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 295054230  26 KIMKVTVKTPKEKEEFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
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 295054230  203 NPQMQQLIQRNPEISHMLNNPDIMRQTLELARNPAMMQEMMRNQD 247
Cdd:pfam17830   1 DPELLAKLAANPETRALLSDPEFVAKLQQIQKNPSSLQQYMQDPR 45

Heat shock chaperonin-binding motif;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 295054230   173 NPEMMvQIMENPFVQSMLS----NPDLMRQLIMANPQMQQLI 210
Cdd:smart00727   1 DPEMA-LRLQNPQVQSLLQdmqqNPDMLAQMLQENPQLLQLI 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 295054230  26 KIMKVTVKTPKEKEEFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:cd01808    1 SIIKVTVKTPKEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

UBA domain of 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 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. 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 ubiquitin-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 ubiquitin-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 UBQLN3, 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 a ubiquitin-like nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and ubiquitin-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 ubiquitin-like (UBL) domain that is responsible for the binding of ubiquitin-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal ubiquitin-associated (UBA) domain that interacts with ubiquitin 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
                 ....*....|....*....|....*....|....*....|
gi 295054230 539 RFQQQLEQLSAMGFLNREANLQALIATGGDINAAIERLLG 578
Cdd:cd14399    1 RYASQLEQLQAMGFVDRQANIQALIATGGNVNAAIERLLG 40

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 295054230  28 MKVTVKTPKEKE-EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIKT 99
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 295054230  541 QQQLEQLSAMGFLnREANLQALIATGGDINAAIERL 576
Cdd:pfam00627   3 EEAIQRLVEMGFD-REQVREALRATGNNVERAAEYL 37

ubiquitin; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 295054230  28 MKVTVKT-PKEKEEFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:PTZ00044   1 MQILIKTlTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQ 72

Heat shock chaperonin-binding motif;

                           10        20        30
                   ....*....|....*....|....*....|...
gi 295054230   384 LMQNMLSAPYMRSMLQSLSQNPDLAAQMMLNNP 416
Cdd:smart00727   3 EMALRLQNPQVQSLLQDMQQNPDMLAQMLQENP 35

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 295054230  26 KIMKVTVKTPKEKEEFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:cd01808    1 SIIKVTVKTPKEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

UBA domain of 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 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. 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 ubiquitin-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 ubiquitin-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 UBQLN3, 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 a ubiquitin-like nuclear protein that interacts with ataxin-1 and further links ataxin-1 with the chaperone and ubiquitin-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 ubiquitin-like (UBL) domain that is responsible for the binding of ubiquitin-interacting motifs (UIMs) expressed by proteasomes and endocytic adaptors, and C-terminal ubiquitin-associated (UBA) domain that interacts with ubiquitin 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
                 ....*....|....*....|....*....|....*....|
gi 295054230 539 RFQQQLEQLSAMGFLNREANLQALIATGGDINAAIERLLG 578
Cdd:cd14399    1 RYASQLEQLQAMGFVDRQANIQALIATGGNVNAAIERLLG 40

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 295054230  30 VTVKTPKEKE-EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLV 96
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 295054230 539 RFQQQLEQLSAMGFLNREANLQALIATGGDINAAIERLL 577
Cdd:cd14323    1 RYQQQLATLKEMGFNDTEKNLQALSATGGNINLAIERLF 39

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 295054230  28 MKVTVKTPKEKE-EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:cd01807    1 MLITVKILQGKEcTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

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 295054230 536 PEVRFQQQLEQLSAMGFLNREANLQALIATGGDINAAIERLL 577
Cdd:cd14324    1 PEERYEEQLRQLNEMGFFDFDRNVRALRRSGGSVQGAVESLL 42

Beta-grasp ubiquitin-like fold; Ubiquitin is a protein modifier that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes. The ubiquitination process comprises 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 proteins have similar ubiquitin beta-grasp fold and attach to other proteins in a ubiquitin-like manner but with biochemically distinct roles. Ubiquitin and ubiquitin-like proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some other ubiquitin-like domains have adaptor roles in ubiquitin-signaling by mediating protein-protein interaction. In addition to Ubiquitin-like (Ubl) domain, Ras-associating (RA) domain, F0/F1 sub-domain of FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, TGS (ThrRS, GTPase and SpoT) domain, Ras-binding domain (RBD), Ubiquitin regulatory domain X (UBX), Dublecortin-like domain, and RING finger- and WD40-associated ubiquitin-like (RAWUL) domain have beta-grasp ubiquitin-like folds, and are included in this superfamily.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 295054230  30 VTVKTPKEKE-EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLV 96
Cdd:cd00196    1 VKVETPSLKKiVVAVPPSTTLRQVLEKVAKRIGLPPDVIRLLFNGQVLDDLMTAKQVGLEPGEELHFV 68

ubiquitin-like (Ubl) domain found in homocysteine-inducible endoplasmic reticulum stress protein HERP; HERP is an endoplasmic reticulum (ER) integral membrane protein containing an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. The Ubl domain is required for the degradation of HERP itself as well as for HERP-mediated anti-apoptotic effects. HERP is induced by the ER stress response pathway and is involved in improving the balance of folding capacity and protein loads in the ER. There are two types of HERP, HERP1 and HERP2, which are encoded by the HERPUD1 and HERPUD2 genes, respectively.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 295054230  32 VKTPKEK---EEFAVPENSSVQQFKEEISKRF--KSHIDQLVLIFAGKILKD----QDTLSQHGIHDGLTVHLV 96
Cdd:cd01790    5 VKSPNQRiqdLTVNCTLGWTVLKLKEHLSEVYpsKPLPEDQKLIYSGKLLEDhqtlKDVLREDDPEQVHTVHLV 78

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 295054230  40 EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDqDTLSQHGIHDGLTVHLV 96
Cdd:cd01804   14 ELSVPPNETVEGLKRRISKKLKVPKERITLLHKEKQLKD-GTLRENGIGDGSKLTLL 69

UBA domain found in proteins involved in ubiquitin-mediated proteolysis; The ubiquitin-associated (UBA) domains are commonly occurring sequence motifs found in proteins involved in ubiquitin-mediated proteolysis. They contribute to ubiquitin (Ub) binding or ubiquitin-like (UbL) domain binding. However, some kinds of UBA domains can only the bind UbL domain, but not the Ub domain. UBA domains are normally comprised of compact three-helix bundles which contain a conserved GF/Y-loop. They can bind polyubiquitin with high affinity. They also bind monoubiquitin and other proteins. Most UBA domain-containing proteins have one UBA domain, but some harbor two or three UBA domains.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 295054230 544 LEQLSAMGFlNREANLQALIATGGDINAAIE 574
Cdd:cd14270    1 LAQLVEMGF-SREQARRALRATNGDVEAAVE 30

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 295054230  28 MKVTVKTPK-EKEEFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHL 95
Cdd:cd01810    1 LSIFVRNEKgQSHTYEVRLTQTVDQLKQKVSGREGVHDDQFWLTFEGRPLEDQLPLGEYGLKPQSTIHM 69

ubiquitin; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 295054230  28 MKVTVKT-PKEKEEFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:PTZ00044   1 MQILIKTlTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGSTIHMVLQ 72

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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 295054230  30 VTVKTPKEKE-EFAVPENSSVQQFKEEISKrfKSHI--DQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVI 97
Cdd:cd01806    1 IKVKTLTGKEiEIDIEPTDKVERIKERVEE--KEGIppQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVL 69

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 295054230  40 EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:cd17052   13 TFDANPQDSVKKINEHVRSKTKVPVQDQVLLLGSKILKPRRRLSSYGIDKEKTIHLTLK 71

ubiquitin-like (Ubl) domain found in IQ and ubiquitin-like domain-containing protein (IQUB) and similar proteins; IQUB is an IQ motif and ubiquitin domain-containing protein that may play roles in cilia formation and/or maintenance. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295054230  30 VTVKT--PKEKEEF--AVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHL 95
Cdd:cd17061    3 ATVKFvlMPSGQVItlAFTLGQTIGELKEHFSSELKIPPDVLQIMFDGKLVEDNTTLVDLGVRPNGTIQL 72

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        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 295054230  48 SVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLViktQNRPQ 104
Cdd:cd01798   20 SILQLKEVVAKRQGVPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAV---QGPKR 73

Ubiquitin-2 like Rad60 SUMO-like;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295054230   40 EFAVPENSSVQQFKEEI--------SKRFKSHIDqLVLIFAGKILKDQDTLSQHG-----IHDGLTV-HLVIKtQNRPQD 105
Cdd:pfam13881  17 PFVFSPATTVADLKEKViaqwpkdkENGPKTVND-VKLINAGKILENNKTLGECRlpvgeTPGGVTTmHVVVR-PNLPEP 94

                          90
                  ....*....|..
gi 295054230  106 NSAQQTNAPGST 117
Cdd:pfam13881  95 NSEKKANKPKQN 106

ubiquitin-like (Ubl) domain found in ubiquitin carboxyl-terminal hydrolase 24 (UBP24) and similar proteins; UBP24 (EC 3.4.19.12), also termed deubiquitinating enzyme 24, or ubiquitin thioesterase 24, or ubiquitin-specific-processing protease 24 (USP24), is a deubiquitinating protein that interacts with damage-specific DNA-binding protein 2 (DDB2) and regulates DDB2 stability. It may also play a role in the pathogenesis of Parkinson's disease (PD). UBP24 proteins contain an N-terminal ubiquitin-associated (UBA) domain, a ubiquitin-like (Ubl) domain, and a C-terminal peptidase C19 domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 295054230  28 MKVTVKTPKEKEEFAVP--ENSSVQQFKEEISKRFKSHIDQLVLIFAGKIL---KDQDTLSQHGIHDGLTV 93
Cdd:cd17065    6 LTLHVTCESTKQEFTLEvhSNETLGSVRQKIAERLNCPVDQVQIFANEKLLpsnKDQKLLHQLGFTDEQIL 76

UBA domain found in plant ubiquitin-conjugating enzyme E2 27 and similar proteins; UBC27, also called ubiquitin carrier protein 27, functions as a class II ubiquitin-conjugating (UBC) enzyme (E2). E2, together with E1 (ubiquitin-activating enzyme UBA) and E3 (ubiquitin ligase), is required in the multi-step reaction of ubiquitin conjugation. Unlike other Arabidopsis UBCs, in addition to an N-terminal ubiquitin-conjugating enzyme E2 catalytic domain (UBCc), UBC27 has an additional C-terminal ubiquitin-associated domain (UBA).

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 295054230 541 QQQLEQLSAMGFlNREANLQALIATGGDINAAIERLL 577
Cdd:cd14312    1 EEKVQRLVEMGF-PRDQAVVALESAGGDENAALEKLL 36

ubiquitin-like (Ubl) domain found in AN1-type zinc finger protein 4 (ZFAND4) and similar proteins; ZFAND4, also termed AN1-type zinc finger and ubiquitin domain-containing protein-like 1 (ANUBL1), may function as an oncogene that promotes proliferation and regulates relevant tumor suppressor genes in gastric cancer, suggesting a role in gastric cancer initiation and progression. ZFAND4contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions, as well as a C-terminal AN1-type zinc finger. Unlike ubiquitin polyproteins and most ubiquitin fusion proteins, the N-terminal Ubl domain of ZFAND4 does not undergo proteolytic processing.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 295054230  40 EFAVPENSSVQQFKEEISKRFKSHIDQLVLIFAGKILKDQDTLSQHGIHDGLTVHLVIK 98
Cdd:cd01802   14 ELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLA 72

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 295054230  28 MKVTV-KTPKEKEEFAVPENSSVQQFKEEISKRF-----KSHIDQLV----------LIFAGKILK-DQDTLSQHGIHDG 90
Cdd:cd17058    2 ITLSVlRLDGESLPVVVPQNATVLDLKKAIERYFtlklkREGGTKKIswkyvwktycLCFDGQKLTdDKAKLKDYGIRNG 81

                 ....*.
gi 295054230  91 LTVHLV 96
Cdd:cd17058   82 DELTFV 87

UBA domain found in ubiquitin-associated domain-containing protein 2 (UBAC2) and similar proteins; UBAC2, also called phosphoglycerate dehydrogenase-like protein 1, is a ubiquitin-associated domain (UBA)-domain containing protein encoded by gene UBAC2 (or PHGDHL1), a risk gene for Behcet's disease (BD). It may play an important role in the development of BD through its transcriptional modulation. Members in this family contain an N-terminal rhomboid-like domain and a C-terminal UBA domain.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 295054230 543 QLEQLSAMGFlNREANLQALIATGGDINAAIERLL 577
Cdd:cd14305    5 QVQQLVDMGF-SREDVLEALRQSNNDVNAATNLLL 38

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana NPL4-like proteins NPL4-1, NPL4-2, and similar proteins; The family includes a group of uncharacterized plant ubiquitin-like (Ubl) domain-containing proteins, including Arabidopsis thaliana NPL4-like protein 1 and NPL4-like protein 2.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 295054230  28 MKVTVKTPKEKEEFAVPENSSVQQFKEEISKRFKSHIDQLVL-IFAGKIL---KDQDTLSQHGIHDGLTVHL 95
Cdd:cd17055    1 MLLRVRSRDGTERVEVPDDATVGDLKEKIAEQLSVPVSDQTLsLDPGPDLltaKSSATLSQLGLKHGDMVFL 72