LRFN2_HUMAN
ID LRFN2_HUMAN Reviewed; 789 AA.
AC Q9ULH4; A5PKU3; Q5SYP9;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Leucine-rich repeat and fibronectin type-III domain-containing protein 2;
DE AltName: Full=Synaptic adhesion-like molecule 1;
DE Flags: Precursor;
GN Name=LRFN2; Synonyms=KIAA1246, SALM1;
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=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP INTERACTION WITH DLG1; DLG2; DLG3 AND DLG4, AND MUTAGENESIS OF
RP 787-SER--VAL-789.
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).
CC -!- FUNCTION: Promotes neurite outgrowth in hippocampal neurons. Enhances
CC the cell surface expression of 2 NMDA receptor subunits GRIN1 and
CC GRIN2A. May play a role in redistributing DLG4 to the cell periphery
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms heteromeric complexes with LRFN1, LRFN3, LRFN4 and
CC LRFN5. Can form homomeric complexes, but not across cell junctions.
CC Directly interacts with 2 NMDA receptor subunits GRIN1 and GRIN2A (By
CC similarity). Interacts with DLG1, DLG2, DLG3 and DLG4. {ECO:0000250,
CC ECO:0000269|PubMed:16630835}.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC Synapse. Postsynaptic cell membrane {ECO:0000250}.
CC -!- DOMAIN: The PDZ-binding motif is required for cell surface expression,
CC neurite outgrowth promotion (By similarity). This motif is also
CC involved in DLG1-, DLG3- and DLG4-binding. {ECO:0000250}.
CC -!- PTM: Glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the LRFN family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86560.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB033072; BAA86560.1; ALT_INIT; mRNA.
DR EMBL; AK291474; BAF84163.1; -; mRNA.
DR EMBL; AL591063; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04006.1; -; Genomic_DNA.
DR EMBL; BC142616; AAI42617.1; -; mRNA.
DR CCDS; CCDS34443.1; -.
DR RefSeq; NP_065788.1; NM_020737.2.
DR RefSeq; XP_011513063.1; XM_011514761.2.
DR RefSeq; XP_011513064.1; XM_011514762.2.
DR RefSeq; XP_016866599.1; XM_017011110.1.
DR AlphaFoldDB; Q9ULH4; -.
DR SMR; Q9ULH4; -.
DR BioGRID; 121564; 18.
DR STRING; 9606.ENSP00000345985; -.
DR GlyGen; Q9ULH4; 4 sites.
DR iPTMnet; Q9ULH4; -.
DR PhosphoSitePlus; Q9ULH4; -.
DR BioMuta; LRFN2; -.
DR DMDM; 62286951; -.
DR jPOST; Q9ULH4; -.
DR MassIVE; Q9ULH4; -.
DR PaxDb; Q9ULH4; -.
DR PeptideAtlas; Q9ULH4; -.
DR PRIDE; Q9ULH4; -.
DR ProteomicsDB; 85027; -.
DR Antibodypedia; 2525; 110 antibodies from 23 providers.
DR DNASU; 57497; -.
DR Ensembl; ENST00000338305.7; ENSP00000345985.6; ENSG00000156564.9.
DR GeneID; 57497; -.
DR KEGG; hsa:57497; -.
DR MANE-Select; ENST00000338305.7; ENSP00000345985.6; NM_020737.3; NP_065788.1.
DR UCSC; uc003oph.2; human.
DR CTD; 57497; -.
DR DisGeNET; 57497; -.
DR GeneCards; LRFN2; -.
DR HGNC; HGNC:21226; LRFN2.
DR HPA; ENSG00000156564; Group enriched (brain, retina).
DR MIM; 612808; gene.
DR neXtProt; NX_Q9ULH4; -.
DR OpenTargets; ENSG00000156564; -.
DR PharmGKB; PA134913285; -.
DR VEuPathDB; HostDB:ENSG00000156564; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000156417; -.
DR HOGENOM; CLU_016998_1_0_1; -.
DR InParanoid; Q9ULH4; -.
DR OMA; EFNCQSA; -.
DR OrthoDB; 151757at2759; -.
DR PhylomeDB; Q9ULH4; -.
DR TreeFam; TF350185; -.
DR PathwayCommons; Q9ULH4; -.
DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR SIGNOR; Q9ULH4; -.
DR BioGRID-ORCS; 57497; 8 hits in 1064 CRISPR screens.
DR ChiTaRS; LRFN2; human.
DR GenomeRNAi; 57497; -.
DR Pharos; Q9ULH4; Tbio.
DR PRO; PR:Q9ULH4; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9ULH4; protein.
DR Bgee; ENSG00000156564; Expressed in cortical plate and 43 other tissues.
DR Genevisible; Q9ULH4; 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 GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl.
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; 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; Postsynaptic cell membrane;
KW Reference proteome; Repeat; Signal; Synapse; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..789
FT /note="Leucine-rich repeat and fibronectin type-III domain-
FT containing protein 2"
FT /id="PRO_0000014838"
FT TOPO_DOM 21..534
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 535..555
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 556..789
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..52
FT /note="LRRNT"
FT REPEAT 53..74
FT /note="LRR 1"
FT REPEAT 77..98
FT /note="LRR 2"
FT REPEAT 101..122
FT /note="LRR 3"
FT REPEAT 125..146
FT /note="LRR 4"
FT REPEAT 150..171
FT /note="LRR 5"
FT REPEAT 174..195
FT /note="LRR 6"
FT REPEAT 198..219
FT /note="LRR 7"
FT DOMAIN 242..288
FT /note="LRRCT"
FT DOMAIN 289..375
FT /note="Ig-like"
FT DOMAIN 421..518
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 383..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 577..602
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 619..654
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 668..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 786..789
FT /note="PDZ-binding"
FT COMPBIAS 383..409
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 584..598
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 29
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 310..359
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VARIANT 770
FT /note="D -> N (in dbSNP:rs3734559)"
FT /id="VAR_049894"
FT MUTAGEN 787..789
FT /note="Missing: Loss of DLG1-, DLG3- and DLG4-binding."
FT /evidence="ECO:0000269|PubMed:16630835"
SQ SEQUENCE 789 AA; 84731 MW; 3D1D298909267F38 CRC64;
METLLGGLLA FGMAFAVVDA CPKYCVCQNL SESLGTLCPS KGLLFVPPDI DRRTVELRLG
GNFIIHISRQ DFANMTGLVD LTLSRNTISH IQPFSFLDLE SLRSLHLDSN RLPSLGEDTL
RGLVNLQHLI VNNNQLGGIA DEAFEDFLLT LEDLDLSYNN LHGLPWDSVR RMVNLHQLSL
DHNLLDHIAE GTFADLQKLA RLDLTSNRLQ KLPPDPIFAR SQASALTATP FAPPLSFSFG
GNPLHCNCEL LWLRRLERDD DLETCGSPGG LKGRYFWHVR EEEFVCEPPL ITQHTHKLLV
LEGQAATLKC KAIGDPSPLI HWVAPDDRLV GNSSRTAVYD NGTLDIFITT SQDSGAFTCI
AANAAGEATA MVEVSIVQLP HLSNSTSRTA PPKSRLSDIT GSSKTSRGGG GSGGGEPPKS
PPERAVLVSE VTTTSALVKW SVSKSAPRVK MYQLQYNCSD DEVLIYRMIP ASNKAFVVNN
LVSGTGYDLC VLAMWDDTAT TLTATNIVGC AQFFTKADYP QCQSMHSQIL GGTMILVIGG
IIVATLLVFI VILMVRYKVC NHEAPSKMAA AVSNVYSQTN GAQPPPPSSA PAGAPPQGPP
KVVVRNELLD FTASLARASD SSSSSSLGSG EAAGLGRAPW RIPPSAPRPK PSLDRLMGAF
ASLDLKSQRK EELLDSRTPA GRGAGTSARG HHSDREPLLG PPAARARSLL PLPLEGKAKR
SHSFDMGDFA AAAAGGVVPG GYSPPRKVSN IWTKRSLSVN GMLLPFEESD LVGARGTFGS
SEWVMESTV
