ID KIRR3_HUMAN Reviewed; 778 AA. AC Q8IZU9; Q3MIJ7; Q6UWJ9; Q6UWL5; Q96JG0; DT 25-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 170. DE RecName: Full=Kin of IRRE-like protein 3; DE AltName: Full=Kin of irregular chiasm-like protein 3; DE AltName: Full=Nephrin-like protein 2 {ECO:0000303|PubMed:12424224}; DE Contains: DE RecName: Full=Processed kin of IRRE-like protein 3 {ECO:0000250|UniProtKB:Q8BR86}; DE Flags: Precursor; GN Name=KIRREL3 {ECO:0000312|HGNC:HGNC:23204}; GN Synonyms=KIAA1867 {ECO:0000303|PubMed:11347906}, NEPH2 GN {ECO:0000303|PubMed:12424224}; GN ORFNames=UNQ5923/PRO4502/PRO19814 {ECO:0000303|PubMed:12975309}; 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] (ISOFORM 1), TISSUE SPECIFICITY, AND INTERACTION RP WITH NPHS2. RC 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 [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11347906; DOI=10.1093/dnares/8.2.85; RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 8:85-95(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 491-778 (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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [5] RP STRUCTURE BY NMR OF 413-521. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the fifth Ig-like domain of human kin of IRRE-like RT 3."; RL Submitted (NOV-2005) to the PDB data bank. RN [6] RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RX PubMed=25488023; DOI=10.1186/s12899-014-0011-3; RA Durcan P.J., Conradie J.D., Van deVyver M., Myburgh K.H.; RT "Identification of novel Kirrel3 gene splice variants in adult human RT skeletal muscle."; RL BMC Physiol. 14:11-11(2014). RN [7] RP INTERACTION WITH ATP1B1; MAP1B; MYO16; SHMT2 AND UFC1. RX PubMed=25902260; DOI=10.1371/journal.pone.0123106; RA Liu Y.F., Sowell S.M., Luo Y., Chaubey A., Cameron R.S., Kim H.G., RA Srivastava A.K.; RT "Autism and intellectual disability-associated KIRREL3 interacts with RT neuronal proteins MAP1B and MYO16 with potential roles in RT neurodevelopment."; RL PLoS ONE 10:E0123106-E0123106(2015). RN [8] RP VARIANTS TRP-40; GLN-336 AND PHE-731, TISSUE SPECIFICITY, SUBCELLULAR RP LOCATION, INTERACTION WITH CASK, AND CHROMOSOMAL TRANSLOCATION WITH CDH15. RX PubMed=19012874; DOI=10.1016/j.ajhg.2008.10.020; RA Bhalla K., Luo Y., Buchan T., Beachem M.A., Guzauskas G.F., Ladd S., RA Bratcher S.J., Schroer R.J., Balsamo J., DuPont B.R., Lilien J., RA Srivastava A.K.; RT "Alterations in CDH15 and KIRREL3 in patients with mild to severe RT intellectual disability."; RL Am. J. Hum. Genet. 83:703-713(2008). CC -!- FUNCTION: Synaptic adhesion molecule required for the formation of CC target-specific synapses. Required for formation of target-specific CC synapses at hippocampal mossy fiber synapses. Required for formation of CC mossy fiber filopodia, the synaptic structures connecting dentate CC granule and GABA neurons. Probably acts as a homophilic adhesion CC molecule that promotes trans-cellular interactions and stabilize mossy CC fiber filipodia contact and subsequent synapse formation. Required for CC the coalescence of vomeronasal sensory neuron axons. May be involved in CC the hematopoietic supportive capacity of stroma cells; the secreted CC extracellular domain is directly responsible for supporting CC hematopoietic stem cells. {ECO:0000250|UniProtKB:Q8BR86}. CC -!- SUBUNIT: Homodimer; mediates homophilic interactions to promote cell CC adhesion. Interacts with NPHS1; forms heterodimers with NPHS1 (By CC similarity). Interacts with NPHS2/podocin (via the C-terminus) CC (PubMed:12424224). Interacts with CASK (PubMed:19012874). Interacts CC (via extracellular region) with MAP1B (PubMed:25902260). Interacts (via CC extracellular region) with MYO16 (PubMed:25902260). Interacts (via CC intracellular region) with ATP1B1 (PubMed:25902260). Interacts (via CC intracellular region) with SHMT2 (PubMed:25902260). Interacts (via CC intracellular region) with UFC1 (PubMed:25902260). CC {ECO:0000250|UniProtKB:Q8BR86, ECO:0000269|PubMed:12424224, CC ECO:0000269|PubMed:19012874, ECO:0000269|PubMed:25902260}. CC -!- INTERACTION: CC Q8IZU9; P05026: ATP1B1; NbExp=4; IntAct=EBI-16427312, EBI-714630; CC Q8IZU9; P15311: EZR; NbExp=5; IntAct=EBI-16427312, EBI-1056902; CC Q8IZU9; PRO_0000018605 [P46821]: MAP1B; NbExp=4; IntAct=EBI-16427312, EBI-9517186; CC Q8IZU9; Q9Y6X6: MYO16; NbExp=4; IntAct=EBI-16427312, EBI-310686; CC Q8IZU9; P35241: RDX; NbExp=5; IntAct=EBI-16427312, EBI-2514878; CC Q8IZU9; P34897: SHMT2; NbExp=4; IntAct=EBI-16427312, EBI-352908; CC Q8IZU9; Q9Y3C8: UFC1; NbExp=4; IntAct=EBI-16427312, EBI-1045733; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19012874}; CC Single-pass type I membrane protein {ECO:0000269|PubMed:19012874}. CC -!- SUBCELLULAR LOCATION: [Processed kin of IRRE-like protein 3]: Secreted CC {ECO:0000250|UniProtKB:Q8BR86}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Kirrel3 A {ECO:0000303|PubMed:25488023}; CC IsoId=Q8IZU9-1; Sequence=Displayed; CC Name=2; Synonyms=Kirrel3 B {ECO:0000303|PubMed:25488023}; CC IsoId=Q8IZU9-2; Sequence=VSP_011799, VSP_011800; CC -!- TISSUE SPECIFICITY: Expressed in fetal and adult brain CC (PubMed:19012874). Also expressed in kidney, specifically in podocytes CC of kidney glomeruli (PubMed:12424224). Also expressed in skeletal CC muscle (PubMed:25488023). {ECO:0000269|PubMed:12424224, CC ECO:0000269|PubMed:19012874, ECO:0000269|PubMed:25488023}. CC -!- PTM: Undergoes proteolysis by a metalloprotease and gives rise to a CC soluble form. {ECO:0000250|UniProtKB:Q8BR86}. CC -!- DISEASE: Note=A chromosomal aberration involving KIRREL3 and CDH15 is CC found in a patient with severe intellectual disability and dysmorphic CC facial features. Translocation t(11;16)(q24.2;q24). CC {ECO:0000269|PubMed:19012874}. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAQ89120.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB47496.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF480410; AAN73042.1; -; mRNA. DR EMBL; AB058770; BAB47496.1; ALT_INIT; mRNA. DR EMBL; AY358743; AAQ89103.1; -; mRNA. DR EMBL; AY358760; AAQ89120.1; ALT_INIT; mRNA. DR EMBL; BC101775; AAI01776.1; -; mRNA. DR EMBL; BC101801; AAI01802.1; -; mRNA. DR CCDS; CCDS53723.1; -. [Q8IZU9-1] DR CCDS; CCDS55796.1; -. [Q8IZU9-2] DR RefSeq; NP_001155179.1; NM_001161707.1. [Q8IZU9-2] DR RefSeq; NP_115920.1; NM_032531.3. [Q8IZU9-1] DR RefSeq; XP_011541333.1; XM_011543031.2. DR RefSeq; XP_016873909.1; XM_017018420.1. DR PDB; 2CRY; NMR; -; A=413-521. DR PDBsum; 2CRY; -. DR AlphaFoldDB; Q8IZU9; -. DR SMR; Q8IZU9; -. DR BioGRID; 124153; 1. DR IntAct; Q8IZU9; 13. DR STRING; 9606.ENSP00000435466; -. DR GlyCosmos; Q8IZU9; 4 sites, No reported glycans. DR GlyGen; Q8IZU9; 4 sites. DR iPTMnet; Q8IZU9; -. DR PhosphoSitePlus; Q8IZU9; -. DR BioMuta; KIRREL3; -. DR DMDM; 55736065; -. DR MassIVE; Q8IZU9; -. DR PaxDb; 9606-ENSP00000435466; -. DR PeptideAtlas; Q8IZU9; -. DR ProteomicsDB; 71433; -. [Q8IZU9-1] DR ProteomicsDB; 71434; -. [Q8IZU9-2] DR Antibodypedia; 33010; 180 antibodies from 30 providers. DR DNASU; 84623; -. DR Ensembl; ENST00000525144.7; ENSP00000435466.2; ENSG00000149571.12. [Q8IZU9-1] DR Ensembl; ENST00000525704.2; ENSP00000435094.2; ENSG00000149571.12. [Q8IZU9-2] DR GeneID; 84623; -. DR KEGG; hsa:84623; -. DR MANE-Select; ENST00000525144.7; ENSP00000435466.2; NM_032531.4; NP_115920.1. DR UCSC; uc001qea.4; human. [Q8IZU9-1] DR AGR; HGNC:23204; -. DR CTD; 84623; -. DR DisGeNET; 84623; -. DR GeneCards; KIRREL3; -. DR HGNC; HGNC:23204; KIRREL3. DR HPA; ENSG00000149571; Tissue enriched (brain). DR MalaCards; KIRREL3; -. DR MIM; 607761; gene. DR neXtProt; NX_Q8IZU9; -. DR OpenTargets; ENSG00000149571; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR PharmGKB; PA134958283; -. DR VEuPathDB; HostDB:ENSG00000149571; -. DR eggNOG; KOG3510; Eukaryota. DR GeneTree; ENSGT00940000157126; -. DR HOGENOM; CLU_013520_1_0_1; -. DR InParanoid; Q8IZU9; -. DR OMA; YNCSAYN; -. DR OrthoDB; 5362512at2759; -. DR PhylomeDB; Q8IZU9; -. DR TreeFam; TF327139; -. DR PathwayCommons; Q8IZU9; -. DR Reactome; R-HSA-373753; Nephrin family interactions. DR SignaLink; Q8IZU9; -. DR SIGNOR; Q8IZU9; -. DR BioGRID-ORCS; 84623; 8 hits in 1138 CRISPR screens. DR ChiTaRS; KIRREL3; human. DR EvolutionaryTrace; Q8IZU9; -. DR GeneWiki; KIRREL3; -. DR GenomeRNAi; 84623; -. DR Pharos; Q8IZU9; Tbio. DR PRO; PR:Q8IZU9; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q8IZU9; Protein. DR Bgee; ENSG00000149571; Expressed in middle temporal gyrus and 129 other cell types or tissues. DR ExpressionAtlas; Q8IZU9; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0008021; C:synaptic vesicle; IDA:CACAO. DR GO; GO:0050839; F:cell adhesion molecule binding; IBA:GO_Central. DR GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central. DR GO; GO:0072102; P:glomerulus morphogenesis; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; ISS:UniProtKB. DR GO; GO:0021766; P:hippocampus development; ISS:UniProtKB. DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; ISS:UniProtKB. DR GO; GO:0002121; P:inter-male aggressive behavior; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0048812; P:neuron projection morphogenesis; IEA:Ensembl. DR GO; GO:0021740; P:principal sensory nucleus of trigeminal nerve development; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; ISS:UniProtKB. DR CDD; cd05759; IgI_2_KIRREL3-like; 1. DR CDD; cd05898; IgI_5_KIRREL3; 1. 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:SF49; KIN OF IRRE-LIKE PROTEIN 3; 1. DR PANTHER; PTHR11640; NEPHRIN; 1. DR Pfam; PF08205; C2-set_2; 1. DR Pfam; PF07679; I-set; 2. DR Pfam; PF13927; Ig_3; 1. DR SMART; SM00409; IG; 4. DR SMART; SM00408; IGc2; 3. DR SUPFAM; SSF48726; Immunoglobulin; 5. DR PROSITE; PS50835; IG_LIKE; 5. DR Genevisible; Q8IZU9; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; KW Chromosomal rearrangement; Disease variant; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Reference proteome; Repeat; Secreted; KW Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..21 FT /evidence="ECO:0000255" FT CHAIN 22..778 FT /note="Kin of IRRE-like protein 3" FT /id="PRO_0000015098" FT CHAIN 22..? FT /note="Processed kin of IRRE-like protein 3" FT /evidence="ECO:0000250|UniProtKB:Q8BR86" FT /id="PRO_0000435799" FT TOPO_DOM 22..535 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 536..556 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 557..778 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 48..142 FT /note="Ig-like C2-type 1" FT DOMAIN 147..243 FT /note="Ig-like C2-type 2" FT DOMAIN 249..330 FT /note="Ig-like C2-type 3" FT DOMAIN 335..415 FT /note="Ig-like C2-type 4" FT DOMAIN 419..515 FT /note="Ig-like C2-type 5" FT REGION 727..778 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 167 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 253 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 498 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 69..127 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 170..227 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 271..314 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 356..398 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 440..499 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 566..600 FT /note="NLKGVVSAKNDIRVEIVHKEPASGREGEEHSTIKQ -> STGGRSGISGRGT FT EKKARLRLPRRASKQECNEQGS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309" FT /id="VSP_011799" FT VAR_SEQ 601..778 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12975309" FT /id="VSP_011800" FT VARIANT 40 FT /note="R -> W (found in a patient with intellectual FT disability; uncertain significance; dbSNP:rs119462978)" FT /evidence="ECO:0000269|PubMed:19012874" FT /id="VAR_054828" FT VARIANT 336 FT /note="R -> Q (found in patients with intellectual FT disability; uncertain significance; dbSNP:rs114378922)" FT /evidence="ECO:0000269|PubMed:19012874" FT /id="VAR_054829" FT VARIANT 731 FT /note="V -> F (found in a patient with intellectual FT disability; uncertain significance; dbSNP:rs119462980)" FT /evidence="ECO:0000269|PubMed:19012874" FT /id="VAR_054830" FT STRAND 422..425 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 440..442 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 449..457 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 462..465 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 468..475 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 478..484 FT /evidence="ECO:0007829|PDB:2CRY" FT HELIX 490..494 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 497..502 FT /evidence="ECO:0007829|PDB:2CRY" FT STRAND 507..512 FT /evidence="ECO:0007829|PDB:2CRY" SQ SEQUENCE 778 AA; 85255 MW; 8AD1694D3B376B0A CRC64; MKPFQLDLLF VCFFLFSQEL GLQKRGCCLV LGYMAKDKFR RMNEGQVYSF SQQPQDQVVV SGQPVTLLCA IPEYDGFVLW IKDGLALGVG RDLSSYPQYL VVGNHLSGEH HLKILRAELQ DDAVYECQAI QAAIRSRPAR LTVLVPPDDP VILGGPVISL RAGDPLNLTC HADNAKPAAS IIWLRKGEVI NGATYSKTLL RDGKRESIVS TLFISPGDVE NGQSIVCRAT NKAIPGGKET SVTIDIQHPP LVNLSVEPQP VLEDNVVTFH CSAKANPAVT QYRWAKRGQI IKEASGEVYR TTVDYTYFSE PVSCEVTNAL GSTNLSRTVD VYFGPRMTTE PQSLLVDLGS DAIFSCAWTG NPSLTIVWMK RGSGVVLSNE KTLTLKSVRQ EDAGKYVCRA VVPRVGAGER EVTLTVNGPP IISSTQTQHA LHGEKGQIKC FIRSTPPPDR IAWSWKENVL ESGTSGRYTV ETISTEEGVI STLTISNIVR ADFQTIYNCT AWNSFGSDTE IIRLKEQGSE MKSGAGLEAE SVPMAVIIGV AVGAGVAFLV LMATIVAFCC ARSQRNLKGV VSAKNDIRVE IVHKEPASGR EGEEHSTIKQ LMMDRGEFQQ DSVLKQLEVL KEEEKEFQNL KDPTNGYYSV NTFKEHHSTP TISLSSCQPD LRPAGKQRVP TGMSFTNIYS TLSGQGRLYD YGQRFVLGMG SSSIELCERE FQRGSLSDSS SFLDTQCDSS VSSSGKQDGY VQFDKASKAS ASSSHHSQSS SQNSDPSRPL QRRMQTHV //