2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus; This is the largely alpha-helical, C-terminal half of 2'-5'-oligoadenylate synthetase 1, being described as domain 2 of the enzyme and homologous to a tandem ubiquitin repeat. It carries the region of enzymic activity between 320 and 344 at the extreme C-terminal end. Oligoadenylate synthetases are antiviral enzymes that counteract vial attack by degrading viral RNA. The enzyme uses ATP in 2'-specific nucleotidyl transfer reactions to synthesize 2'.5'-oligoadenylates, which activate latent ribonuclease, resulting in degradation of viral RNA and inhibition of virus replication. This domain is often associated with NTP_transf_2 pfam01909.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1332564240 163 SCPSSEVYANLIKANGY---PGNFSPSFSELQRNFVKHRPTKLKSLLRLVKHWYQQYVRDKCpRANLPPLYALELLTVYA 239
Cdd:pfam10421   1 SKPSPEVYVDLIRSCTSlakPGEFSPCFTELQRNFVKSRPTKLKSLIRLVKHWYQQCKKKLK-GASLPPQYALELLTVYA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1332564240 240 WEAGTREDaNFRLDEGLATVMELLQDHELLCIYWTKHYTLQHPVIEACVRRQLRGQRPIILDPADPTNNVAEG--YRWDI 317
Cdd:pfam10421  80 WEQGCGKE-DFNTAEGFRTVLELIQQYQQLCIYWTVYYDFEDETVRNFLLKQLKKPRPVILDPADPTGNVGGGdrWRWDL 158

                         170       180       190
                  ....*....|....*....|....*....|
gi 1332564240 318 VAQRANQCLKQDCCYDNRDSPVPSWRVKRA 347
Cdd:pfam10421 159 LAQEAAAWLSQPCFKNGDGSPVPSWDVPPA 188

first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1332564240 429 EIQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVILSK 500
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus; This is the largely alpha-helical, C-terminal half of 2'-5'-oligoadenylate synthetase 1, being described as domain 2 of the enzyme and homologous to a tandem ubiquitin repeat. It carries the region of enzymic activity between 320 and 344 at the extreme C-terminal end. Oligoadenylate synthetases are antiviral enzymes that counteract vial attack by degrading viral RNA. The enzyme uses ATP in 2'-specific nucleotidyl transfer reactions to synthesize 2'.5'-oligoadenylates, which activate latent ribonuclease, resulting in degradation of viral RNA and inhibition of virus replication. This domain is often associated with NTP_transf_2 pfam01909.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1332564240 163 SCPSSEVYANLIKANGY---PGNFSPSFSELQRNFVKHRPTKLKSLLRLVKHWYQQYVRDKCpRANLPPLYALELLTVYA 239
Cdd:pfam10421   1 SKPSPEVYVDLIRSCTSlakPGEFSPCFTELQRNFVKSRPTKLKSLIRLVKHWYQQCKKKLK-GASLPPQYALELLTVYA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1332564240 240 WEAGTREDaNFRLDEGLATVMELLQDHELLCIYWTKHYTLQHPVIEACVRRQLRGQRPIILDPADPTNNVAEG--YRWDI 317
Cdd:pfam10421  80 WEQGCGKE-DFNTAEGFRTVLELIQQYQQLCIYWTVYYDFEDETVRNFLLKQLKKPRPVILDPADPTGNVGGGdrWRWDL 158

                         170       180       190
                  ....*....|....*....|....*....|
gi 1332564240 318 VAQRANQCLKQDCCYDNRDSPVPSWRVKRA 347
Cdd:pfam10421 159 LAQEAAAWLSQPCFKNGDGSPVPSWDVPPA 188

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1332564240 429 EIQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVILSK 500
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1332564240 432 VFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVIL 498
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHL 67

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1332564240 430 IQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVIL 498
Cdd:COG5272     1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHL 69

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1332564240  350 IQVTVQEWGHSDLTFWVNPYEPIKKLKEKIQLSQGYL-GLQRLSFQepggeRQLIRSHCTLAYYGI 414
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPpEQQRLIYK-----GKVLEDDRTLADYGI 61

2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus; This is the largely alpha-helical, C-terminal half of 2'-5'-oligoadenylate synthetase 1, being described as domain 2 of the enzyme and homologous to a tandem ubiquitin repeat. It carries the region of enzymic activity between 320 and 344 at the extreme C-terminal end. Oligoadenylate synthetases are antiviral enzymes that counteract vial attack by degrading viral RNA. The enzyme uses ATP in 2'-specific nucleotidyl transfer reactions to synthesize 2'.5'-oligoadenylates, which activate latent ribonuclease, resulting in degradation of viral RNA and inhibition of virus replication. This domain is often associated with NTP_transf_2 pfam01909.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1332564240 163 SCPSSEVYANLIKANGY---PGNFSPSFSELQRNFVKHRPTKLKSLLRLVKHWYQQYVRDKCpRANLPPLYALELLTVYA 239
Cdd:pfam10421   1 SKPSPEVYVDLIRSCTSlakPGEFSPCFTELQRNFVKSRPTKLKSLIRLVKHWYQQCKKKLK-GASLPPQYALELLTVYA 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1332564240 240 WEAGTREDaNFRLDEGLATVMELLQDHELLCIYWTKHYTLQHPVIEACVRRQLRGQRPIILDPADPTNNVAEG--YRWDI 317
Cdd:pfam10421  80 WEQGCGKE-DFNTAEGFRTVLELIQQYQQLCIYWTVYYDFEDETVRNFLLKQLKKPRPVILDPADPTGNVGGGdrWRWDL 158

                         170       180       190
                  ....*....|....*....|....*....|
gi 1332564240 318 VAQRANQCLKQDCCYDNRDSPVPSWRVKRA 347
Cdd:pfam10421 159 LAQEAAAWLSQPCFKNGDGSPVPSWDVPPA 188

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1332564240 429 EIQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVILSK 500
Cdd:cd16103     1 EIQIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1332564240 432 VFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVIL 498
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHL 67

ubiquitin-like (Ubl) domain 2 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 that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (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 second Ubl domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1332564240 430 IQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVIL 498
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHM 69

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 1332564240 430 IQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVILSK 500
Cdd:cd16106     1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDGHTVHLVK 71

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 1332564240 431 QVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTVIL 498
Cdd:cd16107     1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTGIPSLEQRLIFGGRQLQHSQSLESCKMENDATLFL 68

ubiquitin; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1332564240 430 IQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSVTV 496
Cdd:PTZ00044    1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTI 67

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 1332564240 430 IQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQDSV 494
Cdd:cd01809     1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVDGKV 65

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 1332564240 431 QVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGL-RCQEQRLEFQGHILEDWFDFKSYGIQDSVTVIL 498
Cdd:cd01805     2 KITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGDfPASGQKLIYSGKVLKDDKTLSEYNIKEKDFVVV 70

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1332564240 352 VTVQEWGHSDLTFWVNPYEPIKKLKEKIQLSQGYLG-LQRLSFQepGgerQLIRSHCTLAYYGI 414
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPeQQRLIYS--G---KVLEDDQTLGEYGI 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1332564240 430 IQVFVKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGL-RCQEQRLEFQGHILEDWFDFKSYGIQD 492
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIpPSQQVRLIFDGERLDPNSTVEDLDIED 64

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
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1332564240 434 VKNPDGRSHAYAIHPLDYVLNLKQQIEDRQGLRCQEQRLEFQGHILEDWFDFKSYGIQ 491
Cdd:cd01806     3 VKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIE 60