ID   ISLR2_HUMAN             Reviewed;         745 AA.
AC   Q6UXK2; A8K352; Q9P263;
DT   05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   02-SEP-2026, entry version 168.
DE   RecName: Full=Immunoglobulin superfamily containing leucine-rich repeat protein 2;
DE   AltName: Full=Leucine-rich repeat domain and immunoglobulin domain-containing axon extension protein;
DE   Flags: Precursor;
GN   Name=ISLR2; Synonyms=KIAA1465, LINX; ORFNames=UNQ1885/PRO4329;
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=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   [2]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=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).
CC   -!- FUNCTION: Required for axon extension during neural development.
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Homomultimer. Interacts with NTRK1/TrkA (By similarity).
CC       {ECO:0000250}.
CC   -!- INTERACTION:
CC       Q6UXK2; P54849: EMP1; NbExp=3; IntAct=EBI-1266923, EBI-4319440;
CC       Q6UXK2; P08887: IL6R; NbExp=2; IntAct=EBI-1266923, EBI-299383;
CC       Q6UXK2; Q86VI4: LAPTM4B; NbExp=3; IntAct=EBI-1266923, EBI-3267258;
CC       Q6UXK2; P41159: LEP; NbExp=3; IntAct=EBI-1266923, EBI-12994693;
CC       Q6UXK2; Q96G30: MRAP2; NbExp=3; IntAct=EBI-1266923, EBI-9537218;
CC       Q6UXK2; Q16617: NKG7; NbExp=3; IntAct=EBI-1266923, EBI-3919611;
CC       Q6UXK2; P0DN84: STRIT1; NbExp=3; IntAct=EBI-1266923, EBI-12200293;
CC       Q6UXK2; O75841: UPK1B; NbExp=3; IntAct=EBI-1266923, EBI-12237619;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass membrane
CC       protein {ECO:0000250}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA95989.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AB040898; BAA95989.2; ALT_INIT; mRNA.
DR   EMBL; AY358316; AAQ88682.1; -; mRNA.
DR   EMBL; AK290467; BAF83156.1; -; mRNA.
DR   CCDS; CCDS10259.1; -.
DR   RefSeq; NP_001123608.1; NM_001130136.1.
DR   RefSeq; NP_001123609.1; NM_001130137.1.
DR   RefSeq; NP_001123610.1; NM_001130138.2.
DR   RefSeq; NP_065902.1; NM_020851.3.
DR   RefSeq; XP_011520142.1; XM_011521840.4.
DR   RefSeq; XP_011520143.1; XM_011521841.2.
DR   RefSeq; XP_024305771.1; XM_024450003.2.
DR   RefSeq; XP_024305772.1; XM_024450004.2.
DR   RefSeq; XP_024305773.1; XM_024450005.2.
DR   RefSeq; XP_024305774.1; XM_024450006.2.
DR   RefSeq; XP_024305775.1; XM_024450007.2.
DR   RefSeq; XP_024305776.1; XM_024450008.2.
DR   RefSeq; XP_047288861.1; XM_047432905.1.
DR   RefSeq; XP_054234506.1; XM_054378531.1.
DR   RefSeq; XP_054234507.1; XM_054378532.1.
DR   RefSeq; XP_054234508.1; XM_054378533.1.
DR   RefSeq; XP_054234509.1; XM_054378534.1.
DR   RefSeq; XP_054234510.1; XM_054378535.1.
DR   RefSeq; XP_054234511.1; XM_054378536.1.
DR   RefSeq; XP_054234512.1; XM_054378537.1.
DR   RefSeq; XP_054234513.1; XM_054378538.1.
DR   RefSeq; XP_054234514.1; XM_054378539.1.
DR   AlphaFoldDB; Q6UXK2; -.
DR   SMR; Q6UXK2; -.
DR   BioGRID; 121658; 10.
DR   CORUM; Q6UXK2; -.
DR   FunCoup; Q6UXK2; 22.
DR   IntAct; Q6UXK2; 23.
DR   MINT; Q6UXK2; -.
DR   STRING; 9606.ENSP00000355402; -.
DR   GlyConnect; Q6UXK2; 1 N-Linked glycan (1 site).
DR   GlyCosmos; Q6UXK2; 6 sites, No reported glycans.
DR   GlyGen; Q6UXK2; 7 sites, 1 N-linked glycan (1 site).
DR   iPTMnet; Q6UXK2; -.
DR   PhosphoSitePlus; Q6UXK2; -.
DR   BioMuta; ISLR2; -.
DR   DMDM; 74758577; -.
DR   MassIVE; Q6UXK2; -.
DR   PaxDb; 9606-ENSP00000355402; -.
DR   PeptideAtlas; Q6UXK2; -.
DR   ProteomicsDB; 67633; -.
DR   Antibodypedia; 26861; 80 antibodies from 19 providers.
DR   DNASU; 57611; -.
DR   Ensembl; ENST00000361742.7; ENSP00000355402.3; ENSG00000167178.18.
DR   Ensembl; ENST00000435464.5; ENSP00000411443.1; ENSG00000167178.18.
DR   Ensembl; ENST00000453268.3; ENSP00000411834.2; ENSG00000167178.18.
DR   Ensembl; ENST00000565159.5; ENSP00000455531.1; ENSG00000167178.18.
DR   Ensembl; ENST00000565540.1; ENSP00000458080.1; ENSG00000167178.18.
DR   Ensembl; ENST00000938681.1; ENSP00000608740.1; ENSG00000167178.18.
DR   Ensembl; ENST00000960910.1; ENSP00000630969.1; ENSG00000167178.18.
DR   Ensembl; ENST00000960911.1; ENSP00000630970.1; ENSG00000167178.18.
DR   GeneID; 57611; -.
DR   KEGG; hsa:57611; -.
DR   MANE-Select; ENST00000453268.3; ENSP00000411834.2; NM_020851.3; NP_065902.1.
DR   UCSC; uc002axd.3; human.
DR   AGR; HGNC:29286; -.
DR   ClinPGx; PA143485505; -.
DR   CTD; 57611; -.
DR   DisGeNET; 57611; -.
DR   GeneCards; ISLR2; -.
DR   HGNC; HGNC:29286; ISLR2.
DR   HPA; ENSG00000167178; Group enriched (brain, heart muscle, testis).
DR   MIM; 614179; gene.
DR   OpenTargets; ENSG00000167178; -.
DR   VEuPathDB; HostDB:ENSG00000167178; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00940000162846; -.
DR   HOGENOM; CLU_400948_0_0_1; -.
DR   InParanoid; Q6UXK2; -.
DR   OMA; GHSMVQW; -.
DR   OrthoDB; 2151624at2759; -.
DR   PAN-GO; Q6UXK2; 2 GO annotations based on evolutionary models.
DR   PhylomeDB; Q6UXK2; -.
DR   PathwayCommons; Q6UXK2; -.
DR   SignaLink; Q6UXK2; -.
DR   Agora; ENSG00000167178; -.
DR   BioGRID-ORCS; 57611; 16 hits in 1142 CRISPR screens.
DR   ChiTaRS; ISLR2; human.
DR   GenomeRNAi; 57611; -.
DR   Pharos; Q6UXK2; Tbio.
DR   PRO; PR:Q6UXK2; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q6UXK2; protein.
DR   Bgee; ENSG00000167178; Expressed in cortical plate and 97 other cell types or tissues.
DR   ExpressionAtlas; Q6UXK2; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045773; P:positive regulation of axon extension; ISS:UniProtKB.
DR   FunFam; 2.60.40.10:FF:001899; Immunoglobulin superfamily containing leucine rich repeat 2; 1.
DR   FunFam; 3.80.10.10:FF:000058; immunoglobulin superfamily containing leucine-rich repeat protein 2; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   InterPro; IPR000483; Cys-rich_flank_reg_C.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR001611; Leu-rich_rpt.
DR   InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR   InterPro; IPR032675; LRR_dom_sf.
DR   PANTHER; PTHR24366; IG(IMMUNOGLOBULIN) AND LRR(LEUCINE RICH REPEAT) DOMAINS; 1.
DR   PANTHER; PTHR24366:SF15; IMMUNOGLOBULIN SUPERFAMILY CONTAINING LEUCINE-RICH REPEAT PROTEIN 2; 1.
DR   Pfam; PF13855; LRR_8; 2.
DR   SMART; SM00369; LRR_TYP; 5.
DR   SMART; SM00082; LRRCT; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS51450; LRR; 6.
PE   1: Evidence at protein level;
KW   Cell membrane; Developmental protein; Disulfide bond; Glycoprotein;
KW   Immunoglobulin domain; Leucine-rich repeat; Membrane; Neurogenesis;
KW   Phosphoprotein; Proteomics identification; Reference proteome; Repeat;
KW   Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   CHAIN           19..745
FT                   /note="Immunoglobulin superfamily containing leucine-rich
FT                   repeat protein 2"
FT                   /id="PRO_0000317498"
FT   TOPO_DOM        19..589
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        590..610
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        611..745
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          19..51
FT                   /note="LRRNT"
FT   REPEAT          52..73
FT                   /note="LRR 1"
FT   REPEAT          76..97
FT                   /note="LRR 2"
FT   REPEAT          100..123
FT                   /note="LRR 3"
FT   REPEAT          124..145
FT                   /note="LRR 4"
FT   REPEAT          148..169
FT                   /note="LRR 5"
FT   DOMAIN          181..232
FT                   /note="LRRCT"
FT   DOMAIN          233..371
FT                   /note="Ig-like"
FT   REGION          287..326
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          375..466
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          656..722
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        290..306
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        431..449
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        665..683
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         719
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5RKR3"
FT   MOD_RES         720
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q5RKR3"
FT   CARBOHYD        52
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        121
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        364
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        474
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        563
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        260..355
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VARIANT         137
FT                   /note="S -> F (in dbSNP:rs3889598)"
FT                   /id="VAR_049881"
FT   CONFLICT        19
FT                   /note="S -> P (in Ref. 4; BAF83156)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   745 AA;  78990 MW;  7188FC3003EC2B7E CRC64;
     MFPLRALWLV WALLGVAGSC PEPCACVDKY AHQFADCAYK ELREVPEGLP ANVTTLSLSA
     NKITVLRRGA FADVTQVTSL WLAHNEVRTV EPGALAVLSQ LKNLDLSHNF ISSFPWSDLR
     NLSALQLLKM NHNRLGSLPR DALGALPDLR SLRINNNRLR TLAPGTFDAL SALSHLQLYH
     NPFHCGCGLV WLQAWAASTR VSLPEPDSIA CASPPALQGV PVYRLPALPC APPSVHLSAE
     PPLEAPGTPL RAGLAFVLHC IADGHPTPRL QWQLQIPGGT VVLEPPVLSG EDDGVGAEEG
     EGEGDGDLLT QTQAQTPTPA PAWPAPPATP RFLALANGSL LVPLLSAKEA GVYTCRAHNE
     LGANSTSIRV AVAATGPPKH APGAGGEPDG QAPTSERKST AKGRGNSVLP SKPEGKIKGQ
     GLAKVSILGE TETEPEEDTS EGEEAEDQIL ADPAEEQRCG NGDPSRYVSN HAFNQSAELK
     PHVFELGVIA LDVAEREARV QLTPLAARWG PGPGGAGGAP RPGRRPLRLL YLCPAGGGAA
     VQWSRVEEGV NAYWFRGLRP GTNYSVCLAL AGEACHVQVV FSTKKELPSL LVIVAVSVFL
     LVLATVPLLG AACCHLLAKH PGKPYRLILR PQAPDPMEKR IAADFDPRAS YLESEKSYPA
     GGEAGGEEPE DVQGEGLDED AEQGDPSGDL QREESLAACS LVESQSKANQ EEFEAGSEYS
     DRLPLGAEAV NIAQEINGNY RQTAG
//