KIRR2_MOUSE
ID KIRR2_MOUSE Reviewed; 700 AA.
AC Q7TSU7; Q7TQ98;
DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Kin of IRRE-like protein 2;
DE AltName: Full=Kin of irregular chiasm-like protein 2;
DE Flags: Precursor;
GN Name=Kirrel2; Synonyms=Neph3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Olfactory epithelium;
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 [MRNA] OF 48-376 (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=12837264; DOI=10.1016/s0888-7543(03)00110-1;
RA Sun C., Kilburn D., Lukashin A., Crowell T., Gardner H., Brundiers R.,
RA Diefenbach B., Carulli J.P.;
RT "Kirrel2, a novel immunoglobulin superfamily gene expressed primarily in
RT beta cells of the pancreatic islets.";
RL Genomics 82:130-142(2003).
RN [3]
RP INTERACTION WITH NPHS2, AND TISSUE SPECIFICITY.
RC STRAIN=Swiss Webster; TISSUE=Brain;
RX PubMed=12424224; DOI=10.1096/fj.02-0242fje;
RA Sellin L., Huber T.B., Gerke P., Quack I., Pavenstaedt H., Walz G.;
RT "NEPH1 defines a novel family of podocin interacting proteins.";
RL FASEB J. 17:115-117(2003).
RN [4]
RP INTERACTION WITH NPHS1, AND TISSUE SPECIFICITY.
RX PubMed=19887377; DOI=10.1074/jbc.m109.060657;
RA Nishida K., Hoshino M., Kawaguchi Y., Murakami F.;
RT "Ptf1a directly controls expression of immunoglobulin superfamily molecules
RT Nephrin and Neph3 in the developing central nervous system.";
RL J. Biol. Chem. 285:373-380(2010).
RN [5]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, INTERACTION WITH FYN, PHOSPHORYLATION
RP AT SER-563; TYR-595; TYR-596 AND TYR-653, SUBUNIT, PROTEOLYTIC PROCESSING,
RP DISRUPTION PHENOTYPE, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS
RP OF 595-TYR-TYR-596; 631-TYR-TYR-632 AND TYR-653.
RX PubMed=26324709; DOI=10.1074/jbc.m115.684704;
RA Yesildag B., Bock T., Herrmanns K., Wollscheid B., Stoffel M.;
RT "Kin of IRRE-like protein 2 is a phosphorylated glycoprotein that regulates
RT basal insulin secretion.";
RL J. Biol. Chem. 290:25891-25906(2015).
CC -!- FUNCTION: May regulate basal insulin secretion.
CC {ECO:0000269|PubMed:26324709}.
CC -!- SUBUNIT: Homodimer (PubMed:26324709). Interacts with NPHS2/podocin (via
CC the C-terminus). Interacts with NPHS1 (via the Ig-like domains).
CC Interacts with FYN (PubMed:26324709). {ECO:0000269|PubMed:12424224,
CC ECO:0000269|PubMed:19887377, ECO:0000269|PubMed:26324709}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26324709};
CC Single-pass type I membrane protein {ECO:0000305}. Note=Localized along
CC the sites of the cell contacts (PubMed:26324709). Colocalizes with E-
CC Cadherin and beta-catenin (PubMed:26324709).
CC {ECO:0000269|PubMed:26324709}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7TSU7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TSU7-2; Sequence=VSP_011786;
CC -!- TISSUE SPECIFICITY: Highly expressed in beta-cells of the pancreatic
CC islets. Expression is seen in podocytes of kidney glomeruli, and in the
CC cerebellum and hindbrain at 12.5 dpc, in the spinal cord at 10.5 dpc,
CC and in retina and hypothalamus at 13.5 dpc.
CC {ECO:0000269|PubMed:12424224, ECO:0000269|PubMed:12837264,
CC ECO:0000269|PubMed:19887377}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:26324709}.
CC -!- PTM: Phosphorylated at Ser-548 or Ser-549; due to site ambiguity, the
CC exact position of the serine phosphorylation could not be determined.
CC Phosphorylation at residues Tyr-631 and/or Tyr-632. FYN mediates
CC tyrosine phosphorylation in pancreatic beta-cells.
CC {ECO:0000269|PubMed:26324709}.
CC -!- PTM: The extracellular domain is cleaved leading to the generation of a
CC soluble fragment and a membrane-bound C-terminal fragment, which is
CC further cleaved by gamma-secretase. {ECO:0000269|PubMed:26324709}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. However basal insulin
CC secretion is modestly increased in pancreatic islets of KIRREL2
CC deficient mice. {ECO:0000269|PubMed:26324709}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}.
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DR EMBL; BC052773; AAH52773.1; -; mRNA.
DR EMBL; AY305303; AAP72168.1; -; mRNA.
DR CCDS; CCDS39883.1; -. [Q7TSU7-1]
DR RefSeq; NP_766486.1; NM_172898.3. [Q7TSU7-1]
DR PDB; 7LTW; X-ray; 1.80 A; A/B=22-119.
DR PDBsum; 7LTW; -.
DR AlphaFoldDB; Q7TSU7; -.
DR SASBDB; Q7TSU7; -.
DR SMR; Q7TSU7; -.
DR STRING; 10090.ENSMUSP00000039395; -.
DR GlyGen; Q7TSU7; 3 sites.
DR iPTMnet; Q7TSU7; -.
DR PhosphoSitePlus; Q7TSU7; -.
DR PaxDb; Q7TSU7; -.
DR PRIDE; Q7TSU7; -.
DR ProteomicsDB; 264995; -. [Q7TSU7-1]
DR ProteomicsDB; 264996; -. [Q7TSU7-2]
DR Antibodypedia; 29564; 280 antibodies from 30 providers.
DR DNASU; 243911; -.
DR Ensembl; ENSMUST00000045817; ENSMUSP00000039395; ENSMUSG00000036915. [Q7TSU7-1]
DR GeneID; 243911; -.
DR KEGG; mmu:243911; -.
DR UCSC; uc009gel.1; mouse. [Q7TSU7-1]
DR UCSC; uc012fho.1; mouse. [Q7TSU7-2]
DR CTD; 84063; -.
DR MGI; MGI:2442334; Kirrel2.
DR VEuPathDB; HostDB:ENSMUSG00000036915; -.
DR eggNOG; KOG3510; Eukaryota.
DR GeneTree; ENSGT00940000160603; -.
DR HOGENOM; CLU_013520_1_1_1; -.
DR InParanoid; Q7TSU7; -.
DR OMA; ITWTRRG; -.
DR PhylomeDB; Q7TSU7; -.
DR TreeFam; TF327139; -.
DR Reactome; R-MMU-373753; Nephrin family interactions.
DR BioGRID-ORCS; 243911; 0 hits in 72 CRISPR screens.
DR PRO; PR:Q7TSU7; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q7TSU7; protein.
DR Bgee; ENSMUSG00000036915; Expressed in spinal cord ventricular layer and 43 other tissues.
DR ExpressionAtlas; Q7TSU7; baseline and differential.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0036057; C:slit diaphragm; IDA:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; IGI:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IGI:MGI.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR013162; CD80_C2-set.
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 Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07679; I-set; 1.
DR SMART; SM00409; IG; 5.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 5.
DR PROSITE; PS50835; IG_LIKE; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..700
FT /note="Kin of IRRE-like protein 2"
FT /id="PRO_0000015097"
FT TOPO_DOM 20..507
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 508..528
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 529..700
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..115
FT /note="Ig-like C2-type 1"
FT DOMAIN 120..219
FT /note="Ig-like C2-type 2"
FT DOMAIN 224..304
FT /note="Ig-like C2-type 3"
FT DOMAIN 309..391
FT /note="Ig-like C2-type 4"
FT DOMAIN 395..497
FT /note="Ig-like C2-type 5"
FT REGION 542..576
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 146..148
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 542..558
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 559..576
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 563
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:26324709"
FT MOD_RES 595
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26324709"
FT MOD_RES 596
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26324709"
FT MOD_RES 653
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:26324709"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 143..201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 245..288
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 330..372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 416..482
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 118..136
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12837264"
FT /id="VSP_011786"
FT MUTAGEN 595..596
FT /note="YY->FF: Enhances stability. Modifies the structure
FT of cell contacts. Localization at the plasma membrane is
FT increased. Does not affect dimerization. No change in
FT shedding activity."
FT /evidence="ECO:0000269|PubMed:26324709"
FT MUTAGEN 631..632
FT /note="YY->FF: Does not modifies the structure of cell
FT contacts. No effect on localization at the plasma membrane.
FT No change in shedding activity."
FT /evidence="ECO:0000269|PubMed:26324709"
FT MUTAGEN 653
FT /note="Y->F: Does not modifies the structure of cell
FT contacts. No effect on localization at the plasma membrane.
FT No change in shedding activity."
FT /evidence="ECO:0000269|PubMed:26324709"
FT CONFLICT 48
FT /note="R -> W (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="G -> A (in Ref. 2; AAP72168)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="P -> A (in Ref. 2; AAP72168)"
FT /evidence="ECO:0000305"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:7LTW"
FT TURN 78..81
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 84..89
FT /evidence="ECO:0007829|PDB:7LTW"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 96..102
FT /evidence="ECO:0007829|PDB:7LTW"
FT TURN 103..106
FT /evidence="ECO:0007829|PDB:7LTW"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:7LTW"
SQ SEQUENCE 700 AA; 74529 MW; 5D9404C2E13B18B8 CRC64;
MLASALLVFL CCFKGHAGSS PHFLQQPEDM VVLLGEEARL PCALGAYRGL VQWTKDGLAL
GGERDLPGWS RYWISGNSAS GQHDLHIKPV ELEDEASYEC QASQAGLRSR PAQLHVMVPP
EAPQVLGGPS VSLVAGVPGN LTCRSRGDSR PAPELLWFRD GIRLDGSSFH QTTLKDKATG
TVENTLFLTP SSHDDGATLI CRARSQALPT GRDTAVTLSL QYPPMVTLSA EPQTVQEGEK
VTFLCQATAQ PPVTGYRWAK GGSPVLGARG PRLEVVADAT FLTEPVSCEV SNAVGSANRS
TALEVLYGPI LQAKPKSVSV DVGKDASFSC VWRGNPLPRI TWTRMGGSQV LSSGPTLRLP
SVALEDAGDY VCRAEPRRTG LGGGKAQARL TVNAPPVVTA LQPAPAFLRG PARLQCVVFA
SPAPDSVVWS WDEGFLEAGS LGRFLVEAFP APEVEGGQGP GLISVLHISG TQESDFTTGF
NCSARNRLGE GRVQIHLGRR DLLPTVRIVA GAASAATSLL MVITGVVLCC WRHGSLSKQK
NLVRIPGSSE GSSSRGPEEE TGSSEDRGPI VHTDHSDLVL EEKEALETKD PTNGYYRVRG
VSVSLSLGEA PGGGLFLPPP SPIGLPGTPT YYDFKPHLDL VPPCRLYRAR AGYLTTPHPR
AFTSYMKPTS FGPPELSSGT PPFPYATLSP PSHQRLQTHV
