P57679 (EVC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ellis-van Creveld syndrome protein

Alternative name(s):
DWF-1

Gene names

Name:

EVC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	992 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a positive mediator of Hedgehog signaling indispensable for normal endochondral growth and skeletal development By similarity.
Subunit structure	Interacts with EVC2 By similarity.
Subcellular location	Cell membrane; Single-pass membrane protein By similarity. Cytoplasm › cytoskeleton › cilium basal body By similarity. Cell projection › cilium By similarity. Cell projection › cilium membrane By similarity. Note: EVC2 is required for the localization of EVC at the base of primary cilia By similarity.
Tissue specificity	Found in the developing vertebral bodies, ribs, upper and lower limbs, heart, kidney, lung.
Involvement in disease	Defects in EVC are a cause of Ellis-van Creveld syndrome (EVC) [MIM:225500]; also known as chondroectodermal dysplasia. EVC is an autosomal recessive disorder characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital heart defects, most commonly an atrioventricular septal defect, are observed in 60% of affected individuals. Ref.1 Ref.4 Ref.5 Defects in EVC are a cause of acrofacial dysostosis Weyers type (WAD) [MIM:193530]; also known as Curry-Hall syndrome. Acrofacial dysostoses are a heterogeneous group of disorders combining limb defects with facial abnormalities. WAD is an autosomal dominant disorder characterized by dysplastic nails, postaxial polydactyly, acrofacial dysostosis, short limbs and short stature. The phenotype is milder than Ellis-van Creveld syndrome. Ref.1

Ontologies

Keywords
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Polymorphism
Disease	Ciliopathy Disease mutation Dwarfism Ectodermal dysplasia
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	endochondral bone growth Inferred from sequence or structural similarity. Source: UniProtKB muscle organ development Traceable author statement. Source: ProtInc positive regulation of smoothened signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cilium membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microtubule basal body Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 992	992	Ellis-van Creveld syndrome protein		PRO_0000087102
Regions
	Topological domain	1 – 25	25	Extracellular Potential
	Transmembrane	26 – 48	23	Helical; Potential
	Topological domain	49 – 992	944	Cytoplasmic Potential
Natural variations
	Natural variant	74	1	Q → P. Ref.1 Corresponds to variant rs2291157 [ dbSNP | Ensembl ].		VAR_009942
	Natural variant	114	1	A → V. Corresponds to variant rs16837598 [ dbSNP | Ensembl ].		VAR_033852
	Natural variant	206	1	S → N in EVC. Ref.5		VAR_066447
	Natural variant	258	1	Y → H. Ref.1 Corresponds to variant rs6414624 [ dbSNP | Ensembl ].		VAR_009943
	Natural variant	307	1	S → P in WAD. Ref.1		VAR_009944
	Natural variant	372	1	T → M. Corresponds to variant rs28483498 [ dbSNP | Ensembl ].		VAR_033853
	Natural variant	403	1	G → S. Ref.1		VAR_009945
	Natural variant	443	1	R → Q in EVC. Ref.1 Corresponds to variant rs35953626 [ dbSNP | Ensembl ].		VAR_009946
	Natural variant	449	1	T → K. Ref.1 Corresponds to variant rs2302075 [ dbSNP | Ensembl ].		VAR_009947
	Natural variant	576	1	R → Q. Ref.1 Corresponds to variant rs1383180 [ dbSNP | Ensembl ].		VAR_009948
	Natural variant	623	1	L → P in EVC; atypical phenotype with septal cardiac defects, rhizomelic limb shortening and polydactyly without the typical lip, dental and nail abnormalities of EVC. Ref.4		VAR_066448
	Natural variant	760	1	R → Q. Ref.1 Corresponds to variant rs2279252 [ dbSNP | Ensembl ].		VAR_009949
	Natural variant	953	1	D → G. Ref.1		VAR_009950
	Natural variant	965	1	Missing.		VAR_009951
Experimental info
	Sequence conflict	966	1	Missing in AAF44682. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P57679 [UniParc]. Last modified December 1, 2000. Version 1. Checksum: E3ED42401138B5D4	FASTA	992	111,990
	10 20 30 40 50 60 MARGGAACKS DARLLLGRDA LRPAPALLAP AVLLGAALGL GLGLWLGCRA GRQRTRHQKD 70 80 90 100 110 120 DTQNLLKNLE SNAQTPSETG SPSRRRKREV QMSKDKEAVD ECEPPSNSNI TAFALKAKVI 130 140 150 160 170 180 YPINQKFRPL ADGSSNPSLH ENLKQAVLPH QPVEASPSSS LGSLSQGEKD DCSSSSSVHS 190 200 210 220 230 240 ATSDDRFLSR TFLRVNAFPE VLACESVDVD LCIYSLHLKD LLHLDTALRQ EKHMMFIQIF 250 260 270 280 290 300 KMCLLDLLPK KKSDDELYQK ILSKQEKDLE ELEKGLQVKL SNTEMSGAGD SEYITLADVE 310 320 330 340 350 360 KKEREYSEQL IDNMEAFWKQ MANIQHFLVD QFKCSSSKAR QLMMTLTERM IAAEGLLCDS 370 380 390 400 410 420 QELQALDALE RTMGRAHMAK VIEFLKLQVQ EETRCRLAAI SHGLELLAGE GKLSGRQKEE 430 440 450 460 470 480 LLTQQHKAFW QEAERFSREF VQRGKDLVTA SLAHQVEGTA KLTLAQEEEQ RSFLAEAQPT 490 500 510 520 530 540 ADPEKFLEAF HEVLERQRLM QCDLEEEENV RATEAVVALC QELYFSTVDT FQKFVDALFL 550 560 570 580 590 600 QTLPGMTGLP PEECDYLRQE VQENAAWQLG KSNRFRRQQW KLFQELLEQD QQVWMEECAL 610 620 630 640 650 660 SSVLQTHLRE DHEGTIRGVL GRLGGLTEES TRCVLQGHDL LLRSALRRLA LRGNALATLT 670 680 690 700 710 720 QMRLSGKKHL LQELREQRAL EQGSSQCLDE HQWQLLRALE ARVLEEASRL EEEAQQTRLQ 730 740 750 760 770 780 LQQRLLAEAQ EVGQLLQQHM ECAIGQALLV HARNAATKSR AKDRDDFKRT LMEAAVESVY 790 800 810 820 830 840 VTSAGVSRLV QAYYQQIGRI MEDHEERKLQ HLKTLQGERM ENYKLRKKQE LSNPSSGSRT 850 860 870 880 890 900 AGGAHETSQA VHQRMLSQQK RFLAQFPVHQ QMRLHAQQQQ AGVMDLLEAQ LETQLQEAEQ 910 920 930 940 950 960 NFISELAALA RVPLAESKLL PAKRGLLEKP LRTKRKKPLP QERGDLGVPN NEDLASGDQT 970 980 990 SGSLSSKRLS QQESEAGDSG NSKKMLKRRS NL

References

[1]	"Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis." Ruiz-Perez V.L., Ide S.E., Strom T.M., Lorenz B., Wilson D., Woods K., King L., Francomano C., Freisinger P., Spranger S., Marino B., Dallapiccola B., Wright M., Meitinger T., Polymeropoulos M.H., Goodship J. Nat. Genet. 24:283-286(2000) [PubMed: 10700184] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT WAD PRO-307, VARIANT EVC GLN-443, VARIANTS PRO-74; HIS-258; SER-403; LYS-449; GLN-576; GLN-760 AND GLY-953. Tissue: Brain and Heart.
[2]	Erratum Ruiz-Perez V.L., Ide S.E., Strom T.M., Lorenz B., Wilson D., Woods K., King L., Francomano C., Freisinger P., Spranger S., Marino B., Dallapiccola B., Wright M., Meitinger T., Polymeropoulos M.H., Goodship J. Nat. Genet. 25:125-125(2000)
[3]	"Candidate gene for Ellis-van Creveld disorder." Galdzicka M., Damschroder-Williams P., Hirshman H.G., Winfield S.L., Simmons A., Lovett M., Martin B.M., Ginns E.I. Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene." Ulucan H., Gul D., Sapp J.C., Cockerham J., Johnston J.J., Biesecker L.G. BMC Med. Genet. 9:92-92(2008) [PubMed: 18947413] [Abstract] Cited for: VARIANT EVC PRO-623.
[5]	"A novel missense mutation in the EVC gene underlies Ellis-van Creveld syndrome in a Pakistani family." Kalsoom U.-E., Wasif N., Tariq M., Ahmad W. Pediatr. Int. 52:240-246(2010) [PubMed: 19744229] [Abstract] Cited for: VARIANT EVC ASN-206.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF216184 mRNA. Translation: AAF37216.1. AF216185 mRNA. Translation: AAF37217.1. AF239742 mRNA. Translation: AAF44682.1.
IPI	IPI00027718.
RefSeq	NP_714928.1. NM_153717.2.
UniGene	Hs.646899. Hs.649902.
3D structure databases
ProteinModelPortal	P57679.
ModBase	Search...
Protein-protein interaction databases
STRING	P57679.
Polymorphism databases
DMDM	12229783.
Proteomic databases
PRIDE	P57679.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264956; ENSP00000264956; ENSG00000072840. ENST00000382674; ENSP00000372120; ENSG00000072840.
GeneID	2121.
KEGG	hsa:2121.
UCSC	uc003gil.1. human.
Organism-specific databases
CTD	2121.
GeneCards	GC04P005777.
H-InvDB	HIX0004056.
HGNC	HGNC:3497. EVC.
HPA	HPA008703. HPA016046.
MIM	193530. phenotype. 225500. phenotype. 604831. gene.
neXtProt	NX_P57679.
Orphanet	952. Acrofacial dysostosis, Weyers type. 289. Ellis Van Creveld syndrome.
PharmGKB	PA27911.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06961.
HOGENOM	HBG279951.
HOVERGEN	HBG003937.
InParanoid	P57679.
OMA	DQFKCSS.
OrthoDB	EOG4ZGPBV.
PhylomeDB	P57679.
Gene expression databases
ArrayExpress	P57679.
Bgee	P57679.
CleanEx	HS_EVC.
Genevestigator	P57679.
GermOnline	ENSG00000072840. Homo sapiens.
Family and domain databases
ProtoNet	Search...
Other
NextBio	8575.
SOURCE	Search...

Entry information

Entry name

EVC_HUMAN

Accession

Primary (citable) accession number: P57679

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.