KIRR3_HUMAN
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 03-AUG-2022, entry version 161.
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},
GN NEPH2 {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};
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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. [Q8IZU9-1]
DR RefSeq; XP_016873909.1; XM_017018420.1. [Q8IZU9-1]
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 GlyGen; Q8IZU9; 4 sites.
DR iPTMnet; Q8IZU9; -.
DR PhosphoSitePlus; Q8IZU9; -.
DR BioMuta; KIRREL3; -.
DR DMDM; 55736065; -.
DR MassIVE; Q8IZU9; -.
DR PaxDb; Q8IZU9; -.
DR PeptideAtlas; Q8IZU9; -.
DR PRIDE; Q8IZU9; -.
DR ProteomicsDB; 71433; -. [Q8IZU9-1]
DR ProteomicsDB; 71434; -. [Q8IZU9-2]
DR Antibodypedia; 33010; 144 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 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; LMVEHEE; -.
DR OrthoDB; 269917at2759; -.
DR PhylomeDB; Q8IZU9; -.
DR TreeFam; TF327139; -.
DR PathwayCommons; Q8IZU9; -.
DR Reactome; R-HSA-373753; Nephrin family interactions.
DR SignaLink; Q8IZU9; -.
DR BioGRID-ORCS; 84623; 8 hits in 1060 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 128 other tissues.
DR ExpressionAtlas; Q8IZU9; baseline and differential.
DR Genevisible; Q8IZU9; HS.
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:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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 Gene3D; 2.60.40.10; -; 5.
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; PF07679; I-set; 2.
DR Pfam; PF13895; Ig_2; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 3.
DR SUPFAM; SSF48726; SSF48726; 5.
DR PROSITE; PS50835; IG_LIKE; 5.
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; unknown pathological significance;
FT 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; unknown pathological significance;
FT 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; unknown pathological significance;
FT 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
