UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251    2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSIS---CEESQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMVSQKKST 78
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGkdaYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251   79 KTKVTEPPIAPESATTPGreNSTEASPSTDASAAPAATAPEGSQPQEEQTATTERTESASTP--------GFVVGTERNE 150
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPT--PSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPssgsdaasTLVVGSERET 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  151 TIERIMEMGYQREEVERALRAAFNNPDRAVEYLLMGIPENLRQPepqqqTAAAAEQPSTAATTAEQPAEDDLFAQAAQGg 230
Cdd:TIGR00601 159 TIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQP-----EPVQQTAASTAAATTETPQHGSVFEQAAQG- 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  231 nassgalGTTGGATDAAQGGPPGSIGLTVEDLLSLRQVVSGNPEALAPLLENISARYPQLREHIMANPEVFVSMLLEAVG 310
Cdd:TIGR00601 233 -------GTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVG 305

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  311 DnmqdvMEGADDMVEGedievTGEAAAAGLGQGEgegsfQVDYTPEDDQAISRLCELGFERDLVIQVYFACDKNEEAAAN 390
Cdd:TIGR00601 306 E-----LASESDMEGG-----VGAIAEAGLPQMN-----QIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAAN 370

                  ....*...
gi 398364251  391 ILFSDHAD 398
Cdd:TIGR00601 371 YLLSQNFD 378

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251    2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSIS---CEESQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMVSQKKST 78
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGkdaYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251   79 KTKVTEPPIAPESATTPGreNSTEASPSTDASAAPAATAPEGSQPQEEQTATTERTESASTP--------GFVVGTERNE 150
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPT--PSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPssgsdaasTLVVGSERET 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  151 TIERIMEMGYQREEVERALRAAFNNPDRAVEYLLMGIPENLRQPepqqqTAAAAEQPSTAATTAEQPAEDDLFAQAAQGg 230
Cdd:TIGR00601 159 TIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQP-----EPVQQTAASTAAATTETPQHGSVFEQAAQG- 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  231 nassgalGTTGGATDAAQGGPPGSIGLTVEDLLSLRQVVSGNPEALAPLLENISARYPQLREHIMANPEVFVSMLLEAVG 310
Cdd:TIGR00601 233 -------GTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVG 305

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  311 DnmqdvMEGADDMVEGedievTGEAAAAGLGQGEgegsfQVDYTPEDDQAISRLCELGFERDLVIQVYFACDKNEEAAAN 390
Cdd:TIGR00601 306 E-----LASESDMEGG-----VGAIAEAGLPQMN-----QIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAAN 370

                  ....*...
gi 398364251  391 ILFSDHAD 398
Cdd:TIGR00601 371 YLLSQNFD 378

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 398364251    4 LTFKNFKKEKVPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMVSQK 75
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398364251   7 KNFKKEKVPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSECGLKDGDqVVFMVSQ 74
Cdd:PTZ00044   6 KTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQIRLIYSGKQMSDDLKLSDYKVVPGS-TIHMVLQ 72

UV excision repair protein Rad23; All proteins in this family for which functions are known are components of a multiprotein complex used for targeting nucleotide excision repair to specific parts of the genome. In humans, Rad23 complexes with the XPC protein. This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251    2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSIS---CEESQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMVSQKKST 78
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGkdaYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251   79 KTKVTEPPIAPESATTPGreNSTEASPSTDASAAPAATAPEGSQPQEEQTATTERTESASTP--------GFVVGTERNE 150
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPT--PSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPssgsdaasTLVVGSERET 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  151 TIERIMEMGYQREEVERALRAAFNNPDRAVEYLLMGIPENLRQPepqqqTAAAAEQPSTAATTAEQPAEDDLFAQAAQGg 230
Cdd:TIGR00601 159 TIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQP-----EPVQQTAASTAAATTETPQHGSVFEQAAQG- 232

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  231 nassgalGTTGGATDAAQGGPPGSIGLTVEDLLSLRQVVSGNPEALAPLLENISARYPQLREHIMANPEVFVSMLLEAVG 310
Cdd:TIGR00601 233 -------GTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVG 305

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 398364251  311 DnmqdvMEGADDMVEGedievTGEAAAAGLGQGEgegsfQVDYTPEDDQAISRLCELGFERDLVIQVYFACDKNEEAAAN 390
Cdd:TIGR00601 306 E-----LASESDMEGG-----VGAIAEAGLPQMN-----QIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAAN 370

                  ....*...
gi 398364251  391 ILFSDHAD 398
Cdd:TIGR00601 371 YLLSQNFD 378

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 398364251   2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSIS-CEESQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMV 72
Cdd:cd01805    1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGdFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFVVVMV 72

UBA2 domain of Schizosaccharomyces pombe UV excision repair protein Rhp23p and its fungal homologs; The subfamily contains several fungal multiubiquitin receptors, including Schizosaccharomyces pombe Rhp23p and Saccharomyces cerevisiae Rad23p, both of which are orthologs of human HR23A. They play roles in nucleotide excision repair (NER) and in cell cycle regulation. They also function as shuttle proteins transporting ubiquitinated substrates destined for degradation from the E3 ligase to the 26S proteasome. For instance, S. pombe Rhp23p forms a complex with Rhp41p to recognize photolesions and help initiate DNA repair, and it also protects ubiquitin chains against disassembly by deubiquitinating enzymes. Like human HR23A, members in this subfamily interact with the proteasome through their N-terminal ubiquitin-like domain (UBL), and with ubiquitin (Ub), or multi-ubiquitinated substrates, through their two ubiquitin-associated domains (UBA), termed internal UBA1 and C-terminal UBA2. In addition, they contain a xeroderma pigmentosum group C (XPC) protein-binding domain that might be necessary for its efficient NER function. This model corresponds to the UBA2 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 398364251 356 EDDQAISRLCELGFERDLVIQVYFACDKNEEAAANILFSD 395
Cdd:cd14381    1 EEDQAIDRLCELGFDRDLVIQAYLACDKNEEMAANFLFEN 40

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 398364251     2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMVS 73
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGIPPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

UBA1 domain of Rad23 proteins found in metazoa; The family includes mammalian orthologs of yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe). 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 a ubiquitin-like (UBL) and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. UBL domain is responsible for the binding to proteasome. UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates which suggests Rad23 proteins might be involved in certain pathways of ubiquitin metabolism. Both UBL domain and XPC-binding domain are necessary for efficient NER function of Rad23 proteins. This model corresponds to the UBA1 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 398364251 147 ERNETIERIMEMGYQREEVERALRAAFNNPDRAVEYLLMG 186
Cdd:cd14377    1 EYENMVTEIMSMGFERDQVVRALRASFNNPDRAVEYLLSG 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 398364251   4 LTFKNFKKEKVPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSECGLKDGDqVVFMV 72
Cdd:cd17039    1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGS-TIHLV 68

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 398364251   2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSECGLKDGdQVVFMV 72
Cdd:cd16106    1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSDIPAEQQRLIYKGKILKDEETLSSYKIQDG-HTVHLV 70

UBA2 domain of Rad23 proteins found in metazoa; The family includes mammalian orthologs of yeast nucleotide excision repair (NER) proteins, Rad23p (in Saccharomyces cerevisiae) and Rhp23p (in Schizosaccharomyces pombe). 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 a ubiquitin-like (UBL) and two ubiquitin-associated (UBA) domains, as well as a xeroderma pigmentosum group C (XPC) protein-binding domain. UBL domain is responsible for the binding to proteasome. UBA domains are important for binding of ubiquitin (Ub) or multi-ubiquitinated substrates which suggests Rad23 proteins might be involved in certain pathways of ubiquitin metabolism. Both UBL domain and XPC-binding domain are necessary for efficient NER function of Rad23 proteins. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 398364251 356 EDDQAISRLCELGFERDLVIQVYFACDKNEEAAANILFS 394
Cdd:cd14380    1 EEREAIERLKALGFPEGLVIQAYFACDKNENLAANFLLS 39

XPC-binding domain; Members of this family adopt a structure consisting of four alpha helices, arranged in an array. They bind specifically and directly to the xeroderma pigmentosum group C protein (XPC) to initiate nucleotide excision repair.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 398364251  265 LRQVVSGNPEALAPLLENISARYPQLREHIMANPEVFVSMLLEAV 309
Cdd:pfam09280  13 LRQLVQQNPQLLQPLLQQLAQSNPQLAQLIQQNQEEFLQLLNEPG 57

UBA2 domain of UV excision repair protein RAD23 homolog A (HR23A) found in vertebrates; HR23A, also called Rad23A, is a DNA repair protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation which is required for efficient nucleotide excision repair (NER), a primary mechanism for removing UV-induced DNA lesions. HR23A also plays a critical role in the interaction of HIV-1 viral protein R (Vpr) with proteasome, especially facilitating Vpr to promote protein poly-ubiquitination. HR23A contains an N-terminal ubiquitin-like (UBL) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 398364251 356 EDDQAISRLCELGFERDLVIQVYFACDKNEEAAANILFS 394
Cdd:cd14427    1 QEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLS 39

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 398364251  356 EDDQAISRLCELGFERDLVIQVYFACDKNEEAAANIL 392
Cdd:pfam00627   1 EDEEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 398364251  11 KEKVPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSECGLKDG 65
Cdd:cd01808   11 KEKEDFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDG 65

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 398364251 152 IERIMEMGYQREEVERALRAAFNNPDRAVEYL 183
Cdd:cd14291    5 LQQLMEMGFSEAEARLALRACNGNVERAVDYI 36

UBA2 domain found in ubiquitin carboxyl-terminal hydrolase 13 (UBP13); UBP13, also called deubiquitinating enzyme 13, Isopeptidase T-3 (isoT3), ubiquitin thioesterase 13, or ubiquitin-specific-processing protease 13 is an ortholog of UBP5 implicated in catalyzing hydrolysis of various ubiquitin (Ub)-chains. It contains a zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. Due to the non-activating catalysis for K63-polyubiquitin chains, UBP13 may function differently from USP5 in cellular deubiquitination processes. Moreover, the zinc finger (ZnF) domain of USP13 cannot bind to Ub. Its tandem UBA domains can bind with different types of diUb but preferentially with K63-linked.USP13 can also regulate the protein level of CD3delta in cells via its UBA domains. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 398364251 149 NETIERIMEMGYQREEVERALRAAFNNPDRAVEYL 183
Cdd:cd14387    1 EESIAILMSMGFPRNRAIEALKRTNNNLDRALDWL 35

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 398364251 152 IERIMEMGYQREEVERALRAAFNNPDRAVE 181
Cdd:cd14270    1 LAQLVEMGFSREQARRALRATNGDVEAAVE 30

UBA2 domain found in Kip1 ubiquitination-promoting complex protein 2 (KPC2) and similar proteins; KPC2, also called ubiquitin-associated domain-containing protein 1 (UBAC1), or glialblastoma cell differentiation-related protein 1, is one of two subunits of Kip1 ubiquitination-promoting complex (KPC), a novel E3 ubiquitin-protein ligase that also contains KPC1 subunit and regulates the ubiquitin-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor p27 at G1 phase. KPC2 contains a ubiquitin-like (UBL) domain and two ubiquitin-associated (UBA) domains. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 398364251 150 ETIERIMEMGYQREEVERALRAAFNNPDRAVEYLL 184
Cdd:cd14304    4 RAVQSLMEMGFEEEDVLEALRVTRNNQNAACEWLL 38

UBA domain found in vacuolar protein sorting-associated protein 13D (VP13D) and similar proteins; VP13D is a chorea-acanthocytosis (CHAC)-similar protein encoded by gene VPS13D. it contains two putative domains, ubiquitin-associated (UBA) domain and lectin domain of ricin B chain profile (ricin-B-lectin), suggesting it may interact with, and be involved in the trafficking of, proteins modified with ubiquitin and/or carbohydrate molecules. Further investigation is required.

                         10        20        30
                 ....*....|....*....|....*....|...
gi 398364251 152 IERIMEMGYQREEVERALRAAFNNPDRAVEYLL 184
Cdd:cd14306    1 VAKLMELGFPEEDCIRALRACGGNVEEAANWLL 33

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 398364251   4 LTFKNFKKEKV-PLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQ-DSKTVSECGLKDGDQVV 69
Cdd:cd01796    3 LTVTTEDDDRLfSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLTdDKKTLEALGLKDGDLLL 70

UBA domain found in Saccharomyces cerevisiae DNA-damage response protein Ddi1 and similar proteins; Ddi1, also called v-SNARE-master 1 (Vsm1), is a ubiquitin receptor involved in regulation of the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as a ubiquitin association domain (UBA)- ubiquitin-like-domain (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. Ddi1 contains an N-terminal UBL domain and a C-terminal UBA domain. It also harbors a central retroviral aspartyl-protease-like domain (RVP) which may be important in cell-cycle control. At this point, Ddi1 may function proteolytically during regulated protein turnover in the cell. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also called transporter regulator RS1 (RS1) which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 398364251 358 DQAISRLCELGFERDLVIQVYFACDKNEEAAANILF 393
Cdd:cd14309    1 EEKIAQLMDLGFSREEAIQALEATNGNVELAASLLF 36

UBA domain found in Arabidopsis thaliana E3 ubiquitin-protein ligase UPL1 (atUPL1), UPL2 (atUPL2) and similar proteins; The family includes two highly similar 405-kDa HECT E3 ubiquitin-protein ligases (UPLs), UPL1 and UPL2, from Arabidopsis thaliana. The HECT E3 UPL family plays a prominent role in the ubiquitination of plant proteins. The biological functions of UPL1 and UPL2 remain unclear. Both of them contain a ubiquitin-associated (UBA) domain and a C-terminal HECT domain. UBA domain may be involved in ubiquitin metabolism. HECT domain is necessary and sufficient for their E3 catalytic activity, but requires ATP, E1 and an E2 of the Arabidopsis UBC8 family to ubiquitinate proteins.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 398364251 150 ETIERIMEMGYQREEVERALRAA-FNNPDRAVEYLL 184
Cdd:cd14327    1 EAVAQLVEMGFSRERAEEALRAVgTNSVELAMEWLF 36

UBA2 domain found in ubiquitin carboxyl-terminal hydrolase 13 (UBP13); UBP13, also called deubiquitinating enzyme 13, Isopeptidase T-3 (isoT3), ubiquitin thioesterase 13, or ubiquitin-specific-processing protease 13 is an ortholog of UBP5 implicated in catalyzing hydrolysis of various ubiquitin (Ub)-chains. It contains a zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. Due to the non-activating catalysis for K63-polyubiquitin chains, UBP13 may function differently from USP5 in cellular deubiquitination processes. Moreover, the zinc finger (ZnF) domain of USP13 cannot bind to Ub. Its tandem UBA domains can bind with different types of diUb but preferentially with K63-linked.USP13 can also regulate the protein level of CD3delta in cells via its UBA domains. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 398364251 358 DQAISRLCELGFERDLVIQVYFACDKNEEAAANIL 392
Cdd:cd14387    1 EESIAILMSMGFPRNRAIEALKRTNNNLDRALDWL 35

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog A (HR23A); HR23A, also termed RAD23A, is a DNA repair protein that binds to 19S subunit of the 26S proteasome and shuttles ubiquitinated proteins to the proteasome for degradation, which is required for efficient nucleotide excision repair (NER), a primary mechanism for removing UV-induced DNA lesions. HR23A also plays a critical role in the interaction of HIV-1 viral protein R (Vpr) with the proteasome, especially facilitating Vpr to promote protein poly-ubiquitination. HR23A contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 398364251   2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSISCEE---SQIKLIYSGKVLQDSKTVSECGLKDGDQVVFMVSQ 74
Cdd:cd17126    1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAfpvAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTK 76

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B contains an N-terminal ubiquitin-like (Ubl) domain that binds proteasomes and two C-terminal ubiquitin-associated (UBA) domains that bind ubiquitin or multi-ubiquitinated substrates. In addition, it has a XPC protein-binding domain that might be necessary for its efficient NER function.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 398364251   2 VSLTFKNFKKEKVPLDLEPSNTILETKTKLAQSISCEESQI---KLIYSGKVLQDSKTVSECGLKDGDQVVFMVSQKK 76
Cdd:cd16126    1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVagqKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPK 78

UBA domain found in vacuolar protein sorting-associated protein 13D (VP13D) and similar proteins; VP13D is a chorea-acanthocytosis (CHAC)-similar protein encoded by gene VPS13D. it contains two putative domains, ubiquitin-associated (UBA) domain and lectin domain of ricin B chain profile (ricin-B-lectin), suggesting it may interact with, and be involved in the trafficking of, proteins modified with ubiquitin and/or carbohydrate molecules. Further investigation is required.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 398364251 361 ISRLCELGFERDLVIQVYFACDKNEEAAANILFS 394
Cdd:cd14306    1 VAKLMELGFPEEDCIRALRACGGNVEEAANWLLE 34

ubiquitin-like (Ubl) domain 2 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 second Ubl domain of FAT10. Some family members contain only one Ubl domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 398364251   4 LTFKNFKKEKVPLDLEPSNTILETKTKL-AQSISCEESQIkLIYSGKVLQDS-KTVSECGLKDGDQV 68
Cdd:cd17053    3 VNSKLLTGTVHTLQVSRSTTVAQVKAMIeDQSGVPPNEQI-LVYNGKRLEDGdKTLGEYGIKTGDTL 68

UBA domain found in yeast UBA domain-containing protein RUP1p and similar proteins; RUP1p is a ubiquitin-associated (UBA) domain-containing protein encoded by a nonessential yeast gene RUP1. It can mediate the association of Rsp5 and Ubp2. The N-terminal UBA domain is responsible for antagonizing Rsp5 function, as well as bridging the Rsp5-Ubp2 interaction. No other characterized functional domains or motifs are found in RUP1p.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 398364251 359 QAISRLCELGFERDLVIQVYFACDKNEEAAANILFS 394
Cdd:cd14307    2 EAVASLLEMGIPREVAIEALRETNGDVEAAANYIFS 37

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
                 ....*....|....*....|....*....|....*....|....*.
gi 398364251  14 VPLDLEPSNTILETKTKLAQSISCEESQIKLIYSGKVLQDSKTVSE 59
Cdd:cd01803   13 ITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSD 58

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 398364251 150 ETIERIMEMGYQREEVERALRAAFNNPDRAVEYLL 184
Cdd:cd14305    4 EQVQQLVDMGFSREDVLEALRQSNNDVNAATNLLL 38

UBA domain found in Saccharomyces cerevisiae DNA-damage response protein Ddi1 and similar proteins; Ddi1, also called v-SNARE-master 1 (Vsm1), is a ubiquitin receptor involved in regulation of the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as a ubiquitin association domain (UBA)- ubiquitin-like-domain (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. Ddi1 contains an N-terminal UBL domain and a C-terminal UBA domain. It also harbors a central retroviral aspartyl-protease-like domain (RVP) which may be important in cell-cycle control. At this point, Ddi1 may function proteolytically during regulated protein turnover in the cell. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also called transporter regulator RS1 (RS1) which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 398364251 150 ETIERIMEMGYQREEVERALRAAFNNPDRAVEYLL 184
Cdd:cd14309    2 EKIAQLMDLGFSREEAIQALEATNGNVELAASLLF 36

Ubiquitin-like domain; This entry includes N-terminal ubiquitin-like domain from proteins such as NEDD8 ultimate buster protein.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 398364251   23 TILETK----TKLAQSISCEES---QIKLIYSGKVLQDSKTVSECGLKDGDQVvfMV 72
Cdd:pfam18037  34 NYLETKldvtGQELRSRIAETFglqYIKLILNGKTLQLDKTLEEQGVKHNSKV--MV 88