LIN7C_HUMAN
ID LIN7C_HUMAN Reviewed; 197 AA.
AC Q9NUP9;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Protein lin-7 homolog C;
DE Short=Lin-7C;
DE AltName: Full=Mammalian lin-seven protein 3;
DE Short=MALS-3;
DE AltName: Full=Vertebrate lin-7 homolog 3;
DE Short=Veli-3;
GN Name=LIN7C; Synonyms=MALS3, VELI3;
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 [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [3]
RP PROTEIN SEQUENCE OF 2-12; 17-23 AND 77-92, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Osteosarcoma;
RA Bienvenut W.V., Lao L., Ryan K.M.;
RL Submitted (JUN-2009) to UniProtKB.
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 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).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 3-64 IN COMPLEX WITH MPP7 AND
RP DLG1, AND SUBUNIT.
RX PubMed=20702775; DOI=10.1096/fj.10-163857;
RA Yang X., Xie X., Chen L., Zhou H., Wang Z., Zhao W., Tian R., Zhang R.,
RA Tian C., Long J., Shen Y.;
RT "Structural basis for tandem L27 domain-mediated polymerization.";
RL FASEB J. 24:4806-4815(2010).
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:O88952}.
CC -!- SUBUNIT: Forms a complex with CASK and APBA1 or CASKIN1 (By
CC similarity). Component of the brain-specific heterotrimeric complex
CC (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and
CC LIN7, which associates with the motor protein KIF17 to transport
CC vesicles along microtubules (By similarity). Can also interact with
CC other modular proteins containing protein-protein interaction domains
CC like PALS1, PALS2, MPP7, DLG1, DLG2 and DLG3 through its L27 domain.
CC Interacts with DLG4 and GRIN2B 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). Interacts with MAPK12
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:O88952}.
CC -!- INTERACTION:
CC Q9NUP9; Q14168-4: MPP2; NbExp=7; IntAct=EBI-1171517, EBI-14385193;
CC Q9NUP9; Q13368: MPP3; NbExp=7; IntAct=EBI-1171517, EBI-716157;
CC Q9NUP9; Q5T2T1: MPP7; NbExp=4; IntAct=EBI-1171517, EBI-2514004;
CC Q9NUP9; Q8N3R9: PALS1; NbExp=4; IntAct=EBI-1171517, EBI-2513978;
CC Q9NUP9; Q9NZW5: PALS2; NbExp=6; IntAct=EBI-1171517, EBI-2683764;
CC Q9NUP9; P07947: YES1; NbExp=3; IntAct=EBI-1171517, EBI-515331;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12967566};
CC Peripheral membrane protein {ECO:0000269|PubMed:12967566}. Basolateral
CC cell membrane {ECO:0000269|PubMed:12967566}; Peripheral membrane
CC protein {ECO:0000269|PubMed:12967566}. Cell junction {ECO:0000250}.
CC Postsynaptic density membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Cell junction, tight junction {ECO:0000250}.
CC Note=Mainly basolateral in renal epithelial cells. {ECO:0000250}.
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; AK002077; BAA92072.1; -; mRNA.
DR EMBL; BC053907; AAH53907.1; -; mRNA.
DR CCDS; CCDS7864.1; -.
DR RefSeq; NP_060832.1; NM_018362.3.
DR PDB; 3LRA; X-ray; 2.95 A; A=3-64.
DR PDBsum; 3LRA; -.
DR AlphaFoldDB; Q9NUP9; -.
DR SMR; Q9NUP9; -.
DR BioGRID; 120608; 108.
DR CORUM; Q9NUP9; -.
DR IntAct; Q9NUP9; 57.
DR MINT; Q9NUP9; -.
DR STRING; 9606.ENSP00000278193; -.
DR GlyGen; Q9NUP9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NUP9; -.
DR MetOSite; Q9NUP9; -.
DR PhosphoSitePlus; Q9NUP9; -.
DR BioMuta; LIN7C; -.
DR DMDM; 59798474; -.
DR EPD; Q9NUP9; -.
DR jPOST; Q9NUP9; -.
DR MassIVE; Q9NUP9; -.
DR MaxQB; Q9NUP9; -.
DR PaxDb; Q9NUP9; -.
DR PeptideAtlas; Q9NUP9; -.
DR PRIDE; Q9NUP9; -.
DR ProteomicsDB; 82705; -.
DR Antibodypedia; 25423; 143 antibodies from 27 providers.
DR DNASU; 55327; -.
DR Ensembl; ENST00000278193.7; ENSP00000278193.2; ENSG00000148943.12.
DR GeneID; 55327; -.
DR KEGG; hsa:55327; -.
DR MANE-Select; ENST00000278193.7; ENSP00000278193.2; NM_018362.4; NP_060832.1.
DR UCSC; uc001mrl.4; human.
DR CTD; 55327; -.
DR DisGeNET; 55327; -.
DR GeneCards; LIN7C; -.
DR HGNC; HGNC:17789; LIN7C.
DR HPA; ENSG00000148943; Low tissue specificity.
DR MIM; 612332; gene.
DR neXtProt; NX_Q9NUP9; -.
DR OpenTargets; ENSG00000148943; -.
DR PharmGKB; PA134891786; -.
DR VEuPathDB; HostDB:ENSG00000148943; -.
DR eggNOG; KOG3550; Eukaryota.
DR GeneTree; ENSGT00940000153222; -.
DR InParanoid; Q9NUP9; -.
DR OMA; MENRFER; -.
DR OrthoDB; 1335138at2759; -.
DR PhylomeDB; Q9NUP9; -.
DR TreeFam; TF316850; -.
DR PathwayCommons; Q9NUP9; -.
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; Q9NUP9; -.
DR SIGNOR; Q9NUP9; -.
DR BioGRID-ORCS; 55327; 42 hits in 1078 CRISPR screens.
DR ChiTaRS; LIN7C; human.
DR EvolutionaryTrace; Q9NUP9; -.
DR GeneWiki; LIN7C; -.
DR GenomeRNAi; 55327; -.
DR Pharos; Q9NUP9; Tbio.
DR PRO; PR:Q9NUP9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9NUP9; protein.
DR Bgee; ENSG00000148943; Expressed in esophagus squamous epithelium and 203 other tissues.
DR ExpressionAtlas; Q9NUP9; baseline and differential.
DR Genevisible; Q9NUP9; 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; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0097025; C:MPP7-DLG1-LIN7 complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0008092; F:cytoskeletal protein binding; IPI:UniProtKB.
DR GO; GO:0097016; F:L27 domain binding; IDA:UniProtKB.
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:0002011; P:morphogenesis of an epithelial sheet; IMP:UniProtKB.
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 IDEAL; IID00521; -.
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; Acetylation; Cell junction; Cell membrane;
KW Direct protein sequencing; Exocytosis; Membrane;
KW Postsynaptic cell membrane; Protein transport; Reference proteome; Synapse;
KW Tight junction; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.3, ECO:0007744|PubMed:22814378"
FT CHAIN 2..197
FT /note="Protein lin-7 homolog C"
FT /id="PRO_0000189629"
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 MOTIF 2..13
FT /note="Kinase interacting site"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.3, ECO:0007744|PubMed:22814378"
FT HELIX 7..26
FT /evidence="ECO:0007829|PDB:3LRA"
FT HELIX 33..43
FT /evidence="ECO:0007829|PDB:3LRA"
FT HELIX 45..60
FT /evidence="ECO:0007829|PDB:3LRA"
SQ SEQUENCE 197 AA; 21834 MW; 7410FBFA3BD24F45 CRC64;
MAALGEPVRL ERDICRAIEL LEKLQRSGEV PPQKLQALQR VLQSEFCNAV REVYEHVYET
VDISSSPEVR ANATAKATVA AFAASEGHSH PRVVELPKTE EGLGFNIMGG KEQNSPIYIS
RIIPGGIADR HGGLKRGDQL LSVNGVSVEG EHHEKAVELL KAAQGKVKLV VRYTPKVLEE
MESRFEKMRS AKRRQQT
