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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16753207  31 KIIKVTVKTPKEKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:cd01808   1 SIIKVTVKTPKEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

STI1 domain; This entry corresponds to the STI1 domain that is found in two copies in the Sti1 protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 16753207   208 NPQMQQLIQRNPEISHLLNNPDIMRQTLEIARNPAMMQEMMRNQDL 253
Cdd:pfam17830   1 DPELLAKLAANPETRALLSDPEFVAKLQQIQKNPSSLQQYMQDPRV 46

Heat shock chaperonin-binding motif;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 16753207    182 MIQIMENPFVQSMLS----NPDLMRQLIMANPQMQQLI 215
Cdd:smart00727   4 MALRLQNPQVQSLLQdmqqNPDMLAQMLQENPQLLQLI 41

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16753207  31 KIIKVTVKTPKEKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:cd01808   1 SIIKVTVKTPKEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

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 16753207    35 VTVKT-PKEKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:pfam00240   1 ITVKTlDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLR 70

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16753207  33 IKVTVKTPKEKE-EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIKS 104
Cdd:COG5272   1 MQIFVKTLTGKTiTLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRT 73

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 16753207   583 QQQLEQLNAMGFLnREANLQALIATGGDINAAIERL 618
Cdd:pfam00627   3 EEAIQRLVEMGFD-REQVREALRATGNNVERAAEYL 37

STI1 domain; This entry corresponds to the STI1 domain that is found in two copies in the Sti1 protein.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 16753207   208 NPQMQQLIQRNPEISHLLNNPDIMRQTLEIARNPAMMQEMMRNQDL 253
Cdd:pfam17830   1 DPELLAKLAANPETRALLSDPEFVAKLQQIQKNPSSLQQYMQDPRV 46

Heat shock chaperonin-binding motif;

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 16753207    182 MIQIMENPFVQSMLS----NPDLMRQLIMANPQMQQLI 215
Cdd:smart00727   4 MALRLQNPQVQSLLQdmqqNPDMLAQMLQENPQLLQLI 41

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16753207  31 KIIKVTVKTPKEKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:cd01808   1 SIIKVTVKTPKEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

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 16753207    35 VTVKT-PKEKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:pfam00240   1 ITVKTlDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLR 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 16753207  35 VTVKTPKEKE-EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLV 101
Cdd:cd17039   1 ITVKTLDGKTyTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

UBA domain of eukaryotic protein linking integrin-associated protein with cytoskeleton (PLIC) proteins, Saccharomyces cerevisiae proteins Dsk2p and Gts1p, and similar proteins; The PLIC proteins (or ubiquilins) family contains human homologs of the yeast ubiquitin-like Dsk2 protein, PLIC-1 (also called ubiquilin-1), PLIC-2 (also called ubiquilin-2 or Chap1), PLIC-3 (also called ubiquilin-3) and PLIC-4 (also called ubiquilin-4, Ataxin-1 interacting ubiquitin-like protein, A1Up, Connexin43-interacting protein of 75 kDa, or CIP75), and mouse PLIC proteins. They are ubiquitin-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. Saccharomyces 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. Gts1p, also called protein LSR1, is encoded by a pleiotropic gene GTS1 in budding yeast. The formation of Gts1p-mediated protein aggregates may induce reactive oxygen species (ROS) production and apoptosis. Gts1p also plays an important role in the regulation of heat and other stress responses under glucose-limited or -depleted conditions in either batch or continuous culture.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 16753207 581 RFQQQLEQLNAMGFLNREANLQALIATGGDINAAIERLL 619
Cdd:cd14323   1 RYQQQLATLKEMGFNDTEKNLQALSATGGNINLAIERLF 39

UBA domain of Saccharomyces cerevisiae proteasome interacting protein Dsk2p and its homologs found in fungi; The family contains several fungal multi-ubiquitin 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 ubiquitin-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 a ubiquitin 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 ubiquitin chains against disassembly by deubiquitinating enzymes.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 16753207 578 PEVRFQQQLEQLNAMGFLNREANLQALIATGGDINAAIERLL 619
Cdd:cd14324   1 PEERYEEQLRQLNEMGFFDFDRNVRALRRSGGSVQGAVESLL 42

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 16753207  33 IKVTVKTPKEKE-EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:cd01807   1 MLITVKILQGKEcTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

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 16753207  34 KVTVKTPK-EKEEFAVPENSSVQQFKEAISKRFKSQT-DQLVLIFAGKILKDQDTLIQHGIHDGLTV 98
Cdd:cd01805   2 KITFKTLQqQTFEIEVEPSDTVLELKEKIEQEQGDFPaSGQKLIYSGKVLKDDKTLSEYNIKEKDFV 68

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 16753207  45 EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDqDTLIQHGIHDGLTVHLV 101
Cdd:cd01804  14 ELSVPPNETVEGLKRRISKKLKVPKERITLLHKEKQLKD-GTLRENGIGDGSKLTLL 69

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16753207  33 IKVTVKTPKEKE-EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIKS 104
Cdd:COG5272   1 MQIFVKTLTGKTiTLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRT 73

UBA/TS-N domain; This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU. The domain has been found in non EF-TS proteins such as alpha-NAC and MJ0280.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 16753207   583 QQQLEQLNAMGFLnREANLQALIATGGDINAAIERL 618
Cdd:pfam00627   3 EEAIQRLVEMGFD-REQVREALRATGNNVERAAEYL 37

ubiquitin-like (Ubl) domain found in parkin and similar proteins; Parkin, also termed Parkinson juvenile disease protein 2, is a RBR-type E3 ubiquitin-protein ligase that is associated with recessive early onset Parkinson's disease (PD), and exerts a protective effect against dopamine-induced alpha-synuclein-dependent cell toxicity. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Parkin functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPT5, TOMM20, USP30, ZNF746 and AIMP2. It mediates monoubiquitination as well as Lys-6-, Lys-11-, Lys-48- and Lys-63-linked polyubiquitination of substrates depending on the context. Parkin may enhance cell viability and protects dopaminergic neurons from oxidative stress-mediated death by regulating mitochondrial function. It also limits the production of reactive oxygen species (ROS), and regulates cyclin-E during neuronal apoptosis. Moreover, parkin displays a ubiquitin ligase-independent function in transcriptional repression of p53. Parkin contains an N-terminal ubiquitin-like (Ubl) domain and a C-terminal RBR domain that was previously known as RING-BetweenRING-RING domain or TRIAD [two RING fingers and a DRIL (double RING finger linked)] domain. Based on current understanding of the structural biology of RBR ligases, the nomenclature of RBR has been corrected as RING-BRcat (benign-catalytic)-Rcat (required-for-catalysis) recently. The RBR (RING1-BRcat-Rcat) domain use an auto-inhibitory mechanism to modulate ubiquitination activity, as well as a hybrid mechanism that combines aspects from both RING and HECT E3 ligase function to facilitate the ubiquitination reaction.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 16753207  53 SVQQFKEAISKRFKSQTDQLVLIFAGKILKDqDTLIQ 89
Cdd:cd01798  20 SILQLKEVVAKRQGVPPDQLRIIFAGKELSD-DLTLQ 55

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
                ....*....|....*....|....*....|....*....|....*....|....*
gi 16753207  46 FAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHL 100
Cdd:cd01810  15 YEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHM 69

ubiquitin-like (Ubl) domain found in small ubiquitin-related modifier (SUMO) and similar proteins; SUMO (also known as "Smt3" and "sentrin" in other organisms) resembles ubiquitin (Ub) in structure, ligation to other proteins, and the mechanism of ligation. Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of a cascade of E1, E2 and E3 enzymes that results in a covalent bond between the C-terminus of Ub and the epsilon-amino group of a substrate lysine. SUMOs, like Ub, are covalently conjugated to lysine residues in a wide variety of target proteins in eukaryotic cells and regulate numerous cellular processes, such as transcription, epigenetic gene control, genomic instability, and protein degradation. The mammalian SUMOs have four paralogs, SUMO1 through SUMO4, which all regulate different cellular functions by conjugating to different proteins. SUMO2-4 are more closely related to each other than to SUMO1.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 16753207  33 IKVTVKTPKEKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDG 95
Cdd:cd01763   4 IKVRGQDGGKKVRFKVKKTTKLKKLFDAYAEKKGLDPDSLRFTFDGERISPNDTPESLGLEDG 66

UBA domain of next to BRCA1 gene 1 protein (NBR1) and similar proteins; NBR1, also called cell migration-inducing gene 19 protein, membrane component chromosome 17 surface marker 2, neighbor of BRCA1 gene 1 protein, or protein 1A1-3B, is a scaffold protein that may be involved in signal transmission downstream of the serine/protein kinase from the giant muscle protein titin. Moreover, NBR1 functions as an autophagic receptor for ubiquitinated cargo. It interacts with ATG8-family proteins for its degradation by autophagy. NBR1 contains an N-terminal Phox and Bem1p (PB1) domain that plays a critical role in mediating protein-protein interactions with both titin kinase and with another scaffold protein, p62. NBR1 also has a LC3-interaction region (LIR) and a ubiquitin-associated (UBA) domain. The LIR is required for the autophagic clearance of NBR1. UBA domain is responsible for the ubiquitin binding which is necessary for the puromycin-induced formation of ubiquitinated protein aggregates.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 16753207 585 QLEQLNAMGFLNREANLQALIATGGDINAAIERLL 619
Cdd:cd14319   5 ELEQLFEMGFTDRDLNQELLKKHNGDLDRVVDELL 39

UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also called negative regulator of ubiquitin-like proteins 1, 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 three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif. This model corresponds to UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|...
gi 16753207 584 QQLEQLNAMGFLNREANLqALIATGGDINAAIE 616
Cdd:cd14291   3 DKLQQLMEMGFSEAEARL-ALRACNGNVERAVD 34

ubiquitin-like (Ubl) domain found in small nuclear ribonucleoprotein U11/U12 subunit 25 (SNRNP25) and similar proteins; SNRNP25, also termed U11/U12 small nuclear ribonucleoprotein 25 kDa protein, U11/U12 snRNP 25 kDa protein (U11/U12-25K), or minus-99 protein, is a component of the U11/U12 snRNPs that are part of the U12-type spliceosome. It contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16753207  33 IKVTV-KTPKEKEEFAVPENSSVQQFKEAISKRFK-SQTDQLV--------------LIFAGKILKDQDTLIQH-GIHDG 95
Cdd:cd17058   2 ITLSVlRLDGESLPVVVPQNATVLDLKKAIERYFTlKLKREGGtkkiswkyvwktycLCFDGQKLTDDKAKLKDyGIRNG 81

                ....*.
gi 16753207  96 LTVHLV 101
Cdd:cd17058  82 DELTFV 87

WXG100 protein secretion system (Wss), protein YukD; The YukD protein family members participate in the formation of a translocon required for the secretion of WXG100 proteins (pfam06013) in monoderm bacteria, with the WXG100 protein secretion system (Wss). Like the cytoplasmic protein EsaC in Staphylococcus aureus, YukD was hypothesized to play a role of a chaperone. YukD adopts a ubiquitin-like fold. Usually, ubiquitin covalently binds to protein and flags them for protein degradation, however conjugation assays have indicated that the classical YukD lacks the capacity for covalent bond formation with other proteins. In contrast to the situation in firmicutes, YukD-like proteins in actinobacteria are often fused to a transporter involved in the ESAT-6/ESX/Wss secretion pathway. Members of the YukD family are also associated in gene neighborhoods with other enzymatic members of the ubiquitin signaling and degradation pathway such as the E1, E2 and E3 trienzyme complex that catalyze ubiquitin transfer to substrates, and the JAB family metallopeptidases that are involved in its release. This suggests that a subset of the YukD family in bacteria are conjugated and released from proteins as in the eukaryotic ubiquitin-mediated signaling and degradation pathway.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 16753207    32 IIKVTVKTPKEKEEFAVPENSSVQQFKEAISKRFKSQTD-------QLVLIFAGKI-LKDQDTLIQHGIHDGLTVHL 100
Cdd:pfam08817   1 LVRVTVLAPNRRVDLALPADVPVAELLPELLRLLGLPLTdpggapgGWVLARLGGRpLDGDRTLADAGVRDGDVLVL 77

ubiquitin-like (Ubl) domain found in ubiquitin; Ubiquitin is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. Ubiquitination is comprised of 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 (Ubl) proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ubiquitin (Ub)and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Ub includes Ubq/RPL40e and Ubq/RPS27a fusions as well as homopolymeric multiubiquitin protein chains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 16753207  33 IKVTVKTPKEKE-EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:cd01803   1 MQIFVKTLTGKTiTLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 72

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 16753207  29 EPKIIKVTVKTPKEKEEFAVPENSSVQQFKEAISKRFKSQT---DQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIKSQ 105
Cdd:cd01815   9 QPLAPKSILQLPETEPGDYPLGGYSISALKQLIAGKLPESLpdpELIDLIYCGRKLKDDQTLDFYGIQSGSTIHVLRKSW 88

                ....
gi 16753207 106 NRPQ 109
Cdd:cd01815  89 PEPD 92

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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 16753207  45 EFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKILKDQDTLIQHGIHDGLTVHLVIK 103
Cdd:cd17052  13 TFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLK 71

ubiquitin-like (Ubl) domain found in autophagy-related 8 (ATG8) and similar proteins; The ATG8 family of proteins constitute a single member in Saccharomyces cerevisiae, Atg8p, and multiple homologs in higher eukaryotes, they are multifunctional ubiquitin-like (Ubl) key regulators of autophagy. The ATG8 system is a Ubl conjugation system that is essential for autophagosome formation. In the ATG8 system, a cysteine protease (ATG4) cleaves a C-terminal arginine from ATG8, and then the exposed C-terminal glycine is conjugated to phosphatidylethanolamine (PE) by ATG7, an E1-like enzyme, and ATG3, an E2-like enzyme. The mammalian ATG8 family is classified into three subfamilies: i) MAP1LC3 (microtubule associated protein 1 light chain 3) which includes MAP1LC3A, MAP1LC3B, MAP1LC3B2, and MAP1LC3C, ii) GABARAP (GABA type A receptor associated protein) which includes GABARAP, GABARAPL1, and GABARAPL3, and iii) GABARAPL2 (GABA type A receptor associated protein like 2), also known as GATE-16 (golgi-associated adenosine triphosphatase enhancer of 16 kDa).

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 16753207  42 EKEEFAVPENSSVQQFKEAISKRFKSQTDQLVLIFAGKIL 81
Cdd:cd16108  19 DKKKFLVPSDLTVGQFMYIIRKRIKLSPEKAIFLFVNNTL 58