LRFN4_HUMAN
ID LRFN4_HUMAN Reviewed; 635 AA.
AC Q6PJG9; Q4VBZ3; Q59GV4; Q8N644; Q9BWJ0;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Leucine-rich repeat and fibronectin type-III domain-containing protein 4;
DE Flags: Precursor;
GN Name=LRFN4; Synonyms=SALM3;
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], AND VARIANT ALA-340.
RC TISSUE=Eye, Lung, and Prostate;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-635, AND VARIANT ALA-340.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RT "Homo sapiens protein coding cDNA.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH DLG1; DLG2; DLG3 AND DLG4, AND MUTAGENESIS OF
RP 633-SER--VAL-635.
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-626, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-585 AND SER-626, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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. May play a
CC role in redistributing DLG4 to the cell periphery (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Can form heteromeric complexes with LRFN1, LRFN2, LRFN3 and
CC LRFN5. Unable to form homophilic interactions across cell junctions (By
CC similarity). Interacts with DLG1, DLG2, DLG3 and DLG4. {ECO:0000250,
CC ECO:0000269|PubMed:16630835}.
CC -!- INTERACTION:
CC Q6PJG9; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-7910762, EBI-10173507;
CC Q6PJG9; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-7910762, EBI-3867333;
CC Q6PJG9; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-7910762, EBI-11959885;
CC Q6PJG9; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-7910762, EBI-11749135;
CC Q6PJG9; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-7910762, EBI-10171774;
CC Q6PJG9; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-7910762, EBI-11962084;
CC Q6PJG9; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-7910762, EBI-945833;
CC Q6PJG9; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-7910762, EBI-22310682;
CC Q6PJG9; P07237: P4HB; NbExp=3; IntAct=EBI-7910762, EBI-395883;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- DOMAIN: The PDZ-binding motif is required for neurite outgrowth
CC promotion (By similarity). This motif is also involved in DLG1-,
CC 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; BC000207; AAH00207.2; -; mRNA.
DR EMBL; BC015581; AAH15581.2; -; mRNA.
DR EMBL; BC027475; AAH27475.2; -; mRNA.
DR EMBL; BC094813; AAH94813.1; -; mRNA.
DR EMBL; AB209005; BAD92242.1; -; mRNA.
DR CCDS; CCDS8153.1; -.
DR RefSeq; NP_076941.2; NM_024036.4.
DR RefSeq; XP_005274296.1; XM_005274239.3.
DR AlphaFoldDB; Q6PJG9; -.
DR SMR; Q6PJG9; -.
DR BioGRID; 122470; 100.
DR IntAct; Q6PJG9; 67.
DR MINT; Q6PJG9; -.
DR STRING; 9606.ENSP00000312535; -.
DR GlyGen; Q6PJG9; 6 sites.
DR iPTMnet; Q6PJG9; -.
DR PhosphoSitePlus; Q6PJG9; -.
DR BioMuta; LRFN4; -.
DR DMDM; 62286924; -.
DR EPD; Q6PJG9; -.
DR jPOST; Q6PJG9; -.
DR MassIVE; Q6PJG9; -.
DR MaxQB; Q6PJG9; -.
DR PaxDb; Q6PJG9; -.
DR PeptideAtlas; Q6PJG9; -.
DR PRIDE; Q6PJG9; -.
DR ProteomicsDB; 67206; -.
DR Antibodypedia; 30278; 51 antibodies from 21 providers.
DR DNASU; 78999; -.
DR Ensembl; ENST00000309602.5; ENSP00000312535.4; ENSG00000173621.9.
DR GeneID; 78999; -.
DR KEGG; hsa:78999; -.
DR MANE-Select; ENST00000309602.5; ENSP00000312535.4; NM_024036.5; NP_076941.2.
DR UCSC; uc001ojr.4; human.
DR CTD; 78999; -.
DR DisGeNET; 78999; -.
DR GeneCards; LRFN4; -.
DR HGNC; HGNC:28456; LRFN4.
DR HPA; ENSG00000173621; Low tissue specificity.
DR MalaCards; LRFN4; -.
DR MIM; 612810; gene.
DR neXtProt; NX_Q6PJG9; -.
DR OpenTargets; ENSG00000173621; -.
DR PharmGKB; PA134922153; -.
DR VEuPathDB; HostDB:ENSG00000173621; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000162195; -.
DR InParanoid; Q6PJG9; -.
DR OMA; EAYPDCH; -.
DR OrthoDB; 151757at2759; -.
DR PhylomeDB; Q6PJG9; -.
DR TreeFam; TF350185; -.
DR PathwayCommons; Q6PJG9; -.
DR Reactome; R-HSA-8849932; Synaptic adhesion-like molecules.
DR SignaLink; Q6PJG9; -.
DR SIGNOR; Q6PJG9; -.
DR BioGRID-ORCS; 78999; 14 hits in 1078 CRISPR screens.
DR GenomeRNAi; 78999; -.
DR Pharos; Q6PJG9; Tbio.
DR PRO; PR:Q6PJG9; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6PJG9; protein.
DR Bgee; ENSG00000173621; Expressed in ganglionic eminence and 138 other tissues.
DR ExpressionAtlas; Q6PJG9; baseline and differential.
DR Genevisible; Q6PJG9; HS.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; 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:0099151; P:regulation of postsynaptic density assembly; IBA:GO_Central.
DR GO; GO:1905606; P:regulation of presynapse assembly; IBA:GO_Central.
DR GO; GO:0099560; P:synaptic membrane adhesion; IBA:GO_Central.
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.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Leucine-rich repeat;
KW Membrane; Phosphoprotein; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..635
FT /note="Leucine-rich repeat and fibronectin type-III domain-
FT containing protein 4"
FT /id="PRO_0000014843"
FT TOPO_DOM 17..518
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 519..539
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 540..635
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 17..48
FT /note="LRRNT"
FT REPEAT 49..70
FT /note="LRR 1"
FT REPEAT 73..94
FT /note="LRR 2"
FT REPEAT 97..118
FT /note="LRR 3"
FT REPEAT 121..142
FT /note="LRR 4"
FT REPEAT 146..161
FT /note="LRR 5"
FT REPEAT 170..191
FT /note="LRR 6"
FT REPEAT 194..215
FT /note="LRR 7"
FT DOMAIN 234..280
FT /note="LRRCT"
FT DOMAIN 281..367
FT /note="Ig-like"
FT DOMAIN 405..502
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT REGION 373..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 632..635
FT /note="PDZ-binding"
FT COMPBIAS 566..580
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 585
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 626
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 440
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 302..351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VARIANT 340
FT /note="V -> A (in dbSNP:rs3741194)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT /id="VAR_024499"
FT MUTAGEN 633..635
FT /note="Missing: Loss of DLG1-, DLG3- and DLG4-binding."
FT /evidence="ECO:0000269|PubMed:16630835"
SQ SEQUENCE 635 AA; 66860 MW; 13E66645A17A92EE CRC64;
MAPPLLLLLL ASGAAACPLP CVCQNLSESL STLCAHRGLL FVPPNVDRRT VELRLADNFI
QALGPPDFRN MTGLVDLTLS RNAITRIGAR AFGDLESLRS LHLDGNRLVE LGTGSLRGPV
NLQHLILSGN QLGRIAPGAF DDFLESLEDL DLSYNNLRQV PWAGIGAMPA LHTLNLDHNL
IDALPPGAFA QLGQLSRLDL TSNRLATLAP DPLFSRGRDA EASPAPLVLS FSGNPLHCNC
ELLWLRRLAR PDDLETCASP PGLAGRYFWA VPEGEFSCEP PLIARHTQRL WVLEGQRATL
RCRALGDPAP TMHWVGPDDR LVGNSSRARA FPNGTLEIGV TGAGDAGGYT CIATNPAGEA
TARVELRVLA LPHGGNSSAE GGRPGPSDIA ASARTAAEGE GTLESEPAVQ VTEVTATSGL
VSWGPGRPAD PVWMFQIQYN SSEDETLIYR IVPASSHHFL LKHLVPGADY DLCLLALSPA
AGPSDLTATR LLGCAHFSTL PASPLCHALQ AHVLGGTLTV AVGGVLVAAL LVFTVALLVR
GRGAGNGRLP LKLSHVQSQT NGGPSPTPKA HPPRSPPPRP QRSCSLDLGD AGCYGYARRL
GGAWARRSHS VHGGLLGAGC RGVGGSAERL EESVV
