Rhomboid family; This family contains integral membrane proteins that are related to Drosophila rhomboid protein. Members of this family are found in bacteria and eukaryotes. Rhomboid promotes the cleavage of the membrane-anchored TGF-alpha-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Analysis has shown that Rhomboid-1 is an intramembrane serine protease (EC:3.4.21.105). Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73921121    58 IISRFQVYRFYTAIIFHGSLLHVLFNMMALVPMGSELERIMGSVRLLYLTVLLATTNAVLHLLIASLagynpfyqydhlm 137
Cdd:pfam01694   1 PVQPGQLWRLITSMFLHAGWLHLLFNMLALLFFGGPLERILGSVRFLLLYLLSGIAGSLLSYLFSPL------------- 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 73921121   138 NECAIGFSGILFSMIVIETSLSGVTSRSVFGLFNVPAKLYPWILLIVFQLLMT--NVSLLGHLCGILSGFSYSYGLFNF 214
Cdd:pfam01694  68 STPSVGASGAIFGLLGALLVLGPRNRILLFGLIGALLALLLFILLNLVLGLLPgnGVSNLAHLGGLLVGLLLGFILLRR 146

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 73921121   299 TLSTARDPTAPAGETDPNLHArlleDSSSPDRLSDATVNTVADSRQAPIANAAVLPQ-------SQGRVAAS-------- 363
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSP----PASPASGMSAAPASAVEEKSPSEESATATAPEspstsvpSSGSDAAStlvvgser 156

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 73921121   364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILMS 400
Cdd:TIGR00601 157 ETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLT 193

Rhomboid family; This family contains integral membrane proteins that are related to Drosophila rhomboid protein. Members of this family are found in bacteria and eukaryotes. Rhomboid promotes the cleavage of the membrane-anchored TGF-alpha-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Analysis has shown that Rhomboid-1 is an intramembrane serine protease (EC:3.4.21.105). Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73921121    58 IISRFQVYRFYTAIIFHGSLLHVLFNMMALVPMGSELERIMGSVRLLYLTVLLATTNAVLHLLIASLagynpfyqydhlm 137
Cdd:pfam01694   1 PVQPGQLWRLITSMFLHAGWLHLLFNMLALLFFGGPLERILGSVRFLLLYLLSGIAGSLLSYLFSPL------------- 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 73921121   138 NECAIGFSGILFSMIVIETSLSGVTSRSVFGLFNVPAKLYPWILLIVFQLLMT--NVSLLGHLCGILSGFSYSYGLFNF 214
Cdd:pfam01694  68 STPSVGASGAIFGLLGALLVLGPRNRILLFGLIGALLALLLFILLNLVLGLLPgnGVSNLAHLGGLLVGLLLGFILLRR 146

UBA domain found in uncharacterized protein At3g58460 from Arabidopsis thaliana and its homologs from other plants; The uncharacterized protein At3g58460 from Arabidopsis thaliana is also known as rhomboid-like protein 15 which is encoded by RBL15 gene. Although the biological function of the family members remains unclear, they all contain an N-terminal rhomboid-like domain and a C-terminal ubiquitin-associated (UBA) domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILM 399
Cdd:cd14287   1 EALVQSLVAMGFEKHRARRALDAAGGDINTAVEILM 36

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 73921121   363 SEEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEIL 398
Cdd:pfam00627   2 DEEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

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 73921121   299 TLSTARDPTAPAGETDPNLHArlleDSSSPDRLSDATVNTVADSRQAPIANAAVLPQ-------SQGRVAAS-------- 363
Cdd:TIGR00601  81 TGKVAPPAATPTSAPTPTPSP----PASPASGMSAAPASAVEEKSPSEESATATAPEspstsvpSSGSDAAStlvvgser 156

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 73921121   364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILMS 400
Cdd:TIGR00601 157 ETTIEEIMEMGYEREEVERALRAAFNNPDRAVEYLLT 193

Rhomboid family; This family contains integral membrane proteins that are related to Drosophila rhomboid protein. Members of this family are found in bacteria and eukaryotes. Rhomboid promotes the cleavage of the membrane-anchored TGF-alpha-like growth factor Spitz, allowing it to activate the Drosophila EGF receptor. Analysis has shown that Rhomboid-1 is an intramembrane serine protease (EC:3.4.21.105). Parasite-encoded rhomboid enzymes are also important for invasion of host cells by Toxoplasma and the malaria parasite.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 73921121    58 IISRFQVYRFYTAIIFHGSLLHVLFNMMALVPMGSELERIMGSVRLLYLTVLLATTNAVLHLLIASLagynpfyqydhlm 137
Cdd:pfam01694   1 PVQPGQLWRLITSMFLHAGWLHLLFNMLALLFFGGPLERILGSVRFLLLYLLSGIAGSLLSYLFSPL------------- 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 73921121   138 NECAIGFSGILFSMIVIETSLSGVTSRSVFGLFNVPAKLYPWILLIVFQLLMT--NVSLLGHLCGILSGFSYSYGLFNF 214
Cdd:pfam01694  68 STPSVGASGAIFGLLGALLVLGPRNRILLFGLIGALLALLLFILLNLVLGLLPgnGVSNLAHLGGLLVGLLLGFILLRR 146

UBA domain found in uncharacterized protein At3g58460 from Arabidopsis thaliana and its homologs from other plants; The uncharacterized protein At3g58460 from Arabidopsis thaliana is also known as rhomboid-like protein 15 which is encoded by RBL15 gene. Although the biological function of the family members remains unclear, they all contain an N-terminal rhomboid-like domain and a C-terminal ubiquitin-associated (UBA) domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILM 399
Cdd:cd14287   1 EALVQSLVAMGFEKHRARRALDAAGGDINTAVEILM 36

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 73921121   363 SEEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEIL 398
Cdd:pfam00627   2 DEEAIQRLVEMGFDREQVREALRATGNNVERAAEYL 37

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

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILMS 400
Cdd:cd14297   1 EDLVKQLVDMGFTEAQARKALRKTNNNVERAVDWLFE 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.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILMS 400
Cdd:cd14280   3 EATINNIMSMGFEREQVVRALRAAFNNPDRAVEYLLS 39

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 73921121 367 IQKLVAMGFDRTQVEVALAAADDDLTVAVE 396
Cdd:cd14270   1 LAQLVEMGFSREQARRALRATNGDVEAAVE 30

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 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILM 399
Cdd:cd14309   1 EEKIAQLMDLGFSREEAIQALEATNGNVELAASLLF 36

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.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILM 399
Cdd:cd14314   2 EEKIKKLLEMGFPRDQARKALEKNGWDETLALNTLL 37

UBA domain of vertebrate ubiquitin-conjugating enzyme E2 K (UBE2K); UBE2K, also called Huntingtin-interacting protein 2 (HIP-2), ubiquitin carrier protein, ubiquitin-conjugating enzyme E2-25 kDa (E2-25K), or ubiquitin-protein ligase is a multi-ubiquitinating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains which is involved in the ubiquitin (Ub)-dependent proteolytic pathway. It interacts with the frameshift mutant of ubiquitin B and functions as a crucial factor regulating amyloid-beta neurotoxicity. It has also been characterized as Huntingtin-interacting protein that modulates the neurotoxicity of Amyloid-beta (Abeta), the principal protein involved in Alzheimer's disease pathogenesis. Moreover, E2-25K increases aggregate the formation of expanded polyglutamine proteins and polyglutamine-induced cell death in the pathology of polyglutamine diseases. UBE2K and its yeast homolog UBC1 are unique class II E2 conjugating enzymes, both of which contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 73921121 365 EQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILMS 400
Cdd:cd14390   2 KKIENLCAMGFDRNAVIVALSSKSWDVETATELLLS 37

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
                ....*....|....*....|....*....|....*..
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEILMS 400
Cdd:cd14378   8 NQTVQNIMEMGYEREQVERALRASFNNPDRAVEYLLT 44

UBA domain found in vertebrate ubiquitin-conjugating enzyme E2 K (UBE2K), Drosophila melanogaster ubiquitin-conjugating enzyme E2-22 kDa (UbcD4) and similar proteins; UBE2K, also called Huntingtin-interacting protein 2 (HIP-2), ubiquitin carrier protein, ubiquitin-conjugating enzyme E2-25 kDa (E2-25K), or ubiquitin-protein ligase, is a multi-ubiquitinating enzyme with the ability to synthesize Lys48-linked polyubiquitin chains which is involved in the ubiquitin (Ub)-dependent proteolytic pathway. It interacts with the frameshift mutant of ubiquitin B and functions as a crucial factor regulating amyloid-beta neurotoxicity. It has also been characterized as Huntingtin-interacting protein that modulates the neurotoxicity of Amyloid-beta (Abeta), the principal protein involved in Alzheimer's disease pathogenesis. Moreover, E2-25K increases aggregate the formation of expanded polyglutamine proteins and polyglutamine-induced cell death in the pathology of polyglutamine diseases. UbcD4, also called ubiquitin carrier protein, or ubiquitin-protein ligase, is encoded by Drosophila E2 gene which is only expressed in pole cells in embryos. It is a putative E2 enzyme homologous to the Huntingtin interacting protein-2 (HIP2) of human. UbcD4 specifically interacts with the polyubiquitin-binding subunit of the proteasome. This family also includes a putative ubiquitin conjugating enzyme from plasmodium Yoelii (pyUCE). It shows a high level of sequence similarity with UBE2K and may also plays a role in the ubiquitin-mediated protein degradation pathway. All family members are class II E2 conjugating enzymes which contain a C-terminal ubiquitin-associated (UBA) domain in addition to an N-terminal catalytic ubiquitin-conjugating enzyme E2 (UBCc) domain.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 73921121 364 EEQIQKLVAMGFDRTQVEVALAAADDDLTVAVEIL 398
Cdd:cd14313   1 KKKVDKLVDMGFDRDEAIVALSSNNWNLERATEYL 35

UBA domain found in ubiquitin carboxyl-terminal hydrolase 24 (UBP24) and similar proteins; UBP24, also called deubiquitinating enzyme 24, ubiquitin thioesterase 24, or ubiquitin-specific-processing protease 24, is a deubiquitinating protein that interacts with damage-specific DNA-binding protein 2 (DDB2) and regulates DDB2 stability. It may also play a role in the pathogenesis of Parkinson's disease (PD). UBP24 proteins contain an N-terminal ubiquitin-associated (UBA) domain and a C-terminal peptidase C19 domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 73921121 364 EEQIQKLVAMGF-DRTQVEVALAAADDDLTVAVEIL 398
Cdd:cd14286   1 EEHVTTLLCMGFsDPEEIRKALRLAKNDLNEAVAIL 36