ID LIN7B_HUMAN Reviewed; 207 AA. AC Q9HAP6; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 24-JAN-2024, entry version 187. DE RecName: Full=Protein lin-7 homolog B; DE Short=Lin-7B; DE Short=hLin7B; DE AltName: Full=Mammalian lin-seven protein 2; DE Short=MALS-2; DE AltName: Full=Vertebrate lin-7 homolog 2; DE Short=Veli-2; DE Short=hVeli2; GN Name=LIN7B; Synonyms=MALS2, VELI2; ORFNames=UNQ3116/PRO10200; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, FUNCTION, AND INTERACTION RP WITH KCNJ4 AND CASK (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=11742811; DOI=10.1152/ajpcell.00249.2001; RA Olsen O., Liu H., Wade J.B., Merot J., Welling P.A.; RT "Basolateral membrane expression of the Kir 2.3 channel is coordinated by RT PDZ interaction with Lin-7/CASK complex."; RL Am. J. Physiol. 282:C183-C195(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP SUBCELLULAR LOCATION, AND INTERACTION WITH EGFR. RX PubMed=12967566; DOI=10.1016/j.devcel.2003.08.001; RA Shelly M., Mosesson Y., Citri A., Lavi S., Zwang Y., Melamed-Book N., RA Aroeti B., Yarden Y.; RT "Polar expression of ErbB-2/HER2 in epithelia. Bimodal regulation by RT Lin-7."; RL Dev. Cell 5:475-486(2003). RN [5] RP INTERACTION WITH ASIC3. RX PubMed=15317815; DOI=10.1074/jbc.m405874200; RA Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J.; RT "PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have RT opposite effects on H+- gated current."; RL J. Biol. Chem. 279:46962-46968(2004). RN [6] RP INTERACTION WITH RTKN. RX PubMed=16979770; DOI=10.1016/j.neures.2006.08.003; RA Sudo K., Ito H., Iwamoto I., Morishita R., Asano T., Nagata K.; RT "Identification of a cell polarity-related protein, Lin-7B, as a binding RT partner for a Rho effector, Rhotekin, and their possible interaction in RT neurons."; RL Neurosci. Res. 56:347-355(2006). RN [7] RP INTERACTION WITH MPP7 AND DLG1. RX PubMed=17237226; DOI=10.1074/jbc.m610002200; RA Bohl J., Brimer N., Lyons C., Vande Pol S.B.; RT "The stardust family protein MPP7 forms a tripartite complex with LIN7 and RT DLG1 that regulates the stability and localization of DLG1 to cell RT junctions."; RL J. Biol. Chem. 282:9392-9400(2007). RN [8] RP STRUCTURE BY NMR OF 93-172. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the PDZ domain from human LIN-7 homolog B."; RL Submitted (OCT-2006) to the PDB data bank. CC -!- FUNCTION: Plays a role in establishing and maintaining the asymmetric CC distribution of channels and receptors at the plasma membrane of CC polarized cells. Forms membrane-associated multiprotein complexes that CC may regulate delivery and recycling of proteins to the correct membrane CC domains. The tripartite complex composed of LIN7 (LIN7A, LIN7B or CC LIN7C), CASK and APBA1 associates with the motor protein KIF17 to CC transport vesicles containing N-methyl-D-aspartate (NMDA) receptor CC subunit NR2B along microtubules (By similarity). This complex may have CC the potential to couple synaptic vesicle exocytosis to cell adhesion in CC brain. Ensures the proper localization of GRIN2B (subunit 2B of the CC NMDA receptor) to neuronal postsynaptic density and may function in CC localizing synaptic vesicles at synapses where it is recruited by beta- CC catenin and cadherin. Required to localize Kir2 channels, GABA CC transporter (SLC6A12) and EGFR/ERBB1, ERBB2, ERBB3 and ERBB4 to the CC basolateral membrane of epithelial cells. May increase the amplitude of CC ASIC3 acid-evoked currents by stabilizing the channel at the cell CC surface (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O88951, CC ECO:0000269|PubMed:11742811}. CC -!- SUBUNIT: Forms a complex with CASK and CASKIN1 (By similarity). CC Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2- CC LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which CC associates with the motor protein KIF17 to transport vesicles along CC microtubules (By similarity). Forms a heterotrimeric complex composed CC of MMP5, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts CC with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 CC interacts with the L27 domain of LIN7B (By similarity). Forms a CC heterotrimeric complex with DLG1 and CASK via their L27 domains CC (PubMed:11742811, PubMed:17237226). Interacts with DLG4 and GRIN2B as CC well as CDH1 and CTNNB1, the channels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and CC probably KCNJ2/Kir2.1 and SLC6A12/BGT-1 via its PDZ domain CC (PubMed:11742811). The association of LIN7A with cadherin and beta- CC catenin is calcium-dependent, occurs at synaptic junctions and requires CC the actin cytoskeleton. Interacts with EGFR, ERBB2, ERBB3 and ERBB4 CC with both PDZ and KID domains (PubMed:12967566). Associates with KIF17 CC via APBA1 (By similarity). Interacts with ASIC3 (PubMed:15317815). CC Interacts with TOPK. Interacts with RTKN (PubMed:16979770). Interacts CC with APBA1 (By similarity). Interacts with MPP7 (PubMed:17237226). CC Interacts with DLG2 (By similarity). Interacts with DLG3 (By CC similarity). {ECO:0000250|UniProtKB:O88951, CC ECO:0000250|UniProtKB:Q9Z252, ECO:0000269|PubMed:11742811, CC ECO:0000269|PubMed:12967566, ECO:0000269|PubMed:15317815, CC ECO:0000269|PubMed:16979770, ECO:0000269|PubMed:17237226}. CC -!- INTERACTION: CC Q9HAP6; O14936-4: CASK; NbExp=3; IntAct=EBI-821335, EBI-12007726; CC Q9HAP6; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-821335, EBI-744099; CC Q9HAP6; Q9BXY0: MAK16; NbExp=3; IntAct=EBI-821335, EBI-5280229; CC Q9HAP6; Q14168-4: MPP2; NbExp=3; IntAct=EBI-821335, EBI-14385193; CC Q9HAP6; Q13368: MPP3; NbExp=8; IntAct=EBI-821335, EBI-716157; CC Q9HAP6; Q5T2T1: MPP7; NbExp=3; IntAct=EBI-821335, EBI-2514004; CC Q9HAP6; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-821335, EBI-741158; CC Q9HAP6; Q8N3R9: PALS1; NbExp=3; IntAct=EBI-821335, EBI-2513978; CC Q9HAP6; Q9NZW5: PALS2; NbExp=5; IntAct=EBI-821335, EBI-2683764; CC Q9HAP6; P20618: PSMB1; NbExp=3; IntAct=EBI-821335, EBI-372273; CC Q9HAP6; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-821335, EBI-11955057; CC Q9HAP6; Q8WVT3: TRAPPC12; NbExp=3; IntAct=EBI-821335, EBI-2819919; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O88951}; CC Peripheral membrane protein {ECO:0000250|UniProtKB:O88951}. Basolateral CC cell membrane {ECO:0000269|PubMed:11742811, CC ECO:0000269|PubMed:12967566}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:O88951}. Cell junction CC {ECO:0000250|UniProtKB:O88951}. Postsynaptic density membrane CC {ECO:0000250|UniProtKB:O88951}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:O88951}. Cell junction, tight junction CC {ECO:0000250|UniProtKB:O88951}. Note=Mainly basolateral in renal CC epithelial cells. {ECO:0000269|PubMed:11742811}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9HAP6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9HAP6-2; Sequence=VSP_042156; CC -!- DOMAIN: The kinase interacting site is required for proper delivery of CC ERBB2 to the basolateral membrane. {ECO:0000250}. CC -!- DOMAIN: The PDZ domain regulates endocytosis and recycling of the CC receptor at the membrane. {ECO:0000250}. CC -!- DOMAIN: The L27 domain mediates interaction with CASK and is involved CC in the formation of multimeric complexes and the association of LIN7 to CC membranes. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the lin-7 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF311862; AAG34117.1; -; mRNA. DR EMBL; AY358744; AAQ89104.1; -; mRNA. DR EMBL; AI826082; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC027618; AAH27618.1; -; mRNA. DR CCDS; CCDS12757.1; -. [Q9HAP6-1] DR CCDS; CCDS77328.1; -. [Q9HAP6-2] DR RefSeq; NP_001295348.1; NM_001308419.1. [Q9HAP6-2] DR RefSeq; NP_071448.1; NM_022165.2. [Q9HAP6-1] DR PDB; 2DKR; NMR; -; A=93-172. DR PDBsum; 2DKR; -. DR AlphaFoldDB; Q9HAP6; -. DR SMR; Q9HAP6; -. DR BioGRID; 122079; 36. DR ComplexPortal; CPX-7743; LIN-10-LIN-2-LIN-7 complex, LIN7B variant. DR IntAct; Q9HAP6; 16. DR MINT; Q9HAP6; -. DR STRING; 9606.ENSP00000221459; -. DR iPTMnet; Q9HAP6; -. DR PhosphoSitePlus; Q9HAP6; -. DR BioMuta; LIN7B; -. DR DMDM; 59798472; -. DR EPD; Q9HAP6; -. DR jPOST; Q9HAP6; -. DR MassIVE; Q9HAP6; -. DR MaxQB; Q9HAP6; -. DR PaxDb; 9606-ENSP00000221459; -. DR PeptideAtlas; Q9HAP6; -. DR ProteomicsDB; 81416; -. [Q9HAP6-1] DR ProteomicsDB; 81417; -. [Q9HAP6-2] DR Antibodypedia; 31908; 303 antibodies from 27 providers. DR DNASU; 64130; -. DR Ensembl; ENST00000221459.7; ENSP00000221459.2; ENSG00000104863.12. [Q9HAP6-1] DR Ensembl; ENST00000391864.7; ENSP00000375737.3; ENSG00000104863.12. [Q9HAP6-2] DR GeneID; 64130; -. DR KEGG; hsa:64130; -. DR MANE-Select; ENST00000221459.7; ENSP00000221459.2; NM_022165.3; NP_071448.1. DR UCSC; uc002pmp.3; human. [Q9HAP6-1] DR AGR; HGNC:17788; -. DR CTD; 64130; -. DR DisGeNET; 64130; -. DR GeneCards; LIN7B; -. DR HGNC; HGNC:17788; LIN7B. DR HPA; ENSG00000104863; Tissue enhanced (brain, skeletal muscle). DR MIM; 612331; gene. DR neXtProt; NX_Q9HAP6; -. DR OpenTargets; ENSG00000104863; -. DR PharmGKB; PA134914453; -. DR VEuPathDB; HostDB:ENSG00000104863; -. DR eggNOG; KOG3550; Eukaryota. DR GeneTree; ENSGT00940000153222; -. DR HOGENOM; CLU_097962_0_0_1; -. DR InParanoid; Q9HAP6; -. DR OMA; PLGLERX; -. DR OrthoDB; 4175920at2759; -. DR PhylomeDB; Q9HAP6; -. DR TreeFam; TF316850; -. DR PathwayCommons; Q9HAP6; -. DR Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle. DR Reactome; R-HSA-5666185; RHO GTPases Activate Rhotekin and Rhophilins. DR Reactome; R-HSA-6794361; Neurexins and neuroligins. DR Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors. DR SignaLink; Q9HAP6; -. DR BioGRID-ORCS; 64130; 12 hits in 1159 CRISPR screens. DR EvolutionaryTrace; Q9HAP6; -. DR GeneWiki; LIN7B; -. DR GenomeRNAi; 64130; -. DR Pharos; Q9HAP6; Tbio. DR PRO; PR:Q9HAP6; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9HAP6; Protein. DR Bgee; ENSG00000104863; Expressed in lower esophagus mucosa and 173 other cell types or tissues. DR ExpressionAtlas; Q9HAP6; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central. DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell. DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central. DR GO; GO:0097025; C:MPP7-DLG1-LIN7 complex; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0045202; C:synapse; IBA:GO_Central. DR GO; GO:0097016; F:L27 domain binding; IBA:GO_Central. DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW. DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; IBA:GO_Central. DR GO; GO:0007269; P:neurotransmitter secretion; IBA:GO_Central. DR GO; GO:1903361; P:protein localization to basolateral plasma membrane; IBA:GO_Central. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR CDD; cd00992; PDZ_signaling; 1. DR Gene3D; 2.30.42.10; -; 1. DR Gene3D; 1.10.287.650; L27 domain; 1. DR InterPro; IPR014775; L27_C. DR InterPro; IPR004172; L27_dom. DR InterPro; IPR036892; L27_dom_sf. DR InterPro; IPR017365; LIN7. DR InterPro; IPR001478; PDZ. DR InterPro; IPR036034; PDZ_sf. DR PANTHER; PTHR14063; PROTEIN LIN-7 HOMOLOG; 1. DR PANTHER; PTHR14063:SF7; PROTEIN LIN-7 HOMOLOG B; 1. DR Pfam; PF02828; L27; 1. DR Pfam; PF00595; PDZ; 1. DR PIRSF; PIRSF038039; Lin-7_homologue; 1. DR SMART; SM00569; L27; 1. DR SMART; SM00228; PDZ; 1. DR SUPFAM; SSF101288; L27 domain; 1. DR SUPFAM; SSF50156; PDZ domain-like; 1. DR PROSITE; PS51022; L27; 1. DR PROSITE; PS50106; PDZ; 1. DR Genevisible; Q9HAP6; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Cell membrane; KW Exocytosis; Membrane; Postsynaptic cell membrane; Protein transport; KW Reference proteome; Synapse; Tight junction; Transport. FT CHAIN 1..207 FT /note="Protein lin-7 homolog B" FT /id="PRO_0000189626" FT DOMAIN 10..65 FT /note="L27" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00365" FT DOMAIN 93..175 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT REGION 187..207 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1..13 FT /note="Kinase interacting site" FT /evidence="ECO:0000250" FT VAR_SEQ 77..146 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_042156" FT CONFLICT 65 FT /note="G -> R (in Ref. 3; AI826082)" FT /evidence="ECO:0000305" FT STRAND 93..97 FT /evidence="ECO:0007829|PDB:2DKR" FT STRAND 105..108 FT /evidence="ECO:0007829|PDB:2DKR" FT STRAND 110..114 FT /evidence="ECO:0007829|PDB:2DKR" FT STRAND 118..122 FT /evidence="ECO:0007829|PDB:2DKR" FT HELIX 127..131 FT /evidence="ECO:0007829|PDB:2DKR" FT STRAND 139..143 FT /evidence="ECO:0007829|PDB:2DKR" FT HELIX 153..162 FT /evidence="ECO:0007829|PDB:2DKR" FT STRAND 165..171 FT /evidence="ECO:0007829|PDB:2DKR" SQ SEQUENCE 207 AA; 22896 MW; 63189D82706B9B00 CRC64; MAALVEPLGL ERDVSRAVEL LERLQRSGEL PPQKLQALQR VLQSRFCSAI REVYEQLYDT LDITGSAEIR AHATAKATVA AFTASEGHAH PRVVELPKTD EGLGFNIMGG KEQNSPIYIS RVIPGGVADR HGGLKRGDQL LSVNGVSVEG EQHEKAVELL KAAQGSVKLV VRYTPRVLEE MEARFEKMRS ARRRQQHQSY SSLESRG //