ID   LIN7A_HUMAN             Reviewed;         233 AA.
AC   O14910; A4FTY3; Q147W1; Q6LES3; Q7LDS4;
DT   15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 2.
DT   24-JAN-2024, entry version 181.
DE   RecName: Full=Protein lin-7 homolog A;
DE            Short=Lin-7A;
DE            Short=hLin-7;
DE   AltName: Full=Mammalian lin-seven protein 1;
DE            Short=MALS-1;
DE   AltName: Full=Tax interaction protein 33;
DE            Short=TIP-33;
DE   AltName: Full=Vertebrate lin-7 homolog 1;
DE            Short=Veli-1;
GN   Name=LIN7A; Synonyms=MALS1, VELI1;
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], AND INTERACTION WITH APBA1; CASK; DLG2 AND
RP   DLG3.
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Corpus callosum;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary gland;
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   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 32-233, AND INTERACTION WITH VIRAL
RP   ONCOPROTEIN TAX.
RX   PubMed=9482110; DOI=10.1038/sj.onc.1201567;
RA   Rousset R., Fabre S., Desbois C., Bantignies F., Jalinot P.;
RT   "The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the
RT   PDZ domain of cellular proteins.";
RL   Oncogene 16:643-654(1998).
RN   [7]
RP   INTERACTION WITH PALS2, AND TISSUE SPECIFICITY.
RX   PubMed=11311936; DOI=10.1016/s0167-4781(01)00191-9;
RA   Tseng T.-C., Marfatia S.M., Bryant P.J., Pack S., Zhuang Z., O'Brien J.E.,
RA   Lin L., Hanada T., Chishti A.H.;
RT   "VAM-1: a new member of the MAGUK family binds to human Veli-1 through a
RT   conserved domain.";
RL   Biochim. Biophys. Acta 1518:249-259(2001).
RN   [8]
RP   SUBCELLULAR LOCATION, INTERACTION WITH EGFR; ERBB2; ERBB3 AND ERBB4,
RP   FUNCTION, AND DOMAIN.
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   [9]
RP   INTERACTION WITH DLG1 AND MPP7.
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).
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:12967566}.
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). Can also interact with other modular
CC       proteins containing protein-protein interaction domains like PALS1,
CC       PALS2, MPP7, DLG1, DLG2 and DLG3 through its L27 domain. Interacts with
CC       DLG4, GRIN2B and MARCHF11 as well as CDH1 and CTNNB1, the channels
CC       KCNJ12/Kir2.2, KCNJ4/Kir2.3 and probably KCNJ2/Kir2.1 and SLC6A12/BGT-1
CC       via its PDZ domain. 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. Associates with KIF17 via APBA1.
CC       Interacts with HTR4 (By similarity). Forms a tripartite complex
CC       composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C). {ECO:0000250,
CC       ECO:0000250|UniProtKB:Q8JZS0, ECO:0000269|PubMed:11311936,
CC       ECO:0000269|PubMed:12967566, ECO:0000269|PubMed:17237226,
CC       ECO:0000269|PubMed:9482110, ECO:0000269|PubMed:9753324}.
CC   -!- INTERACTION:
CC       O14910; O14936: CASK; NbExp=7; IntAct=EBI-2513988, EBI-1215506;
CC       O14910; O14936-4: CASK; NbExp=3; IntAct=EBI-2513988, EBI-12007726;
CC       O14910; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-2513988, EBI-947551;
CC       O14910; Q16610: ECM1; NbExp=3; IntAct=EBI-2513988, EBI-947964;
CC       O14910; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-2513988, EBI-10175124;
CC       O14910; Q08379: GOLGA2; NbExp=3; IntAct=EBI-2513988, EBI-618309;
CC       O14910; Q99750: MDFI; NbExp=3; IntAct=EBI-2513988, EBI-724076;
CC       O14910; Q14168-2: MPP2; NbExp=4; IntAct=EBI-2513988, EBI-10181752;
CC       O14910; Q14168-4: MPP2; NbExp=7; IntAct=EBI-2513988, EBI-14385193;
CC       O14910; Q13368: MPP3; NbExp=5; IntAct=EBI-2513988, EBI-716157;
CC       O14910; Q5T2T1: MPP7; NbExp=9; IntAct=EBI-2513988, EBI-2514004;
CC       O14910; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2513988, EBI-945833;
CC       O14910; Q8N3R9: PALS1; NbExp=9; IntAct=EBI-2513988, EBI-2513978;
CC       O14910; Q9NZW5: PALS2; NbExp=4; IntAct=EBI-2513988, EBI-2683764;
CC       O14910; Q15942: ZYX; NbExp=3; IntAct=EBI-2513988, EBI-444225;
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   -!- TISSUE SPECIFICITY: Expressed in brain, testis, kidney, placenta and
CC       liver. {ECO:0000269|PubMed:11311936}.
CC   -!- DOMAIN: The kinase interacting site is required for proper delivery of
CC       ERBB2 to the basolateral membrane. {ECO:0000269|PubMed:12967566}.
CC   -!- DOMAIN: The PDZ domain regulates endocytosis and recycling of the
CC       receptor at the membrane. {ECO:0000269|PubMed:12967566}.
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; AF087693; AAC78481.1; -; mRNA.
DR   EMBL; AF173081; AAD48500.1; -; mRNA.
DR   EMBL; CR407680; CAG28608.1; -; mRNA.
DR   EMBL; AK315321; BAG37724.1; -; mRNA.
DR   EMBL; BC099921; AAH99921.1; -; mRNA.
DR   EMBL; BC118609; AAI18610.1; -; mRNA.
DR   EMBL; BC122561; AAI22562.1; -; mRNA.
DR   EMBL; AF028826; AAB84251.1; -; mRNA.
DR   CCDS; CCDS9021.1; -.
DR   RefSeq; NP_004655.1; NM_004664.3.
DR   AlphaFoldDB; O14910; -.
DR   SMR; O14910; -.
DR   BioGRID; 114352; 61.
DR   ComplexPortal; CPX-7744; LIN-10-LIN-2-LIN-7 complex, LIN7A variant.
DR   CORUM; O14910; -.
DR   IntAct; O14910; 35.
DR   MINT; O14910; -.
DR   STRING; 9606.ENSP00000447488; -.
DR   iPTMnet; O14910; -.
DR   PhosphoSitePlus; O14910; -.
DR   BioMuta; LIN7A; -.
DR   EPD; O14910; -.
DR   jPOST; O14910; -.
DR   MassIVE; O14910; -.
DR   MaxQB; O14910; -.
DR   PaxDb; 9606-ENSP00000447488; -.
DR   PeptideAtlas; O14910; -.
DR   ProteomicsDB; 48294; -.
DR   Pumba; O14910; -.
DR   Antibodypedia; 29812; 205 antibodies from 26 providers.
DR   DNASU; 8825; -.
DR   Ensembl; ENST00000552864.6; ENSP00000447488.1; ENSG00000111052.8.
DR   GeneID; 8825; -.
DR   KEGG; hsa:8825; -.
DR   MANE-Select; ENST00000552864.6; ENSP00000447488.1; NM_004664.4; NP_004655.1.
DR   UCSC; uc001szi.4; human.
DR   AGR; HGNC:17787; -.
DR   CTD; 8825; -.
DR   DisGeNET; 8825; -.
DR   GeneCards; LIN7A; -.
DR   HGNC; HGNC:17787; LIN7A.
DR   HPA; ENSG00000111052; Tissue enhanced (bone marrow, retina).
DR   MIM; 603380; gene.
DR   neXtProt; NX_O14910; -.
DR   OpenTargets; ENSG00000111052; -.
DR   PharmGKB; PA134881936; -.
DR   VEuPathDB; HostDB:ENSG00000111052; -.
DR   eggNOG; KOG3550; Eukaryota.
DR   GeneTree; ENSGT00940000153222; -.
DR   InParanoid; O14910; -.
DR   OMA; EHETEFI; -.
DR   OrthoDB; 4175920at2759; -.
DR   PhylomeDB; O14910; -.
DR   TreeFam; TF316850; -.
DR   PathwayCommons; O14910; -.
DR   Reactome; R-HSA-212676; Dopamine Neurotransmitter Release Cycle.
DR   Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR   Reactome; R-HSA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR   SignaLink; O14910; -.
DR   BioGRID-ORCS; 8825; 6 hits in 1149 CRISPR screens.
DR   ChiTaRS; LIN7A; human.
DR   GeneWiki; LIN7A; -.
DR   GenomeRNAi; 8825; -.
DR   Pharos; O14910; Tbio.
DR   PRO; PR:O14910; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; O14910; Protein.
DR   Bgee; ENSG00000111052; Expressed in Brodmann (1909) area 23 and 149 other cell types or tissues.
DR   ExpressionAtlas; O14910; 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:0070062; C:extracellular exosome; HDA:UniProtKB.
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; IPI:BHF-UCL.
DR   GO; GO:0006887; P:exocytosis; TAS:ProtInc.
DR   GO; GO:0048839; P:inner ear development; IEA:Ensembl.
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   GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR   GO; GO:0048489; P:synaptic vesicle transport; IEA:Ensembl.
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:SF4; PROTEIN LIN-7 HOMOLOG A; 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; O14910; HS.
PE   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Exocytosis; Membrane;
KW   Postsynaptic cell membrane; Protein transport; Reference proteome; Synapse;
KW   Tight junction; Transport.
FT   CHAIN           1..233
FT                   /note="Protein lin-7 homolog A"
FT                   /id="PRO_0000189623"
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   CONFLICT        157
FT                   /note="S -> P (in Ref. 3; CAG28608)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   233 AA;  25997 MW;  D8D05EF16A93BE7B CRC64;
     MLKPSVTSAP TADMATLTVV QPLTLDRDVA RAIELLEKLQ ESGEVPVHKL QSLKKVLQSE
     FCTAIREVYQ YMHETITVNG CPEFRARATA KATVAAFAAS EGHSHPRVVE LPKTDEGLGF
     NVMGGKEQNS PIYISRIIPG GVAERHGGLK RGDQLLSVNG VSVEGEHHEK AVELLKAAKD
     SVKLVVRYTP KVLEEMEARF EKLRTARRRQ QQQLLIQQQQ QQQQQQTQQN HMS
//