LBN_HUMAN
ID LBN_HUMAN Reviewed; 1308 AA.
AC Q86UK5; Q86YT3; Q86YT4; Q8NG49;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Limbin;
DE AltName: Full=Ellis-van Creveld syndrome protein 2;
DE Short=EVC2;
DE Flags: Precursor;
GN Name=EVC2; Synonyms=LBN;
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 2).
RC TISSUE=Kidney;
RX PubMed=12136126; DOI=10.1073/pnas.152337899;
RA Takeda H., Takami M., Oguni T., Tsuji T., Yoneda K., Sato H., Ihara N.,
RA Itoh T., Kata S.R., Mishina Y., Womack J.E., Moritomo Y., Sugimoto Y.,
RA Kunieda T.;
RT "Positional cloning of the gene LIMBIN responsible for bovine
RT chondrodysplastic dwarfism.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10549-10554(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT EVC ARG-283.
RX PubMed=12571802; DOI=10.1086/368063;
RA Ruiz-Perez V.L., Tompson S.W.J., Blair H.J., Espinoza-Valdez C.,
RA Lapunzina P., Silva E.O., Hamel B.C.J., Gibbs J.L., Young I.D.,
RA Wright M.J., Goodship J.A.;
RT "Mutations in two nonhomologous genes in a head-to-head configuration cause
RT Ellis-van Creveld syndrome.";
RL Am. J. Hum. Genet. 72:728-732(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 75-1308 (ISOFORMS 1 AND 3), TISSUE
RP SPECIFICITY, AND VARIANT EVC TRP-950.
RX PubMed=12468274; DOI=10.1016/s1096-7192(02)00178-6;
RA Galdzicka M., Patnala S., Hirshman M.G., Cai J.-F., Nitowsky H.,
RA Egeland J.A., Ginns E.I.;
RT "A new gene, EVC2, is mutated in Ellis-van Creveld syndrome.";
RL Mol. Genet. Metab. 77:291-295(2002).
RN [4]
RP INVOLVEMENT IN WEYERS ACROFACIAL DYSOSTOSIS.
RX PubMed=16404586; DOI=10.1007/s00439-005-0129-2;
RA Ye X., Song G., Fan M., Shi L., Jabs E.W., Huang S., Guo R., Bian Z.;
RT "A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial
RT dysostosis.";
RL Hum. Genet. 119:199-205(2006).
RN [5]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-630 AND VAL-994.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Component of the EvC complex that positively regulates
CC ciliary Hedgehog (Hh) signaling. Plays a critical role in bone
CC formation and skeletal development. May be involved in early embryonic
CC morphogenesis. {ECO:0000250|UniProtKB:Q8K1G2}.
CC -!- SUBUNIT: Component of the EvC complex composed of EFCAB7, IQCE, EVC2
CC and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE.
CC Interacts with EVC. Interacts (via N-terminal end) with EFCAB7.
CC Interacts (via N-terminal end) with IQCE.
CC {ECO:0000250|UniProtKB:Q8K1G2}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8K1G2};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q8K1G2}.
CC Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q8K1G2}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q8K1G2}. Cell projection, cilium membrane
CC {ECO:0000250|UniProtKB:Q8K1G2}. Nucleus {ECO:0000250|UniProtKB:Q8K1G2}.
CC Note=The EvC complex localizes at the base of cilia in the EvC zone of
CC primary cilia in a EFCAB7-dependent manner.
CC {ECO:0000250|UniProtKB:Q8K1G2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q86UK5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q86UK5-2; Sequence=VSP_008848;
CC Name=3;
CC IsoId=Q86UK5-3; Sequence=VSP_008849;
CC -!- TISSUE SPECIFICITY: Found in the heart, placenta, lung, liver, skeletal
CC muscle, kidney and pancreas. {ECO:0000269|PubMed:12468274}.
CC -!- DISEASE: Ellis-van Creveld syndrome (EVC) [MIM:225500]: An autosomal
CC recessive condition characterized by the clinical tetrad of
CC chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac
CC anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial
CC polydactyly, and dysplastic nails and teeth. Congenital heart defects,
CC most commonly an atrioventricular septal defect, are observed in 60% of
CC affected individuals. {ECO:0000269|PubMed:12468274,
CC ECO:0000269|PubMed:12571802}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Acrofacial dysostosis, Weyers type (WAD) [MIM:193530]: An
CC autosomal dominant condition characterized by dysplastic nails,
CC postaxial polydactyly, dental anomalies, short limbs, short stature and
CC normal intelligence. The phenotype is milder than Ellis-van Creveld
CC syndrome. {ECO:0000269|PubMed:16404586}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN86577.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAN86578.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB083067; BAC06590.1; -; mRNA.
DR EMBL; AY185210; AAO22066.1; -; mRNA.
DR EMBL; AY152402; AAN86577.1; ALT_INIT; mRNA.
DR EMBL; AY152403; AAN86578.1; ALT_INIT; mRNA.
DR CCDS; CCDS3382.2; -. [Q86UK5-1]
DR CCDS; CCDS54718.1; -. [Q86UK5-2]
DR RefSeq; NP_001159608.1; NM_001166136.1. [Q86UK5-2]
DR RefSeq; NP_667338.3; NM_147127.4. [Q86UK5-1]
DR RefSeq; XP_016863225.1; XM_017007736.1. [Q86UK5-2]
DR RefSeq; XP_016863226.1; XM_017007737.1. [Q86UK5-2]
DR AlphaFoldDB; Q86UK5; -.
DR SMR; Q86UK5; -.
DR BioGRID; 126340; 85.
DR IntAct; Q86UK5; 84.
DR MINT; Q86UK5; -.
DR STRING; 9606.ENSP00000342144; -.
DR GlyGen; Q86UK5; 1 site.
DR iPTMnet; Q86UK5; -.
DR PhosphoSitePlus; Q86UK5; -.
DR BioMuta; EVC2; -.
DR DMDM; 38257827; -.
DR EPD; Q86UK5; -.
DR jPOST; Q86UK5; -.
DR MassIVE; Q86UK5; -.
DR PaxDb; Q86UK5; -.
DR PeptideAtlas; Q86UK5; -.
DR PRIDE; Q86UK5; -.
DR Antibodypedia; 22606; 134 antibodies from 30 providers.
DR DNASU; 132884; -.
DR Ensembl; ENST00000310917.6; ENSP00000311683.2; ENSG00000173040.13. [Q86UK5-2]
DR Ensembl; ENST00000344408.10; ENSP00000342144.5; ENSG00000173040.13. [Q86UK5-1]
DR GeneID; 132884; -.
DR KEGG; hsa:132884; -.
DR MANE-Select; ENST00000344408.10; ENSP00000342144.5; NM_147127.5; NP_667338.3.
DR UCSC; uc003gij.4; human. [Q86UK5-1]
DR CTD; 132884; -.
DR DisGeNET; 132884; -.
DR GeneCards; EVC2; -.
DR HGNC; HGNC:19747; EVC2.
DR HPA; ENSG00000173040; Low tissue specificity.
DR MalaCards; EVC2; -.
DR MIM; 193530; phenotype.
DR MIM; 225500; phenotype.
DR MIM; 607261; gene.
DR neXtProt; NX_Q86UK5; -.
DR OpenTargets; ENSG00000173040; -.
DR Orphanet; 952; Acrofacial dysostosis, Weyers type.
DR Orphanet; 289; Ellis Van Creveld syndrome.
DR PharmGKB; PA134989044; -.
DR VEuPathDB; HostDB:ENSG00000173040; -.
DR eggNOG; ENOG502QQ5U; Eukaryota.
DR GeneTree; ENSGT00940000154127; -.
DR HOGENOM; CLU_007621_0_0_1; -.
DR InParanoid; Q86UK5; -.
DR OMA; QYLRQWR; -.
DR OrthoDB; 90381at2759; -.
DR PhylomeDB; Q86UK5; -.
DR TreeFam; TF331379; -.
DR PathwayCommons; Q86UK5; -.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR SignaLink; Q86UK5; -.
DR BioGRID-ORCS; 132884; 16 hits in 1070 CRISPR screens.
DR ChiTaRS; EVC2; human.
DR GenomeRNAi; 132884; -.
DR Pharos; Q86UK5; Tbio.
DR PRO; PR:Q86UK5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q86UK5; protein.
DR Bgee; ENSG00000173040; Expressed in pancreatic ductal cell and 120 other tissues.
DR ExpressionAtlas; Q86UK5; baseline and differential.
DR Genevisible; Q86UK5; HS.
DR GO; GO:0060170; C:ciliary membrane; IBA:GO_Central.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0098797; C:plasma membrane protein complex; IBA:GO_Central.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR InterPro; IPR022076; Limbin.
DR InterPro; IPR026501; Limbin/Ellis-van_Creveld.
DR PANTHER; PTHR16795; PTHR16795; 1.
DR Pfam; PF12297; EVC2_like; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Ciliopathy; Cilium;
KW Coiled coil; Cytoplasm; Cytoskeleton; Disease variant; Dwarfism;
KW Ectodermal dysplasia; Glycoprotein; Membrane; Nucleus; Reference proteome;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1308
FT /note="Limbin"
FT /id="PRO_0000084363"
FT TOPO_DOM 27..300
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 301..321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 322..1308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 36..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 784..816
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 455..578
FT /evidence="ECO:0000255"
FT COILED 636..800
FT /evidence="ECO:0000255"
FT COILED 1001..1113
FT /evidence="ECO:0000255"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..80
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12136126"
FT /id="VSP_008848"
FT VAR_SEQ 1220..1308
FT /note="SILKKTCLPLRERMIFSGKGSWPHLSLEPIGELAPVPIVGAETIDLLNTGEK
FT LFIFRNPKEPEISLHVPPRKKKNFLNAKKAMRALGMD -> RSGNQESFWQYLVGTPEI
FT GLIEWMSEK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12468274"
FT /id="VSP_008849"
FT VARIANT 230
FT /note="S -> G (in dbSNP:rs4689278)"
FT /id="VAR_051089"
FT VARIANT 283
FT /note="I -> R (in EVC; dbSNP:rs137852926)"
FT /evidence="ECO:0000269|PubMed:12571802"
FT /id="VAR_017209"
FT VARIANT 630
FT /note="A -> S (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035933"
FT VARIANT 699
FT /note="T -> A (in dbSNP:rs730469)"
FT /id="VAR_017210"
FT VARIANT 950
FT /note="R -> W (in EVC; dbSNP:rs137852928)"
FT /evidence="ECO:0000269|PubMed:12468274"
FT /id="VAR_017211"
FT VARIANT 994
FT /note="L -> V (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035934"
FT CONFLICT 1106
FT /note="L -> W (in Ref. 3; AAN86577)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1308 AA; 147948 MW; D1EC635F43495A9A CRC64;
MDPSGSRGRP TWVLAGGLLA VALALGGRGC LGASSRPRWR PLGAQPPRDP QVAPRSGPGL
RIPPGRSGAG PESSTQDLPC MIWPKVECCH FKTAVEAPLG MKLDKKMEVF IPLSTSAASS
GPWAHSLFAF IPSWPKKNLF KRESPITHRL YGDISREVQG TSENGVIFQK CALVSGSSEA
QTARIWLLVN NTKTTSSANL SELLLLDSIA GLTIWDSVGN RTSEGFQAFS KKFLQVGDAF
AVSYAATLQA GDLGNGESLK LPAQLTFQSS SRNRTQLKVL FSITAEENVT VLPHHGLHAA
GFFIAFLLSL VLTWAALFLM VRYQCLKGNM LTRHRVWQYE SKLEPLPFTS ADGVNEDLSL
NDQMIDILSS EDPGSMLQAL EELEIATLNR ADADLEACRT QISKDIIALL LKNLTSSGHL
SPQVERKMSA VFKKQFLLLE NEIQEEYDRK MVALTAECDL ETRKKMENQY QREMMAMEEA
EELLKRAGER SAVECSNLLR TLHGLEQEHL RKSLALQQEE DFAKAHRQLA VFQRNELHSI
FFTQIKSAIF KGELKPEAAK MLLQNYSKIQ ENVEELMDFF QASKRYHLSK RFGHREYLVQ
NLQSSETRVQ GLLSTAAAQL THLIQKHERA GYLDEDQMEM LLERAQTEVF SIKQKLDNDL
KQEKKKLHQK LITKRRRELL QKHREQRREQ ASVGEAFRTV EDAGQYLHQK RSLMEEHGAT
LEELQERLDQ AALDDLRTLT LSLFEKATDE LRRLQNSAMT QELLKRGVPW LFLQQILEEH
GKEMAARAEQ LEGEERDRDQ EGVQSVRQRL KDDAPEAVTE EQAELRRWEH LIFMKLCSSV
FSLSEEELLR MRQEVHGCFA QMDRSLALPK IRARVLLQQF QTAWREAEFV KLDQAVAAPE
LQQQSKVRKS RSKSKSKGEL LKKCIEDKIH LCEEQASEDL VEKVRGELLR ERVQRMEAQE
GGFAQSLVAL QFQKASRVTE TLSAYTALLS IQDLLLEELS ASEMLTKSAC TQILESHSRE
LQELERKLED QLVQQEAAQQ QQALASWQQW VADGPGILNE PGEVDSERQV STVLHQALSK
SQTLLEQHQQ CLREEQQNSV VLEDLLENME ADTFATLCSQ ELRLASYLAR MAMVPGATLR
RLLSVVLPTA SQPQLLALLD SATERHVDHA AESDGGAEQA DVGRRRKHQS WWQALDGKLR
GDLISRGLEK MLWARKRKQS ILKKTCLPLR ERMIFSGKGS WPHLSLEPIG ELAPVPIVGA
ETIDLLNTGE KLFIFRNPKE PEISLHVPPR KKKNFLNAKK AMRALGMD
