KIRR1_MOUSE
ID KIRR1_MOUSE Reviewed; 789 AA.
AC Q80W68; Q8CIJ4; Q8CJ59; Q923L4;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Kin of IRRE-like protein 1;
DE AltName: Full=Kin of irregular chiasm-like protein 1;
DE AltName: Full=Nephrin-like protein 1;
DE Flags: Precursor;
GN Name=Kirrel1; Synonyms=Kirrel, Neph1;
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 [MRNA] (ISOFORM 1), INTERACTION WITH NPHS2, MUTAGENESIS
RP OF PRO-633 AND TYR-637, AND PHOSPHORYLATION.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH NPHS1 AND TJP1,
RP AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=12865409; DOI=10.1172/jci200318242;
RA Liu G., Kaw B., Kurfis J., Rahmanuddin S., Kanwar Y.S., Chugh S.S.;
RT "Neph1 and nephrin interaction in the slit diaphragm is an important
RT determinant of glomerular permeability.";
RL J. Clin. Invest. 112:209-221(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-421, AND FUNCTION.
RX PubMed=11416156; DOI=10.1128/mcb.21.14.4829-4836.2001;
RA Donoviel D.B., Freed D.D., Vogel H., Potter D.G., Hawkins E., Barrish J.P.,
RA Mathur B.N., Turner C.A., Geske R., Montgomery C.A., Starbuck M.,
RA Brandt M., Gupta A., Ramirez-Solis R., Zambrowicz B.P., Powell D.R.;
RT "Proteinuria and perinatal lethality in mice lacking NEPH1, a novel protein
RT with homology to NEPHRIN.";
RL Mol. Cell. Biol. 21:4829-4836(2001).
RN [5]
RP SUBUNIT, GLYCOSYLATION, AND INTERACTION WITH NPHS1.
RX PubMed=12660326; DOI=10.1097/01.asn.0000057853.05686.89;
RA Gerke P., Huber T.B., Sellin L., Benzing T., Walz G.;
RT "Homodimerization and heterodimerization of the glomerular podocyte
RT proteins nephrin and NEPH1.";
RL J. Am. Soc. Nephrol. 14:918-926(2003).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-329.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Required for proper function of the glomerular filtration
CC barrier. It is involved in the maintenance of a stable podocyte
CC architecture with interdigitating foot processes connected by
CC specialized cell-cell junctions, known as the slit diaphragm
CC (PubMed:11416156). Is a signaling protein that needs the presence of
CC TEC kinases to fully trans-activate the transcription factor AP-1.
CC {ECO:0000269|PubMed:11416156}.
CC -!- SUBUNIT: Interacts with TJP1/ZO-1 and with NPHS2/podocin (via the C-
CC terminus). Interacts with NPHS1/nephrin (via the Ig-like domains); this
CC interaction is dependent on KIRREL1 glycosylation. Homodimer (via the
CC Ig-like domains). Interacts when tyrosine-phosphorylated with GRB2 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}. Note=Predominantly located at podocyte
CC slit diaphragm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q80W68-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q80W68-2; Sequence=VSP_011736, VSP_011737;
CC -!- TISSUE SPECIFICITY: Abundantly expressed in kidney. Specifically
CC expressed in podocytes of kidney glomeruli.
CC {ECO:0000269|PubMed:12865409}.
CC -!- PTM: Phosphorylation probably regulates the interaction with NPHS2.
CC Phosphorylated at Tyr-637 and Tyr-638 by FYN, leading to GRB2 binding
CC (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12660326,
CC ECO:0000269|PubMed:19349973}.
CC -!- MISCELLANEOUS: Knockout of this gene results in perinatal lethality
CC accompanied by proteinuria, and effacement of glomerular podocytes.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK00528.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK00528.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF480411; AAN73043.1; -; mRNA.
DR EMBL; AY243095; AAO91769.1; -; mRNA.
DR EMBL; BC023765; AAH23765.3; -; mRNA.
DR EMBL; AY017368; AAK00528.1; ALT_SEQ; mRNA.
DR CCDS; CCDS17450.1; -. [Q80W68-1]
DR RefSeq; NP_001164456.1; NM_001170985.1. [Q80W68-1]
DR RefSeq; NP_570937.2; NM_130867.3. [Q80W68-1]
DR PDB; 4OFD; X-ray; 3.94 A; A/B=48-253.
DR PDBsum; 4OFD; -.
DR AlphaFoldDB; Q80W68; -.
DR SMR; Q80W68; -.
DR BioGRID; 228359; 2.
DR STRING; 10090.ENSMUSP00000103243; -.
DR GlyGen; Q80W68; 4 sites.
DR iPTMnet; Q80W68; -.
DR PhosphoSitePlus; Q80W68; -.
DR MaxQB; Q80W68; -.
DR PaxDb; Q80W68; -.
DR PeptideAtlas; Q80W68; -.
DR PRIDE; Q80W68; -.
DR ProteomicsDB; 263544; -. [Q80W68-1]
DR ProteomicsDB; 263545; -. [Q80W68-2]
DR Antibodypedia; 34235; 142 antibodies from 26 providers.
DR DNASU; 170643; -.
DR Ensembl; ENSMUST00000041732; ENSMUSP00000043756; ENSMUSG00000041734. [Q80W68-2]
DR Ensembl; ENSMUST00000107618; ENSMUSP00000103243; ENSMUSG00000041734. [Q80W68-1]
DR Ensembl; ENSMUST00000159976; ENSMUSP00000125525; ENSMUSG00000041734. [Q80W68-1]
DR GeneID; 170643; -.
DR KEGG; mmu:170643; -.
DR UCSC; uc008pru.2; mouse. [Q80W68-1]
DR UCSC; uc008prx.2; mouse. [Q80W68-2]
DR CTD; 170643; -.
DR MGI; MGI:1891396; Kirrel.
DR VEuPathDB; HostDB:ENSMUSG00000041734; -.
DR eggNOG; KOG3510; Eukaryota.
DR GeneTree; ENSGT00940000155795; -.
DR HOGENOM; CLU_013520_0_0_1; -.
DR InParanoid; Q80W68; -.
DR OMA; TIIWYRD; -.
DR OrthoDB; 269917at2759; -.
DR PhylomeDB; Q80W68; -.
DR TreeFam; TF327139; -.
DR Reactome; R-MMU-373753; Nephrin family interactions.
DR BioGRID-ORCS; 170643; 6 hits in 76 CRISPR screens.
DR PRO; PR:Q80W68; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q80W68; protein.
DR Bgee; ENSMUSG00000041734; Expressed in vault of skull and 182 other tissues.
DR Genevisible; Q80W68; MM.
DR GO; GO:0031253; C:cell projection membrane; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0043198; C:dendritic shaft; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0017022; F:myosin binding; ISO:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IDA:MGI.
DR GO; GO:0045217; P:cell-cell junction maintenance; ISO:MGI.
DR GO; GO:0003094; P:glomerular filtration; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IGI:MGI.
DR GO; GO:0097017; P:renal protein absorption; IMP: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; 2.
DR SUPFAM; SSF48726; SSF48726; 5.
DR PROSITE; PS50835; IG_LIKE; 5.
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..47
FT /evidence="ECO:0000255"
FT CHAIN 48..789
FT /note="Kin of IRRE-like protein 1"
FT /id="PRO_0000015094"
FT TOPO_DOM 48..531
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 532..552
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 553..789
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 49..147
FT /note="Ig-like C2-type 1"
FT DOMAIN 152..248
FT /note="Ig-like C2-type 2"
FT DOMAIN 255..331
FT /note="Ig-like C2-type 3"
FT DOMAIN 340..419
FT /note="Ig-like C2-type 4"
FT DOMAIN 424..520
FT /note="Ig-like C2-type 5"
FT REGION 687..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 437..439
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOD_RES 606
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96J84"
FT MOD_RES 637
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250|UniProtKB:Q6X936"
FT MOD_RES 638
FT /note="Phosphotyrosine; by FYN"
FT /evidence="ECO:0000250|UniProtKB:Q6X936"
FT MOD_RES 654
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96J84"
FT MOD_RES 657
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96J84"
FT MOD_RES 756
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q96J84"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 503
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 74..132
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 175..232
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 276..319
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 361..403
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 445..504
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 606..634
FT /note="SFKDDVDLKQDLRCDTIDTREEYEMKDPT -> VRIMLLSTWPRLFIVLRPA
FT PPAFNDFRYL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011736"
FT VAR_SEQ 635..789
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011737"
FT MUTAGEN 633
FT /note="P->S: No effect on interaction with NPHS2."
FT /evidence="ECO:0000269|PubMed:12424224"
FT MUTAGEN 637
FT /note="Y->A: Inhibits interaction with NPHS2."
FT /evidence="ECO:0000269|PubMed:12424224"
FT CONFLICT 355
FT /note="S -> F (in Ref. 2; AAN73043)"
FT /evidence="ECO:0000305"
FT CONFLICT 442
FT /note="K -> E (in Ref. 2; AAN73043)"
FT /evidence="ECO:0000305"
FT CONFLICT 727
FT /note="F -> L (in Ref. 2; AAN73043)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 789 AA; 87176 MW; 27FB31FFCCC25A2A CRC64;
MTLESPSTRL MTCQSSLLPE KPRFLSQKMW APHLVVAYLI FVTLALALPG TQTRFSQEPA
DQTVVAGQRA VLPCVLLNYS GIVQWTKDGL ALGMGQGLKA WPRYRVVGSA DAGQYNLEIT
DAELSDDASY ECQATEAALR SRRAKLTVLI PPEETRIDGG PVILLQAGTP YNLTCRAFNA
KPAATIIWFR DGTQQEGAVT STELLKDGKR ETTISQLLIE PTDLDIGRVF TCRSMNEAIP
NGKETSIELD VHHPPTVTLS IEPQTVLEGE RVIFTCQATA NPEILGYRWA KGGFLIEDAH
ESRYETNVDY SFFTEPVSCE VYNKVGSTNV STLVNVHFAP RIVVYPKPTT TDIGSDVTLT
CVWVGNPPLT LTWTKKDSNM VLSNSNQLLL KSVTQADAGT YTCRAIVPRI GVAEREVPLY
VNGPPIISSE AVQFAVRGDG GKVECFIGST PPPDRIAWAW KENFLEVGTL ERYTVERTNS
GSGVLSTLTI NNVMEADFQT HYNCTAWNSF GPGTAIIQLE EREVLPVGII AGATIGAGIL
VVFSFAALVF FLYRRRKGSR KDVTLRKLDI KVETVNREPL TMHSDREDDT ASISTATRVM
KAIYSSFKDD VDLKQDLRCD TIDTREEYEM KDPTNGYYNV RAHEDRPSSR AVLYADYRAP
GPTRFDGRPS SRLSHSSGYA QLNTYSRAPA SDYGTEPTPS GPSAPGGTDT TSQLSYENYE
KFNSHPFPGA AGYPTYRLGY PQAPPSGLER TPYEAYDPIG KYATATRFSY TSQHSDYGQR
FQQRMQTHV
