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 392996951    3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTKTKAG 82
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951   83 QGTSAPPEASPTAAPESSTSFPPAPTSGMSHPPPAAREDKSPSEESAPTTSPESVSGSVPSSGSsgreeDAASTLVTGSE 162
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGS-----DAASTLVVGSE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951  163 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIPGSPE-------------------PEHGSVQESQV---SE 220
Cdd:TIGR00601 156 RETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEqpepvqqtaastaaattetPQHGSVFEQAAqggTE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951  221 QPATEAA-GENPLEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQ---------------------------- 271
Cdd:TIGR00601 236 QPATEAAqGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQqisqhpeqflqmlnepvgelasesdmeg 315

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392996951  272 ----------------------------LKALGFPESLVIQAYFACEKNENLAANFLLSQNFD 306
Cdd:TIGR00601 316 gvgaiaeaglpqmnqiqvtpeekeaierLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 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 392996951    3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTKTKAG 82
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951   83 QGTSAPPEASPTAAPESSTSFPPAPTSGMSHPPPAAREDKSPSEESAPTTSPESVSGSVPSSGSsgreeDAASTLVTGSE 162
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGS-----DAASTLVVGSE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951  163 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIPGSPE-------------------PEHGSVQESQV---SE 220
Cdd:TIGR00601 156 RETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEqpepvqqtaastaaattetPQHGSVFEQAAqggTE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951  221 QPATEAA-GENPLEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQ---------------------------- 271
Cdd:TIGR00601 236 QPATEAAqGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQqisqhpeqflqmlnepvgelasesdmeg 315

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392996951  272 ----------------------------LKALGFPESLVIQAYFACEKNENLAANFLLSQNFD 306
Cdd:TIGR00601 316 gvgaiaeaglpqmnqiqvtpeekeaierLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 378

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 392996951     3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRdafPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVT 77
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGI---PPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392996951   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVagqKLIYAGKILSDDVPIRDYRI 66
Cdd:PTZ00044   3 ILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQI---RLIYSGKQMSDDLKLSDYKV 61

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 392996951    3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTKTKAG 82
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951   83 QGTSAPPEASPTAAPESSTSFPPAPTSGMSHPPPAAREDKSPSEESAPTTSPESVSGSVPSSGSsgreeDAASTLVTGSE 162
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGS-----DAASTLVVGSE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951  163 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIPGSPE-------------------PEHGSVQESQV---SE 220
Cdd:TIGR00601 156 RETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEqpepvqqtaastaaattetPQHGSVFEQAAqggTE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392996951  221 QPATEAA-GENPLEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQ---------------------------- 271
Cdd:TIGR00601 236 QPATEAAqGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQqisqhpeqflqmlnepvgelasesdmeg 315

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392996951  272 ----------------------------LKALGFPESLVIQAYFACEKNENLAANFLLSQNFD 306
Cdd:TIGR00601 316 gvgaiaeaglpqmnqiqvtpeekeaierLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 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 392996951   3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdAFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMV 76
Cdd:cd01805    1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQG--DFPASGQKLIYSGKVLKDDKTLSEYNIKEKDFVVVMV 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 392996951 162 EYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTG 201
Cdd:cd14377    1 EYENMVTEIMSMGFERDQVVRALRASFNNPDRAVEYLLSG 40

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 392996951    5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTKT 79
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEG---VPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

UBA1 domain of Rad23 proteins found in eukaryotes; 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 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
                 ....*....|....*....|....*....|....*....
gi 392996951 162 EYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLT 200
Cdd:cd14280    1 ELEATINNIMSMGFEREQVVRALRAAFNNPDRAVEYLLS 39

UBA1 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 UBA1 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 392996951 162 EYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTG 201
Cdd:cd14425    1 EYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTG 40

UBA2 domain of UV excision repair protein RAD23 homolog B (HR23B) found in vertebrates; HR23B, also called 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 26 S 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. This model corresponds to the UBA2 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 392996951 264 QENPQLLQLKALGFPESLVIQAYFACEKNENLAANFLLSQNFDDE 308
Cdd:cd14428    1 QEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQNFDDD 45

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392996951   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVM 75
Cdd:cd17039    1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTG---IPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

UBA2 domain of Rad23 proteins found in eukaryotes; 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 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 392996951 271 QLKALGFPESLVIQAYFACEKNENLAANFLL 301
Cdd:cd14281    8 RLVALGFSRDQAIEAYLACDKNEELAANYLF 38

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 392996951   3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRIdEKNFVVVMV 76
Cdd:cd16106    1 IKVTVKCSNGKKFTVEVEPDATVLELKELIAEKSD---IPAEQQRLIYKGKILKDEETLSSYKI-QDGHTVHLV 70

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 392996951   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRIDE 68
Cdd:cd01806    1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEG---IPPQQQRLIFSGKQMNDEKTAADYKIEG 61

ubiquitin-like (Ubl) domain found in BCL2-associated athanogene 6 (BAG6) and similar proteins; BAG6, also termed large proline-rich protein BAG6, or BAG family molecular chaperone regulator 6, or HLA-B-associated transcript 3 (Bat3), or protein Scythe, or protein G3, is a nucleo-cytoplasmic shuttling chaperone protein that is highly conserved in eukaryotes. It functions in two distinct biological pathways, ubiquitin-mediated protein degradation of defective polypeptides and tail-anchored transmembrane protein biogenesis in mammals. BAG6 is a component of the heterotrimeric BAG6 sortase complex composed of BAG6, transmembrane recognition complex 35 (TRC35) and ubiquitin-like protein 4A (UBL4A). The BAG6 complex together with the cochaperone small, glutamine-rich, tetratricopeptide repeat-containing, protein alpha (SGTA) plays a role in the biogenesis of tail-anchored membrane proteins and subsequently shown to regulate the ubiquitination and proteasomal degradation of mislocalized proteins. Moreover, BAG6 acts as an apoptotic regulator that binds reaper, a potent apoptotic inducer. BAG6/reaper is thought to signal apoptosis, in part through regulating the folding and activity of apoptotic signaling molecules. It is also likely a key regulator of the molecular chaperone Heat Shock Protein A2 (HSPA2) stability/function in human germ cells. Furthermore, aspartyl protease-mediated cleavage of BAG6 is necessary for autophagy and fungal resistance in plants. BAG6 contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392996951   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRIDEK 69
Cdd:cd01809    3 VTVKTLDSQNRTFTVPEEITVKEFKEHIASSVN---IPAEKQRLIFQGRVLQDDKKLKEYDVDGK 64

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
                 ....*....|....*....|....*....|....*....
gi 392996951 264 QENPQLLQLKALGFPESLVIQAYFACEKNENLAANFLLS 302
Cdd:cd14381    1 EEDQAIDRLCELGFDRDLVIQAYLACDKNEEMAANFLFE 39

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 392996951 164 ETMLTEIMSMGYERERVVAALRASYNNPHRAVEYL 198
Cdd:cd14387    1 EESIAILMSMGFPRNRAIEALKRTNNNLDRALDWL 35

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 392996951  268 QLLQLKALGFPESLVIQAYFACEKNENLAANFL 300
Cdd:pfam00627   5 AIQRLVEMGFDREQVREALRATGNNVERAAEYL 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        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 392996951   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRI 66
Cdd:cd01803    3 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEG---IPPDQQRLIFAGKQLEDGRTLSDYNI 61

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 392996951   3 VTITLKTLQQ--QTFKIRMEPDETVKVLKEKIEaekgrDAFP----VAGQKLIYAGKILSDDVPIRD 63
Cdd:cd01790    1 VTLVVKSPNQriQDLTVNCTLGWTVLKLKEHLS-----EVYPskplPEDQKLIYSGKLLEDHQTLKD 62

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 392996951 167 LTEIMSMGYERERVVAALRASYNNPHRAVE 196
Cdd:cd14270    1 LAQLVEMGFSREQARRALRATNGDVEAAVE 30

Ubiquitin associated domain; Present in Rad23, SNF1-like kinases. The newly-found UBA in p62 is known to bind ubiquitin.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 392996951   268 QLLQLKALGFPESLVIQAYFACEKNENLAANFLL 301
Cdd:smart00165   4 KIDQLLEMGFSREEALKALRAANGNVERAAEYLL 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        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 392996951  14 TFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRD 63
Cdd:cd01798   10 GFPVEVDSDWSILQLKEVVAKRQG---VPPDQLRIIFAGKELSDDLTLQN 56

ubiquitin-like (Ubl) domain found in Sacsin and similar proteins; Sacsin, also termed DnaJ homolog subfamily C member 29 (DNAJC29), is encoded by SACS gene that is highly expressed in the brain. Mutations in SACS can cause the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) which is characterized by early-onset spastic ataxia. Sacsin is a modular protein that is localized on the mitochondrial surface and possibaly required for normal mitochondrial network organization. Sacsin knockdown resulted in a reduction in cells expressing plyglutamine-expanded ataxin-1, which correlated with a loss of cells with large nuclear ataxin-1 incusions. At the N-terminus, sacsin contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which can interact with the proteasome. At the C-terminus, sacsin harbors a protein-protein interaction J-domain followed by an higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain. The J-domain is typically associated with DnaJ-like co-chaperones involved in regulation of the Hsp70 heat shock system.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 392996951   3 VTITLKTLQQQTFKIrmEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRD 63
Cdd:cd17049    5 VTVLHEYIGCRTFEV--PPSAAVRDIKELIYEETD---FPVSEQQLWHNGKELSDWVKIGG 60

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 392996951 271 QLKALGFPESLVIQAYFACEKNENLAANFLLSQ 303
Cdd:cd14306    3 KLMELGFPEEDCIRALRACGGNVEEAANWLLEN 35

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 392996951 166 MLTEIMSMGYERERVVAALRA-SYNNPHRAVEYLLTG 201
Cdd:cd14327    2 AVAQLVEMGFSRERAEEALRAvGTNSVELAMEWLFTN 38

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 392996951  20 EPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIRDYRIDE 68
Cdd:cd16103   19 NPEDTILDLKEKIEEQGG---PPVEDQILLFQGQELRDKKSLKYYGIKD 64

ubiquitin-like (Ubl) domain found in homocysteine-inducible endoplasmic reticulum stress protein HERP1 and similar proteins; HERP1, also termed homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 protein (HERPUD1), or methyl methanesulfonate (MMF)-inducible fragment protein 1 (MIF1), is an endoplasmic reticulum (ER) integral membrane protein containing an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. HERP1 is a component of the ER quality control (ERQC) system, also called ER-associated degradation (ERAD), which is involved in ubiquitin-dependent degradation of misfolded ER proteins. It promotes the degradation of ER-resident Ca2+ channels. It is also involved in ubiquitin ligase HRD1-dependent protein degradation at the ER. Moreover, HERP1 plays a role in regulating the cell cycle, apoptosis and steroid hormone biosynthesis in mouse granulosa cells.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 392996951   2 AVTITLKT--LQQQTFKIRMEPDETVKVLKEKIEAEKgRDAFPVAGQKLIYAGKILSDDVPIRD-YRIDEKNFVVVMV 76
Cdd:cd17118    1 EVTLLIKSpsQRHEDLELRGDRGWTVRRLKTQLRREY-PDHPPEQEQRLIYSGKLLLDHLYLREvLPKDEERHVLHLV 77

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 392996951 170 IMSMGYERERVVAALRASYNNPHRAVEYLL 199
Cdd:cd14305    9 LVDMGFSREDVLEALRQSNNDVNAATNLLL 38

UBA2 domain found in Schizosaccharomyces pombe ubiquitin carboxyl-terminal hydrolase 14 (spUBP14) and similar proteins; spUBP14, also called deubiquitinating enzyme 14, UBA domain-containing protein 2, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, functions as a deubiquitinating enzyme that is involved in protein degradation in fission yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA2 domain.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 392996951 164 ETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTG 201
Cdd:cd14297    1 EDLVKQLVDMGFTEAQARKALRKTNNNVERAVDWLFEG 38