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 145360542   77 VTVK-FPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDyRNLNEYGITEFSEIVVFLK 146
Cdd:pfam00240   1 ITVKtLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDD-QTLGEYGIEDGSTIHLVLR 70

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 145360542 172 NGARIPVEIKDTCTISEMREGLQANKTLPRDEYIFVHKQRIMRENCSLRWHGVENGDTLFVF 233
Cdd:cd17039    7 DGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

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 145360542   77 VTVK-FPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDyRNLNEYGITEFSEIVVFLK 146
Cdd:pfam00240   1 ITVKtLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDD-QTLGEYGIEDGSTIHLVLR 70

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 145360542    75 IHVTVK-FPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDyRNLNEYGITEFSEIVVFLK 146
Cdd:smart00213   1 IELTVKtLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDD-RTLADYGIQDGSTIHLVLR 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
                  ....*....|....*....|....*....|....*....|....*..
gi 145360542    1 MEISEQESVLEVKKRLGQFLQIPTSSITLFVSCWELIDGLDIEDYPI 47
Cdd:pfam00240  13 LEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGI 59

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 145360542   77 VTVK-FPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDyRNLNEYGITEFSEIVVFLK 146
Cdd:pfam00240   1 ITVKtLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDD-QTLGEYGIEDGSTIHLVLR 70

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 145360542    75 IHVTVK-FPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDyRNLNEYGITEFSEIVVFLK 146
Cdd:smart00213   1 IELTVKtLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDD-RTLADYGIQDGSTIHLVLR 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145360542  75 IHVTVKFPS-KQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDyRNLNEYGI 135
Cdd:cd16106    1 IKVTVKCSNgKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDE-ETLSSYKI 61

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 145360542  75 IHVTVKFPSKQF-TVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDYRNLNEYGITEFSEIVVFL 145
Cdd:cd17057    2 ITIRLKFLNETErVVYARPEDTVGDFKRRHFPDELAQGKRVRLIYQGQLLRDDSRTLSSYGIQDGSVIHCHI 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145360542  77 VTVKFPSKQ--FTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELADDYRNLNEYGITEFSEIVV 143
Cdd:cd01796    3 LTVTTEDDDrlFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTDDKKTLEALGLKDGDLLLL 71

ubiquitin-like (Ubl) domain found in tubulin-specific chaperone cofactor E-like protein (TBCEL) and similar proteins; TBCEL, also termed leucine-rich repeat-containing protein 35 (LRRC35), or E-like (EL), is a novel regulator of tubulin stability, suggesting a link between tubulin turnover and vesicle transport. TBCEL is abundantly expressed in testis, but is also present in several tissues at a much lower level. It is required for the synchronous movement of the investment cones and is important for normal male fertility. TBCEL shows high sequence similarity to tubulin-specific chaperone cofactor E (TBCE), a component of the multimolecular complex required for tubulin heterodimer formation in all eukaryotic cells. It contains a leucine-rich repeat protein-protein interaction domain and a C-terminal ubiquitin-like (Ubl) domain, but does not harbor the cytoskeleton-associated protein with glycine-rich segment (CAP-Gly) domain found in TBCE.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 145360542  73 RKIHVTVKFPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGIELAD--------DYRNLNEYGITEFSEIVVF 144
Cdd:cd17045    6 KSAKVTVHFEDQVESMDIDLDQTVAELKKQLKNLVGLPPSKMRLYYIDIEMSIfgpeelrfPSRALYSYNIRDGDEILVE 85

                 ..
gi 145360542 145 LK 146
Cdd:cd17045   86 PK 87

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 145360542  73 RKIHVTVKFPSKQFTVEVDRTETVSSLKDKIHIVENTPIKRMQLYYSGiELADDYRNLNEYGI 135
Cdd:cd01808    1 SIIKVTVKTPKEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAG-KILKDQDTLSQHGI 62

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 145360542 172 NGARIPVEIKDTCTISEMREGLQANKTLPRDEYIFVHKQRIMRENCSLRWHGVENGDTLFVF 233
Cdd:cd17039    7 DGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 145360542   83 SKQFTVE--VDRTETVSSLKDKIHIVENTPIKRMQLYYSG------IELADDYRNLNEYGITEFSEIVV 143
Cdd:pfam14560  10 TKAVSSErrFDKSLTIEELKEKLELITGTPPSSMRLQLYDdddnlvAKLDDDDALLGSYGVRDGMRIHV 78