Ubiquitin regulatory domain X (UBX) found in FAS associated factor 1 (FAF1, also known as UBXN3A) and similar proteins; UBX domain-containing protein 3A (UBXN3A),also termed UBX domain-containing protein 12 (UBXD12), or FAF1, 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. In addition, FAF1 contains two tandem ubiquitin-like (Ubl) domains, which shows high structural similarity with UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to UBX domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 554 TESVSKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEEFKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLEAK 633
Cdd:cd01771     1 TEPISKLRFRLPGGEFLTRRFLASEPLQVLLNFVASKGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQETLFLEER 80

ubiquitin-like (Ubl) domain 1 found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin (Ub) regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) fold, but without the C-terminal double glycine motif. The UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, FAF1 contains two tandem Ubl domains, which show high structural similarity with the UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. The family corresponds to the first Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1935115458  85 MLDFRVEYRDRNVDVVLEDSCTVGEIKHILENELQIPVSKMLLKGWKTGDLDDSTVLKTLHLPKNNSLYVLTP 157
Cdd:cd17129     1 MLTFNVEYRDRTIDVVLPDTETVGDIKQILENELGIPPCKQILKGWKARTVSDSTVLRSLHLPKENSLYLLTP 73

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 1 (FAF1, also known as UBXN3A) and similar proteins; UBX domain-containing protein 3A (UBXN3A),also termed UBX domain-containing protein 12 (UBXD12), or FAF1, 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. In addition, FAF1 contains two tandem ubiquitin-like (Ubl) domains, which shows high structural similarity with UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to UBX domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 554 TESVSKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEEFKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLEAK 633
Cdd:cd01771     1 TEPISKLRFRLPGGEFLTRRFLASEPLQVLLNFVASKGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQETLFLEER 80

ubiquitin-like (Ubl) domain 1 found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin (Ub) regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) fold, but without the C-terminal double glycine motif. The UBX domain is typically located at the carboxyl terminus of proteins, and participates broadly in the regulation of protein degradation. In addition, FAF1 contains two tandem Ubl domains, which show high structural similarity with the UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. The family corresponds to the first Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1935115458  85 MLDFRVEYRDRNVDVVLEDSCTVGEIKHILENELQIPVSKMLLKGWKTGDLDDSTVLKTLHLPKNNSLYVLTP 157
Cdd:cd17129     1 MLTFNVEYRDRTIDVVLPDTETVGDIKQILENELGIPPCKQILKGWKARTVSDSTVLRSLHLPKENSLYLLTP 73

UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1935115458 555 ESVSKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEE-FKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLE 631
Cdd:pfam00789   2 EDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDLEpFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTLVLE 79

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 474 QQQEDIKDEDEREARENVKrEQDEAYRISLEADRAKREAQEREQAEQFRLEQirkeqEEEREAIRLSLEQSLPPEPKKES 553
Cdd:pfam09731 301 KKLAELKKREEKHIERALE-KQKEELDKLAEELSARLEEVRAADEAQLRLEF-----EREREEIRESYEEKLRTELERQA 374

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1935115458 554 TESVSKLR--IRTPSGEfFERRFLASSKLQV 582
Cdd:pfam09731 375 EAHEEHLKdvLVEQEIE-LQREFLQDIKEKV 404

Archaeal/vacuolar-type H+-ATPase subunit H [Energy production and conversion]; Archaeal/vacuolar-type H+-ATPase subunit H is part of the Pathway/BioSystem: A/V-type ATP synthase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1935115458 461 MMRLMAAMEIFSAQQQ-EDIKDEDEREARENVKREQDEAYRIsleADRAKREAQEREQAeqfRLEQIRKEQEEEREAIR 538
Cdd:COG2811     1 MDRPEVLKEIKEAEEEaDEIIEEAKEEREERIAEAREEAEEI---IEQAEEEAEEEAQE---RLEEAREEAEAEAEEII 73

polyubiquitin binding domain of NEMO and related proteins; NEMO (NF-kappaB essential modulator) is a regulatory subunit of the kinase complex IKK, which is involved in the activation of NF-kappaB via phosporylation of inhibitory IkappaBs. This mechanism requires the binding of NEMO to ubiquinated substrates. Binding is achieved via the UBAN motif (ubiquitin binding in ABIN and NEMO), which is described in this model. This region of NEMO has also been named CoZi (for coiled-coil 2 and leucine zipper). ABINs (A20-binding inhibitors of NF-kappaB) are sensors for ubiquitin that are involved in regulation of apoptosis, ABIN-1 is presumed to inhibit signalling via the NF-kappaB route. The UBAN motif is also found in optineurin, the product of a gene associated with glaucoma, which has been characterized as a negative regulator of NF-kappaB as well.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 457 VDELMMRLMAAMEIFSAQQQ--EDIKDEDE--REARENVK--REQDEAYRISLEADRAKRE--AQEREQ-AEQfrLEQIR 527
Cdd:cd09803     3 IDELAARLQEAEEALALKQEdiDELKEEIAqqEADLETIPvlKAQAEIYKSDFEAERAAREklHQEKEQlAEQ--LEYLQ 80

                  ....*
gi 1935115458 528 KEQEE 532
Cdd:cd09803    81 RENQE 85

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 1 (FAF1, also known as UBXN3A) and similar proteins; UBX domain-containing protein 3A (UBXN3A),also termed UBX domain-containing protein 12 (UBXD12), or FAF1, 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. In addition, FAF1 contains two tandem ubiquitin-like (Ubl) domains, which shows high structural similarity with UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to UBX domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 554 TESVSKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEEFKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLEAK 633
Cdd:cd01771     1 TEPISKLRFRLPGGEFLTRRFLASEPLQVLLNFVASKGYPPDEYKLLTTFPRRDLTQLDPSKTLEELKLFPQETLFLEER 80

ubiquitin-like (Ubl) domain found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) 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, FAF1 contains two tandem Ubl domains, which show high structural similarity with UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to Ubl domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1935115458 179 MLIITHRevQREYNLNFSGSSTIQEVKRNVYDLTSIPVRHQLWEGWPPSATDDSMTIaASGLTYPCHRLTVGRR 252
Cdd:cd17056     1 DFRVEYR--DRNVDVVLEDTCTVGEIKQILENELQIPVSKMLLKGWKTGDVEDSTVL-KSLHLPKNNSLYVLTP 71

UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting domain. FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 337 FIGSLEAAFQEAFYGKardrKLLAIYLHHDESVLTNVFCSQMLCAESIVSYLSQNFITWAWDMTKEaNRARFLTMCtrhf 416
Cdd:cd02958     2 FQGSFEDAKQEAKSEK----KWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIFWQCDIDSS-EGQRFLQSY---- 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1935115458 417 gsvvaqtirtqKTDQFPLFLIIMGKrsSNEVLNVIQGNTTVDELMMRLMAAMEIF 471
Cdd:cd02958    73 -----------KVDKYPHIAIIDPR--TGEVLKVWSGNITPEDLLSQLIEFLEEF 114

UBX domain; This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1935115458 555 ESVSKLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEE-FKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLE 631
Cdd:pfam00789   2 EDVTRLQIRLPDGSRLVRRFNSSDKLQTVYDFVDSNRYDDLEpFSLNTPFPRRPLTDLDYSKTLKEAGLLPNSTLVLE 79

Ubiquitin regulatory domain X (UBX) structurally similar to a beta-grasp ubiquitin-like fold; The UBXD family of proteins 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. Members in this family function as cofactors 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. Based on domain composition, UBXD proteins can be divided into two main groups, with and without ubiquitin-associated (UBA) domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1935115458 559 KLRIRTPSGEFFERRFLASSKLQVVFDFVASK-GYPWEEFKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFLE 631
Cdd:cd01767     1 RIQIRLPDGSRIQRRFSKSDTLQDLYDFVESNlGDSPSSFSLVTSFPRRVLTDEDSDKTLEELGLTPNAVLFVE 74

Ubiquitin regulatory domain X (UBX) found in FAS associated factor 2 (FAF2, also known as UBXN3B) and similar proteins; UBX domain-containing protein 3B (UBXN3B), also termed protein ETEA, or FAF2, or UBX domain-containing protein 8 (UBXD8), 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. FAF2 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. The p97-UBXD8 complex destabilizes mRNA by promoting release of ubiquitinated the RNA-binding protein HuR from messenger ribonucleoprotein (mRNP). Moreover, FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. A yeast two-hybrid assay showed that FAF2 can interact with Fas.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1935115458 559 KLRIRTPSGEFFERRFLASSKLQVVFDFVASKGYPWEEFKLLGTFPRRDVT-----QLDPNKSLLEVKLYPQETLF 629
Cdd:cd16120     2 KILFKLPNGTRLERRFLKSDSLKVLYDFVFSHEDSPDKFQLVTNFPRRVLPcqpteEQPNPPTLEEAGLGKSEVLF 77

Ubiquitin regulatory domain X (UBX) found in UBX domain protein 4 (UBXN4) and similar proteins; UBXN4, also termed ERAD (endoplasmic-reticulum-associated protein degradation) substrate erasing protein (erasin), or UBX domain-containing protein 2 (UBXD2), or UBXDC1, 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. UBXN4 is an endoplasmic reticulum (ER) localized protein that interacts with p97 (also known as VCP or Cdc48) via its UBX domain. Erasin exists in a complex with other p97/VCP-associated factors involved in endoplasmic-reticulum-associated protein degradation (ERAD). p97 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. The overexpression of UBXN4 increases degradation of a classical ERAD substrate and UBXN4 levels are increased in ER stressed cells. Anti-UBXN4 staining is increased in neuropathological lesions in brains of patients with Alzheimer's disease.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1935115458 557 VSKLRIRTPSGEFFERRFLASSKLQVVFDFVASK-GYPWEEFKLLGTFPRRDVTQLDPNKSLLEVKLYPQETLFL 630
Cdd:cd16117     1 TARIQFRLPDGSSFTNQFPSDAPLEEARQFVAQTvGPAYGPFSLATTFPRREFTDDDYQKTLLELELAPSAALVV 75

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 474 QQQEDIKDEDEREARENVKrEQDEAYRISLEADRAKREAQEREQAEQFRLEQirkeqEEEREAIRLSLEQSLPPEPKKES 553
Cdd:pfam09731 301 KKLAELKKREEKHIERALE-KQKEELDKLAEELSARLEEVRAADEAQLRLEF-----EREREEIRESYEEKLRTELERQA 374

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1935115458 554 TESVSKLR--IRTPSGEfFERRFLASSKLQV 582
Cdd:pfam09731 375 EAHEEHLKdvLVEQEIE-LQREFLQDIKEKV 404

Chromatin assembly factor 1 complex p150 subunit, N-terminal; CAF-1_p150 is a polypeptide subunit of CAF-1, which functions in depositing newly synthesized and acetylated histones H3/H4 into chromatin during DNA replication and repair. CAF-1_p150 includes the HP1 interaction site, the PEST, KER and ED interacting sites. CAF-1_p150 interacts directly with newly synthesized and acetylated histones through the acidic KER and ED domains. The PEST domain is associated with proteins that undergo rapid proteolysis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 476 QEDIKDEDEReARENVKREQDEAYRISLEADRAKREAQEREQAEQFRL-EQIRKEQEEEREAirlSLEQSLPPEPKKEST 554
Cdd:pfam11600  42 KEEAKAEKER-AKEEARRKKEEEKELKEKERREKKEKDEKEKAEKLRLkEEKRKEKQEALEA---KLEEKRKKEEEKRLK 117

                          90       100
                  ....*....|....*....|....*....
gi 1935115458 555 EsvSKLRIRTPSGEFfeRRFLASSKLQVV 583
Cdd:pfam11600 118 E--EEKRIKAEKAEI--TRFLQKPKTQQA 142

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 445 NEVLNVIQGNTTVDELMMRlmaamEIFSAQQQEDIKDEDEREARENVKREQ-------------------DEAYRISLEA 505
Cdd:pfam17380 272 NQLLHIVQHQKAVSERQQQ-----EKFEKMEQERLRQEKEEKAREVERRRKleeaekarqaemdrqaaiyAEQERMAMER 346

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1935115458 506 ----DRAKREAQEREQaEQFRLEQIRKEQEEEREAIRLSLEQSLPPEPKKESTESVSKLRI 562
Cdd:pfam17380 347 erelERIRQEERKREL-ERIRQEEIAMEISRMRELERLQMERQQKNERVRQELEAARKVKI 406

Archaeal/vacuolar-type H+-ATPase subunit H [Energy production and conversion]; Archaeal/vacuolar-type H+-ATPase subunit H is part of the Pathway/BioSystem: A/V-type ATP synthase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1935115458 461 MMRLMAAMEIFSAQQQ-EDIKDEDEREARENVKREQDEAYRIsleADRAKREAQEREQAeqfRLEQIRKEQEEEREAIR 538
Cdd:COG2811     1 MDRPEVLKEIKEAEEEaDEIIEEAKEEREERIAEAREEAEEI---IEQAEEEAEEEAQE---RLEEAREEAEAEAEEII 73

DDRGK domain; This is a family of proteins of approximately 300 residues, found in plants and vertebrates. They contain a highly conserved DDRGK motif.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1935115458 466 AAMEIFSAQQQEDIKDEDEREARENVKREQDEAYRISLEADRAKREAQEREQAEQfRLEQIRKEQEE 532
Cdd:pfam09756   9 AKLELKEAKRQQREAEEEEREEREKLEEKREEEYKEREEREEEAEKEKEEEERKQ-EEEQERKEQEE 74

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458  473 AQQQEDIKDEDEREAR--ENVKREQDEAyriSLEADRAKREAQEreqaEQFRLEQIRKEQEEEREAIRLSLEQSLPPEPK 550
Cdd:PTZ00121  1701 AKKAEELKKKEAEEKKkaEELKKAEEEN---KIKAEEAKKEAEE----DKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEI 1773

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1935115458  551 KESTESVSKLRIRTpsgEFFERRFLASSKLQVVFD 585
Cdd:PTZ00121  1774 RKEKEAVIEEELDE---EDEKRRMEVDKKIKDIFD 1805

MAEBL; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458  459 ELMMRLMAAMEIFSAQQQEdiKDEDEREARENVKREQDEAYRISleaDRAKREAQEREQAEQFRLEQ----------IRK 528
Cdd:PTZ00121  1595 EEVMKLYEEEKKMKAEEAK--KAEEAKIKAEELKKAEEEKKKVE---QLKKKEAEEKKKAEELKKAEeenkikaaeeAKK 1669

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1935115458  529 EQEEEREAIRLSLEQslppEPKKESTESVSK 559
Cdd:PTZ00121  1670 AEEDKKKAEEAKKAE----EDEKKAAEALKK 1696

Arginine and glutamate-rich 1; ARGLU, arginine and glutamate-rich 1 protein family, is required for the oestrogen-dependent expression of ESR1 target genes. It functions in cooperation with MED1. The family of proteins is found in eukaryotes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 459 ELMMRLMAAMEIFSAQQQEDIKDEDEREARENVKRE------QDEAYRISLEADRAKREAQEREQAEQFR-LEQIRKEQE 531
Cdd:pfam15346  38 EVERRVEEARKIMEKQVLEELEREREAELEEERRKEeeerkkREELERILEENNRKIEEAQRKEAEERLAmLEEQRRMKE 117

                          90
                  ....*....|..
gi 1935115458 532 EEREAIRLSLEQ 543
Cdd:pfam15346 118 ERQRREKEEEER 129

Vacuolar (H+)-ATPase G subunit; This family represents vacuolar (H+)-ATPase G subunit from several bacterial and archaeal species. Subunit G is a component of the peripheral stalk of the ATPase complex

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1935115458 473 AQQQEdikdEDEREARENVKREQDEAYRISLEAD-RAKREAQEREQAEQFRLEQIRKE----QEEEREAIRLSLEQSL 545
Cdd:pfam16999  18 DQQIE----AARKEAEREVEAAEAEAARILREAEaKAKALQAEYRQELAAETARIREEararAEAEAQAVRTRAEGRL 91

cell envelope integrity inner membrane protein TolA; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 452 QGNTTVDELMMRLMAAMEIFSAQQQEDIKDEDEREARENVKREQDEAYRISLEAD--RAKREAQEREQAeqfrlEQIRKE 529
Cdd:PRK09510   45 GGGSVIDAVMVDPGAVVEQYNRQQQQQKSAKRAEEQRKKKEQQQAEELQQKQAAEqeRLKQLEKERLAA-----QEQKKQ 119

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1935115458 530 QEEEReaiRLSLEQSLPPEPKKESTESVSKLR 561
Cdd:PRK09510  120 AEEAA---KQAALKQKQAEEAAAKAAAAAKAK 148

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1935115458 560 LRIRTPSGEFFERRFLASSKLQVVFDFV----ASKGYPweeFKLLGTFPRRDVTqlDPNKSLLEVKLYP 624
Cdd:cd16118     3 IRVQFPDRLVLQAFFRPLETVRALYDFVkshlADPDLP---FYLYTTPPKRVLK--DKNKTLYQAGLVP 66

ATP synthase, F0 subunit b; This model describes the F1/F0 ATP synthase b subunit in bacteria only. Scoring just below the trusted cutoff are the N-terminal domains of Mycobacterial b/delta fusion proteins and a subunit from an archaeon, Methanosarcina barkeri, in which the ATP synthase homolog differs in architecture and is not experimentally confirmed. This model helps resolve b from the related b' subunit. Within the family is an example from a sodium-translocating rather than proton-translocating ATP synthase. [Energy metabolism, ATP-proton motive force interconversion]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 464 LMAAMEifsaQQQEDIkdEDEREARENVKREQDEAY-RISLEADRAKREAQER-EQAEQFR---LEQIRKEQEEEREAIR 538
Cdd:TIGR01144  20 LAKAIE----TRQKKI--ADGLASAERAKKEAALAQkKAQVILKEAKDEAQEIiENANKRGseiLEEAKAEAREEREKIK 93

                          90       100
                  ....*....|....*....|...
gi 1935115458 539 LSLEQslppEPKKESTESVSKLR 561
Cdd:TIGR01144  94 AQARA----EIEAEKEQAREELR 112

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1935115458 462 MRLMAAMEifsAQQQEDIKDEDEREARENVKREQdeaYRISLEADRAKREAQEREQAEQFRLE------QIRKEQEEERE 535
Cdd:pfam13868  43 RRLDEMME---EERERALEEEEEKEEERKEERKR---YRQELEEQIEEREQKRQEEYEEKLQEreqmdeIVERIQEEDQA 116

                  ....*...
gi 1935115458 536 AIRLSLEQ 543
Cdd:pfam13868 117 EAEEKLEK 124

Uncharacterized membrane protein YqiK, contains Band7/PHB/SPFH domain [Function unknown];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1935115458 473 AQQQEDIK----DEDEREARENVKREQDEAYRISLEADRAKREAQEREQAEQFRLEQIR--KEQEEERE-AIRLSLEQS 544
Cdd:COG2268   208 AERETEIAiaqaNREAEEAELEQEREIETARIAEAEAELAKKKAEERREAETARAEAEAayEIAEANAErEVQRQLEIA 286

ubiquitin-like (Ubl) domain found in Arabidopsis thaliana NPL4-like proteins NPL4-1, NPL4-2, and similar proteins; The family includes a group of uncharacterized plant ubiquitin-like (Ubl) domain-containing proteins, including Arabidopsis thaliana NPL4-like protein 1 and NPL4-like protein 2.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1935115458  89 RVEYRDRNVDVVLEDSCTVGEIKHILENELQIPVSKMLLK 128
Cdd:cd17055     4 RVRSRDGTERVEVPDDATVGDLKEKIAEQLSVPVSDQTLS 43

ubiquitin-like (Ubl) domain found in FAS-associated factor 1 (FAF1) and similar proteins; FAF1, also termed UBX domain-containing protein 12 (UBXD12), or UBX domain-containing protein 3A (UBXN3A), belongs to the UBXD family of proteins that contains the ubiquitin regulatory domain X (UBX) with a beta-grasp ubiquitin-like (Ubl) 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, FAF1 contains two tandem Ubl domains, which show high structural similarity with UBX domain. FAF1 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. The FAF1-p97 complex inhibits the proteasomal protein degradation in which p97 acts as a co-chaperone. Moreover, FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF1 is widely expressed in adult and embryonic tissues, and in tumor cell lines, and is localized not only in the cytoplasm where it interacts with Fas, but also in the nucleus. FAF1 contains phosphorylation sites for protein kinase CK2 within the nuclear targeting domain. Phosphorylation influences nuclear localization of FAF1 but does not affect its potentiation of Fas-induced apoptosis. Other functions have also been attributed to FAF1. It inhibits nuclear factor-kappaB (NF-kappaB) by interfering with the nuclear translocation of the p65 subunit. Although the precise role of FAF1 in the ubiquitination pathway remains unclear, FAF1 interacts with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. This family corresponds to Ubl domains.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1935115458  90 VEYRDRNVDVVLEDSCTVGEIKHILENELQIPVSKMLLKGWKTGDLDDSTVLKT 143
Cdd:cd17056     4 VEYRDRNVDVVLEDTCTVGEIKQILENELQIPVSKMLLKGWKTGDVEDSTVLKS 57