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 387849175    1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPKAV 80
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   81 STPapattqqsapasttaitsstattvAQAPTPVPALAPTSTPAsiTPASATASSEPAPASATKQEKPAEKPAETPVATS 160
Cdd:TIGR00601  81 TGK------------------------VAPPAATPTSAPTPTPS--PPASPASGMSAAPASAVEEKSPSEESATATAPES 134

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  161 PTATDSTSGDssrsnlfeDATSALVTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIPGDRESQAVVD 240
Cdd:TIGR00601 135 PSTSVPSSGS--------DAASTLVVGSERETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQPEPVQ 206

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  241 PPQA------ASTGAPQSSAVAAAAATTTATTTTTSSGGHPLEFLRNQPQFQQMRQIIQQNPSLLPALLQQIGRENPQLL 314
Cdd:TIGR00601 207 QTAAstaaatTETPQHGSVFEQAAQGGTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLL 286

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  315 QQISQHQEHFIQMLNEPVQEAgGQGGGGGGGSGGIAEAGSGHMNYIQVTPQEKEAIERLKALGFPEGLVIQAYFACEKNE 394
Cdd:TIGR00601 287 QQISQHPEQFLQMLNEPVGEL-ASESDMEGGVGAIAEAGLPQMNQIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNE 365

                         410
                  ....*....|...
gi 387849175  395 NLAANFLLQQNFD 407
Cdd:TIGR00601 366 ELAANYLLSQNFD 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 387849175    1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPKAV 80
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   81 STPapattqqsapasttaitsstattvAQAPTPVPALAPTSTPAsiTPASATASSEPAPASATKQEKPAEKPAETPVATS 160
Cdd:TIGR00601  81 TGK------------------------VAPPAATPTSAPTPTPS--PPASPASGMSAAPASAVEEKSPSEESATATAPES 134

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  161 PTATDSTSGDssrsnlfeDATSALVTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIPGDRESQAVVD 240
Cdd:TIGR00601 135 PSTSVPSSGS--------DAASTLVVGSERETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQPEPVQ 206

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  241 PPQA------ASTGAPQSSAVAAAAATTTATTTTTSSGGHPLEFLRNQPQFQQMRQIIQQNPSLLPALLQQIGRENPQLL 314
Cdd:TIGR00601 207 QTAAstaaatTETPQHGSVFEQAAQGGTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLL 286

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  315 QQISQHQEHFIQMLNEPVQEAgGQGGGGGGGSGGIAEAGSGHMNYIQVTPQEKEAIERLKALGFPEGLVIQAYFACEKNE 394
Cdd:TIGR00601 287 QQISQHPEQFLQMLNEPVGEL-ASESDMEGGVGAIAEAGLPQMNQIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNE 365

                         410
                  ....*....|...
gi 387849175  395 NLAANFLLQQNFD 407
Cdd:TIGR00601 366 ELAANYLLSQNFD 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 387849175  276 LEFLRNQPQFQQMRQIIQQNPSLLPALLQQIGRENPQLLQQISQHQEHFIQMLNEPV 332
Cdd:pfam09280   1 LDFLRNNPQFQQLRQLVQQNPQLLQPLLQQLAQSNPQLAQLIQQNQEEFLQLLNEPG 57

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVagqKLIYAGKILNDDTALKEYKI 64
Cdd:PTZ00044   1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQI---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 387849175    1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPKAV 80
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGKDAYPVAQQKLIYSGKILSDDKTVKEYKIKEKDFVVVMVSKPKTG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   81 STPapattqqsapasttaitsstattvAQAPTPVPALAPTSTPAsiTPASATASSEPAPASATKQEKPAEKPAETPVATS 160
Cdd:TIGR00601  81 TGK------------------------VAPPAATPTSAPTPTPS--PPASPASGMSAAPASAVEEKSPSEESATATAPES 134

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  161 PTATDSTSGDssrsnlfeDATSALVTGQSYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMGIPGDRESQAVVD 240
Cdd:TIGR00601 135 PSTSVPSSGS--------DAASTLVVGSERETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLTGIPEDPEQPEPVQ 206

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  241 PPQA------ASTGAPQSSAVAAAAATTTATTTTTSSGGHPLEFLRNQPQFQQMRQIIQQNPSLLPALLQQIGRENPQLL 314
Cdd:TIGR00601 207 QTAAstaaatTETPQHGSVFEQAAQGGTEQPATEAAQGGNPLEFLRNQPQFQQLRQVVQQNPQLLPPLLQQIGQENPQLL 286

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  315 QQISQHQEHFIQMLNEPVQEAgGQGGGGGGGSGGIAEAGSGHMNYIQVTPQEKEAIERLKALGFPEGLVIQAYFACEKNE 394
Cdd:TIGR00601 287 QQISQHPEQFLQMLNEPVGEL-ASESDMEGGVGAIAEAGLPQMNQIQVTPEEKEAIERLCALGFDRGLVIQAYFACDKNE 365

                         410
                  ....*....|...
gi 387849175  395 NLAANFLLQQNFD 407
Cdd:TIGR00601 366 ELAANYLLSQNFD 378

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 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTK 76
Cdd:cd17126    1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAEKGRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKNFVVVMVTK 76

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 387849175  276 LEFLRNQPQFQQMRQIIQQNPSLLPALLQQIGRENPQLLQQISQHQEHFIQMLNEPV 332
Cdd:pfam09280   1 LDFLRNNPQFQQLRQLVQQNPQLLQPLLQQLAQSNPQLAQLIQQNQEEFLQLLNEPG 57

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 387849175 189 SYENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMG 228
Cdd:cd14377    1 EYENMVTEIMSMGFERDQVVRALRASFNNPDRAVEYLLSG 40

Ubiquitin homologues; Ubiquitin-mediated proteolysis is involved in the regulated turnover of proteins required for controlling cell cycle progression

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 387849175     1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKdafPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVT 75
Cdd:smart00213   1 IELTVKTLDGKTITLEVKPSDTVSELKEKIAELTGI---PPEQQRLIYKGKVLEDDRTLADYGIQDGSTIHLVLR 72

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 387849175 365 QEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQN 405
Cdd:cd14427    1 QEKEAIERLKALGFPESLVIQAYFACEKNENLAANFLLSQN 41

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 387849175 190 YENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLL 226
Cdd:cd14280    2 LEATINNIMSMGFEREQVVRALRAAFNNPDRAVEYLL 38

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 387849175   3 VTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVM 73
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 387849175 362 VTPQEKEAIERLKALGFPEGLVIQAYFACEKNENLAANFLLQQ 404
Cdd:cd14382    1 VTPEEREAIERLEAMGFDRALVIEAFLACDKNEELAANYLLEH 43

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
                 ....*....|....*....|....*....|....*....
gi 387849175 190 YENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLLMG 228
Cdd:cd14425    2 YETMLTEIMSMGYERERVVAALRASYNNPHRAVEYLLTG 40

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 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEK 67
Cdd:cd01809    1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVN---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 387849175   3 VTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDE 66
Cdd:cd01806    1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEG---IPPQQQRLIFSGKQMNDEKTAADYKIEG 61

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 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKI--DEKNFVVV 72
Cdd:cd01807    1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLN---VPVSQQRLVFKGKTLADEHSLSDYSIgpGSKIHLVV 71

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

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 387849175   190 YENMVTEIMSMGYEREQVIAALRASFNNPDRAVEYLL 226
Cdd:smart00165   1 DEEKIDQLLEMGFSREEALKALRAANGNVERAAEYLL 37

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 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDE 66
Cdd:cd01802    1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEG---IPVSQQHLIWSGRELEDDYCLHDYNITD 63

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 387849175   2 QVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKI 64
Cdd:cd16107    1 QIFVRTYCGKTIVLHAKASDTVESLHQQIEARTG---IPSLEQRLIFGGRQLQHSQSLESCKM 60

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 387849175  368 EAIERLKALGFPEGLVIQAYFACEKNENLAANFL 401
Cdd:pfam00627   4 EAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

ubiquitin; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDAFPVagqKLIYAGKILNDDTALKEYKI 64
Cdd:PTZ00044   1 MQILIKTLTGKKQSFNFEPDNTVQQVKMALQEKEGIDVKQI---RLIYSGKQMSDDLKLSDYKV 61

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387849175  11 QTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGkILNDDTALKEYKIdeKNFVVVMV 74
Cdd:cd17047   10 EKYDVKFPLDSTIAELKEHIETLTG---VPPAMQKLMYKG-LLKDDKTLRELKV--TKGAKVMV 67

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 387849175 194 VTEIMSMGYEREQVIAALRASFNNPDRAVE 223
Cdd:cd14270    1 LAQLVEMGFSREQARRALRATNGDVEAAVE 30

Ubiquitin-2 like Rad60 SUMO-like; The small ubiquitin-related modifier SUMO-1 is a Ub/Ubl family member, and although SUMO-1 shares structural similarity to Ub, SUMO's cellular functions remain distinct insomuch as SUMO modification alters protein function through changes in activity, cellular localization, or by protecting substrates from ubiquitination. Rad60 family members contain functionally enigmatic, integral SUMO-like domains (SLDs). Despite their divergence from SUMO, each Rad60 SLD interacts with a subset of SUMO pathway enzymes: SLD2 specifically binds the SUMO E2 conjugating enzyme (Ubc9)), whereas SLD1 binds the SUMO E1 (Fub2, also called Uba2) activating and E3 (Pli1, also called Siz1 and Siz2) specificity enzymes. Structural analysis of PDB:2uyz reveals a mechanistic basis for the near-synonymous roles of Rad60 and SUMO in survival of genotoxic stress and suggest unprecedented DNA-damage-response functions for SLDs in regulating SUMOylation. The Rad60 branch of this family is also known as RENi (Rad60-Esc2-Nip45), and biologically it should be two distinct families SUMO and RENi (Rad60-Esc2-Nip45).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387849175    1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIESEKGKDafPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMV 74
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIP--PSQQVRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 387849175  19 PEETVKALKEKIESE--KGKDAFP--VAGQKLIYAGKILNDDTALKEYKI---DEKNFVVVM 73
Cdd:cd01814   21 SATTVATLKEKVIAEwpKDKENGPksINDVKLIYAGKVLENGKTLADSRTpgkVPPGGVITM 82

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 387849175   1 MQVTLKTLQQQTFKIDIDPEETVKALKEKIEsekGKDAFPVAGQKLIYAGKILNDDTALKEYKI 64
Cdd:cd01810    1 LSIFVRNEKGQSHTYEVRLTQTVDQLKQKVS---GREGVHDDQFWLTFEGRPLEDQLPLGEYGL 61

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 387849175 192 NMVTEIMSMGYEREQVIAALRA-SFNNPDRAVEYLL 226
Cdd:cd14327    1 EAVAQLVEMGFSRERAEEALRAvGTNSVELAMEWLF 36

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   76 KPKAVSTPAPATTQQSAPASTTAITSSTATTVAQAPTPVPALAPTSTPASI-TPASATASSEPAPASATKQEKPAEKPAE 154
Cdd:PRK12270   37 GPGSTAAPTAAAAAAAAAASAPAAAPAAKAPAAPAPAPPAAAAPAAPPKPAaAAAAAAAPAAPPAAAAAAAPAAAAVEDE 116

                          90       100
                  ....*....|....*....|
gi 387849175  155 TPVATSPTATDSTSGDSSRS 174
Cdd:PRK12270  117 VTPLRGAAAAVAKNMDASLE 136

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   3 VTL--KTLQQ--QTFKIDIDPEETVKALKEKIEsekgkDAFP----VAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMV 74
Cdd:cd01790    1 VTLvvKSPNQriQDLTVNCTLGWTVLKLKEHLS-----EVYPskplPEDQKLIYSGKLLEDHQTLKDVLREDDPEQVHTV 75

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   87 TTQQSAPASTTAITSSTATTVAQAPTPVPALAPTSTPASITPASATASSEPAPASATKQEKPAEKPAETPVATSPTATDS 166
Cdd:PRK12270   34 ADYGPGSTAAPTAAAAAAAAAASAPAAAPAAKAPAAPAPAPPAAAAPAAPPKPAAAAAAAAAPAAPPAAAAAAAPAAAAV 113

ubiquitin-like (Ubl) domain 1 found in leukocyte antigen F (HLA-F) adjacent transcript 10 (FAT10) and similar proteins; FAT10, also termed ubiquitin D (UBD), or diubiquitin, is a cytokine-inducible ubiquitin-like (Ubl) modifer that is highly expressed in the thymus, and targets substrates covalently for 26S proteasomal degradation. It is also associated with cancer development, antigen processing and antimicrobial defense, chromosomal stability and cell cycle regulation. FAT10 is presented on immune cells and under the inflammatory conditions, is synergistically induced by interferon gamma (IFNgamma) and tumor necrosis factor (TNFalpha) in the non-immune (liver parenchymal) cells. FAT10 contains two Ubl domains. The family corresponds to the first Ubl domain of FAT10. Some family members contain only one Ubl domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 387849175  11 QTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEKN 68
Cdd:cd17052   10 DLMTFDANPQDSVKKINEHVRSKTK---VPVQDQVLLLGSKILKPRRRLSSYGIDKEK 64

DNA polymerase III subunit gamma/tau;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175  76 KPKAVSTPAPAT----TQQSAPASTTAITSSTATTVAQAPTPVPALAPTSTPASITPASATASSEPAPASATKQEKPAEK 151
Cdd:PRK07003 405 AAGAALAPKAAAaaaaTRAEAPPAAPAPPATADRGDDAADGDAPVPAKANARASADSRCDERDAQPPADSGSASAPASDA 484

                         90       100       110
                 ....*....|....*....|....*....|..
gi 387849175 152 PAETPVATSPTATDSTSGDSSRSNLFEDATSA 183
Cdd:PRK07003 485 PPDAAFEPAPRAAAPSAATPAAVPDARAPAAA 516

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   77 PKAVSTPAPATTQQSAPASTTAITSSTATTVAQAPTPVPALAPTSTPASITPASATASSEPAPASATKQEKPAEKPAETP 156
Cdd:PHA03247 2733 PALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVL 2812

                          90
                  ....*....|.
gi 387849175  157 VATSPTATDST 167
Cdd:PHA03247 2813 APAAALPPAAS 2823

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 387849175 370 IERLKALGFPEGLVIQAYFACEKNENLAANFLLQQ 404
Cdd:cd14306    1 VAKLMELGFPEEDCIRALRACGGNVEEAANWLLEN 35

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 387849175  12 TFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEKNFVVVMVTKPK 78
Cdd:cd01798   10 GFPVEVDSDWSILQLKEVVAKRQG---VPPDQLRIIFAGKELSDDLTLQNCDLGQQSIVHAVQGPKR 73

ubiquitin-like (Ubl) domain found in transmembrane and ubiquitin-like domain-containing proteins TMUB1, TMUB2, and similar proteins; TMUB1, also termed dendritic cell-derived ubiquitin-like protein (DULP), or hepatocyte odd protein shuttling protein, or ubiquitin-like protein SB144, or HOPS, is highly expressed in the nervous system. It is involved in the termination of liver regeneration and plays a negative role in interleukin-6-induced hepatocyte proliferation. The overexpression of Tmub1 has been shown to play a role in the inhibition of cell proliferation. TMUB1 has been implicated in the regulation of locomotor activity and wakefulness in mice, perhaps acting through its interaction with CAMLG. It also facilitates the recycling of AMPA receptors into synaptic membrane in cultured primary neurons. TMUB1 contains transmembrane domains and a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold. TMUB2 is an uncharacterized transmembrane domain and Ubl domain-containing protein that shows high sequence similarity to TMUB1.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 387849175   3 VTLKTLQQQTFKIDIDPEETVKALKEKiesekgkdAFPV---AGQ--KLIYAGKILNDDTA-LKEYKIDEKNFVVVMVT 75
Cdd:cd17057    4 IRLKFLNETERVVYARPEDTVGDFKRR--------HFPDelaQGKrvRLIYQGQLLRDDSRtLSSYGIQDGSVIHCHIS 74

Cell division protein DedD (periplasmic protein involved in septation) [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 387849175 108 AQAPTPVPALAPTSTPASITPASATASSEPAPASATKQEKPAEKPAETPVATSPTATDS 166
Cdd:COG3147    6 AAAPAAAAAPAAPAAAAAPAPAAAAAAAAPKPAAKPAAPKPAAAAAAAPAAKAAAPAGG 64

UBA domain found in Saccharomyces cerevisiae DNA-damage response protein Ddi1 and similar proteins; Ddi1, also called v-SNARE-master 1 (Vsm1), is a ubiquitin receptor involved in regulation of the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as a ubiquitin association domain (UBA)- ubiquitin-like-domain (UBL) shuttle protein that is required for the proteasome to enable ubiquitin-dependent degradation of its ligands. For instance, Ddi1 plays an essential role in the final stages of proteasomal degradation of Ho endonuclease and of its cognate FBP, Ufo1. Moreover, Ddi1 and its associated protein Rad23p play a cooperative role as negative regulators in yeast PHO pathway. Ddi1 contains an N-terminal UBL domain and a C-terminal UBA domain. It also harbors a central retroviral aspartyl-protease-like domain (RVP) which may be important in cell-cycle control. At this point, Ddi1 may function proteolytically during regulated protein turnover in the cell. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also called transporter regulator RS1 (RS1) which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 387849175 368 EAIERLKALGFPEGLVIQAYFACEKNENLAANFLL 402
Cdd:cd14309    2 EKIAQLMDLGFSREEAIQALEATNGNVELAASLLF 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387849175   3 VTLKTLQQQTfKIDIDPEETVKALKEKIeSEKGKDafPVAGQKLIYAGKILNDDTALKEYKIDEkNFVVVMVTK 76
Cdd:cd01808    5 VTVKTPKEKE-DFEVPEDSSVKEFKEEI-SKKFKA--PVEQLVLIFAGKILKDQDTLSQHGIKD-GLTVHLVIK 73

multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 387849175   75 TKPKAVSTPAPATTQQSAPASTTAITSSTATTVAQAPTPVPALAPTSTPASITPASATASSEPAPASATKQEKPAEKPAE 154
Cdd:PRK12270   42 AAPTAAAAAAAAAASAPAAAPAAKAPAAPAPAPPAAAAPAAPPKPAAAAAAAAAPAAPPAAAAAAAPAAAAVEDEVTPLR 121