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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77917606    92 WNKTKHDVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKGLVPED-KTLREIKVTSGAKIMVVGSTI 157
Cdd:pfam00240   6 LDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDdQTLGEYGIEDGSTIHLVLRQR 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 77917606    92 WNKTKHDVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKGLVPED-KTLREIKVTSGAKIMVVGSTI 157
Cdd:pfam00240   6 LDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDdQTLGEYGIEDGSTIHLVLRQR 72

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77917606  88 LKIIW-NKTKHDVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKG-LVPEDKTLREIKVTSGAKIMVV 153
Cdd:cd17039   1 ITVKTlDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGkELKDDKTLSDYGIKDGSTIHLV 68

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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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77917606  88 LKIIWNKTKHDVKVPLDSTGS----ELKQKIHSITGLPPAMQKVMYKG--LVPEDKTLREIKVTSGAKIMVVGS 155
Cdd:cd01812   3 VTVIHGSNKHTIELPSQDEDEptlqDLAEAIEEVTGVPVENQKLIFKGksLKDPEQPLSALGVKNGSKIMLIGK 76

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), which may function in the regulation of cell cycle progression. NUB1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77917606  93 NKTKHDVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKG-LVPEDKTLREIKVTSGAKIMVV 153
Cdd:cd17062  15 KKKKITLETSLDITGSELREKIAEELGVPEDRIKLISNGkVLKDEKTLAEQGVKNNSQVMVL 76

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77917606  93 NKTKHDVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKGLVPED-KTLREIKVTSGAKIMVV 153
Cdd:cd16106   9 NGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDeETLSSYKIQDGHTVHLV 70

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77917606  85 LVDLKIIWNKTKHDVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKGLVPEDKTLREIK-VTSGAKIMVV 153
Cdd:cd17054   1 TIKIKVSHGAVYHEVTVSAQATFGDLKKLLVQDTGLQPQEQKLLFRGKEKDDKDFLDLAgVKDKAKVVLV 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 77917606  85 LVDLKIIWNKTkHDVKVPLDSTGSELKQKIHSITGL-PPAMQKVMYKGLVPED-KTLREIKVT 145
Cdd:cd01805   2 KITFKTLQQQT-FEIEVEPSDTVLELKEKIEQEQGDfPASGQKLIYSGKVLKDdKTLSEYNIK 63

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
                ....*....|....*....|....*....|....*
gi 77917606  98 DVKVPLDSTGSELKQKIHSITGLPPAMQKVMYKGL 132
Cdd:cd01800  25 ELTLPLTDTISVLKEKIHEELGMPANKQKLQVEGG 59