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 1212979648 167 VRLKFLNDTE-ELAVArPEDTVGALKSKYFPGQE---SQMKLIYQGRLLQDpARTLRSLNITDNCVIHCHRSPP 236
Cdd:pfam00240   1 ITVKTLDGKKiTLEVD-PTDTVLELKEKIAEKEGvppEQQRLIYSGKVLED-DQTLGEYGIEDGSTIHLVLRQR 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]

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212979648 181 ARPEDTVGALKSK--------YFPgqESQMKLIYQGRLLQDpARTLRSLNITDNCVIHCHRSPP-----GSAVPGPSASL 247
Cdd:TIGR00601  17 MEPDETVKELKEKieaeqgkdAYP--VAQQKLIYSGKILSD-DKTVKEYKIKEKDFVVVMVSKPktgtgKVAPPAATPTS 93

                          90       100
                  ....*....|....*....|
gi 1212979648 248 APSATEPPSLGVNVGSLMVP 267
Cdd:TIGR00601  94 APTPTPSPPASPASGMSAAP 113

ubiquitin-like (Ubl) domain found in transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1); 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 also 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212979648 165 ITVRLKFLNDTEELAVARPEDTVGALKSKYFPGQESQMKLIYQGRLLQDPARTLRSLNITDNCVIHCHRS 234
Cdd:cd17131     2 IVLRLKFLNDTERLARVKPEDTIGSLKRTYFPGQEHQVRLIYQGQLLGDDSQTLASLHLTDNCVLHCHIS 71

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 1212979648 167 VRLKFLNDTE-ELAVArPEDTVGALKSKYFPGQE---SQMKLIYQGRLLQDpARTLRSLNITDNCVIHCHRSPP 236
Cdd:pfam00240   1 ITVKTLDGKKiTLEVD-PTDTVLELKEKIAEKEGvppEQQRLIYSGKVLED-DQTLGEYGIEDGSTIHLVLRQR 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 1212979648 167 VRLKFLNDTEELAVARPEDTVGALKSK---YFPGQESQMKLIYQGRLLQDpARTLRSLNITDNCVIHCH 232
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKieeKTGIPVEQQRLIYNGKELKD-DKTLSDYGIKDGSTIHLV 68

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1212979648 164 LITVRLKFLNDTEELAVArPEDTVGALK---SKYFPGQESQMKLIYQGRLLQDPaRTLRSLNITDNCVIH 230
Cdd:cd01808     2 IIKVTVKTPKEKEDFEVP-EDSSVKEFKeeiSKKFKAPVEQLVLIFAGKILKDQ-DTLSQHGIKDGLTVH 69

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 1212979648 198 QESQmKLIYQGRLLQDPARTLRSLNITDNCVI 229
Cdd:cd01812    41 VENQ-KLIFKGKSLKDPEQPLSALGVKNGSKI 71

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 1212979648 165 ITVRLKFLNDTE-ELAVArPEDTVGALKSKYFPGQE---SQMKLIYQGRLLQDpARTLRSLNITDNCVIHCHRSP 235
Cdd:cd16106     1 IKVTVKCSNGKKfTVEVE-PDATVLELKELIAEKSDipaEQQRLIYKGKILKD-EETLSSYKIQDGHTVHLVKGA 73