LIN7A_RAT
ID LIN7A_RAT Reviewed; 232 AA.
AC Q9Z250; Q9Z251;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Protein lin-7 homolog A;
DE Short=Lin-7A;
DE AltName: Full=Mammalian lin-seven protein 1;
DE Short=MALS-1;
DE AltName: Full=Vertebrate lin-7 homolog 1;
DE Short=Veli-1;
GN Name=Lin7a; Synonyms=Mals1, Veli1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-125.
RA Farkas R.H., Qian J., Goldberg J.L., Quigley H.A., Zack D.J.;
RT "Gene expression profiling of highly purified rat retinal ganglion cells.";
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-232 (ISOFORMS 1 AND 2), TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10362251; DOI=10.1038/sj.onc.1202652;
RA Irie M., Hata Y., Deguchi M., Ide N., Hirao K., Yao I., Nishioka H.,
RA Takai Y.;
RT "Isolation and characterization of mammalian homologues of Caenorhabditis
RT elegans lin-7: localization at cell-cell junctions.";
RL Oncogene 18:2811-2817(1999).
RN [3]
RP PROTEIN SEQUENCE OF 39-49; 86-107; 114-126; 151-170 AND 192-199, AND
RP INTERACTION WITH KCNJ12.
RX PubMed=15024025; DOI=10.1074/jbc.m400285200;
RA Leonoudakis D., Conti L.R., Anderson S., Radeke C.M., McGuire L.M.,
RA Adams M.E., Froehner S.C., Yates J.R. III, Vandenberg C.A.;
RT "Protein trafficking and anchoring complexes revealed by proteomic analysis
RT of inward rectifier potassium channel (Kir2.x)-associated proteins.";
RL J. Biol. Chem. 279:22331-22346(2004).
RN [4]
RP TISSUE SPECIFICITY, AND INTERACTION WITH CASK AND APBA1.
RC TISSUE=Testis;
RX PubMed=9753324; DOI=10.1016/s0092-8674(00)81736-5;
RA Butz S., Okamoto M., Suedhof T.C.;
RT "A tripartite protein complex with the potential to couple synaptic vesicle
RT exocytosis to cell adhesion in brain.";
RL Cell 94:773-782(1998).
RN [5]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND
RP INTERACTION WITH DLG4 AND GRIN2B.
RX PubMed=10341223; DOI=10.1523/jneurosci.19-11-04189.1999;
RA Jo K., Derin R., Li M., Bredt D.S.;
RT "Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7
RT homologs enriched at brain synapses in association with the postsynaptic
RT density-95/NMDA receptor postsynaptic complex.";
RL J. Neurosci. 19:4189-4199(1999).
RN [6]
RP INDUCTION.
RX PubMed=12393911; DOI=10.1074/jbc.m207826200;
RA Sanna B., Kramer D., Genazzani A.A.;
RT "The expression of the PDZ protein MALS-1/velis is regulated by calcium and
RT calcineurin in cerebellar granule cells.";
RL J. Biol. Chem. 277:49585-49590(2002).
RN [7]
RP INTERACTION WITH CASK; APBA1 AND CASKIN1.
RX PubMed=12040031; DOI=10.1523/jneurosci.22-11-04264.2002;
RA Tabuchi K., Biederer T., Butz S., Suedhof T.C.;
RT "CASK participates in alternative tripartite complexes in which Mint 1
RT competes for binding with Caskin 1, a novel CASK-binding protein.";
RL J. Neurosci. 22:4264-4273(2002).
RN [8]
RP INTERACTION WITH KCNJ12; CASK AND DLG1, AND FUNCTION.
RX PubMed=14960569; DOI=10.1074/jbc.m400284200;
RA Leonoudakis D., Conti L.R., Radeke C.M., McGuire L.M., Vandenberg C.A.;
RT "A multiprotein trafficking complex composed of SAP97, CASK, Veli, and
RT Mint1 is associated with inward rectifier Kir2 potassium channels.";
RL J. Biol. Chem. 279:19051-19063(2004).
RN [9]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15494546; DOI=10.1152/ajprenal.00235.2004;
RA Olsen O., Wade J.B., Morin N., Bredt D.S., Welling P.A.;
RT "Differential localization of the Mammalian Lin 7 (MALS/Veli) PDZ proteins
RT in the kidney.";
RL Am. J. Physiol. 288:F345-F352(2005).
RN [10]
RP INTERACTION WITH MARCHF11.
RX PubMed=17604280; DOI=10.1074/jbc.m700414200;
RA Morokuma Y., Nakamura N., Kato A., Notoya M., Yamamoto Y., Sakai Y.,
RA Fukuda H., Yamashina S., Hirata Y., Hirose S.;
RT "MARCH-XI, a novel transmembrane ubiquitin ligase implicated in ubiquitin-
RT dependent protein sorting in developing spermatids.";
RL J. Biol. Chem. 282:24806-24815(2007).
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.
CC {ECO:0000250|UniProtKB:Q8JZS0, ECO:0000269|PubMed:14960569}.
CC -!- SUBUNIT: Forms a complex with CASK and CASKIN1. Component of the brain-
CC specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed
CC of at least APBA1, CASK, and LIN7, which associates with the motor
CC protein KIF17 to transport vesicles along microtubules (By similarity).
CC Can also interact with other modular proteins containing protein-
CC protein interaction domains like PALS1, PALS2, MPP7, DLG1, DLG2 and
CC DLG3 through its L27 domain. Interacts with DLG4 and GRIN2B as well as
CC CDH1 and CTNNB1, the channels KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably
CC KCNJ2/Kir2.1 and SLC6A12/BGT-1 via its PDZ domain. The association of
CC LIN7A with cadherin and beta-catenin is calcium-dependent, occurs at
CC synaptic junctions and requires the actin cytoskeleton. Interacts with
CC EGFR, ERBB2, ERBB3 and ERBB4 with both PDZ and KID domains. Associates
CC with KIF17 via APBA1. Interacts with HTR4. Forms a tripartite complex
CC composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C) (By similarity).
CC Interacts with MARCHF11. {ECO:0000250, ECO:0000250|UniProtKB:Q8JZS0,
CC ECO:0000269|PubMed:10341223, ECO:0000269|PubMed:12040031,
CC ECO:0000269|PubMed:14960569, ECO:0000269|PubMed:15024025,
CC ECO:0000269|PubMed:17604280, ECO:0000269|PubMed:9753324}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8JZS0};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q8JZS0}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:Q8JZS0}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q8JZS0}. Cell junction
CC {ECO:0000250|UniProtKB:Q8JZS0}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q8JZS0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8JZS0}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:Q8JZS0}. Note=Mainly basolateral in renal
CC epithelial cells. {ECO:0000250|UniProtKB:Q8JZS0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=rTIP33, LIN7Bb, Lin-7-Bb;
CC IsoId=Q9Z250-1; Sequence=Displayed;
CC Name=2; Synonyms=LIN7Ba, Lin-7-Ba;
CC IsoId=Q9Z250-2; Sequence=VSP_012860, VSP_012861;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in brain and detected in
CC lung, liver and testis (at protein level). Expression was detected only
CC in brain. {ECO:0000269|PubMed:10341223, ECO:0000269|PubMed:10362251,
CC ECO:0000269|PubMed:15494546, ECO:0000269|PubMed:9753324}.
CC -!- DEVELOPMENTAL STAGE: Detected only after the second postnatal week.
CC {ECO:0000269|PubMed:10341223}.
CC -!- INDUCTION: Up-regulated by cell depolarization and calcium entry
CC through L-type calcium channels. {ECO:0000269|PubMed:12393911}.
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; CF978128; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF090134; AAC78073.1; -; mRNA.
DR EMBL; AF090135; AAC78074.1; -; mRNA.
DR RefSeq; NP_445966.1; NM_053514.1.
DR AlphaFoldDB; Q9Z250; -.
DR SMR; Q9Z250; -.
DR BioGRID; 250083; 3.
DR CORUM; Q9Z250; -.
DR IntAct; Q9Z250; 2.
DR STRING; 10116.ENSRNOP00000006083; -.
DR iPTMnet; Q9Z250; -.
DR PhosphoSitePlus; Q9Z250; -.
DR PaxDb; Q9Z250; -.
DR PRIDE; Q9Z250; -.
DR GeneID; 85327; -.
DR UCSC; RGD:621256; rat. [Q9Z250-1]
DR CTD; 8825; -.
DR RGD; 621256; Lin7a.
DR eggNOG; KOG3550; Eukaryota.
DR InParanoid; Q9Z250; -.
DR OrthoDB; 1335138at2759; -.
DR PhylomeDB; Q9Z250; -.
DR Reactome; R-RNO-212676; Dopamine Neurotransmitter Release Cycle.
DR PRO; PR:Q9Z250; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
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:0016020; C:membrane; ISO:RGD.
DR GO; GO:0097025; C:MPP7-DLG1-LIN7 complex; IBA:GO_Central.
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; IDA:RGD.
DR GO; GO:0097016; F:L27 domain binding; ISO:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0006887; P:exocytosis; IEA:UniProtKB-KW.
DR GO; GO:0048839; P:inner ear development; ISO:RGD.
DR GO; GO:0045199; P:maintenance of epithelial cell apical/basal polarity; IBA:GO_Central.
DR GO; GO:0007269; P:neurotransmitter secretion; ISO:RGD.
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 GO; GO:0048489; P:synaptic vesicle transport; ISO:RGD.
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 Alternative splicing; Cell junction; Cell membrane;
KW Direct protein sequencing; Exocytosis; Membrane;
KW Postsynaptic cell membrane; Protein transport; Reference proteome; Synapse;
KW Tight junction; Transport.
FT CHAIN 1..232
FT /note="Protein lin-7 homolog A"
FT /id="PRO_0000189625"
FT DOMAIN 25..80
FT /note="L27"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00365"
FT DOMAIN 108..190
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT MOTIF 14..28
FT /note="Kinase interacting site"
FT /evidence="ECO:0000250"
FT VAR_SEQ 162..195
FT /note="SVEGEHHEKAVELLKAAKDSVKLVVRYTPKVLEE -> ALEEKLAGQSSNSH
FT KFGNPCSGIPAHRKRKRKYQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10362251"
FT /id="VSP_012860"
FT VAR_SEQ 196..232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10362251"
FT /id="VSP_012861"
FT CONFLICT 39
FT /note="L -> P (in Ref. 2; AAC78074)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="P -> A (in Ref. 1; CF978128)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 232 AA; 25865 MW; C37984D803B90A63 CRC64;
MLKPSVTSAP TADMATLTVV QPLTLDRDVA RAIELLEKLQ ESGEVPVHKL QSLKKVLQSE
FCTAIREVYQ YMHETITVNG CPEFRARATA KATVAAFAAS EGHSHPRVVE LPKTDEGLGF
NVMGGKEQNS PIYISRIIPG GVAERHGGLK RGDQLLSVNG VSVEGEHHEK AVELLKAAKD
SVKLVVRYTP KVLEEMEARF EKLRTARRRQ QQQLLIQQQQ QQQQQPQQNH MS
