LIN7B_HUMAN
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 03-AUG-2022, entry version 179.
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 Lin-
RT 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}.
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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 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; Q9HAP6; -.
DR PeptideAtlas; Q9HAP6; -.
DR PRIDE; Q9HAP6; -.
DR ProteomicsDB; 81416; -. [Q9HAP6-1]
DR ProteomicsDB; 81417; -. [Q9HAP6-2]
DR Antibodypedia; 31908; 265 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 CTD; 64130; -.
DR DisGeNET; 64130; -.
DR GeneCards; LIN7B; -.
DR HGNC; HGNC:17788; LIN7B.
DR HPA; ENSG00000104863; Tissue enhanced (skeletal).
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; YYHPGKE; -.
DR OrthoDB; 1335138at2759; -.
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 1080 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 171 other tissues.
DR ExpressionAtlas; Q9HAP6; baseline and differential.
DR Genevisible; Q9HAP6; HS.
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: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 Gene3D; 2.30.42.10; -; 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 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; SSF101288; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS51022; L27; 1.
DR PROSITE; PS50106; PDZ; 1.
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
