Ubiquitin-like (Ubl) domain found at the N-terminus of mammalian ASPSCR1 (alveolar soft part sarcoma chromosomal region candidate gene 1 protein), Saccharomyces cerevisie Ubx4p, and similar proteins; ASPSCR1 (alveolar soft part sarcoma chromosomal region candidate gene 1 protein) is also known as alveolar soft part sarcoma locus protein (ASPL), tether containing UBX domain for GLUT4, TUG, UBX domain protein 9, UBXD9, UBXN9 or renal papillary cell carcinoma protein 17 (RCC17). The majority of members of this family contain two beta-grasp ubiquitin-like fold domains: the N-terminal UBL domain (described in this CD), and a C-terminal UBX domain. This UBL domain lacks the characteristic C-terminal double glycine motif. ASPSCR1 functions as a cofactor of the hexameric AAA (ATPase associated with various activities) ATPase complex, known as p97 or VCP in mammals and Cdc48p in yeast. In mammalian cells, ASPSCR1 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4 and assembly of the Golgi apparatus; ASPSCR1 also plays a role in controlling vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. Ubx4p and ASPSCR1 have only partially overlapping functions: both interact with p97/Cdc48p; however, Ubx4p is important for the ERAD (endoplasmic reticulum-associated protein degradation) pathway while ASPSCR1 appears not to be.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6323712    4 VTVKY-NFQLFKCKVSLNSTLNDVLHQSIQFFQLHTSSnDWSLIHLDKPVPLDLPWRLLNLPTGVNLELSKS 74
Cdd:cd16105   1 LTVLYpNGRRQTVKVTPNTPLSQVLEEACKKFGLDPSS-EYSLKHNRKPLDLSLPFRLSNLPNNAKLELVKS 71

Ubiquitin-like (Ubl) domain found at the N-terminus of mammalian ASPSCR1 (alveolar soft part sarcoma chromosomal region candidate gene 1 protein), Saccharomyces cerevisie Ubx4p, and similar proteins; ASPSCR1 (alveolar soft part sarcoma chromosomal region candidate gene 1 protein) is also known as alveolar soft part sarcoma locus protein (ASPL), tether containing UBX domain for GLUT4, TUG, UBX domain protein 9, UBXD9, UBXN9 or renal papillary cell carcinoma protein 17 (RCC17). The majority of members of this family contain two beta-grasp ubiquitin-like fold domains: the N-terminal UBL domain (described in this CD), and a C-terminal UBX domain. This UBL domain lacks the characteristic C-terminal double glycine motif. ASPSCR1 functions as a cofactor of the hexameric AAA (ATPase associated with various activities) ATPase complex, known as p97 or VCP in mammals and Cdc48p in yeast. In mammalian cells, ASPSCR1 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4 and assembly of the Golgi apparatus; ASPSCR1 also plays a role in controlling vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. Ubx4p and ASPSCR1 have only partially overlapping functions: both interact with p97/Cdc48p; however, Ubx4p is important for the ERAD (endoplasmic reticulum-associated protein degradation) pathway while ASPSCR1 appears not to be.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6323712    4 VTVKY-NFQLFKCKVSLNSTLNDVLHQSIQFFQLHTSSnDWSLIHLDKPVPLDLPWRLLNLPTGVNLELSKS 74
Cdd:cd16105   1 LTVLYpNGRRQTVKVTPNTPLSQVLEEACKKFGLDPSS-EYSLKHNRKPLDLSLPFRLSNLPNNAKLELVKS 71

TUG ubiquitin-like domain; TUG is a GLUT4 regulating protein and functions to retain membrane vesicles containing GLUT4 intracellularly. TUG releases the GLUT4 containing vesicles to the cellular exocytic machinery in response to insulin stimulation which allows translocation to the plasma membrane. TUG has an N-terminal ubiquitin-like domain (UBL1) which in similar proteins appears to participate in protein-protein interactions. The region does have a area of negative electrostatic potential and increased backbone motility which leads to suggestions of a potential protein-protein interaction site. This domain is also found at the N-terminus of yeast UBX4.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6323712      6 VKYNFQLFKCKVSLNSTLNDVLHQSIQFFQLhTSSNDWSLIHLDKPVPLDLPWRLLNLPTGVNLEL 71
Cdd:pfam11470   1 VTYNFRRKKVKVTPNTTLNDVLEEACKKFKL-DDSDSYTLKHNNKPLDLSLPFRLSNLPNGAKLEL 65

Ubiquitin regulatory domain X (UBX) 2 found in UBX domain protein 9 (UBXN9, UBXD9, or ASPSCR1) and similar proteins; UBXN9, also termed tether containing UBX domain for GLUT4 (TUG), or alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1), or alveolar soft part sarcoma locus (ASPL), or renal papillary cell carcinoma protein 17 (RCC17), belongs to the UBXD family of proteins that contains two ubiquitin regulatory domains X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, UBXN9 contains an N-terminal ubiquitin-like (Ubl) domain. UBXN9 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. However, high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers; the extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers.UBXN9 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4, assembly of the Golgi apparatus. In addition to GLUT4, UBXN9 also controls vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. UBXN9 and its budding yeast ortholog, Ubx4p, are multifunctional proteins that share some, but not all functions. Yeast Ubx4p is important for endoplasmic reticulum-associated protein degradation (ERAD) but UBXN9 appears not to share this function.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 6323712  278 CLLRVKFPDRSHIQIAFKPNEDMRTVYNVVSQFLIDENMPFTLNQSHPFKPL 329
Cdd:cd16118   1 AVIRVQFPDRLVLQAFFRPLETVRALYDFVKSHLADPDLPFYLYTTPPKRVL 52

Ubiquitin-like (Ubl) domain found at the N-terminus of mammalian ASPSCR1 (alveolar soft part sarcoma chromosomal region candidate gene 1 protein), Saccharomyces cerevisie Ubx4p, and similar proteins; ASPSCR1 (alveolar soft part sarcoma chromosomal region candidate gene 1 protein) is also known as alveolar soft part sarcoma locus protein (ASPL), tether containing UBX domain for GLUT4, TUG, UBX domain protein 9, UBXD9, UBXN9 or renal papillary cell carcinoma protein 17 (RCC17). The majority of members of this family contain two beta-grasp ubiquitin-like fold domains: the N-terminal UBL domain (described in this CD), and a C-terminal UBX domain. This UBL domain lacks the characteristic C-terminal double glycine motif. ASPSCR1 functions as a cofactor of the hexameric AAA (ATPase associated with various activities) ATPase complex, known as p97 or VCP in mammals and Cdc48p in yeast. In mammalian cells, ASPSCR1 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4 and assembly of the Golgi apparatus; ASPSCR1 also plays a role in controlling vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. Ubx4p and ASPSCR1 have only partially overlapping functions: both interact with p97/Cdc48p; however, Ubx4p is important for the ERAD (endoplasmic reticulum-associated protein degradation) pathway while ASPSCR1 appears not to be.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6323712    4 VTVKY-NFQLFKCKVSLNSTLNDVLHQSIQFFQLHTSSnDWSLIHLDKPVPLDLPWRLLNLPTGVNLELSKS 74
Cdd:cd16105   1 LTVLYpNGRRQTVKVTPNTPLSQVLEEACKKFGLDPSS-EYSLKHNRKPLDLSLPFRLSNLPNNAKLELVKS 71

TUG ubiquitin-like domain; TUG is a GLUT4 regulating protein and functions to retain membrane vesicles containing GLUT4 intracellularly. TUG releases the GLUT4 containing vesicles to the cellular exocytic machinery in response to insulin stimulation which allows translocation to the plasma membrane. TUG has an N-terminal ubiquitin-like domain (UBL1) which in similar proteins appears to participate in protein-protein interactions. The region does have a area of negative electrostatic potential and increased backbone motility which leads to suggestions of a potential protein-protein interaction site. This domain is also found at the N-terminus of yeast UBX4.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6323712      6 VKYNFQLFKCKVSLNSTLNDVLHQSIQFFQLhTSSNDWSLIHLDKPVPLDLPWRLLNLPTGVNLEL 71
Cdd:pfam11470   1 VTYNFRRKKVKVTPNTTLNDVLEEACKKFKL-DDSDSYTLKHNNKPLDLSLPFRLSNLPNGAKLEL 65

Ubiquitin regulatory domain X (UBX) 2 found in UBX domain protein 9 (UBXN9, UBXD9, or ASPSCR1) and similar proteins; UBXN9, also termed tether containing UBX domain for GLUT4 (TUG), or alveolar soft part sarcoma chromosomal region candidate gene 1 protein (ASPSCR1), or alveolar soft part sarcoma locus (ASPL), or renal papillary cell carcinoma protein 17 (RCC17), belongs to the UBXD family of proteins that contains two ubiquitin regulatory domains X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, UBXN9 contains an N-terminal ubiquitin-like (Ubl) domain. UBXN9 functions as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. However, high-affinity interacting protein ASPL efficiently promotes p97 hexamer disassembly, resulting in the formation of stable p97:ASPL heterotetramers; the extended UBX domain (eUBX) in ASPL is critical for p97 hexamer disassembly and facilitates the assembly of p97:ASPL heterotetramers.UBXN9 is involved in insulin-stimulated redistribution of the glucose transporter GLUT4, assembly of the Golgi apparatus. In addition to GLUT4, UBXN9 also controls vesicle translocation by interacting with insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. UBXN9 and its budding yeast ortholog, Ubx4p, are multifunctional proteins that share some, but not all functions. Yeast Ubx4p is important for endoplasmic reticulum-associated protein degradation (ERAD) but UBXN9 appears not to share this function.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 6323712  278 CLLRVKFPDRSHIQIAFKPNEDMRTVYNVVSQFLIDENMPFTLNQSHPFKPL 329
Cdd:cd16118   1 AVIRVQFPDRLVLQAFFRPLETVRALYDFVKSHLADPDLPFYLYTTPPKRVL 52

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 6 (UBXN6) and similar proteins; UBXN6, also termed UBX domain-containing protein 1 (UBXD1), and UBXDC2, belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like fold, but without the C-terminal double glycine motif. UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. UBXN6 acts as a cofactor of p97 (also known as VCP or Cdc48), which is a homohexameric AAA ATPase (ATPase associated with a variety of activities) involved in a variety of functions ranging from cell-cycle regulation to membrane fusion and protein degradation. Unlike other p97 cofactors that binds the N-domain of p97 through their UBX domain, UBXN6 binds p97 in two regions, at the p97 C terminus via a PUB domain and at the p97 N-domain with a short linear interaction motif termed VIM. Its UBX domain is not functional for the binding of p97. The UBXN6-p97 complex regulates the endolysosomal sorting of ubiquitylated plasma membrane protein caveolin-1 (CAV1), as well as the trafficking of ERGIC-53-containing vesicles by controlling the interaction of transport factors with the cytoplasmic tail of ERGIC-53. In addition, UBXN6 is a regulatory component of endoplasmic reticulum-associated degradation (ERAD) that may modulate the adaptor binding to p97.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 6323712  278 CLLRVKFPDRSHIQIAFKPNEDMRTVYNVVSQFLIDENMPFTLNQSHPFKPL 329
Cdd:cd16119   2 TLIRVRFPDGVILQGTFYAREKLSAVREFVREALANDWLPFELVTPGGQKLT 53