LRFN1_HUMAN
ID LRFN1_HUMAN Reviewed; 771 AA.
AC Q9P244; Q8TBS9;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Leucine-rich repeat and fibronectin type III domain-containing protein 1;
DE AltName: Full=Synaptic adhesion-like molecule 2;
DE Flags: Precursor;
GN Name=LRFN1; Synonyms=KIAA1484, SALM2;
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 GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 72-771.
RC TISSUE=Brain;
RX PubMed=10819331; DOI=10.1093/dnares/7.2.143;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:143-150(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 230-771.
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 [4]
RP INTERACTION WITH DLG1; DLG2; DLG3 AND DLG4.
RX PubMed=16630835; DOI=10.1016/j.neuron.2006.04.005;
RA Ko J., Kim S., Chung H.S., Kim K., Han K., Kim H., Jun H., Kaang B.-K.,
RA Kim E.;
RT "SALM synaptic cell adhesion-like molecules regulate the differentiation of
RT excitatory synapses.";
RL Neuron 50:233-245(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-613, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-718, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Promotes neurite outgrowth in hippocampal neurons. Involved
CC in the regulation and maintenance of excitatory synapses. Induces the
CC clustering of excitatory postsynaptic proteins, including DLG4, DLGAP1,
CC GRIA1 and GRIN1 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Can form heteromeric complexes with LRFN2, LRFN3, LRFN4 and
CC LRFN5 (By similarity). Forms homomeric complexes, but not across cell
CC junctions (By similarity). Interacts with DLG1, DLG2, DLG3 and DLG4.
CC Interacts with 2 AMPA receptor subunits GRIA1 and GRIA2 and NMDA
CC receptor subunit GRIN1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Synapse {ECO:0000250}. Postsynaptic
CC density membrane {ECO:0000250}. Note=Detected in excitatory, but not
CC inhibitory, synaptic plasma membrane. {ECO:0000250}.
CC -!- DOMAIN: The PDZ-binding motif is required for neurite outgrowth
CC promotion and for DLG1-, DLG3- and DLG4-binding. {ECO:0000250}.
CC -!- PTM: Glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the LRFN family. {ECO:0000305}.
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DR EMBL; AC011445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB040917; BAA96008.1; -; mRNA.
DR EMBL; BC025310; AAH25310.1; -; mRNA.
DR CCDS; CCDS46071.1; -.
DR RefSeq; NP_065913.1; NM_020862.1.
DR RefSeq; XP_005259159.1; XM_005259102.4.
DR RefSeq; XP_016882522.1; XM_017027033.1.
DR AlphaFoldDB; Q9P244; -.
DR SMR; Q9P244; -.
DR BioGRID; 121668; 143.
DR IntAct; Q9P244; 18.
DR MINT; Q9P244; -.
DR STRING; 9606.ENSP00000248668; -.
DR GlyGen; Q9P244; 2 sites.
DR iPTMnet; Q9P244; -.
DR PhosphoSitePlus; Q9P244; -.
DR BioMuta; LRFN1; -.
DR DMDM; 189028858; -.
DR jPOST; Q9P244; -.
DR MassIVE; Q9P244; -.
DR MaxQB; Q9P244; -.
DR PaxDb; Q9P244; -.
DR PeptideAtlas; Q9P244; -.
DR PRIDE; Q9P244; -.
DR ProteomicsDB; 83729; -.
DR Antibodypedia; 30291; 74 antibodies from 24 providers.
DR DNASU; 57622; -.
DR Ensembl; ENST00000248668.5; ENSP00000248668.4; ENSG00000128011.5.
DR GeneID; 57622; -.
DR KEGG; hsa:57622; -.
DR MANE-Select; ENST00000248668.5; ENSP00000248668.4; NM_020862.2; NP_065913.1.
DR UCSC; uc002okw.3; human.
DR CTD; 57622; -.
DR GeneCards; LRFN1; -.
DR HGNC; HGNC:29290; LRFN1.
DR HPA; ENSG00000128011; Tissue enhanced (brain).
DR MIM; 612807; gene.
DR neXtProt; NX_Q9P244; -.
DR OpenTargets; ENSG00000128011; -.
DR PharmGKB; PA134871732; -.
DR VEuPathDB; HostDB:ENSG00000128011; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160922; -.
DR HOGENOM; CLU_016998_0_1_1; -.
DR InParanoid; Q9P244; -.
DR OMA; TRVRWDG; -.
DR OrthoDB; 151757at2759; -.
DR PhylomeDB; Q9P244; -.
DR TreeFam; TF350185; -.
DR PathwayCommons; Q9P244; -.
DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR SignaLink; Q9P244; -.
DR SIGNOR; Q9P244; -.
DR BioGRID-ORCS; 57622; 13 hits in 1080 CRISPR screens.
DR ChiTaRS; LRFN1; human.
DR GenomeRNAi; 57622; -.
DR Pharos; Q9P244; Tdark.
DR PRO; PR:Q9P244; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9P244; protein.
DR Bgee; ENSG00000128011; Expressed in medial globus pallidus and 134 other tissues.
DR Genevisible; Q9P244; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR CDD; cd00063; FN3; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR Pfam; PF00041; fn3; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF13855; LRR_8; 2.
DR SMART; SM00060; FN3; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00369; LRR_TYP; 6.
DR SMART; SM00082; LRRCT; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR PROSITE; PS50853; FN3; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51450; LRR; 6.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Leucine-rich repeat; Membrane; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Repeat; Signal; Synapse; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..771
FT /note="Leucine-rich repeat and fibronectin type III domain-
FT containing protein 1"
FT /id="PRO_0000334145"
FT TOPO_DOM 32..536
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 537..557
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 558..771
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..65
FT /note="LRRNT"
FT REPEAT 66..87
FT /note="LRR 1"
FT REPEAT 90..111
FT /note="LRR 2"
FT REPEAT 114..135
FT /note="LRR 3"
FT REPEAT 138..159
FT /note="LRR 4"
FT REPEAT 163..184
FT /note="LRR 5"
FT REPEAT 187..208
FT /note="LRR 6"
FT REPEAT 211..232
FT /note="LRR 7"
FT DOMAIN 252..298
FT /note="LRRCT"
FT DOMAIN 299..386
FT /note="Ig-like"
FT DOMAIN 424..520
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 397..422
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 654..743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 768..771
FT /note="PDZ-binding"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 718
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 87
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 321..370
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 771 AA; 82318 MW; 9B8D0CD3F1E7B9FC CRC64;
MAPGPFSSAL LSPPPAALPF LLLLWAGASR GQPCPGRCIC QNVAPTLTML CAKTGLLFVP
PAIDRRVVEL RLTDNFIAAV RRRDFANMTS LVHLTLSRNT IGQVAAGAFA DLRALRALHL
DSNRLAEVRG DQLRGLGNLR HLILGNNQIR RVESAAFDAF LSTVEDLDLS YNNLEALPWE
AVGQMVNLNT LTLDHNLIDH IAEGTFVQLH KLVRLDMTSN RLHKLPPDGL FLRSQGTGPK
PPTPLTVSFG GNPLHCNCEL LWLRRLTRED DLETCATPEH LTDRYFWSIP EEEFLCEPPL
ITRQAGGRAL VVEGQAVSLR CRAVGDPEPV VHWVAPDGRL LGNSSRTRVR GDGTLDVTIT
TLRDSGTFTC IASNAAGEAT APVEVCVVPL PLMAPPPAAP PPLTEPGSSD IATPGRPGAN
DSAAERRLVA AELTSNSVLI RWPAQRPVPG IRMYQVQYNS SVDDSLVYRM IPSTSQTFLV
NDLAAGRAYD LCVLAVYDDG ATALPATRVV GCVQFTTAGD PAPCRPLRAH FLGGTMIIAI
GGVIVASVLV FIVLLMIRYK VYGDGDSRRV KGSRSLPRVS HVCSQTNGAG TGAAQAPALP
AQDHYEALRE VESQAAPAVA VEAKAMEAET ASAEPEVVLG RSLGGSATSL CLLPSEETSG
EESRAAVGPR RSRSGALEPP TSAPPTLALV PGGAAARPRP QQRYSFDGDY GALFQSHSYP
RRARRTKRHR STPHLDGAGG GAAGEDGDLG LGSARACLAF TSTEWMLEST V
