LRRC7_RAT
ID LRRC7_RAT Reviewed; 1490 AA.
AC P70587; Q9JI42;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Leucine-rich repeat-containing protein 7;
DE AltName: Full=Densin-180;
DE Short=Densin;
DE AltName: Full=Protein LAP1;
GN Name=Lrrc7; Synonyms=Lap1;
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] (ISOFORMS 1 AND 3), PROTEIN SEQUENCE OF 582-595;
RP 715-725 AND 947-959, GLYCOSYLATION, PHOSPHORYLATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=8824323; DOI=10.1523/jneurosci.16-21-06839.1996;
RA Apperson M.L., Moon I.S., Kennedy M.B.;
RT "Characterization of densin-180, a new brain-specific synaptic protein of
RT the O-sialoglycoprotein family.";
RL J. Neurosci. 16:6839-6852(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 898-1490 (ISOFORMS 1; 2; 4 AND 5),
RP DEVELOPMENTAL STAGE, MUTAGENESIS OF SER-1288 AND SER-1392, INTERACTION WITH
RP CAMKII, PHOSPHORYLATION AT SER-1288 AND SER-1392, AND PHOSPHORYLATION AT
RP 1288 (ISOFORM 2).
RC STRAIN=Sprague-Dawley;
RX PubMed=10827168; DOI=10.1074/jbc.c000319200;
RA Strack S., Robison A.J., Bass M.A., Colbran R.J.;
RT "Association of calcium/calmodulin-dependent kinase II with developmentally
RT regulated splice variants of the postsynaptic density protein densin-180.";
RL J. Biol. Chem. 275:25061-25064(2000).
RN [3]
RP INTERACTION WITH CNKSR2 AND DLG4.
RX PubMed=12390249; DOI=10.1046/j.1365-2443.2002.00589.x;
RA Ohtakara K., Nishizawa M., Izawa I., Hata Y., Matsushima S., Taki W.,
RA Inada H., Takai Y., Inagaki M.;
RT "Densin-180, a synaptic protein, links to PSD-95 through its direct
RT interaction with MAGUIN-1.";
RL Genes Cells 7:1149-1160(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439; SER-441; SER-443;
RP SER-850; THR-865; SER-947; SER-949 AND SER-1392, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Required for normal synaptic spine architecture and function.
CC Necessary for DISC1 and GRM5 localization to postsynaptic density
CC complexes and for both N-methyl D-aspartate receptor-dependent and
CC metabotropic glutamate receptor-dependent long term depression (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CNKSR2 and DLG4 (PubMed:12390249). Interacts
CC with CTNND2/Catenin delta-2. Forms a complex with N-cadherin through
CC CTNND2 (By similarity). Interacts with CAMK2A (PubMed:10827168).
CC {ECO:0000250|UniProtKB:Q96NW7, ECO:0000269|PubMed:10827168,
CC ECO:0000269|PubMed:12390249}.
CC -!- INTERACTION:
CC P70587; P11275: Camk2a; NbExp=2; IntAct=EBI-7798464, EBI-2640645;
CC P70587; Q9Z1T4: Cnksr2; NbExp=3; IntAct=EBI-7798464, EBI-8548356;
CC P70587; P31016: Dlg4; NbExp=5; IntAct=EBI-7798464, EBI-375655;
CC P70587; P11798: Camk2a; Xeno; NbExp=2; IntAct=EBI-7798464, EBI-400384;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Postsynaptic density
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=Variant A;
CC IsoId=P70587-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant D;
CC IsoId=P70587-2; Sequence=VSP_010799;
CC Name=3;
CC IsoId=P70587-3; Sequence=VSP_010798;
CC Name=4; Synonyms=Variant B;
CC IsoId=P70587-4; Sequence=VSP_010800;
CC Name=5; Synonyms=Variant C;
CC IsoId=P70587-5; Sequence=VSP_010801;
CC -!- TISSUE SPECIFICITY: Brain-specific. Highly concentrated at synapses.
CC {ECO:0000269|PubMed:8824323}.
CC -!- DEVELOPMENTAL STAGE: Expression of isoform 2 is predominant at E18, but
CC decreased during postnatal development paralleling increased expression
CC of isoform 4 and isoform 5. {ECO:0000269|PubMed:10827168}.
CC -!- PTM: O-glycosylated and phosphorylated. {ECO:0000269|PubMed:8824323}.
CC -!- MISCELLANEOUS: [Isoform 2]: This is the only isoform to have a
CC potential transmembrane domain. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the LAP (LRR and PDZ) protein family.
CC {ECO:0000305}.
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DR EMBL; U66707; AAC52881.1; -; mRNA.
DR EMBL; AF266164; AAF76466.1; -; mRNA.
DR PIR; T31434; T31434.
DR RefSeq; NP_476483.1; NM_057142.1.
DR AlphaFoldDB; P70587; -.
DR SMR; P70587; -.
DR BioGRID; 250730; 8.
DR CORUM; P70587; -.
DR IntAct; P70587; 9.
DR MINT; P70587; -.
DR STRING; 10116.ENSRNOP00000016453; -.
DR iPTMnet; P70587; -.
DR PhosphoSitePlus; P70587; -.
DR SwissPalm; P70587; -.
DR PaxDb; P70587; -.
DR PRIDE; P70587; -.
DR Ensembl; ENSRNOT00000116114; ENSRNOP00000093706; ENSRNOG00000011980. [P70587-5]
DR GeneID; 117284; -.
DR KEGG; rno:117284; -.
DR CTD; 57554; -.
DR RGD; 708527; Lrrc7.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000156262; -.
DR InParanoid; P70587; -.
DR OrthoDB; 40683at2759; -.
DR Reactome; R-RNO-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P70587; -.
DR Proteomes; UP000002494; Chromosome 2.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043194; C:axon initial segment; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR GO; GO:0030054; C:cell junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0030175; C:filopodium; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IDA:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IBA:GO_Central.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:RGD.
DR GO; GO:0043113; P:receptor clustering; IBA:GO_Central.
DR GO; GO:0097120; P:receptor localization to synapse; IBA:GO_Central.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 3.80.10.10; -; 3.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR Pfam; PF13855; LRR_8; 3.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00369; LRR_TYP; 11.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS51450; LRR; 15.
DR PROSITE; PS50106; PDZ; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing; Glycoprotein;
KW Leucine-rich repeat; Methylation; Phosphoprotein; Reference proteome;
KW Repeat; Synapse.
FT CHAIN 1..1490
FT /note="Leucine-rich repeat-containing protein 7"
FT /id="PRO_0000188300"
FT REPEAT 23..44
FT /note="LRR 1"
FT REPEAT 47..68
FT /note="LRR 2"
FT REPEAT 70..91
FT /note="LRR 3"
FT REPEAT 93..114
FT /note="LRR 4"
FT REPEAT 116..137
FT /note="LRR 5"
FT REPEAT 139..161
FT /note="LRR 6"
FT REPEAT 162..183
FT /note="LRR 7"
FT REPEAT 185..206
FT /note="LRR 8"
FT REPEAT 208..229
FT /note="LRR 9"
FT REPEAT 231..253
FT /note="LRR 10"
FT REPEAT 254..275
FT /note="LRR 11"
FT REPEAT 277..298
FT /note="LRR 12"
FT REPEAT 300..321
FT /note="LRR 13"
FT REPEAT 323..344
FT /note="LRR 14"
FT REPEAT 346..367
FT /note="LRR 15"
FT REPEAT 369..391
FT /note="LRR 16"
FT REPEAT 392..413
FT /note="LRR 17"
FT DOMAIN 1398..1488
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 663..709
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 775..808
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 822..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1194..1218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1238..1265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1282..1312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..709
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 775..798
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 832..853
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1285..1305
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 831
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80TE7"
FT MOD_RES 850
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 865
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 869
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TE7"
FT MOD_RES 947
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 949
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TE7"
FT MOD_RES 1149
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q80TE7"
FT MOD_RES 1233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80TE7"
FT MOD_RES 1288
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10827168"
FT MOD_RES 1392
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10827168,
FT ECO:0007744|PubMed:22673903"
FT VAR_SEQ 1218..1241
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8824323"
FT /id="VSP_010798"
FT VAR_SEQ 1285
FT /note="R -> RNAAYKHNTVNLGMLPYGGISAMHAGRSMTLNLQTKSKFDLQDLPLQ
FT K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10827168"
FT /id="VSP_010799"
FT VAR_SEQ 1286..1325
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10827168"
FT /id="VSP_010800"
FT VAR_SEQ 1326..1399
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10827168"
FT /id="VSP_010801"
FT MUTAGEN 1288
FT /note="S->D: Decrease in the level of phosphorylation.
FT Strong decrease in the level of phosphorylation; when
FT associated with D-1392."
FT /evidence="ECO:0000269|PubMed:10827168"
FT MUTAGEN 1392
FT /note="S->D: Strong decrease in the level of
FT phosphorylation; when associated with D-1288."
FT /evidence="ECO:0000269|PubMed:10827168"
FT CONFLICT 722
FT /note="W -> R (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT MOD_RES P70587-4:1288
FT /note="Phosphoserine"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1490 AA; 166879 MW; 30DC3E92EB44F2A5 CRC64;
MTTKRKLIGR LVPCRCFRGE EEIISVLDYS HCSLQQVPKE VFNFERTLEE LYLDANQIEE
LPKQLFNCQA LRKLSIPDND LSSLPTSIAS LVNLKELDIS KNGVQEFPEN IKCCKCLTII
EASVNPISKL PDGFTQLLNL TQLYLNDAFL EFLPANFGRL VKLRILELRE NHLKTLPKSM
HKLAQLERLD LGNNEFSELP EVLDQIQNLR ELWMDNNALQ VLPGSIGKLK MLVYLDMSKN
RIETVDMDIS GCEALEDLLL SSNMLQQLPD SIGLLKKLTT LKVDDNQLTM LPNTIGNLSL
LEEFDCSCNE LESLPPTIGY LHSLRTLAVD ENFLPELPRE IGSCKNVTVM SLRSNKLEFL
PEEIGQMQRL RVLNLSDNRL KNLPFSFTKL KELAALWLSD NQSKALIPLQ TEAHPETKQR
VLTNYMFPQQ PRGDEDFQSD SDSFNPTLWE EQRQQRMTVA FEFEDKKEDD ESAGKVKALS
CQAPWDRGQR GITLQPARLS GDCCTPWARC DQQIQDMPVP QSDPQLAWGC ISGLQQERSM
CAPLPVAAQS TTLPSLSGRQ VEINLKRYPT PYPEDLKNMV KSVQNLVGKP SHGVRVENAN
PTANTEQTVK EKFEHKWPVA PKEITVEDSF VHPANEMRIG ELHPSLAETP LYPPKLVLLG
KDKKESTDES EVDKTHCLNN SVSSGTYSDY SPSQASSASS NTRVKVGSLQ PTTKDAVHNS
LWGNRIAPPF PQPLDAKPLL TQREAVPPGN LPQRPDRLPM SDAFPDNWTD GSHYDNTGFV
SEEATGENAN NNPLLSSKAR SVPAHGRRPL IRQERIVGVP LELEQSTHRH TPETEVPPSN
PWQNWTRTPS PFEDRTAFPS KLETTPTTSP LPERKDHMKE PTETPGPFSP GVPWEYHDPT
PNRSLGNVFS QIHCRPDSSK GVIAISKSTE RLSPLMKDIK SNKFKKSQSI DEIDVGTYKV
YNIPLENYAS GSDHLGSHER PDKFLGPEHG MSSMSRSQSV PMLDDEMLMY GSSKGPPQQK
ASMTKKVYQF DQSFNPQGAV EVKAEKRIPP PFAHNSEYVQ QPGKNIAKDL VSPRAYRGYP
PMEQMFSFSQ PSVNEDAMVN AQFASQGPRA GFLRRADSLA SSTEMAMFRR VSEPHELPPG
DRYGRAAYRG GLEGQSSVSM TDPQFLKRNG RYEDEHPSYQ EVKAQAGSFP AKNLTQRRPL
SARSYSTESY GASQTRPVSA RPTMAALLEK IPSDYNLGNY GDKTSDNSDI KTRPTPVKGE
ESCGKMPADW RQQLLRHIEA RRLDRTPSQQ SNILDNGQED VSPSGQWNPY PLGRRDVPPD
TITKKAGSHI QTLMGSQSLQ HRSREQQPYE GNINKVTIQQ FQSPLPIQIP SSQATRGPQP
GRCLIQTKGQ RSMDGYPEQF CVRIEKNPGL GFSISGGISG QGNPFKPSDK GIFVTRVQPD
GPASNLLQPG DKILQANGHS FVHMEHEKAV LLLKSFQNTV DLVIQRELTV
