGSYGVRDGMRIHVI 79

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.

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               ....*....|....*....|....*....|....*....|....*....|....*....|
3OJ3_E      14 KTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGkQLEDGRTLSDYNIQKESTLHLV 73
Cdd:cd17047 10 EKYDVKFPLDSTIAELKEHIETLTGVPPAMQKLMYKG-LLKDDKTLRELKVTKGAKVMVV 68

Ubiquitin-2 like Rad60 SUMO-like;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
3OJ3_E         21 EPSDTIENVKAKI-----QDKEGIPPDQQ--RLIFAGKQLEDGRTLSDYNI------QKESTLHLVLR 75
Cdd:pfam13881  21 SPATTVADLKEKViaqwpKDKENGPKTVNdvKLINAGKILENNKTLGECRLpvgetpGGVTTMHVVVR 88

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.

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               ....*....|....*....|....*....|....*....|....*....|....*....
3OJ3_E      16 ITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQL-EDGRTLSDYNIQKESTLHLV 73
Cdd:cd01812 16 LPSQDEDEPTLQDLAEAIEEVTGVPVENQKLIFKGKSLkDPEQPLSALGVKNGSKIMLI 74

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana NPL4-like proteins NPL4-1, NPL4-2, and similar proteins; The family includes a group of uncharacterized plant ubiquitin-like (Ubl) domain-containing proteins, including Arabidopsis thaliana NPL4-like protein 1 and NPL4-like protein 2.

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               ....*....|....*....|....*....|....*....|....*....|....*....
3OJ3_E      18 LEVEPSDTIENVKAKIQDKEGIPPDQQRL-IFAGKQL---EDGRTLSDYNIQKESTLHL 72
Cdd:cd17055 14 VEVPDDATVGDLKEKIAEQLSVPVSDQTLsLDPGPDLltaKSSATLSQLGLKHGDMVFL 72

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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               ....*....|....*....|....*....|....*....|
3OJ3_E      17 TLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDG 56
Cdd:cd17049 16 TFEVPPSAAVRDIKELIYEETDFPVSEQQLWHNGKELSDW 55

ubiquitin-like (Ubl) domain found in ubiquitin-like protein 7 (UBL7) and similar proteins; UBL7, also termed bone marrow stromal cell ubiquitin-like (Ubl)protein (BMSC-UbP), or ubiquitin-like protein SB132, is a novel Ubl protein that may play roles in regulation of bone marrow stromal cell (BMSC) function or cell differentiation via an evocator-associated and cell-specific pattern. UBL7 contains an N-terminal Ubl domain with a beta-grasp Ubl fold, and a C-terminal ubiquitin-associated (UBA) domain. The Ubl domain interacts with 26S proteasome-dependent degradation, and the UBA domain links cellular processes and the ubiquitin system.

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               ....*....|....*....|....*....|....*
3OJ3_E      41 PDQQRLIFAGKQLEDGRTLSDYNIQKESTLHlVLR 75
Cdd:cd01815 52 PELIDLIYCGRKLKDDQTLDFYGIQSGSTIH-VLR 85

ubiquitin-like (Ubl) domain found in retinoblastoma 1-inducible coiled-coil protein 1 (RB1CC1) and similar proteins; RB1CC1, also termed FAK family kinase-interacting protein of 200 kDa (FIP200), is the mammalian counterpart of the yeast Atg17 gene and functions as a component of the ULK1/Atg13/RB1CC1/Atg101 complex essential for induction of autophagy. RB1CC1 is a key signaling node to regulate cellular proliferation and differentiation. As a DNA-binding transcription factor, RB1CC1 has been implicated in the regulation of retinoblastoma 1 (RB1) expression. RB1CC1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, as well as a nuclear localization signal (KPRK), a leucine zipper motif and a coiled-coil structure.

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               ....*....|....*....|....*....|....*....|....*....|....
3OJ3_E      12 TGKTITLEVE-PSDTIENVKAKIQDKEGIPPDQQRLIFAGKQ-LEDGRTLSDYN 63
Cdd:cd17060  9 TGTMLTFDMSlAVQSVSDLKEAIEEKTKIPVEKQVLLVSGGEsLDPDKRVSSYS 62

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.

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               ....*....|....*....|....*....|....*....|....*..
3OJ3_E      18 LEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNI 64
Cdd:cd16104 16 VELDTDEPPLVFKAQLFALTGVPPERQKIMVKGGVLKDDDDLSKLKL 62