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 1825909221 313 PMLSAAFV-DENLPDGTHLQPGTKFIKHWRMKNTGNVKWSTDTKLKFMWGNLTLASTeKKDVLVPCLKAGHVGVVSVEFI 391
Cdd:cd14947     1 PGLSAAFVeDVTIPDGTVVPPGTEFTKTWRLRNTGTVPWPAGTLLRFVGGDPGLLSA-PERVPVPSTVPGEEVDVSVELR 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1825909221 392 APALEGTYTSHWRLSHK-GQQFGPRVWCSIIVD 423
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 1825909221 856 QTAALMAHLFEMGFCDRQLNLRLLKKHNYNILQVVTELL 894
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 1825909221 313 PMLSAAFV-DENLPDGTHLQPGTKFIKHWRMKNTGNVKWSTDTKLKFMWGNLTLASTeKKDVLVPCLKAGHVGVVSVEFI 391
Cdd:cd14947     1 PGLSAAFVeDVTIPDGTVVPPGTEFTKTWRLRNTGTVPWPAGTLLRFVGGDPGLLSA-PERVPVPSTVPGEEVDVSVELR 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1825909221 392 APALEGTYTSHWRLSHK-GQQFGPRVWCSIIVD 423
Cdd:cd14947    80 APSEPGRYISYWRLVTPdGLPFGDRLWVDITVE 112

Ig-like domain from next to BRCA1 gene; Domain present between positions 365-485 in the human next to BRCA1 gene 1 protein Q14596 (NBR1_HUMAN) Distant homology and fold prediction analysis suggests this domain has an immunoglobulin like fold and is distantly homologous to domains involved in cell adhesion such as CARDB (PF07705). JCSG construct was crystalized confirming the domain boundaries

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825909221 323 NLPDGTHLQPGTKFIKHWRMKNTGNVKWSTDTKLKFMWGNLTLASTekkDVLVPCLKAGHVGVVSVEFIAPALEGTYTSH 402
Cdd:pfam16158   1 TIPDGTVVPPGTEFTKTWRLRNSGNVAWPAGTSLRFVGGDNMGNVS---TVLVPPVAPGEEVDVSVELKAPSRPGRYISY 77

                          90       100
                  ....*....|....*....|.
gi 1825909221 403 WRLSHK-GQQFGPRVWCSIIV 422
Cdd:pfam16158  78 WRLKTPdGTPFGDRLWVDITV 98

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825909221    4 QVTLNVTFKNEIQSFLVsdPENTTWADIEAMVKVSFDL--NTIQIKYLDEENEEVSINSQGEYEEALKMAVKQGNQ-LQM 80
Cdd:smart00666   1 TVDVKLRYGGETRRLSV--PRDISFEDLRSKVAKRFGLdnQSFTLKYQDEDGDLVSLTSDEDLEEAIEEYDSLGSKkLRL 78

                   ...
gi 1825909221   81 QVH 83
Cdd:smart00666  79 HVF 81

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
                  ....*....|....*..
gi 1825909221 215 IACNNCQRRIVGVRYQC 231
Cdd:cd02340     1 VICDGCQGPIVGVRYKC 17

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 1825909221 313 PMLSAAFV-DENLPDGTHLQPGTKFIKHWRMKNTGNVKWSTDTKLKFMWGNLTLASTeKKDVLVPCLKAGHVGVVSVEFI 391
Cdd:cd14947     1 PGLSAAFVeDVTIPDGTVVPPGTEFTKTWRLRNTGTVPWPAGTLLRFVGGDPGLLSA-PERVPVPSTVPGEEVDVSVELR 79

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1825909221 392 APALEGTYTSHWRLSHK-GQQFGPRVWCSIIVD 423
Cdd:cd14947    80 APSEPGRYISYWRLVTPdGLPFGDRLWVDITVE 112

Ig-like domain from next to BRCA1 gene; Domain present between positions 365-485 in the human next to BRCA1 gene 1 protein Q14596 (NBR1_HUMAN) Distant homology and fold prediction analysis suggests this domain has an immunoglobulin like fold and is distantly homologous to domains involved in cell adhesion such as CARDB (PF07705). JCSG construct was crystalized confirming the domain boundaries

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825909221 323 NLPDGTHLQPGTKFIKHWRMKNTGNVKWSTDTKLKFMWGNLTLASTekkDVLVPCLKAGHVGVVSVEFIAPALEGTYTSH 402
Cdd:pfam16158   1 TIPDGTVVPPGTEFTKTWRLRNSGNVAWPAGTSLRFVGGDNMGNVS---TVLVPPVAPGEEVDVSVELKAPSRPGRYISY 77

                          90       100
                  ....*....|....*....|.
gi 1825909221 403 WRLSHK-GQQFGPRVWCSIIV 422
Cdd:pfam16158  78 WRLKTPdGTPFGDRLWVDITV 98

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825909221    4 QVTLNVTFKNEIQSFLVsdPENTTWADIEAMVKVSFDL--NTIQIKYLDEENEEVSINSQGEYEEALKMAVKQGNQ-LQM 80
Cdd:smart00666   1 TVDVKLRYGGETRRLSV--PRDISFEDLRSKVAKRFGLdnQSFTLKYQDEDGDLVSLTSDEDLEEAIEEYDSLGSKkLRL 78

                   ...
gi 1825909221   81 QVH 83
Cdd:smart00666  79 HVF 81

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1825909221   5 VTLNVTFKNEIQSFLVSDPeNTTWADIEAMVKVSFDLN--TIQIKYLDEENEEVSINSQGEYEEALKMAVKQGN-QLQMQ 81
Cdd:cd05992     1 VRVKVKYGGEIRRFVVVSR-SISFEDLRSKIAEKFGLDavSFKLKYPDEDGDLVTISSDEDLEEAIEEARRSGSkKLRLF 79

                  ..
gi 1825909221  82 VH 83
Cdd:cd05992    80 VF 81

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
                   ....*....|....*....|....*...
gi 1825909221  211 FSWHIACNNCQRRIVGVRYQCRLQKQVD 238
Cdd:smart00291   1 VHHSYSCDTCGKPIVGVRYHCLVCPDYD 28