LHPL4_HUMAN
ID LHPL4_HUMAN Reviewed; 247 AA.
AC Q7Z7J7; A6NH76; Q29RV7;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=LHFPL tetraspan subfamily member 4 protein {ECO:0000312|HGNC:HGNC:29568};
DE AltName: Full=GABAA receptor regulatory Lhfpl4 {ECO:0000250|UniProtKB:Q5U4E0};
DE AltName: Full=Lipoma HMGIC fusion partner-like 4 protein {ECO:0000312|HGNC:HGNC:29568};
GN Name=LHFPL4 {ECO:0000312|HGNC:HGNC:29568};
GN Synonyms=GARLH4 {ECO:0000312|HGNC:HGNC:29568};
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].
RA Huang C.Q., Wu S.L., Liu S.;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP INTERACTION WITH GABAARS, AND INTERACTION WITH GABRA1.
RX PubMed=28978485; DOI=10.1016/j.celrep.2017.09.025;
RA Davenport E.C., Pendolino V., Kontou G., McGee T.P., Sheehan D.F.,
RA Lopez-Domenech G., Farrant M., Kittler J.T.;
RT "An essential role for the tetraspanin LHFPL4 in the cell-type-specific
RT targeting and clustering of synaptic GABAA ceceptors.";
RL Cell Rep. 21:70-83(2017).
CC -!- FUNCTION: Plays a role in the regulation of inhibitory synapse
CC formation and function by being involved in maintening gamma-
CC aminobutyric acid receptors (GABAARs) clustering and their associated
CC scaffold proteins at inhibitory synaptic sites. Acts in concert with
CC NLGN2 to recruit or stabilize GABAARs. {ECO:0000250|UniProtKB:Q5U4E0}.
CC -!- SUBUNIT: Interacts with GABA(A) receptor subunits (PubMed:28978485).
CC Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1,
CC GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with GABRB3 (By
CC similarity). Interacts with GABRA2 (By similarity). Interacts with
CC GABRG2 (By similarity). Interacts with GABRA1 (PubMed:28978485).
CC Interacts with NLGN2; leading to mutual regulation of protein level and
CC synaptic clustering (By similarity). {ECO:0000250|UniProtKB:Q5U4E0,
CC ECO:0000250|UniProtKB:Q7TSY2, ECO:0000269|PubMed:28978485}.
CC -!- INTERACTION:
CC Q7Z7J7; Q9Y6I9: TEX264; NbExp=3; IntAct=EBI-18016128, EBI-10329860;
CC -!- SUBCELLULAR LOCATION: Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q7TSY2}. Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q5U4E0}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Specifically localizes to inhibitory postsynaptic
CC sites (By similarity). Colocalizes with GPHN, GABRG2 and NLGN2 at
CC inhibitory postsynaptic sites (By similarity).
CC {ECO:0000250|UniProtKB:Q5U4E0, ECO:0000250|UniProtKB:Q7TSY2}.
CC -!- SIMILARITY: Belongs to the LHFP family. {ECO:0000305}.
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DR EMBL; AY278320; AAP37013.1; -; mRNA.
DR EMBL; AC026194; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS33691.1; -.
DR RefSeq; NP_940962.1; NM_198560.2.
DR RefSeq; XP_016861848.1; XM_017006359.1.
DR AlphaFoldDB; Q7Z7J7; -.
DR SMR; Q7Z7J7; -.
DR BioGRID; 131972; 43.
DR IntAct; Q7Z7J7; 5.
DR STRING; 9606.ENSP00000287585; -.
DR TCDB; 1.A.82.1.7; the lhfpl tetraspan protein (ltsp) family.
DR PhosphoSitePlus; Q7Z7J7; -.
DR BioMuta; LHFPL4; -.
DR DMDM; 74713775; -.
DR MassIVE; Q7Z7J7; -.
DR PaxDb; Q7Z7J7; -.
DR PeptideAtlas; Q7Z7J7; -.
DR PRIDE; Q7Z7J7; -.
DR ProteomicsDB; 69553; -.
DR Antibodypedia; 51961; 25 antibodies from 9 providers.
DR DNASU; 375323; -.
DR Ensembl; ENST00000287585.8; ENSP00000287585.6; ENSG00000156959.9.
DR GeneID; 375323; -.
DR KEGG; hsa:375323; -.
DR MANE-Select; ENST00000287585.8; ENSP00000287585.6; NM_198560.3; NP_940962.1.
DR UCSC; uc003bry.3; human.
DR CTD; 375323; -.
DR DisGeNET; 375323; -.
DR GeneCards; LHFPL4; -.
DR HGNC; HGNC:29568; LHFPL4.
DR HPA; ENSG00000156959; Group enriched (brain, pituitary gland, retina).
DR MIM; 610240; gene.
DR neXtProt; NX_Q7Z7J7; -.
DR OpenTargets; ENSG00000156959; -.
DR VEuPathDB; HostDB:ENSG00000156959; -.
DR eggNOG; KOG4026; Eukaryota.
DR GeneTree; ENSGT00990000203541; -.
DR HOGENOM; CLU_084868_1_2_1; -.
DR InParanoid; Q7Z7J7; -.
DR OMA; SHMYATN; -.
DR OrthoDB; 1219117at2759; -.
DR PhylomeDB; Q7Z7J7; -.
DR TreeFam; TF321143; -.
DR PathwayCommons; Q7Z7J7; -.
DR SignaLink; Q7Z7J7; -.
DR BioGRID-ORCS; 375323; 21 hits in 1071 CRISPR screens.
DR ChiTaRS; LHFPL4; human.
DR GenomeRNAi; 375323; -.
DR Pharos; Q7Z7J7; Tdark.
DR PRO; PR:Q7Z7J7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q7Z7J7; protein.
DR Bgee; ENSG00000156959; Expressed in cerebellar vermis and 88 other tissues.
DR Genevisible; Q7Z7J7; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0060077; C:inhibitory synapse; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0050811; F:GABA receptor binding; IBA:GO_Central.
DR GO; GO:0097112; P:gamma-aminobutyric acid receptor clustering; ISS:UniProtKB.
DR GO; GO:1905702; P:regulation of inhibitory synapse assembly; ISS:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IBA:GO_Central.
DR InterPro; IPR019372; LHFPL.
DR PANTHER; PTHR12489; PTHR12489; 1.
DR Pfam; PF10242; L_HMGIC_fpl; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Membrane; Postsynaptic cell membrane;
KW Reference proteome; Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..247
FT /note="LHFPL tetraspan subfamily member 4 protein"
FT /id="PRO_0000285961"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
SQ SEQUENCE 247 AA; 27007 MW; 911F73F696DBE515 CRC64;
MLPSQEASKL YHEHYMRNSR AIGVLWAIFT ICFAIINVVV FIQPYWVGDS VSTPKPGYFG
LFHYCVGSGL AGRELTCRGS FTDFSTIPSS AFKAAAFFVL LSMVLILGCI TCFSLFFFCN
TATVYKICAW MQLLAALCLV LGCMIFPDGW DAETIRDMCG AKTGKYSLGD CSVRWAYILA
IIGILNALIL SFLAFVLGNR QTDLLQEELK PENKDFVGST VSSVLRPGGD VSGWGVLPCP
VAHSQGP
