EVC_HUMAN
ID EVC_HUMAN Reviewed; 992 AA.
AC P57679;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=EvC complex member EVC {ECO:0000305};
DE AltName: Full=DWF-1;
DE AltName: Full=Ellis-van Creveld syndrome protein;
GN Name=EVC;
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], VARIANT WAD PRO-307, VARIANT EVC GLN-443, AND
RP VARIANTS PRO-74; HIS-258; SER-403; LYS-449; GLN-576; GLN-760 AND GLY-953.
RC TISSUE=Brain, and Heart;
RX PubMed=10700184; DOI=10.1038/73508;
RA Ruiz-Perez V.L., Ide S.E., Strom T.M., Lorenz B., Wilson D., Woods K.,
RA King L., Francomano C., Freisinger P., Spranger S., Marino B.,
RA Dallapiccola B., Wright M., Meitinger T., Polymeropoulos M.H., Goodship J.;
RT "Mutations in a new gene in Ellis-van Creveld syndrome and Weyers
RT acrodental dysostosis.";
RL Nat. Genet. 24:283-286(2000).
RN [2]
RP ERRATUM OF PUBMED:10700184.
RA Ruiz-Perez V.L., Ide S.E., Strom T.M., Lorenz B., Wilson D., Woods K.,
RA King L., Francomano C., Freisinger P., Spranger S., Marino B.,
RA Dallapiccola B., Wright M., Meitinger T., Polymeropoulos M.H., Goodship J.;
RL Nat. Genet. 25:125-125(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Galdzicka M., Damschroder-Williams P., Hirshman H.G., Winfield S.L.,
RA Simmons A., Lovett M., Martin B.M., Ginns E.I.;
RT "Candidate gene for Ellis-van Creveld disorder.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP VARIANT EVC PRO-623.
RX PubMed=18947413; DOI=10.1186/1471-2350-9-92;
RA Ulucan H., Gul D., Sapp J.C., Cockerham J., Johnston J.J., Biesecker L.G.;
RT "Extending the spectrum of Ellis van Creveld syndrome: a large family with
RT a mild mutation in the EVC gene.";
RL BMC Med. Genet. 9:92-92(2008).
RN [5]
RP VARIANT EVC ASN-206.
RX PubMed=19744229; DOI=10.1111/j.1442-200x.2009.02953.x;
RA Kalsoom U.-E., Wasif N., Tariq M., Ahmad W.;
RT "A novel missense mutation in the EVC gene underlies Ellis-van Creveld
RT syndrome in a Pakistani family.";
RL Pediatr. Int. 52:240-246(2010).
CC -!- FUNCTION: Component of the EvC complex that positively regulates
CC ciliary Hedgehog (Hh) signaling. Involved in endochondral growth and
CC skeletal development. {ECO:0000250|UniProtKB:P57680}.
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 EVC2. Interacts with EFCAB7. Interacts with IQCE.
CC {ECO:0000250|UniProtKB:P57680}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P57680};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:P57680}. Cytoplasm,
CC cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:P57680}. Cell
CC projection, cilium {ECO:0000250|UniProtKB:P57680}. Cell projection,
CC cilium membrane {ECO:0000250|UniProtKB:P57680}. Note=EVC2 is required
CC for the localization of EVC at the base of primary cilia. The EvC
CC complex localizes at the base of cilia in the EvC zone of primary cilia
CC in a EFCAB7-dependent manner. {ECO:0000250|UniProtKB:P57680}.
CC -!- TISSUE SPECIFICITY: Found in the developing vertebral bodies, ribs,
CC upper and lower limbs, heart, kidney, lung.
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:10700184,
CC ECO:0000269|PubMed:18947413, ECO:0000269|PubMed:19744229}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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:10700184}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
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; AF216184; AAF37216.1; -; mRNA.
DR EMBL; AF216185; AAF37217.1; -; mRNA.
DR EMBL; AF239742; AAF44682.1; -; mRNA.
DR CCDS; CCDS3383.1; -.
DR RefSeq; NP_001293019.1; NM_001306090.1.
DR RefSeq; NP_001293021.1; NM_001306092.1.
DR RefSeq; NP_714928.1; NM_153717.2.
DR AlphaFoldDB; P57679; -.
DR SMR; P57679; -.
DR BioGRID; 108422; 5.
DR IntAct; P57679; 1.
DR STRING; 9606.ENSP00000264956; -.
DR iPTMnet; P57679; -.
DR PhosphoSitePlus; P57679; -.
DR BioMuta; EVC; -.
DR DMDM; 12229783; -.
DR EPD; P57679; -.
DR jPOST; P57679; -.
DR MassIVE; P57679; -.
DR PaxDb; P57679; -.
DR PeptideAtlas; P57679; -.
DR PRIDE; P57679; -.
DR ProteomicsDB; 57006; -.
DR Antibodypedia; 2233; 96 antibodies from 15 providers.
DR DNASU; 2121; -.
DR Ensembl; ENST00000264956.11; ENSP00000264956.6; ENSG00000072840.13.
DR GeneID; 2121; -.
DR KEGG; hsa:2121; -.
DR MANE-Select; ENST00000264956.11; ENSP00000264956.6; NM_153717.3; NP_714928.1.
DR UCSC; uc003gil.2; human.
DR CTD; 2121; -.
DR DisGeNET; 2121; -.
DR GeneCards; EVC; -.
DR HGNC; HGNC:3497; EVC.
DR HPA; ENSG00000072840; Low tissue specificity.
DR MalaCards; EVC; -.
DR MIM; 193530; phenotype.
DR MIM; 225500; phenotype.
DR MIM; 604831; gene.
DR neXtProt; NX_P57679; -.
DR OpenTargets; ENSG00000072840; -.
DR Orphanet; 952; Acrofacial dysostosis, Weyers type.
DR Orphanet; 289; Ellis Van Creveld syndrome.
DR PharmGKB; PA27911; -.
DR VEuPathDB; HostDB:ENSG00000072840; -.
DR eggNOG; ENOG502QUDD; Eukaryota.
DR GeneTree; ENSGT00940000154127; -.
DR HOGENOM; CLU_014037_0_0_1; -.
DR InParanoid; P57679; -.
DR OMA; QMRMSRK; -.
DR OrthoDB; 133009at2759; -.
DR PhylomeDB; P57679; -.
DR TreeFam; TF335835; -.
DR PathwayCommons; P57679; -.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR SignaLink; P57679; -.
DR BioGRID-ORCS; 2121; 14 hits in 1063 CRISPR screens.
DR ChiTaRS; EVC; human.
DR GenomeRNAi; 2121; -.
DR Pharos; P57679; Tbio.
DR PRO; PR:P57679; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P57679; protein.
DR Bgee; ENSG00000072840; Expressed in sural nerve and 100 other tissues.
DR ExpressionAtlas; P57679; baseline and differential.
DR Genevisible; P57679; HS.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0060170; C:ciliary membrane; IBA:GO_Central.
DR GO; GO:0005929; C:cilium; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0098797; C:plasma membrane protein complex; IBA:GO_Central.
DR GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR GO; GO:0003416; P:endochondral bone growth; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; TAS:ProtInc.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:InterPro.
DR InterPro; IPR026582; Evc.
DR InterPro; IPR026501; Limbin/Ellis-van_Creveld.
DR PANTHER; PTHR16795; PTHR16795; 1.
DR PANTHER; PTHR16795:SF13; PTHR16795:SF13; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Ciliopathy; Cilium; Cytoplasm;
KW Cytoskeleton; Disease variant; Dwarfism; Ectodermal dysplasia; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..992
FT /note="EvC complex member EVC"
FT /id="PRO_0000087102"
FT TOPO_DOM 1..25
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..48
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..992
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 66..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 825..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 930..992
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 66..80
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..102
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 829..854
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 953..979
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 74
FT /note="Q -> P (in dbSNP:rs2291157)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009942"
FT VARIANT 114
FT /note="A -> V (in dbSNP:rs16837598)"
FT /id="VAR_033852"
FT VARIANT 206
FT /note="S -> N (in EVC; dbSNP:rs1017946059)"
FT /evidence="ECO:0000269|PubMed:19744229"
FT /id="VAR_066447"
FT VARIANT 258
FT /note="Y -> H (in dbSNP:rs6414624)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009943"
FT VARIANT 307
FT /note="S -> P (in WAD; dbSNP:rs121908426)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009944"
FT VARIANT 372
FT /note="T -> M (in dbSNP:rs28483498)"
FT /id="VAR_033853"
FT VARIANT 403
FT /note="G -> S (in dbSNP:rs183114391)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009945"
FT VARIANT 443
FT /note="R -> Q (in EVC; dbSNP:rs35953626)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009946"
FT VARIANT 449
FT /note="T -> K (in dbSNP:rs2302075)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009947"
FT VARIANT 576
FT /note="R -> Q (in dbSNP:rs1383180)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009948"
FT VARIANT 623
FT /note="L -> P (in EVC; atypical phenotype with septal
FT cardiac defects, rhizomelic limb shortening and polydactyly
FT without the typical lip, dental and nail abnormalities of
FT EVC; dbSNP:rs1373632260)"
FT /evidence="ECO:0000269|PubMed:18947413"
FT /id="VAR_066448"
FT VARIANT 760
FT /note="R -> Q (in dbSNP:rs2279252)"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009949"
FT VARIANT 953
FT /note="D -> G"
FT /evidence="ECO:0000269|PubMed:10700184"
FT /id="VAR_009950"
FT VARIANT 965
FT /note="Missing"
FT /id="VAR_009951"
FT CONFLICT 966
FT /note="Missing (in Ref. 3; AAF44682)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 992 AA; 111990 MW; E3ED42401138B5D4 CRC64;
MARGGAACKS DARLLLGRDA LRPAPALLAP AVLLGAALGL GLGLWLGCRA GRQRTRHQKD
DTQNLLKNLE SNAQTPSETG SPSRRRKREV QMSKDKEAVD ECEPPSNSNI TAFALKAKVI
YPINQKFRPL ADGSSNPSLH ENLKQAVLPH QPVEASPSSS LGSLSQGEKD DCSSSSSVHS
ATSDDRFLSR TFLRVNAFPE VLACESVDVD LCIYSLHLKD LLHLDTALRQ EKHMMFIQIF
KMCLLDLLPK KKSDDELYQK ILSKQEKDLE ELEKGLQVKL SNTEMSGAGD SEYITLADVE
KKEREYSEQL IDNMEAFWKQ MANIQHFLVD QFKCSSSKAR QLMMTLTERM IAAEGLLCDS
QELQALDALE RTMGRAHMAK VIEFLKLQVQ EETRCRLAAI SHGLELLAGE GKLSGRQKEE
LLTQQHKAFW QEAERFSREF VQRGKDLVTA SLAHQVEGTA KLTLAQEEEQ RSFLAEAQPT
ADPEKFLEAF HEVLERQRLM QCDLEEEENV RATEAVVALC QELYFSTVDT FQKFVDALFL
QTLPGMTGLP PEECDYLRQE VQENAAWQLG KSNRFRRQQW KLFQELLEQD QQVWMEECAL
SSVLQTHLRE DHEGTIRGVL GRLGGLTEES TRCVLQGHDL LLRSALRRLA LRGNALATLT
QMRLSGKKHL LQELREQRAL EQGSSQCLDE HQWQLLRALE ARVLEEASRL EEEAQQTRLQ
LQQRLLAEAQ EVGQLLQQHM ECAIGQALLV HARNAATKSR AKDRDDFKRT LMEAAVESVY
VTSAGVSRLV QAYYQQIGRI MEDHEERKLQ HLKTLQGERM ENYKLRKKQE LSNPSSGSRT
AGGAHETSQA VHQRMLSQQK RFLAQFPVHQ QMRLHAQQQQ AGVMDLLEAQ LETQLQEAEQ
NFISELAALA RVPLAESKLL PAKRGLLEKP LRTKRKKPLP QERGDLGVPN NEDLASGDQT
SGSLSSKRLS QQESEAGDSG NSKKMLKRRS NL
