ID KIRR2_HUMAN Reviewed; 708 AA.
AC Q6UWL6; C9JHF1; C9JJ76; F1T0I2; Q6P1R1; Q7Z5P1; Q7Z5P2; Q96IQ8; Q9H0T1;
DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 27-MAR-2024, entry version 167.
DE RecName: Full=Kin of IRRE-like protein 2;
DE AltName: Full=Kin of irregular chiasm-like protein 2;
DE AltName: Full=Nephrin-like protein 3;
DE Flags: Precursor;
GN Name=KIRREL2; Synonyms=NEPH3; ORFNames=UNQ5827/PRO19646;
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 [MRNA] (ISOFORMS 1; 2; 3 AND 5), AND TISSUE
RP 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=21697133; DOI=10.1167/iovs.11-7479;
RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S.,
RA Usami R., Ohtoko K., Kato S.;
RT "Full-length transcriptome analysis of human retina-derived cell lines
RT ARPE-19 and Y79 using the vector-capping method.";
RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Eye;
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 [8]
RP PROTEIN SEQUENCE OF 21-35.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
CC -!- FUNCTION: May regulate basal insulin secretion.
CC {ECO:0000250|UniProtKB:Q7TSU7}.
CC -!- SUBUNIT: Homodimer. Interacts with NPHS2/podocin (via the C-terminus).
CC Interacts with NPHS1 (via the Ig-like domains). Interacts with FYN.
CC {ECO:0000250|UniProtKB:Q7TSU7}.
CC -!- INTERACTION:
CC Q6UWL6; Q13643: FHL3; NbExp=3; IntAct=EBI-10254473, EBI-741101;
CC Q6UWL6; P25788: PSMA3; NbExp=3; IntAct=EBI-10254473, EBI-348380;
CC Q6UWL6-5; Q13643: FHL3; NbExp=3; IntAct=EBI-12794590, EBI-741101;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q7TSU7};
CC Single-pass type I membrane protein {ECO:0000255}. Note=Localized along
CC the sites of the cell contacts. Colocalizes with E-Cadherin and beta-
CC catenin. {ECO:0000250|UniProtKB:Q7TSU7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6UWL6-1; Sequence=Displayed;
CC Name=2; Synonyms=Kirrel2a;
CC IsoId=Q6UWL6-2; Sequence=VSP_011784, VSP_011785;
CC Name=3; Synonyms=Kirrel2b;
CC IsoId=Q6UWL6-3; Sequence=VSP_011780, VSP_011784, VSP_011785;
CC Name=5; Synonyms=Kirrel2c;
CC IsoId=Q6UWL6-5; Sequence=VSP_011781, VSP_011783;
CC -!- TISSUE SPECIFICITY: Highly expressed in beta-cells of the pancreatic
CC islets. {ECO:0000269|PubMed:12837264}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q7TSU7}.
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:0000250|UniProtKB:Q7TSU7}.
CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH64925.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305};
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DR EMBL; AY305301; AAP72166.1; -; mRNA.
DR EMBL; AY305302; AAP72167.1; -; mRNA.
DR EMBL; AL136654; CAB66589.2; -; mRNA.
DR EMBL; AY358742; AAQ89102.1; -; mRNA.
DR EMBL; AB593116; BAJ84056.1; -; mRNA.
DR EMBL; AC002133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AD000864; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007312; AAH07312.1; -; mRNA.
DR EMBL; BC064925; AAH64925.1; ALT_SEQ; mRNA.
DR CCDS; CCDS12479.1; -. [Q6UWL6-2]
DR CCDS; CCDS12480.1; -. [Q6UWL6-3]
DR CCDS; CCDS12481.1; -. [Q6UWL6-1]
DR RefSeq; NP_001316459.1; NM_001329530.1.
DR RefSeq; NP_115499.5; NM_032123.6. [Q6UWL6-2]
DR RefSeq; NP_954648.3; NM_199179.3. [Q6UWL6-3]
DR RefSeq; NP_954649.3; NM_199180.3. [Q6UWL6-1]
DR RefSeq; XP_011525664.1; XM_011527362.1. [Q6UWL6-1]
DR RefSeq; XP_011525665.1; XM_011527363.1. [Q6UWL6-1]
DR AlphaFoldDB; Q6UWL6; -.
DR SMR; Q6UWL6; -.
DR BioGRID; 123858; 15.
DR IntAct; Q6UWL6; 7.
DR STRING; 9606.ENSP00000353331; -.
DR GlyCosmos; Q6UWL6; 3 sites, No reported glycans.
DR GlyGen; Q6UWL6; 3 sites.
DR iPTMnet; Q6UWL6; -.
DR PhosphoSitePlus; Q6UWL6; -.
DR SwissPalm; Q6UWL6; -.
DR BioMuta; KIRREL2; -.
DR DMDM; 308153459; -.
DR MassIVE; Q6UWL6; -.
DR PaxDb; 9606-ENSP00000353331; -.
DR PeptideAtlas; Q6UWL6; -.
DR ProteomicsDB; 67493; -. [Q6UWL6-1]
DR ProteomicsDB; 67494; -. [Q6UWL6-2]
DR ProteomicsDB; 67495; -. [Q6UWL6-3]
DR ProteomicsDB; 67497; -. [Q6UWL6-5]
DR Antibodypedia; 29564; 306 antibodies from 30 providers.
DR DNASU; 84063; -.
DR Ensembl; ENST00000262625.7; ENSP00000262625.6; ENSG00000126259.20. [Q6UWL6-2]
DR Ensembl; ENST00000347900.10; ENSP00000345067.5; ENSG00000126259.20. [Q6UWL6-3]
DR Ensembl; ENST00000360202.10; ENSP00000353331.4; ENSG00000126259.20. [Q6UWL6-1]
DR GeneID; 84063; -.
DR KEGG; hsa:84063; -.
DR MANE-Select; ENST00000360202.10; ENSP00000353331.4; NM_199180.4; NP_954649.3.
DR UCSC; uc002ocb.5; human. [Q6UWL6-1]
DR AGR; HGNC:18816; -.
DR CTD; 84063; -.
DR DisGeNET; 84063; -.
DR GeneCards; KIRREL2; -.
DR HGNC; HGNC:18816; KIRREL2.
DR HPA; ENSG00000126259; Tissue enriched (pancreas).
DR MalaCards; KIRREL2; -.
DR MIM; 607762; gene.
DR neXtProt; NX_Q6UWL6; -.
DR OpenTargets; ENSG00000126259; -.
DR PharmGKB; PA38693; -.
DR VEuPathDB; HostDB:ENSG00000126259; -.
DR eggNOG; KOG3510; Eukaryota.
DR GeneTree; ENSGT00940000160603; -.
DR InParanoid; Q6UWL6; -.
DR OMA; RYEHSYG; -.
DR OrthoDB; 5362512at2759; -.
DR PhylomeDB; Q6UWL6; -.
DR TreeFam; TF327139; -.
DR PathwayCommons; Q6UWL6; -.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR SignaLink; Q6UWL6; -.
DR BioGRID-ORCS; 84063; 37 hits in 1143 CRISPR screens.
DR ChiTaRS; KIRREL2; human.
DR GeneWiki; KIRREL2; -.
DR GenomeRNAi; 84063; -.
DR Pharos; Q6UWL6; Tbio.
DR PRO; PR:Q6UWL6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q6UWL6; Protein.
DR Bgee; ENSG00000126259; Expressed in body of pancreas and 83 other cell types or tissues.
DR ExpressionAtlas; Q6UWL6; baseline and differential.
DR Genevisible; Q6UWL6; HS.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0036057; C:slit diaphragm; IEA:Ensembl.
DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; NAS:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IEA:Ensembl.
DR Gene3D; 2.60.40.10; Immunoglobulins; 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 PANTHER; PTHR11640:SF51; KIN OF IRRE-LIKE PROTEIN 2; 1.
DR PANTHER; PTHR11640; NEPHRIN; 1.
DR Pfam; PF08205; C2-set_2; 1.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF13927; Ig_3; 1.
DR SMART; SM00409; IG; 5.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; Immunoglobulin; 5.
DR PROSITE; PS50835; IG_LIKE; 5.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 21..708
FT /note="Kin of IRRE-like protein 2"
FT /id="PRO_0000015096"
FT TOPO_DOM 21..510
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 511..531
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 532..708
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..118
FT /note="Ig-like C2-type 1"
FT DOMAIN 123..222
FT /note="Ig-like C2-type 2"
FT DOMAIN 227..307
FT /note="Ig-like C2-type 3"
FT DOMAIN 312..394
FT /note="Ig-like C2-type 4"
FT DOMAIN 398..501
FT /note="Ig-like C2-type 5"
FT REGION 545..601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 149..151
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 545..560
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..596
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU7"
FT MOD_RES 603
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU7"
FT MOD_RES 604
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU7"
FT MOD_RES 661
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q7TSU7"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 484
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 45..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 146..204
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 248..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 333..375
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 419..485
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 21..70
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12837264"
FT /id="VSP_011780"
FT VAR_SEQ 37..490
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12837264,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011781"
FT VAR_SEQ 504..538
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:12837264,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011783"
FT VAR_SEQ 611..633
FT /note="VSLSLGEAPGGGLFLPPPSPLGP -> PPASPDSRVTSFQWKSPGISNLP
FT (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12837264"
FT /id="VSP_011784"
FT VAR_SEQ 634..708
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12837264"
FT /id="VSP_011785"
FT VARIANT 19
FT /note="R -> S (in dbSNP:rs446014)"
FT /id="VAR_056098"
FT VARIANT 170
FT /note="A -> T (in dbSNP:rs404299)"
FT /id="VAR_056099"
FT VARIANT 353
FT /note="V -> M (in dbSNP:rs35423326)"
FT /id="VAR_056100"
FT VARIANT 556
FT /note="S -> N (in dbSNP:rs35775934)"
FT /id="VAR_056101"
FT VARIANT 591
FT /note="E -> K (in dbSNP:rs382789)"
FT /id="VAR_067450"
FT CONFLICT 3
FT /note="R -> W (in Ref. 1; AAP72167)"
FT /evidence="ECO:0000305"
FT CONFLICT 155
FT /note="T -> A (in Ref. 3; CAB66589)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="F -> L (in Ref. 1; AAP72166)"
FT /evidence="ECO:0000305"
FT CONFLICT 371
FT /note="G -> D (in Ref. 1; AAP72166/AAP72167)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="A -> V (in Ref. 1; AAP72167)"
FT /evidence="ECO:0000305"
FT CONFLICT 396
FT /note="N -> D (in Ref. 1; AAP72167)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="A -> V (in Ref. 1; AAP72166/AAP72167)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 708 AA; 75093 MW; 97978D0F1D7E3330 CRC64;
MLRMRVPALL VLLFCFRGRA GPSPHFLQQP EDLVVLLGEE ARLPCALGAY WGLVQWTKSG
LALGGQRDLP GWSRYWISGN AANGQHDLHI RPVELEDEAS YECQATQAGL RSRPAQLHVL
VPPEAPQVLG GPSVSLVAGV PANLTCRSRG DARPTPELLW FRDGVLLDGA TFHQTLLKEG
TPGSVESTLT LTPFSHDDGA TFVCRARSQA LPTGRDTAIT LSLQYPPEVT LSASPHTVQE
GEKVIFLCQA TAQPPVTGYR WAKGGSPVLG ARGPRLEVVA DASFLTEPVS CEVSNAVGSA
NRSTALDVLF GPILQAKPEP VSVDVGEDAS FSCAWRGNPL PRVTWTRRGG AQVLGSGATL
RLPSVGPEDA GDYVCRAEAG LSGLRGGAAE ARLTVNAPPV VTALHSAPAF LRGPARLQCL
VFASPAPDAV VWSWDEGFLE AGSQGRFLVE TFPAPESRGG LGPGLISVLH ISGTQESDFS
RSFNCSARNR LGEGGAQASL GRRDLLPTVR IVAGVAAATT TLLMVITGVA LCCWRHSKAS
ASFSEQKNLM RIPGSSDGSS SRGPEEEETG SREDRGPIVH TDHSDLVLEE EGTLETKDPT
NGYYKVRGVS VSLSLGEAPG GGLFLPPPSP LGPPGTPTFY DFNPHLGMVP PCRLYRARAG
YLTTPHPRAF TSYIKPTSFG PPDLAPGTPP FPYAAFPTPS HPRLQTHV
//
