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 341941880    3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVMVTKAKAG 82
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880   83 QGIPAPPEASPTAVPEPSTPFPPVLASGMSHPPPTSREDKSPSEESTTTTSPESISGSVPSSGSsgreeDAASTLVTGSE 162
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGS-----DAASTLVVGSE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880  163 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIPGSPE-------------------PEHGSVQESQA---PE 220
Cdd:TIGR00601 156 RETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEqpepvqqtaastaaattetPQHGSVFEQAAqggTE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880  221 QPATEAA-GENPLEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQQISRHQEQFIQMLNEPPGELADISDVEG 299
Cdd:TIGR00601 236 QPATEAAqGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVGELASESDMEG 315

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 341941880  300 EVGAIGEEA-PQMNYIQVTPQEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQNFD 361
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 341941880    3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVMVTKAKAG 82
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880   83 QGIPAPPEASPTAVPEPSTPFPPVLASGMSHPPPTSREDKSPSEESTTTTSPESISGSVPSSGSsgreeDAASTLVTGSE 162
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGS-----DAASTLVVGSE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880  163 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIPGSPE-------------------PEHGSVQESQA---PE 220
Cdd:TIGR00601 156 RETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEqpepvqqtaastaaattetPQHGSVFEQAAqggTE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880  221 QPATEAA-GENPLEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQQISRHQEQFIQMLNEPPGELADISDVEG 299
Cdd:TIGR00601 236 QPATEAAqGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVGELASESDMEG 315

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 341941880  300 EVGAIGEEA-PQMNYIQVTPQEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQNFD 361
Cdd:TIGR00601 316 GVGAIAEAGlPQMNQIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 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 341941880    5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVMVTK 78
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEG---VPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQ 71

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVagqKLIYAGKILSDDVPIKEYHI 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 341941880    3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVMVTKAKAG 82
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880   83 QGIPAPPEASPTAVPEPSTPFPPVLASGMSHPPPTSREDKSPSEESTTTTSPESISGSVPSSGSsgreeDAASTLVTGSE 162
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGS-----DAASTLVVGSE 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880  163 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIPGSPE-------------------PEHGSVQESQA---PE 220
Cdd:TIGR00601 156 RETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEqpepvqqtaastaaattetPQHGSVFEQAAqggTE 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 341941880  221 QPATEAA-GENPLEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQQISRHQEQFIQMLNEPPGELADISDVEG 299
Cdd:TIGR00601 236 QPATEAAqGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVGELASESDMEG 315

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 341941880  300 EVGAIGEEA-PQMNYIQVTPQEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQNFD 361
Cdd:TIGR00601 316 GVGAIAEAGlPQMNQIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 378

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 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVMVTKAK 80
Cdd:cd16126    3 ITLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPK 78

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        40
                 ....*....|....*....|....*....|....*....|.
gi 341941880 319 QEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQN 359
Cdd:cd14427    1 QEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQN 41

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 341941880 319 QEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLS 357
Cdd:cd14380    1 EEREAIERLKALGFPEGLVIQAYFACDKNENLAANFLLS 39

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 341941880     3 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRdafPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVMVT 77
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGI---PPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

UBA1 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 UBA1 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 341941880 158 VTGSEYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIP 203
Cdd:cd14426    1 VTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIP 46

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 341941880  232 LEFLRDQPQFQNMRQVIQQNPALLPALLQQLGQENPQLLQQISRHQEQFIQMLNEP 287
Cdd:pfam09280   1 LDFLRNNPQFQQLRQLVQQNPQLLQPLLQQLAQSNPQLAQLIQQNQEEFLQLLNEP 56

UBA1 domain of Schizosaccharomyces pombe UV excision repair protein Rhp23p and its homologs; The subfamily contains several fungal multi-ubiquitin 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 UBA1 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 341941880 157 LVTGSEYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTGIP 203
Cdd:cd14378    1 LVVGLDYNQTVQNIMEMGYEREQVERALRASFNNPDRAVEYLLTGIP 47

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 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHIDEKNFVVVM 75
Cdd:cd17039    1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTG---IPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

UBA2 domain of putative DNA repair proteins RAD23 found in plant; The radiation sensitive 23 (RAD23) subfamily consists of four isoforms of putative DNA repair proteins from Arabidopsis thaliana and similar proteins from other plants. The nuclear-enriched RAD23 proteins function in the cell cycle, morphology, and fertility of plants through their delivery of ubiquitin (Ub)/26S proteasome system (UPS) substrates to the 26S proteasome. RAD23 proteins contain an N-terminal ubiquitin-like (UBL) domain that associates with the 26S proteasome Ub receptor RPN10, and two C-terminal ubiquitin-associated (UBA) domains that bind Ub conjugates. This model corresponds to the UBA2 domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 341941880 316 VTPQEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLL 356
Cdd:cd14382    1 VTPEEREAIERLEAMGFDRALVIEAFLACDKNEELAANYLL 41

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 341941880  162 EYETMLTEIMSMGYERERVVAALRASYNNPHRAVEYL 198
Cdd:pfam00627   1 EDEEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

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 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHIDEK 69
Cdd:cd01809    3 VTVKTLDSQNRTFTVPEEITVKEFKEHIASSVN---IPAEKQRLIFQGRVLQDDKKLKEYDVDGK 64

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 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHIDE 68
Cdd:cd01806    1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEG---IPPQQQRLIFSGKQMNDEKTAADYKIEG 61

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHIDE 68
Cdd:cd01802    3 LFIETLTGTAFELRVSPFETVASVKAKIQRLEG---IPVSQQHLIWSGRELEDDYCLHDYNITD 63

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 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHI--DEKNFVVV 74
Cdd:cd01807    3 ITVKILQGKECTIEVSPTESVLTVKQLVAEQLN---VPVSQQRLVFKGKTLADEHSLSDYSIgpGSKIHLVV 71

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 341941880 164 ETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLL 199
Cdd:cd14304    3 PRAVQSLMEMGFEEEDVLEALRVTRNNQNAACEWLL 38

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHI 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 341941880   3 VTITLKTLQQ--QTFKIRMEPDETVKVLKEKIEaekgrDAFP----VAGQKLIYAGKILSDDVPIKE 63
Cdd:cd01790    1 VTLVVKSPNQriQDLTVNCTLGWTVLKLKEHLS-----EVYPskplPEDQKLIYSGKLLEDHQTLKD 62

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana ubiquitin-protein ligase 5 (AtUPL5) and similar proteins; Arabidopsis thaliana AtUPL5, also termed HECT-type E3 ubiquitin transferase UPL5, is an E3 ubiquitin-protein ligase that contains a ubiquitin-like domain (Ubl), a C-type lectin-binding domain, a leucine zipper and a HECT domain. HECT domain containing-ubiquitin-protein ligases have more than one member in different genomes, these proteins have been classified into four sub-families (UPL1/2, UPL3/4, UPL5 and UPL6/7). AtUPL5 fUPL5 regulates leaf senescence in Arabidopsis through degradation of the transcription factor WRKY53.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 341941880   5 ITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHI 66
Cdd:cd16107    2 IFVRTYCGKTIVLHAKASDTVESLHQQIEARTG---IPSLEQRLIFGGRQLQHSQSLESCKM 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.

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                 ....*....|....*....|....*....|....*
gi 341941880 324 IERLKALGFPESLVIQAYFACEKNENLAANFLLSQ 358
Cdd:cd14306    1 VAKLMELGFPEEDCIRALRACGGNVEEAANWLLEN 35

ubiquitin-like (Ubl) domain found in ubiquitin domain-containing protein UBFD1 and similar proteins; UBFD1, also termed ubiquitin-binding protein homolog (UBPH), is a polyubiquitin binding protein containing a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. It may play a role as nuclear factor-kappaB (NF-kappaB) regulator.

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                 ....*....|....*....|....*....|....*....|....*....|.
gi 341941880  13 QTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGkILSDDVPIKE 63
Cdd:cd17047   10 EKYDVKFPLDSTIAELKEHIETLTG---VPPAMQKLMYKG-LLKDDKTLRE 56

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.

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                 ....*....|....*....|....*....|....*
gi 341941880 322 EAIERLKALGFPESLVIQAYFACEKNENLAANFLL 356
Cdd:cd14309    2 EKIAQLMDLGFSREEAIQALEATNGNVELAASLLF 36

ubiquitin-like (Ubl) domain found in plant membrane-anchored ubiquitin-fold proteins (MUBs); The plant MUBs belong to a family of ubiquitin-fold proteins that are plasma membrane-anchored by prenylation. They may serve as docking site to facilitate the association of specific E2s to the plasma membrane. MUBs contain a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold.

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gi 341941880  17 IRMEPDETVKVLKEKIEAE--KGRDAFP--VAGQKLIYAGKILSDDVPIKEYHI---DEKNFVVVM 75
Cdd:cd01814   17 FRYSSATTVATLKEKVIAEwpKDKENGPksINDVKLIYAGKVLENGKTLADSRTpgkVPPGGVITM 82

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 341941880   1 MAVTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGrdaFPVAGQKLIYAGKILSDDVPIKEYHI 66
Cdd:cd01799    5 IKVYVEDKSSSSGPITLKVRPHTTIASLKRQIFLEYG---FPPSVQRWIIGKRLATDDETLLSYGI 67

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.

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gi 341941880 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.

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                 ....*....|....*....|....*....|....*...
gi 341941880 164 ETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTG 201
Cdd:cd14297    1 EDLVKQLVDMGFTEAQARKALRKTNNNVERAVDWLFEG 38

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.

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gi 341941880 322 EAIERLKALGFPESLVIQAYFACEKNENLAANFL 355
Cdd:cd14387    2 ESIAILMSMGFPRNRAIEALKRTNNNLDRALDWL 35