Membrane-associated serine protease, rhomboid family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30688554  12 PVTKAFVIATALFTVFFGIRGGS--SKLGLSYQDIFEkFRIWKLIISAFAFSSTTQLLSGLYLLYFF-RVFERQIGSNKY 88
Cdd:COG0705   4 PVTLALIALNVLVFLLQLLLGGEllNWLALVPARLLL-GELWRLLTSMFLHGGFLHLLFNMLALWVFgPLLERRLGSKRF 82

                        90
                ....*....|....
gi 30688554  89 SVFIFFSGFVSLIL 102
Cdd:COG0705  83 LLLYLLSGLGGGLL 96

UBA domain found in ubiquitin-associated domain-containing protein 2 (UBAC2) and similar proteins; UBAC2, also called phosphoglycerate dehydrogenase-like protein 1, is a ubiquitin-associated domain (UBA)-domain containing protein encoded by gene UBAC2 (or PHGDHL1), a risk gene for Behcet's disease (BD). It may play an important role in the development of BD through its transcriptional modulation. Members in this family contain an N-terminal rhomboid-like domain and a C-terminal UBA domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 30688554 245 PSEEAIATLVSMGFDQNAARQALVHARNDVNAATNILL 282
Cdd:cd14305   1 PSEEQVQQLVDMGFSREDVLEALRQSNNDVNAATNLLL 38

Membrane-associated serine protease, rhomboid family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 30688554  12 PVTKAFVIATALFTVFFGIRGGS--SKLGLSYQDIFEkFRIWKLIISAFAFSSTTQLLSGLYLLYFF-RVFERQIGSNKY 88
Cdd:COG0705   4 PVTLALIALNVLVFLLQLLLGGEllNWLALVPARLLL-GELWRLLTSMFLHGGFLHLLFNMLALWVFgPLLERRLGSKRF 82

                        90
                ....*....|....
gi 30688554  89 SVFIFFSGFVSLIL 102
Cdd:COG0705  83 LLLYLLSGLGGGLL 96

UBA domain found in ubiquitin-associated domain-containing protein 2 (UBAC2) and similar proteins; UBAC2, also called phosphoglycerate dehydrogenase-like protein 1, is a ubiquitin-associated domain (UBA)-domain containing protein encoded by gene UBAC2 (or PHGDHL1), a risk gene for Behcet's disease (BD). It may play an important role in the development of BD through its transcriptional modulation. Members in this family contain an N-terminal rhomboid-like domain and a C-terminal UBA domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 30688554 245 PSEEAIATLVSMGFDQNAARQALVHARNDVNAATNILL 282
Cdd:cd14305   1 PSEEQVQQLVDMGFSREDVLEALRQSNNDVNAATNLLL 38

UBA domain found in Arabidopsis thaliana DNA (cytosine-5)-methyltransferase DRM2 (atDRM2) and similar proteins; atDRM2, also called protein domains rearranged methylase 2, is a homolog of the mammalian de novo methyltransferase DNMT3. It is the major de novo methyltransferase targeted to DNA by small interfering RNAs (siRNAs) in the RNA-directed DNA methylation (RdDM) pathway in Arabidopsis thaliana. atDRM2 is a part of the RdDM effector complex and plays a catalytic role in RdDM. It contains an N-terminal UBA domains and a C-terminal methyltransferase domain, both of which are required for normal RdDM.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILLE 283
Cdd:cd14330   1 EEKIKTLVSMGFSESDARRALERCGYDVAAAADFLFS 37

UBA1 domain found in Saccharomyces cerevisiae ubiquitin carboxyl-terminal hydrolase 14 (scUBP14) and similar proteins; scUBP14, also called deubiquitinating enzyme 14, glucose-induced degradation protein 6, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is the yeast ortholog of human Isopeptidase T (USP5), a deubiquitinating enzyme known to bind the 29-linked polyubiquitin chains. scUBP14 has been identified as a K29-linked polyubiquitin binding protein as well. It is involved in K29-linked polyubiquitin metabolism by binding to the 29-linked Ub4 resin and serving as an internal positive control in budding yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARN-DVNAATNILLE 283
Cdd:cd14296   1 EEAVSQLMSMGFSENAAKRALYYTGNsSVEAAMNWLFE 38

UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also called negative regulator of ubiquitin-like proteins 1, renal carcinoma antigen NY-REN-18, or protein BS4, is a NEDD8-interacting protein that can be induced by interferon. It functions as a strong post-transcriptional down-regulator of the NEDD8 expression and plays critical roles in regulating many biological events, such as cell growth, NF-kappaB signaling, and biological responses to hypoxia. NUB1 can also interact with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) which may function in the regulation of cell cycle progression. NUB1 contains three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif. This model corresponds to UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....
gi 30688554 246 SEEAIATLVSMGFDQNAARQALVHARNDVNAATN 279
Cdd:cd14291   1 DEDKLQQLMEMGFSEAEARLALRACNGNVERAVD 34

UBA2 domain found in Saccharomyces cerevisiae ubiquitin carboxyl-terminal hydrolase 14 (scUBP14) and similar proteins; scUBP14, also called deubiquitinating enzyme 14, glucose-induced degradation protein 6, ubiquitin thioesterase 14, or ubiquitin-specific-processing protease 14, is the yeast ortholog of human Isopeptidase T (USP5), a deubiquitinating enzyme known to bind the 29-linked polyubiquitin chains. scUBP14 has been identified as a K29-linked polyubiquitin binding protein as well. It is involved in K29-linked polyubiquitin metabolism by binding to the 29-linked Ub4 resin and serving as an internal positive control in budding yeast. Members in this family contain two tandem ubiquitin-association (UBA) domains. This model corresponds to the UBA2 domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILL 282
Cdd:cd14298   1 DEALAQLVSMGFDPEVARKALILTNGNVERAIEWLF 36

UBA2 domain found in ubiquitin carboxyl-terminal hydrolase 13 (UBP13); UBP13, also called deubiquitinating enzyme 13, Isopeptidase T-3 (isoT3), ubiquitin thioesterase 13, or ubiquitin-specific-processing protease 13 is an ortholog of UBP5 implicated in catalyzing hydrolysis of various ubiquitin (Ub)-chains. It contains a zinc finger (ZnF) domain, a catalytic ubiquitin-specific processing protease (UBP) domain (catalytic C-box and H-box), and two ubiquitin-associated (UBA) domains. Due to the non-activating catalysis for K63-polyubiquitin chains, UBP13 may function differently from USP5 in cellular deubiquitination processes. Moreover, the zinc finger (ZnF) domain of USP13 cannot bind to Ub. Its tandem UBA domains can bind with different types of diUb but preferentially with K63-linked.USP13 can also regulate the protein level of CD3delta in cells via its UBA domains. This model corresponds to the UBA2 domain.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNIL 281
Cdd:cd14387   1 EESIAILMSMGFPRNRAIEALKRTNNNLDRALDWL 35

UBA domain found in Schizosaccharomyces pombe UBA domain-containing protein mud1 and similar proteins; Schizosaccharomyces pombe mud1 is an ortholog of the Saccharomyces cerevisiae DNA-damage response protein Ddi1. S. cerevisiae Ddi1, also called v-SNARE-master 1 (Vsm1), belongs to a family of proteins known as the ubiquitin receptors which can bind ubiquitinated substrates and the proteasome. It is involved in the degradation of the F-box protein Ufo1, involved in the G1/S transition. It also participates in Mec1-mediated degradation of Ho endonuclease. Both S. pombe mud1 and S. cerevisiae Ddi1 contain an N-terminal ubiquitin-like (UBL) domain, an aspartyl protease-like domain, and a C-terminal ubiquitin-associated (UBA) domain. S. pombe mud1 binds to K48-linked polyubiquitin (polyUb) through UBA domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILL 282
Cdd:cd14308   1 PEKVRQLVDMGFTPTDAGRALKAANGDVTVAAEWLL 36

UBA domain of Tudor domain-containing protein 3 (TDRD3) and similar proteins; TDRD3 is a modular protein containing Tudor domain, a DUF/OB-fold motif and a ubiquitin-associated (UBA) domain. It shows both nucleic acid- and methyl-binding properties and can interact with methylated RNA-binding proteins, such as fragile X mental retardation protein (FMRP) and DEAD/H box-3 (also known as DDX3X/Y, DBX/Y, HLP2 and DDX14) which is implicated in human genetic diseases. At this point, TDRD3 may play a central role in RNA processing regulatory pathways involving arginine methylation. TDRD3 localizes predominantly to the cytoplasm stress granules (SGs). The Tudor domain is essential and sufficient for its recruitment to SGs.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILL 282
Cdd:cd14282   3 EKALRHITEMGFSKEAARQALMDNNNNLEAALNFLL 38

UBA domain found in casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor proteins family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-3. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating the activated tyrosine kinases and targeting them for degradation. Cbl proteins in this family consists of a highly conserved N-terminal half that includes a tyrosine-kinase-binding (TKB) domain and a RING finger domain, both of which are required for Cbl-mediated downregulation of RTKs, and a C-terminal half that includes a ubiquitin-associated (UBA) domain and other protein interaction motifs. The UBA domain contains leucine/isoleucine repeats and may play a role in dimerization of Cbl proteins. In addition, although both c-Cbl and Cbl-b have the C-terminal UBA domain, only the UBA domain from Cbl-b can bind ubiquitin.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILLE 283
Cdd:cd14318   2 LSYIAKLVGEGYSKEDVIRALGIARNNVEMARDILRE 38

UBA domain found in Saccharomyces cerevisiae EH domain-containing and endocytosis protein 1 (Ede1) and similar proteins; Ede1, also bud site selection protein 15, is the mammalian protein Eps15 homolog found in yeast and functions at the internalization step of endocytosis. Both Ede1 and Eps15 are endocytic scaffold proteins that may involve in stabilization of the adaptor-cargo complex. They both contain contains three N-terminal Eps15 homology (EH) domains and C-terminal ubiquitin-binding motifs. Whereas Eps15 has two ubiquitin interacting motifs (UIM), Ede1 harbors a single ubiquitin-associated (UBA) domain. This model corresponds to Ede1 UBA domain that is responsible for the binding of monoubiquitinated proteins and negatively regulates EH domain-mediated protein-protein interactions.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 30688554 249 AIATLVSMGFDQNAARQALVHARNDVNAATNILLE 283
Cdd:cd14285   1 AIEELSGMGFTEEEARKALEKCNWDLEAATNFLLD 35

UBA domain found in yeast UBA domain-containing protein RUP1p and similar proteins; RUP1p is a ubiquitin-associated (UBA) domain-containing protein encoded by a nonessential yeast gene RUP1. It can mediate the association of Rsp5 and Ubp2. The N-terminal UBA domain is responsible for antagonizing Rsp5 function, as well as bridging the Rsp5-Ubp2 interaction. No other characterized functional domains or motifs are found in RUP1p.

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILLE 283
Cdd:cd14307   1 EEAVASLLEMGIPREVAIEALRETNGDVEAAANYIFS 37

UBA1 domain found in ubiquitin carboxyl-terminal hydrolase UBP5, UBP13 and similar proteins; 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. UBP13, also called deubiquitinating enzyme 13, Isopeptidase T-3 (isoT3), ubiquitin thioesterase 13, or ubiquitin-specific-processing protease 13, is an ortholog of UBP5. It has similar domain architecture, but functions differently from USP5 in cellular deubiquitination processes. It exhibits a weak deubiquitinating activity preferring to Lys63-linked polyubiquitin in a non-activation manner. Moreover, the zinc finger (ZnF) domain of USP13 cannot bind to Ub. Its tandem UBA domains can bind with different types of diUb but preferentially with K63-linked.USP13 can also regulate the protein level of CD3delta in cells via its UBA domains. This model corresponds to the UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARND-VNAATNILLE 283
Cdd:cd14294   1 EAVVSQLAEMGFPLEACRKAVYHTNNSgLEAAMNWIME 38

UBA1 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 UBA1 domain.

                        10        20        30
                ....*....|....*....|....*....|....*...
gi 30688554 247 EEAIATLVSMGFDQNAARQALVHARN-DVNAATNILLE 283
Cdd:cd14385   2 AEALAQLLGMGFPEVRCKKALLATGNsDAEAAMNWLFE 39

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 30688554 248 EAIATLVSMGFDQNAARQALVHAR-NDVNAATNILL 282
Cdd:cd14327   1 EAVAQLVEMGFSRERAEEALRAVGtNSVELAMEWLF 36

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 30688554 247 EEAIATLVSMGFDQNAARQALVHARNDVNAATNILL 282
Cdd:cd14281   3 REAIERLVALGFSRDQAIEAYLACDKNEELAANYLF 38