Functionally uncharacterized domain in neighbor of Brca1 Gene 1 and related proteins; NBR1 has been characterized as a specific late endosomal protein, which might play a role in receptor (RTK) trafficking. Specifically, NBR1 was shown to inhibit ligand-mediated receptor internalization from the cell surface. The region covered by this domain model may be involved in that function, as the C-terminus (which contains a UBA domain) was shown to be essential but not sufficient by itself. In an earlier yeast two-hybrid study, the region in mouse NBR1 covered by this domain has been shown to interact with CIB (calcium and integrin-binding protein) and FEZ1 (fasciculation and elongation protein zeta-1). Thus, NBR1 may play a role in cellular signalling pathways and possibly in neural development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 771915230 363 PTMTALFL-DENLPDGTCLEPGTKFIKYWKMRNTGNISWTSDTKLKFMWGNLTLGSrEHKEVAVPFLQPGQVGVVSVAFV 441
Cdd:cd14947    1 PGLSAAFVeDVTIPDGTVVPPGTEFTKTWRLRNTGTVPWPAGTLLRFVGGDPGLLS-APERVPVPSTVPGEEVDVSVELR 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 771915230 442 APLLEGTYTSHWRLAHC-GVQFGPRVWCSIVVV 473
Cdd:cd14947   80 APSEPGRYISYWRLVTPdGLPFGDRLWVDITVE 112

UBA domain of next to BRCA1 gene 1 protein (NBR1) and similar proteins; NBR1, also called cell migration-inducing gene 19 protein, membrane component chromosome 17 surface marker 2, neighbor of BRCA1 gene 1 protein, or protein 1A1-3B, is a scaffold protein that may be involved in signal transmission downstream of the serine/protein kinase from the giant muscle protein titin. Moreover, NBR1 functions as an autophagic receptor for ubiquitinated cargo. It interacts with ATG8-family proteins for its degradation by autophagy. NBR1 contains an N-terminal Phox and Bem1p (PB1) domain that plays a critical role in mediating protein-protein interactions with both titin kinase and with another scaffold protein, p62. NBR1 also has a LC3-interaction region (LIR) and a ubiquitin-associated (UBA) domain. The LIR is required for the autophagic clearance of NBR1. UBA domain is responsible for the ubiquitin binding which is necessary for the puromycin-induced formation of ubiquitinated protein aggregates.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 771915230 939 EDASLMAVLQEMGFSNQPLNQRLLRKHHYNLLDVVNELV 977
Cdd:cd14319    1 EWDSELEQLFEMGFTDRDLNQELLKKHNGDLDRVVDELL 39

Functionally uncharacterized domain in neighbor of Brca1 Gene 1 and related proteins; NBR1 has been characterized as a specific late endosomal protein, which might play a role in receptor (RTK) trafficking. Specifically, NBR1 was shown to inhibit ligand-mediated receptor internalization from the cell surface. The region covered by this domain model may be involved in that function, as the C-terminus (which contains a UBA domain) was shown to be essential but not sufficient by itself. In an earlier yeast two-hybrid study, the region in mouse NBR1 covered by this domain has been shown to interact with CIB (calcium and integrin-binding protein) and FEZ1 (fasciculation and elongation protein zeta-1). Thus, NBR1 may play a role in cellular signalling pathways and possibly in neural development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 771915230 363 PTMTALFL-DENLPDGTCLEPGTKFIKYWKMRNTGNISWTSDTKLKFMWGNLTLGSrEHKEVAVPFLQPGQVGVVSVAFV 441
Cdd:cd14947    1 PGLSAAFVeDVTIPDGTVVPPGTEFTKTWRLRNTGTVPWPAGTLLRFVGGDPGLLS-APERVPVPSTVPGEEVDVSVELR 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 771915230 442 APLLEGTYTSHWRLAHC-GVQFGPRVWCSIVVV 473
Cdd:cd14947   80 APSEPGRYISYWRLVTPdGLPFGDRLWVDITVE 112

The PB1 domain is an essential part of NBR1 protein, next to BRCA1, a scaffold protein mediating specific protein-protein interaction with both titin protein kinase and with another scaffold protein p62. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domain, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. The NBR1 protein contains a type I PB1 domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 771915230   5 VTVKVNFRGNVKKFPVLDTNKAQWETVEAWIKTTFGLSHFQVKYFDEDNEEVCINSQDEYTEALKSAFKQANQLHMNVY 83
Cdd:cd06396    1 VNLKVTYNGESQSFLVSDSENTTWASVEAMVKVSFGLNDIQIKYVDEENEEVSVNSQGEYEEALKSAVRQGNLLQMNVY 79

PB1 domain; Phox and Bem1p domain, present in many eukaryotic cytoplasmic signalling proteins. The domain adopts a beta-grasp fold, similar to that found in ubiquitin and Ras-binding domains. A motif, variously termed OPR, PC and AID, represents the most conserved region of the majority of PB1 domains, and is necessary for PB1 domain function. This function is the formation of PB1 domain heterodimers, although not all PB1 domain pairs associate.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 771915230     4 PVTVKVNFRGNVKKFPVLDTNKaqWETVEAWIKTTFGLS--HFQVKYFDEDNEEVCINSQDEYTEALKSAFKQANQ 77
Cdd:smart00666   1 TVDVKLRYGGETRRLSVPRDIS--FEDLRSKVAKRFGLDnqSFTLKYQDEDGDLVSLTSDEDLEEAIEEYDSLGSK 74

Zinc finger, ZZ type. Zinc finger present in Drosophila ref(2)P, NBR1, Human sequestosome 1 and related proteins. The ZZ motif coordinates two zinc ions and most likely participates in ligand binding or molecular scaffolding. Drosophila ref(2)P appears to control the multiplication of sigma rhabdovirus. NBR1 (Next to BRCA1 gene 1 protein) interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB), and may function in cell signalling pathways. Sequestosome 1 is a phosphotyrosine independent ligand for the Lck SH2 domain and binds noncovalently to ubiquitin via its UBA domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 771915230 213 CSSCKGPATGGGYQCSVCPSCILCEPCSHKHD-PSHNLKR 251
Cdd:cd02340    3 CDGCQGPIVGVRYKCLVCPDYDLCESCEAKGVhPEHAMLK 42

Functionally uncharacterized domain in neighbor of Brca1 Gene 1 and related proteins; NBR1 has been characterized as a specific late endosomal protein, which might play a role in receptor (RTK) trafficking. Specifically, NBR1 was shown to inhibit ligand-mediated receptor internalization from the cell surface. The region covered by this domain model may be involved in that function, as the C-terminus (which contains a UBA domain) was shown to be essential but not sufficient by itself. In an earlier yeast two-hybrid study, the region in mouse NBR1 covered by this domain has been shown to interact with CIB (calcium and integrin-binding protein) and FEZ1 (fasciculation and elongation protein zeta-1). Thus, NBR1 may play a role in cellular signalling pathways and possibly in neural development.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 771915230 363 PTMTALFL-DENLPDGTCLEPGTKFIKYWKMRNTGNISWTSDTKLKFMWGNLTLGSrEHKEVAVPFLQPGQVGVVSVAFV 441
Cdd:cd14947    1 PGLSAAFVeDVTIPDGTVVPPGTEFTKTWRLRNTGTVPWPAGTLLRFVGGDPGLLS-APERVPVPSTVPGEEVDVSVELR 79

                         90       100       110
                 ....*....|....*....|....*....|...
gi 771915230 442 APLLEGTYTSHWRLAHC-GVQFGPRVWCSIVVV 473
Cdd:cd14947   80 APSEPGRYISYWRLVTPdGLPFGDRLWVDITVE 112

The PB1 domain is an essential part of NBR1 protein, next to BRCA1, a scaffold protein mediating specific protein-protein interaction with both titin protein kinase and with another scaffold protein p62. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domain, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. The NBR1 protein contains a type I PB1 domain.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 771915230   5 VTVKVNFRGNVKKFPVLDTNKAQWETVEAWIKTTFGLSHFQVKYFDEDNEEVCINSQDEYTEALKSAFKQANQLHMNVY 83
Cdd:cd06396    1 VNLKVTYNGESQSFLVSDSENTTWASVEAMVKVSFGLNDIQIKYVDEENEEVSVNSQGEYEEALKSAVRQGNLLQMNVY 79

The PB1 domain is a modular domain mediating specific protein-protein interactions which play a role in many critical cell processes, such as osteoclastogenesis, angiogenesis, early cardiovascular development, and cell polarity. A canonical PB1-PB1 interaction, which involves heterodimerization of two PB1 domain, is required for the formation of macromolecular signaling complexes ensuring specificity and fidelity during cellular signaling. The interaction between two PB1 domain depends on the type of PB1. There are three types of PB1 domains: type I which contains an OPCA motif, acidic aminoacid cluster, type II which contains a basic cluster, and type I/II which contains both an OPCA motif and a basic cluster. Interactions of PB1 domains with other protein domains have been described as a noncanonical PB1-interactions. The PB1 domain module is conserved in amoebas, fungi, animals, and plants.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 771915230   5 VTVKVNFRGNVKKFPVLDTNkAQWETVEAWIKTTFGL--SHFQVKYFDEDNEEVCINSQDEYTEALKSA 71
Cdd:cd05992    1 VRVKVKYGGEIRRFVVVSRS-ISFEDLRSKIAEKFGLdaVSFKLKYPDEDGDLVTISSDEDLEEAIEEA 68

PB1 domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 771915230    4 PVTVKVNFRGNVKKFPVLDTNkAQWETVEAWIKTTFGLS--HFQVKYFDEDNEEVCINSQDEYTEALKSAFK 73
Cdd:pfam00564   1 TVRLKLRYGGGIRRFLSVSRG-ISFEELRALVEQRFGLDdvDFKLKYPDEDGDLVSLTSDEDLEEALEEARS 71

Zinc finger, ZZ type. Zinc finger present in dystrophin, CBP/p300 and many other proteins. The ZZ motif coordinates one or two zinc ions and most likely participates in ligand binding or molecular scaffolding. Many proteins containing ZZ motifs have other zinc-binding motifs as well, and the majority serve as scaffolds in pathways involving acetyltransferase, protein kinase, or ubiqitin-related activity. ZZ proteins can be grouped into the following functional classes: chromatin modifying, cytoskeletal scaffolding, ubiquitin binding or conjugating, and membrane receptor or ion-channel modifying proteins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 771915230 213 CSSCKGPATGGGYQCSVCPSCILCEPCSHKHDPSHNLKRTRTPL 256
Cdd:cd02249    3 CDGCLKPIVGVRYHCLVCEDFDLCSSCYAKGKKGHPPDHSFTEI 46

Zinc-binding domain, present in Dystrophin, CREB-binding protein; Putative zinc-binding domain present in dystrophin-like proteins, and CREB-binding protein/p300 homologues. The ZZ in dystrophin appears to bind calmodulin. A missense mutation of one of the conserved cysteines in dystrophin results in a patient with Duchenne muscular dystrophy.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 771915230   212 NCSSCKGPATGGGYQCSVCPSCILCEPC--SHKHDPSHN 248
Cdd:smart00291   6 SCDTCGKPIVGVRYHCLVCPDYDLCQSCfaKGSAGGEHS 44