LHPL4_MOUSE
ID LHPL4_MOUSE Reviewed; 247 AA.
AC Q5U4E0; Q5DTS1; Q8BQU2;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=LHFPL tetraspan subfamily member 4 protein {ECO:0000250|UniProtKB:Q7Z7J7};
DE AltName: Full=GABAA receptor regulatory Lhfpl4 {ECO:0000303|PubMed:28279354};
DE AltName: Full=Lipoma HMGIC fusion partner-like 4 protein {ECO:0000312|MGI:MGI:3057108};
GN Name=Lhfpl4 {ECO:0000312|MGI:MGI:3057108};
GN Synonyms=Garlh4 {ECO:0000303|PubMed:28279354}, Kiaa4027,
GN Lh4 {ECO:0000303|PubMed:28279354};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=26964900; DOI=10.1038/srep23037;
RA Zhao F., Zhou J., Li R., Dudley E.A., Ye X.;
RT "Novel function of LHFPL2 in female and male distal reproductive tract
RT development.";
RL Sci. Rep. 6:23037-23037(2016).
RN [6]
RP INTERACTION WITH GABAARS, INTERACTION WITH GABRB3; GABRA2 AND GABRG2,
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND FUNCTION.
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).
RN [7]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH NLGN2, FUNCTION,
RP AND INTERACTION WITH GABAARS.
RX PubMed=28279354; DOI=10.1016/j.neuron.2017.02.023;
RA Yamasaki T., Hoyos-Ramirez E., Martenson J.S., Morimoto-Tomita M.,
RA Tomita S.;
RT "GARLH family proteins stabilize GABAA receptors at synapses.";
RL Neuron 93:1138-1152(2017).
RN [8]
RP SUBCELLULAR LOCATION, FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY,
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH GABAARS, AND
RP INTERACTION WITH GABRG2; GABRA1 AND NLGN2.
RX PubMed=29742426; DOI=10.1016/j.celrep.2018.04.015;
RA Wu M., Tian H.L., Liu X., Lai J.H.C., Du S., Xia J.;
RT "Impairment of inhibitory synapse formation and motor behavior in mice
RT lacking the NL2 binding partner LHFPL4/GARLH4.";
RL Cell Rep. 23:1691-1705(2018).
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 (PubMed:28978485,
CC PubMed:28279354, PubMed:29742426). Acts in concert with NLGN2 to
CC recruit or stabilize GABAARs (PubMed:29742426).
CC {ECO:0000269|PubMed:28279354, ECO:0000269|PubMed:28978485,
CC ECO:0000269|PubMed:29742426}.
CC -!- SUBUNIT: Interacts with GABA(A) receptor subunits (PubMed:28279354,
CC PubMed:28978485, PubMed:29742426). Interacts with GABRB3
CC (PubMed:28978485). Interacts with GABRA2 (PubMed:28978485). Interacts
CC with GABRG2 (PubMed:28978485, PubMed:29742426). Interacts with GABRA1
CC (PubMed:29742426). Identified in a complex of 720 kDa composed of
CC LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).
CC Interacts with NLGN2; leading to mutual regulation of protein level and
CC synaptic clustering (PubMed:29742426, PubMed:28978485).
CC {ECO:0000250|UniProtKB:Q7TSY2, ECO:0000269|PubMed:28279354,
CC ECO:0000269|PubMed:28978485, ECO:0000269|PubMed:29742426}.
CC -!- SUBCELLULAR LOCATION: Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q7TSY2}. Postsynaptic cell membrane
CC {ECO:0000269|PubMed:28978485, ECO:0000269|PubMed:29742426}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Specifically localizes to
CC inhibitory postsynaptic sites (PubMed:28978485, PubMed:29742426).
CC Colocalizes with GPHN, GABRG2 and NLGN2 at inhibitory postsynaptic
CC sites (By similarity) (PubMed:29742426). {ECO:0000250|UniProtKB:Q7TSY2,
CC ECO:0000269|PubMed:28978485, ECO:0000269|PubMed:29742426}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain, including the
CC cortex, hippocampus, midbrain, olfactory bulb pona plus medulla (at
CC protein level) (PubMed:26964900, PubMed:28279354, PubMed:29742426).
CC Expressed in the in the cerebellar granular layer and in granular
CC layer. Colocalized with GPHN at inhibitory synapses (PubMed:29742426).
CC Weakly expressed in heart, testis, lung, intestine, vagina, ovary and
CC uterus (PubMed:26964900). {ECO:0000269|PubMed:26964900,
CC ECO:0000269|PubMed:28279354, ECO:0000269|PubMed:29742426}.
CC -!- DISRUPTION PHENOTYPE: Contradictory results have been described and may
CC be due to differences in the methods used for gene disruption
CC (PubMed:28978485, PubMed:29742426). No visible phenotype, mice are
CC viable and fertile until adulthood (PubMed:28978485). However cultured
CC hippocampal neurons from deficient mice shown a dramatic decrease in
CC both amplitude and frequency of miniature inhibitory postsynaptic
CC currents (mIPSC) (PubMed:28978485). In contrast, deficient mice exhibit
CC profound impairment of inhibitory synapse formation, prominent motor
CC behavioral deficits and premature death (PubMed:29742426).
CC {ECO:0000269|PubMed:28978485, ECO:0000269|PubMed:29742426}.
CC -!- SIMILARITY: Belongs to the LHFP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD90276.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK046437; BAC32729.1; -; mRNA.
DR EMBL; AK220449; BAD90276.1; ALT_INIT; mRNA.
DR EMBL; BC085130; AAH85130.1; -; mRNA.
DR CCDS; CCDS39591.1; -.
DR RefSeq; NP_808431.2; NM_177763.3.
DR RefSeq; XP_017177089.1; XM_017321600.1.
DR AlphaFoldDB; Q5U4E0; -.
DR SMR; Q5U4E0; -.
DR STRING; 10090.ENSMUSP00000124470; -.
DR iPTMnet; Q5U4E0; -.
DR PhosphoSitePlus; Q5U4E0; -.
DR EPD; Q5U4E0; -.
DR PaxDb; Q5U4E0; -.
DR PRIDE; Q5U4E0; -.
DR ProteomicsDB; 290026; -.
DR Antibodypedia; 51961; 25 antibodies from 9 providers.
DR DNASU; 269788; -.
DR Ensembl; ENSMUST00000162280; ENSMUSP00000124470; ENSMUSG00000042873.
DR GeneID; 269788; -.
DR KEGG; mmu:269788; -.
DR UCSC; uc009dev.1; mouse.
DR CTD; 375323; -.
DR MGI; MGI:3057108; Lhfpl4.
DR VEuPathDB; HostDB:ENSMUSG00000042873; -.
DR eggNOG; KOG4026; Eukaryota.
DR GeneTree; ENSGT00990000203541; -.
DR HOGENOM; CLU_084868_1_2_1; -.
DR InParanoid; Q5U4E0; -.
DR OMA; SHMYATN; -.
DR OrthoDB; 1219117at2759; -.
DR PhylomeDB; Q5U4E0; -.
DR TreeFam; TF321143; -.
DR BioGRID-ORCS; 269788; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Lhfpl4; mouse.
DR PRO; PR:Q5U4E0; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q5U4E0; protein.
DR Bgee; ENSMUSG00000042873; Expressed in habenula and 102 other tissues.
DR ExpressionAtlas; Q5U4E0; baseline and differential.
DR Genevisible; Q5U4E0; MM.
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; IDA: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; IDA:UniProtKB.
DR GO; GO:0050811; F:GABA receptor binding; IDA:UniProtKB.
DR GO; GO:0097112; P:gamma-aminobutyric acid receptor clustering; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:1905702; P:regulation of inhibitory synapse assembly; IMP: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; Neurogenesis;
KW Postsynaptic cell membrane; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..247
FT /note="LHFPL tetraspan subfamily member 4 protein"
FT /id="PRO_0000285962"
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"
FT CONFLICT 155
FT /note="I -> V (in Ref. 1; BAC32729)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 247 AA; 27050 MW; CB1F73E45A0E32BD CRC64;
MLPSQEASKL YHEHYMRNSR AIGVLWAIFT ICFAIINVVV FIQPYWVGDS VSTPKPGYFG
LFHYCVGSGL AGRELTCRGS FTDFSTIPSS AFKAAAFFVL LSMVLILGCI TCFALFFFCN
TATVYKICAW MQLLAALCLV LGCMIFPDGW DAETIRDMCG AKTGKYSLGD CSVRWAYILA
IIGILNALIL SFLAFVLGNR QTDLLQEELK QENKDFVGTT VSSVLRPGGD VSGWGVLPCP
VAHTQGP
