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 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGKDNYPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVMLSKSKTs 80
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKT- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662  81 gsaGQSSTQPAQSTPVAHPILNSTPATQVTPSPTPAPQASTQAQLSAPKNTTSTSDRVTDSMQTDTYGQAASNLVAGNNL 160
Cdd:TIGR00601  80 ---GTGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGSDAASTLVVGSER 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 161 EQTIQQLMDMGggnWDRETVVRALRAAYNNPERAVDYLYSGIPESAEVAVPVGRFGSGPATeteASLPAPASGAPNTAPL 240
Cdd:TIGR00601 157 ETTIEEIMEMG---YEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQPEPVQQTAASTAA---ATTETPQHGSVFEQAA 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 241 NMFPQEALSAGGGGLGSLEFLRNNPQFQALRTMVHTNPQILQPMLQELGKQNPQLLRLIQDHHAEFLQLINEPVDNFEGE 320
Cdd:TIGR00601 231 QGGTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVGELASE 310

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333109662 321 --MFEQ----AEPDMPHA--INVTPDEQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLLENSGD 380
Cdd:TIGR00601 311 sdMEGGvgaiAEAGLPQMnqIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 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 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGKDNYPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVMLSKSKTs 80
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKT- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662  81 gsaGQSSTQPAQSTPVAHPILNSTPATQVTPSPTPAPQASTQAQLSAPKNTTSTSDRVTDSMQTDTYGQAASNLVAGNNL 160
Cdd:TIGR00601  80 ---GTGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGSDAASTLVVGSER 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 161 EQTIQQLMDMGggnWDRETVVRALRAAYNNPERAVDYLYSGIPESAEVAVPVGRFGSGPATeteASLPAPASGAPNTAPL 240
Cdd:TIGR00601 157 ETTIEEIMEMG---YEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQPEPVQQTAASTAA---ATTETPQHGSVFEQAA 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 241 NMFPQEALSAGGGGLGSLEFLRNNPQFQALRTMVHTNPQILQPMLQELGKQNPQLLRLIQDHHAEFLQLINEPVDNFEGE 320
Cdd:TIGR00601 231 QGGTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVGELASE 310

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333109662 321 --MFEQ----AEPDMPHA--INVTPDEQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLLENSGD 380
Cdd:TIGR00601 311 sdMEGGvgaiAEAGLPQMnqIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 378

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 1333109662 259 EFLRNNPQFQALRTMVHTNPQILQPMLQELGKQNPQLLRLIQDHHAEFLQLINEPV 314
Cdd:pfam09280   2 DFLRNNPQFQQLRQLVQQNPQLLQPLLQQLAQSNPQLAQLIQQNQEEFLQLLNEPG 57

BDLF3; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662  71 VVMLSKSKTSGSAGQSSTQPAQSTPVAHPILNSTPATQVTPSPTPAPQASTQAQLSAPKNTTSTSDRVTDSMQTdtyGQA 150
Cdd:PHA03255   43 VTTPSPSASGPSTNQSTTLTTTSAPITTTAILSTNTTTVTSTGTTVTPVPTTSNASTINVTTKVTAQNITATEA---GTG 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 151 ASNLVAGNNLEQTIQQlmdmgggnwdRETVVRALRAAYNNPEravdylysgiPESAevavpvgrfGSGPATETEASLPAP 230
Cdd:PHA03255  120 TSTGVTSNVTTRSSST----------TSATTRITNATTLAPT----------LSSK---------GTSNATKTTAELPTV 170

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 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGKDNYPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVMLSKSKTs 80
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKT- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662  81 gsaGQSSTQPAQSTPVAHPILNSTPATQVTPSPTPAPQASTQAQLSAPKNTTSTSDRVTDSMQTDTYGQAASNLVAGNNL 160
Cdd:TIGR00601  80 ---GTGKVAPPAATPTSAPTPTPSPPASPASGMSAAPASAVEEKSPSEESATATAPESPSTSVPSSGSDAASTLVVGSER 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 161 EQTIQQLMDMGggnWDRETVVRALRAAYNNPERAVDYLYSGIPESAEVAVPVGRFGSGPATeteASLPAPASGAPNTAPL 240
Cdd:TIGR00601 157 ETTIEEIMEMG---YEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQPEPVQQTAASTAA---ATTETPQHGSVFEQAA 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1333109662 241 NMFPQEALSAGGGGLGSLEFLRNNPQFQALRTMVHTNPQILQPMLQELGKQNPQLLRLIQDHHAEFLQLINEPVDNFEGE 320
Cdd:TIGR00601 231 QGGTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLLQQISQHPEQFLQMLNEPVGELASE 310

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1333109662 321 --MFEQ----AEPDMPHA--INVTPDEQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLLENSGD 380
Cdd:TIGR00601 311 sdMEGGvgaiAEAGLPQMnqIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNEELAANYLLSQNFD 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 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGKdnYPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVML 74
Cdd:cd01805     1 MKITFKTLQQQTFEIEVEPSDTVLELKEKIEQEQGD--FPASGQKLIYSGKVLKDDKTLSEYNIKEKDFVVVMV 72

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 1333109662 335 VTPDEQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLLEN 377
Cdd:cd14382     1 VTPEEREAIERLEAMGFDRALVIEAFLACDKNEELAANYLLEH 43

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 1333109662 338 DEQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLL 375
Cdd:cd14281     1 EEREAIERLVALGFSRDQAIEAYLACDKNEELAANYLF 38

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 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGKDNYPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVMLSK 76
Cdd:cd17126     1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTK 76

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 1333109662   3 LTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGkdnYPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVMLSKS 77
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEG---VPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

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 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDiqgKDNYPCGQQLLIHNGKVLKDESTLAENKVSEEG--FLVV 72
Cdd:cd01807     1 MLITVKILQGKECTIEVSPTESVLTVKQLVAE---QLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSkiHLVV 71

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 1333109662 338 DEQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLLEN 377
Cdd:cd14381     1 EEDQAIDRLCELGFDRDLVIQAYLACDKNEEMAANFLFEN 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1333109662   3 LTVKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGKdnyPCGQQLLIHNGKVLKDESTLAENKVSEEGFLVVM 73
Cdd:cd17039     1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGI---PVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

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 1333109662 161 EQTIQQLMDMGggnWDRETVVRALRAAYNNPERAVDYL 198
Cdd:pfam00627   3 EEAIQRLVEMG---FDREQVREALRATGNNVERAAEYL 37

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 1333109662 339 EQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLLENSGDFD 382
Cdd:cd14428     2 EKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQNFDDD 45

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 1333109662 339 EQAAIERLEAMGFDRALVIEAFLACDRNEELAANYL 374
Cdd:pfam00627   2 DEEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

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 1333109662   5 VKTLKGSHFEIRVQPTDTVMAVKKTIEDIQGkdnYPCGQQLLIHNGKVLKDESTLAENKVsEEG 68
Cdd:cd01806     3 VKTLTGKEIEIDIEPTDKVERIKERVEEKEG---IPPQQQRLIFSGKQMNDEKTAADYKI-EGG 62

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

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1333109662  339 EQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLL 375
Cdd:smart00165   1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYLL 37

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 1333109662 343 IERLEAMGFDRALVIEAFLACDRNEELAANYLLENS 378
Cdd:cd14306     1 VAKLMELGFPEEDCIRALRACGGNVEEAANWLLENA 36

ubiquitin-like (Ubl) domain 2 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein that upon viral infection it modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other ubiquitin-like (Ubl) molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the second Ubl domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTiedIQGKDNYPCGQQLLIHNGKVLKDESTLAE 61
Cdd:cd01810     1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQK---VSGREGVHDDQFWLTFEGRPLEDQLPLGE 58

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 1333109662 340 QAAIERLEAMGFDRALVIEAFLACDRNEELAANYLL 375
Cdd:cd14309     1 EEKIAQLMDLGFSREEAIQALEATNGNVELAASLLF 36

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.

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gi 1333109662   2 KLTVKTLKGSHfEIRVQPTDTVMAVKktiEDIQGKDNYPCGQQLLIHNGKVLKDESTLAENKV 64
Cdd:cd01808     4 KVTVKTPKEKE-DFEVPEDSSVKEFK---EEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGI 62

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.

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gi 1333109662 161 EQTIQQLMDMGggnWDRETVVRALRAAYNNPERAVDYLYSG 201
Cdd:cd14425     3 ETMLTEIMSMG---YERERVVAALRASYNNPHRAVEYLLTG 40

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 1333109662 164 IQQLMDMGggnWDRETVVRALRAAYNNPERAVDYLYSG 201
Cdd:cd14297     4 VKQLVDMG---FTEAQARKALRKTNNNVERAVDWLFEG 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.

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gi 1333109662 164 IQQLMDMGggnWDRETVVRALRAAYNNPERAVDYLYSG 201
Cdd:cd14306     1 VAKLMELG---FPEEDCIRALRACGGNVEEAANWLLEN 35

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.

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gi 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIEDiqgKDNYPCGQQLLIHNGKVL-KDESTLAENKVSEEGFLVVM 73
Cdd:cd17053     1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIED---QSGVPPNEQILVYNGKRLeDGDKTLGEYGIKTGDTLYLL 71

UBA domain found in eukaryotic E3 ubiquitin-protein ligase HUWE1 and similar proteins; HUWE1, also called ARF-binding protein 1 (ARF-BP1), HECT, UBA and WWE domain-containing protein 1, homologous to E6AP carboxyl terminus homologs protein 9 (HectH9), large structure of UREB1 (LASU1), Mcl-1 ubiquitin ligase E3 (Mule), upstream regulatory element-binding protein 1 (URE-B1), or URE-binding protein 1, may function as a ubiquitin-protein ligase that involves in the ubiquitination cascade that targets specific substrate proteins in proteolysis. It can ubiquitylate DNA polymerase beta (Pol beta), the major BER DNA polymerase and modulates base excision repair (BER). HUWE1 also acts as a critical mediator of both the p53-independent and p53-dependent tumor suppressor functions of ARF tumor suppressor in p53 regulation. Moreover, HUWE1 is both required and sufficient for the polyubiquitination of Mcl-1, an anti-apoptotic Bcl-2 family member involving in DNA damage-induced apoptosis. Furthermore, HUWE1 plays an important role in the regulation of Cdc6 stability after DNA damage. In addition, HUWE1 works as a partner of N-Myc oncoprotein in neural cells. It ubiquitinates N-Myc and primes it for proteasomal-mediated degradation. HUWE1 contains a ubiquitin-associated (UBA) domain, a WWE domain, and a Bcl-2 homology region 3 (BH3) domain at the N-terminus and a HECT domain at the C-terminus. WWE domain plays a role in the regulation of specific protein-protein interactions in a ubiquitin conjugation system. BH3 domain is responsible for the specific binding to Mcl-1. HECT domain involves in the inhibition of the transcriptional activity of p53 via a ubiquitin-dependent degradation pathway. It also controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein.

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gi 1333109662 161 EQTIQQLMDMGggnWDRETVVRALrAAYNNPERAVDYL 198
Cdd:cd14288     3 EAHLQQLMDMG---FTREHALEAL-LHTSTLEQATEYL 36

UBA2 domain found in ubiquitin carboxyl-terminal hydrolase 5 (UBP5); UBP5, also called deubiquitinating enzyme 5, Isopeptidase T (IsoT), ubiquitin thioesterase 5, or ubiquitin-specific-processing protease 5, is a deubiquitinating enzyme largely responsible for the disassembly of the majority of unanchored polyubiquitin in the cell. Zinc is required for its catalytic activity. UBP5 contains four ubiquitin (Ub)-binding sites including an N-terminal zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. ZnF domain binds the proximal ubiquitin. UBP domain forms the active site. UBA domains are involved in binding linear or K48-linked polyubiquitin. This model corresponds to the UBA2 domain.

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gi 1333109662 337 PDEQAaIERLEAMGFDRALVIEAFLACDRNEELAANYLLENSGD 380
Cdd:cd14386     1 VPEEA-VAMLVSMGFTRDQAIKALKATDNNVERAADWIFSHPDE 43

ubiquitin-like (Ubl) domain found in midnolin and similar proteins; Midnolin, also termed midbrain nucleolar protein, is a nucleolar protein that may be involved in regulation of genes related to neurogenesis in the nucleolus. It is strongly expressed at the mesencephalon (midbrain) of the embryo in day 12.5 (E12.5) mice and its expression is developmentally regulated. Midnolin plays a role in cellular signaling of adult tissues and regulates glucokinase enzyme activity in pancreatic beta cells. It can also control development via regulation of mRNA transport in cells. Midnolin contains an N-terminal conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

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gi 1333109662   1 MKLTVKTLKGSHFEIRVQPTDTVMAVKKTIediqgkdnypcGQQL--------LIHNGKVLKDeSTLAENKVSE 66
Cdd:cd01804     1 INLYIHPTTGGRFELSVPPNETVEGLKRRI-----------SKKLkvpkeritLLHKEKQLKD-GTLRENGIGD 62

UBA domain found in a putative ubiquitin conjugating enzyme from plasmodium Yoelii (pyUCE) and similar proteins; P. Yoelii ubiquitin-conjugating enzyme and other uncharacterized family members show high sequence similarity to the human Huntingtin interacting protein-2 (HIP2) which belongs to a class II E2 ubiquitin-conjugating enzyme family. These proteins may play roles in the ubiquitin-mediated protein degradation pathway. They all contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

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gi 1333109662 339 EQAAIERLEAMGFDRALVIEAFLACDRNEELAANYLL 375
Cdd:cd14314     1 KEEKIKKLLEMGFPRDQARKALEKNGWDETLALNTLL 37

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

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gi 1333109662   8 LKGSHFEIRVQPTDTVMAVKKTIEDIQGkdnYPCG-QQLLIHNGKVLKDESTLA 60
Cdd:cd01800    19 LNGQVLELTLPLTDTISVLKEKIHEELG---MPANkQKLQVEGGGFLKDSNSLA 69

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 1333109662 343 IERLEAMGFDRALVIEAFLACDRNEELAANYLL 375
Cdd:cd14305     6 VQQLVDMGFSREDVLEALRQSNNDVNAATNLLL 38

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 1333109662 161 EQTIQQLMDMGggnWDRETVVRALRAAYNNPERAVDYL 198
Cdd:cd14305     3 EEQVQQLVDMG---FSREDVLEALRQSNNDVNAATNLL 37

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.

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gi 1333109662 341 AAIERLEAMGFDRALVIEAFLACDRNEELAANYLL 375
Cdd:cd14280     4 ATINNIMSMGFEREQVVRALRAAFNNPDRAVEYLL 38