Ribosomal protein S27a; This family of ribosomal proteins consists mainly of the 40S ribosomal protein S27a which is synthesized as a C-terminal extension of ubiquitin (CEP). The S27a domain compromises the C-terminal half of the protein. The synthesis of ribosomal proteins as extensions of ubiquitin promotes their incorporation into nascent ribosomes by a transient metabolic stabilization and is required for efficient ribosome biogenesis. The ribosomal extension protein S27a contains a basic region that is proposed to form a zinc finger; its fusion gene is proposed as a mechanism to maintain a fixed ratio between ubiquitin necessary for degrading proteins and ribosomes a source of proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 13195690   103 LKYYKVDENGKISRLRRECPSdeCGAGVFMGSHFDRHYCGKCCLT 147
Cdd:pfam01599   1 LKYYKVDDDGKVERLRKECPR--CGAGVFMAEHKDRHYCGKCGLT 43

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRG 75
Cdd:COG5272   1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRTLG 75

Ubiquitin family; This family contains a number of ubiquitin-like proteins: SUMO (smt3 homolog), Nedd8, Elongin B, Rub1, and Parkin. A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13195690     3 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLR 74
Cdd:pfam00240   1 ITVKTLDGKKITLEVDPTDTVLELKEKIAEKEGVPPEQQRLIYSGKVLEDDQTLGEYGIEDGSTIHLVLRQR 72

Ribosomal protein S27a; This family of ribosomal proteins consists mainly of the 40S ribosomal protein S27a which is synthesized as a C-terminal extension of ubiquitin (CEP). The S27a domain compromises the C-terminal half of the protein. The synthesis of ribosomal proteins as extensions of ubiquitin promotes their incorporation into nascent ribosomes by a transient metabolic stabilization and is required for efficient ribosome biogenesis. The ribosomal extension protein S27a contains a basic region that is proposed to form a zinc finger; its fusion gene is proposed as a mechanism to maintain a fixed ratio between ubiquitin necessary for degrading proteins and ribosomes a source of proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 13195690   103 LKYYKVDENGKISRLRRECPSdeCGAGVFMGSHFDRHYCGKCCLT 147
Cdd:pfam01599   1 LKYYKVDDDGKVERLRKECPR--CGAGVFMAEHKDRHYCGKCGLT 43

Ribosomal protein S27AE [Translation, ribosomal structure and biogenesis]; Ribosomal protein S27AE is part of the Pathway/BioSystem: Archaeal ribosomal proteins

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 13195690 101 AVLKYYKVdENGKISRLRRECPsdECGAGVFMGSHFDRHYCGKCCLT 147
Cdd:COG1998   8 AVHEYYKV-EDGKIKRKRKFCP--RCGSGVFMAEHKDRWHCGKCGYT 51

Ubiquitin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRG 75
Cdd:COG5272   1 MQIFVKTLTGKTITLEVEPNDTIEAVKAKIQDKEGIPPDQQRLIFAGKQLEDDRTLADYNIQKESTLHLVTRTLG 75

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13195690   3 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 76
Cdd:cd01806   1 IKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIFSGKQMNDEKTAADYKIEGGSVLHLVLALRGG 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13195690   3 IFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLV 70
Cdd:cd17039   1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLIYNGKELKDDKTLSDYGIKDGSTIHLV 68

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLR 74
Cdd:cd01802   1 MELFIETLTGTAFELRVSPFETVASVKAKIQRLEGIPVSQQHLIWSGRELEDDYCLHDYNITDGSTLKLVLAMR 74

Ribosomal protein S27a; This family of ribosomal proteins consists mainly of the 40S ribosomal protein S27a which is synthesized as a C-terminal extension of ubiquitin (CEP). The S27a domain compromises the C-terminal half of the protein. The synthesis of ribosomal proteins as extensions of ubiquitin promotes their incorporation into nascent ribosomes by a transient metabolic stabilization and is required for efficient ribosome biogenesis. The ribosomal extension protein S27a contains a basic region that is proposed to form a zinc finger; its fusion gene is proposed as a mechanism to maintain a fixed ratio between ubiquitin necessary for degrading proteins and ribosomes a source of proteins.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 13195690   103 LKYYKVDENGKISRLRRECPSdeCGAGVFMGSHFDRHYCGKCCLT 147
Cdd:pfam01599   1 LKYYKVDDDGKVERLRKECPR--CGAGVFMAEHKDRHYCGKCGLT 43

ubiquitin-like (Ubl) domain 2 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 second Ubl domain of FAT10. Some family members contain only one Ubl domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDG-RTLSDYNIQKESTLHLV 70
Cdd:cd17053   1 LTVNSKLLTGTVHTLQVSRSTTVAQVKAMIEDQSGVPPNEQILVYNGKRLEDGdKTLGEYGIKTGDTLYLL 71

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 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 72
Cdd:cd01807   1 MLITVKILQGKECTIEVSPTESVLTVKQLVAEQLNVPVSQQRLVFKGKTLADEHSLSDYSIGPGSKIHLVVK 72

ubiquitin-like (Ubl) domain found in ubiquitin-like protein FUBI and similar proteins; FUBI is a pro-apoptotic regulatory gene FAU encoding ubiquitin-like protein with ribosomal protein S30 as a C-terminal extension. FUBI functions as a tumor suppressor protein that may be involved in the ATP-dependent proteolytic activity of ubiquitin. The N-terminal ubiquitin-like (Ubl) domain of FUBI has the beta-grasp Ubl fold, and it may act as a substitute or an inhibitor of ubiquitin or one of ubiquitin's close relatives UCRP, FAT10, and Nedd8.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 13195690   1 MQIFVKTltGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG 76
Cdd:cd01793   1 MQLFVRA--QSLHTLEVSGNETVADIKAHIAALEGIAVEDQVLLYAGAPLEDDVVLGQCGIPDLATLEVAVRLLGG 74

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 13195690     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQ-RLIFAGKQLEDGRTLSDYNIQKESTLHLVL 71
Cdd:pfam11976   1 IKIILKGKDGKEVFIKVKPTTTVSKLINAYRKKRGIPPSQQvRLIFDGERLDPNSTVEDLDIEDGDTIDVVI 72

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQkESTLHLVLR 72
Cdd:cd01809   1 LEVTVKTLDSQNRTFTVPEEITVKEFKEHIASSVNIPAEKQRLIFQGRVLQDDKKLKEYDVD-GKVIHLVER 71

ubiquitin-like (Ubl) domain 2 found in 2'-5'-oligoadenylate synthase-like protein (OASL) and similar proteins; OASL, also termed 2'-5'-OAS-related protein (2'-5'-OAS-RP), or 59 kDa 2'-5'-oligoadenylate synthase-like protein, or thyroid receptor-interacting protein 14, or TR-interacting protein 14 (TRIP-14), or p59 OASL (p59OASL), is an interferon (IFN)-induced antiviral protein that plays an important role in the IFNs-mediated antiviral signaling pathway. It inhibits respiratory syncytial virus replication and is targeted by the viral nonstructural protein 1 (NS1). It also displays antiviral activity against encephalomyocarditis virus (EMCV) and hepatitis C virus (HCV) via an alternative antiviral pathway independent of RNase L. Moreover, OASL does not have 2'-5'-OAS activity, but can bind double-stranded RNA (dsRNA) to enhance RIG-I signaling. OASL belongs to the 2'-5' oligoadenylate synthase (OAS) family. While each member of this family has a conserved N-terminal OAS catalytic domain, only OASL has two tandem C-terminal ubiquitin-like (Ubl) repeats, which are required for its antiviral activity. This family corresponds to the second Ubl domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13195690   2 QIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVL 71
Cdd:cd16103   3 QIFVKFPDGTSKPYAINPEDTILDLKEKIEEQGGPPVEDQILLFQGQELRDKKSLKYYGIKDGDTLQLSL 72

ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family; The eukaryotic Ddi1 family, including yeast aspartyl protease DNA-damage inducible 1 (Ddi1) and Ddi1-like proteins from vertebrates and other eukaryotes, has been characterized by containing an N-terminal ubiquitin-like (Ubl) domain and a conserved retroviral aspartyl-protease-like domain (RVP) that is important in cell-cycle control. Yeast Ddi1 and many family members also contain a C-terminal ubiquitin-association (UBA) domain, however, Ddi1-like proteins from all vertebrates lack the UBA domain. Ddi1, also termed v-SNARE-master 1 (Vsm1), is an ubiquitin receptor involved in the cell cycle and late secretory pathway in Saccharomyces cerevisiae. It functions as an UBA-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. This family also includes mammalian regulatory solute carrier protein family 1 member 1 (RSC1A1), also termed transporter regulator RS1 (RS1), which mediates transcriptional and post-transcriptional regulation of Na(+)-D-glucose cotransporter SGLT1. Ddi1-like proteins play a significant role in cell cycle control, growth control, and trafficking in yeast and may play a crucial role in embryogenesis in higher eukaryotes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13195690   1 MQIFVKTL-TGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQL-EDGRTLSDYNIQ 62
Cdd:cd01796   1 MKLTVTTEdDDRLFSLEVSPDMTLEDLKALCEAETGIPAAEQVLLHNGQPLtDDKKTLEALGLK 64

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13195690     1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEG---IPPDQQRLIFAGKQLEDGRTLSDYNI 61
Cdd:TIGR00601   1 MTLTFKTLQQQKFKIDMEPDETVKELKEKIEAEQGkdaYPVAQQKLIYSGKILSDDKTVKEYKI 64

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) through interacting with HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a set- and ring-associated (SRA) domain, and a C-terminal RING finger.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13195690   1 MQIFVKTLTG-KTITLEVEPSDT-IENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 72
Cdd:cd01797   1 MWIQVRTMDGkKEARVDGLSKLTkIEDLRERIEEKFDVEPELQRLFYRGKQLEDGHTLFDYDVGLNDIIQLMVR 74

ubiquitin-like (Ubl) domain found in splicing factor 3A 120kDa subunit (SF3a120) and similar proteins; Mammalian splicing factor SF3a consists of three subunits of 60, 66, and 120 kDa and functions early during pre-mRNA splicing by converting the U2 snRNP to its active form. The 120kDa subunit SF3a120, also termed splicing factor 3A subunit 1 (SF3A1), or spliceosome-associated protein 114 (SAP114), is the U2 snRNP-specific protein that is critical for spliceosome assembly and normal splicing events. During splicing, SF3a120, together with the U2 snRNP and other proteins, are recruited to the 3' splicing site to generate the splicing complex A after the recognition of the 3' splicing site. SF3a120 contains two N-terminal SWAP (suppressor-of-white-apricot) domains, referred to collectively as the SURP module, as well as a C-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13195690   8 LTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLifagkQLEDGRTLSD------YNIQKESTLHLVLR 72
Cdd:cd01800  19 LNGQVLELTLPLTDTISVLKEKIHEELGMPANKQKL-----QVEGGGFLKDsnslafYNLGSGTVLTLSLK 84

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 13195690   3 IFVKTLTGKTiTLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 72
Cdd:cd01808   5 VTVKTPKEKE-DFEVPEDSSVKEFKEEISKKFKAPVEQLVLIFAGKILKDQDTLSQHGIKDGLTVHLVIK 73

ubiquitin-like (Ubl) domain found in ubiquitin-like PHD and RING finger domain-containing protein 1(UHRF1); UHRF1, also termed inverted CCAAT box-binding protein of 90 kDa, or nuclear protein 95, or nuclear zinc finger protein Np95 (Np95), or RING finger protein 106, or transcription factor ICBP90, or E3 ubiquitin-protein ligase UHRF1, is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma, gastric cancer, esophageal squamous cell carcinoma, colorectal cancer, prostate cancer, and breast cancer. UHRF1 can acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21.Moreover, UHRF1-dependent repression of factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination ofTIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF1 contains an N-terminal ubiquitin-like domain (Ubl), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitination has an essential role in maintenance DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibits both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 13195690   1 MQIFVKTLTGK-TITLEVEPSDT-IENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLR 72
Cdd:cd17122   1 MWIQVRTMDGKeTHRIDSLSKLTkVEELRQKIQELFGVEPERQRLFYRGKQMEDGHTLFDYSVGLNDIVQLLVR 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQD---KEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKES 65
Cdd:cd17126   1 VTITLKTLQQQTFKIRMEPDETVKVLKEKIEAekgRDAFPVAGQKLIYAGKILSDDVPIRDYRIDEKN 68

ubiquitin-like (Ubl) domain found in UV excision repair protein RAD23 homolog B (HR23B); HR23B, also termed xeroderma pigmentosum group C (XPC) repair-complementing complex 58 kDa protein (p58), is tightly complexed with XPC protein to form the XPC-HR23B complex. Although it displays a high affinity for both single- and double-stranded DNA, the XPC-HR23B complex functions as a global genome repair (GGR)-specific repair factor that is specifically involved in global genome but not transcription-coupled nucleotide excision repair (NER). HR23B also interacts specifically with S5a subunit of the human 26S proteasome, and plays an important role in shuttling ubiquitinated cargo proteins to the proteasome. HR23B 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13195690   1 MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEG---IPPDQQRLIFAGKQLEDGRTLSDYNIQKES 65
Cdd:cd16126   1 MQITLKTLQQQTFKIDIDPEETVKALKEKIESEKGkdaFPVAGQKLIYAGKILNDDTALKEYKIDEKN 68

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13195690  11 KTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLI-FAGKQLEDGRTLSDYNIQKESTLHLV 70
Cdd:cd17129  11 RTIDVVLPDTETVGDIKQILENELGIPPCKQILKgWKARTVSDSTVLRSLHLPKENSLYLL 71

ubiquitin-like (Ubl) domain found in heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1) and similar proteins; HOIL-1, also termed RBCK1, or HOIL-1L, or RanBP-type and C3HC4-type zinc finger-containing protein 1, HBV-associated factor 4, or Hepatitis B virus X-associated protein 4, or RING finger protein 54 (RNF54), or ubiquitin-conjugating enzyme 7-interacting protein 3, or UbcM4-interacting protein 28 (UIP28), together with E3 ubiquitin-protein ligase RNF31 (also known as HOIP) and SHANK-associated RH domain interacting protein (SHARPIN), forms the E3-ligase complex (also known as linear-ubiquitin-chain assembly complex LUBAC) that regulates NF-kappaB activity and apoptosis through conjugation of linear polyubiquitin chains to NF-kappaB essential modulator (also known as NEMO or IKBKG). HOIL-1 plays a crucial role in TNF-alpha-mediated NF-kappaB activation. It also functions as an ubiquitin-protein ligase E3 that interacts with not only PKCbeta but also PKCzeta. It can recognize heme-oxidized IRP2 (iron regulatory protein2) and is thought to affect the turnover of oxidatively damaged proteins. HOIL-1 contains an N-terminal ubiqutin-like (UBL) domain and an Npl4 zinc-finger (NZF) domain, which regulate the interaction with the LUBAC subunit RNF31 and ubiquitin, respectively. The NZF domain belongs to RanBP2-type zinc finger (zf-RanBP2) domain superfamily. In addition, HOIL-1 has a 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.

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gi 13195690   1 MQIFV--KTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFaGKQL-EDGRTLSDYNIQKEST---LHLV 70
Cdd:cd01799   5 IKVYVedKSSSSGPITLKVRPHTTIASLKRQIFLEYGFPPSVQRWII-GKRLaTDDETLLSYGIKDSGDpafLYLV 79

30S ribosomal protein S27ae; Validated

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                 ....*....|....*....|....*....|....*....|....
gi 13195690  101 AVLKYYKVDeNGKISRLRRECPsdECGAGvFMGSHFDRHYCGKC 144
Cdd:PRK00432   4 AKREYYEVD-GGKVKRKNKFCP--RCGSG-FMAEHLDRWHCGKC 43

ubiquitin-like (Ubl) domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins; NUB1, also termed negative regulator of ubiquitin-like proteins 1, or 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 a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, three ubiquitin-associated domains (UBA), a bipartite nuclear localization signal (NLS) and a PEST motif.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13195690  13 ITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLhLVLRL 73
Cdd:cd17062  19 ITLETSLDITGSELREKIAEELGVPEDRIKLISNGKVLKDEKTLAEQGVKNNSQV-MVLVL 78

ubiquitin-like (Ubl) domain found in transcription elongation factor B (Elongin B) and similar proteins; Elongin B, also termed Elongin 18 kDa subunit, or EloB, or RNA polymerase II transcription factor SIII subunit B (SIII p18), is part of an E3 ubiquitin ligase complex called VEC that activates ubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5. VEC is composed of von Hippel-Lindau tumor suppressor protein (pVHL), elongin C, cullin 2, NEDD8, and Rbx1. ElonginB binds elonginC to form the elonginBC complex which is a positive regulator of RNA polymerase II elongation factor Elongin A. The BC complex then binds VHL (von Hippel-Lindau) tumor suppressor protein to form a VCB ternary complex. Elongin B has a ubiquitin-like (Ubl) domain. Ub has a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. Ub is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13195690  11 KTITLEVEPSDTIENVKAKIqdkEGI---PPDQQRLIFAGKQLEDGRTLSDYNI-------QKESTLHLVLRLRGGAKKR 80
Cdd:cd01788  11 TTIFTDAKESTTVFELKKII---EGIlkrPPEDQRLYKDDQLLDDTKTLGDCGFtsqtaraQAPATLGLAFRADGEFEPL 87

                ....*...
gi 13195690  81 KKKSYTTP 88
Cdd:cd01788  88 EITPLSSP 95

ubiquitin-like (Ubl) domain found in ubiquitin-like domain-containing CTD phosphatase 1 (UBLCP1) and similar proteins; UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity. It is localized in the nucleus and it contains conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which directly interacts with the proteasome. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. UBLCP1 may also play a role in the regulation of phosphorylation state of RNA polymerase II C-terminal domain, a key event during mRNA metabolism.

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                ....*....|....*....|....*....|....*....|....*....|....*.
gi 13195690  10 GKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLI---FAGKQLEDGRTLSDYNIQ 62
Cdd:cd01813   9 GKEYPVTVLSSDTVLDLKQRIFELTGVLPKRQKLLglkVKGKPADDDVKLSSLKLK 64

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 13195690  11 KTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGkQLEDGRTLSDYNIQKESTLHLV 70
Cdd:cd17047  10 EKYDVKFPLDSTIAELKEHIETLTGVPPAMQKLMYKG-LLKDDKTLRELKVTKGAKVMVV 68

ubiquitin-like (Ubl) domain found in BAG family molecular chaperone regulator 1 (BAG1) and similar proteins; BAG1, also termed Bcl-2-associated athanogene 1, or HAP, is a multifunctional protein involved in a variety of cellular functions such as apoptosis, transcription, and proliferative pathways, as well as in cell signaling and differentiation. It delivers chaperone-recognized unfolded substrates to the proteasome for degradation. BAG1 functions as a co-chaperone for Hsp70/Hsc70 to increase Hsp70 foldase activity. It also suppresses apoptosis and enhances neuronal differentiation. As an anti-apoptotic factor, BAG1 interacts with tau and regulates its proteasomal degradation. It also binds to BCR-ABL with a high affinity, and directly routes immature BCR-ABL for proteasomal degradation. It acts as a potential therapeutic target in Parkinson's disease. It also modulates huntingtin toxicity, aggregation, degradation, and subcellular distribution, suggesting a role in Huntington's disease. There are at least four isoforms of Bag1 protein that are formed by alternative initiation of translation within a common mRNA. BAG1 contains an N-terminal ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, and a C-terminal BAG domain.

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                ....*....|....*....|....*....|....*....|....*....|....*....
gi 13195690  13 ITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQL-EDGRTLSDYNIQKESTLHLV 70
Cdd:cd01812  16 LPSQDEDEPTLQDLAEAIEEVTGVPVENQKLIFKGKSLkDPEQPLSALGVKNGSKIMLI 74

ubiquitin-like (Ubl) domain found in trans-2,3-enoyl-CoA reductase (TECR) and similar proteins; This family includes TECR and many TECR-like proteins, such as TECRL. TECR, also termed very-long-chain enoyl-CoA reductase, or synaptic glycoprotein SC2, or TER, or GPSN2, is a synaptic glycoprotein that catalyzes the fourth reaction in the synthesis of very long-chain fatty acids (VLCFA) which is the reduction step of the microsomal fatty acyl-elongation process. Diseases involving perturbations to normal synthesis and degradation of VLCFA (e.g. adrenoleukodystrophy and Zellweger syndrome) have significant neurological consequences. The mammalian TECR P182L mutation causes nonsyndromic mental retardation. Deletion of the yeast TECR (TSC13) homolog is lethal. TECR contains 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 catalytic domain. TECRL, also termed steroid 5-alpha-reductase 2-like 2 protein (SRD5A2L2), is associated with life-threatening inherited arrhythmias displaying features of both long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). Both TECR and TECRL contain an N-terminal Ubl domain with a beta-grasp Ubl fold, and a C-terminal catalytic domain.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 13195690   2 QIFVKTLTGKT--ITLEVEPSDTIENVKAKI-QDKEGIPPDQQRL---IFAGKQLEDGRTLSDYNIQKESTL 67
Cdd:cd01801   1 KIEVVSRKGGKqiITLEVSSSATVADLKKAIhKKKKKLYPERQRLrleVPKGKVLKDDKTLSSYGVKDGSTL 72

ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinases, IKK-alpha and IKK-beta, and similar proteins; IKK, also termed IkappaB kinase, is an enzyme complex involved in propagating the cellular response to inflammation. It is part of the upstream nuclear factor kappa-B kinase (NF-kappaB) signal transduction cascade, and plays an important role in regulating the NF-kappaB transcription factor. IKK is composed of three subunits, IKK-alpha/CHUK, IKK-beta/IKBKB, and IKK-gamma/NEMO. The IKK-alpha and IKK-beta subunits together are catalytically active whereas the IKK-gamma subunit serves a regulatory function. IKK-alpha and IKK-beta phosphorylate the IkappaB proteins, marking them for degradation via ubiquitination and allowing NF-kappaB transcription factors to go into the nucleus. IKK-alpha, also known as IKK-A, or IkappaB kinase A (IkBKA), or conserved helix-loop-helix ubiquitous kinase (CHUK), or I-kappa-B kinase 1 (IKK1), or nuclear factor NF-kappa-B inhibitor kinase alpha (NFKBIKA), or transcription factor 16 (TCF-16), belongs to the serine/threonine protein kinase family. In addition to NF-kappaB response, it has many additional cellular targets in an NF-kappaB-independent manner. For instance, it plays a role in epidermal differentiation, as well as in the regulation of the cell cycle protein cyclin D1. IKK-beta, also known as IKK-B, or IkappaB kinase B (IkBKB), or I-kappa-B kinase 2 (IKK2), or nuclear factor NF-kappa-B inhibitor kinase beta (NFKBIKB), belongs to the serine/threonine protein kinase family as well. It interacts with many different protein partners and has been implicated in the treatment of many inflammatory diseases and cancers. Both IKK-alpha and IKK-beta contain an N-terminal catalytic domain followed by a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions.

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                ....*....|....*....|....*....|....*....|....*....|..
gi 13195690   9 TGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFA-GKQLEDGRTLSDY 59
Cdd:cd17046  10 TYRILSYEVTEDTSLSTLQSWIERDTGIPVEDQELLLPtGVSLDPEKPASQC 61

ubiquitin-like (Ubl) domain found in Sacsin and similar proteins; Sacsin, also termed DnaJ homolog subfamily C member 29 (DNAJC29), is encoded by SACS gene that is highly expressed in the brain. Mutations in SACS can cause the neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) which is characterized by early-onset spastic ataxia. Sacsin is a modular protein that is localized on the mitochondrial surface and possibaly required for normal mitochondrial network organization. Sacsin knockdown resulted in a reduction in cells expressing plyglutamine-expanded ataxin-1, which correlated with a loss of cells with large nuclear ataxin-1 incusions. At the N-terminus, sacsin contains a ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, which can interact with the proteasome. At the C-terminus, sacsin harbors a protein-protein interaction J-domain followed by an higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domain. The J-domain is typically associated with DnaJ-like co-chaperones involved in regulation of the Hsp70 heat shock system.

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                ....*....|....*....|....*....|....*....|
gi 13195690  14 TLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDG 53
Cdd:cd17049  16 TFEVPPSAAVRDIKELIYEETDFPVSEQQLWHNGKELSDW 55

ubiquitin-like (Ubl) domain found in ubiquitin-like protein 7 (UBL7) and similar proteins; UBL7, also termed bone marrow stromal cell ubiquitin-like (Ubl)protein (BMSC-UbP), or ubiquitin-like protein SB132, is a novel Ubl protein that may play roles in regulation of bone marrow stromal cell (BMSC) function or cell differentiation via an evocator-associated and cell-specific pattern. UBL7 contains an N-terminal Ubl domain with a beta-grasp Ubl fold, and a C-terminal ubiquitin-associated (UBA) domain. The Ubl domain interacts with 26S proteasome-dependent degradation, and the UBA domain links cellular processes and the ubiquitin system.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 13195690  38 PDQQRLIFAGKQLEDGRTLSDYNIQKESTLHlVLR 72
Cdd:cd01815  52 PELIDLIYCGRKLKDDQTLDFYGIQSGSTIH-VLR 85

ubiquitin-like (Ubl) domain found in retinoblastoma 1-inducible coiled-coil protein 1 (RB1CC1) and similar proteins; RB1CC1, also termed FAK family kinase-interacting protein of 200 kDa (FIP200), is the mammalian counterpart of the yeast Atg17 gene and functions as a component of the ULK1/Atg13/RB1CC1/Atg101 complex essential for induction of autophagy. RB1CC1 is a key signaling node to regulate cellular proliferation and differentiation. As a DNA-binding transcription factor, RB1CC1 has been implicated in the regulation of retinoblastoma 1 (RB1) expression. RB1CC1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, as well as a nuclear localization signal (KPRK), a leucine zipper motif and a coiled-coil structure.

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                ....*....|....*....|....*....|....*....|....*....|....
gi 13195690   9 TGKTITLEVE-PSDTIENVKAKIQDKEGIPPDQQRLIFAGKQ-LEDGRTLSDYN 60
Cdd:cd17060   9 TGTMLTFDMSlAVQSVSDLKEAIEEKTKIPVEKQVLLVSGGEsLDPDKRVSSYS 62