P0CG37 (CFC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cryptic protein

Alternative name(s):
Cryptic family protein 1

Gene names

Name:

CFC1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	223 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NODAL coreceptor involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation. Ref.1
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Secreted. Note: Does not exhibit a typical GPI-signal sequence. The C-ter hydrophilic extension of the GPI-signal sequence reduces the efficiency of processing and could lead to the production of an secreted unprocessed form. This extension is found only in primates. Ref.5
Post-translational modification	N-glycosylated By similarity.
Involvement in disease	Heterotaxy, visceral, 2, autosomal (HTX2) [MIM:605376]: A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. Visceral heterotaxy or situs ambiguus results in randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another. It can been associated with variety of congenital defects including cardiac malformations. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Transposition of the great arteries dextro-looped 2 (DTGA2) [MIM:613853]: A congenital heart defect consisting of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. The presence or absence of associated cardiac anomalies defines the clinical presentation and surgical management of patients with transposition of the great arteries. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Conotruncal heart malformations (CTHM) [MIM:217095]: A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Contains 1 EGF-like domain.
Caution	This gene differs from CFC1B by only one residue at position 78:R -> W. R78W is also thought to be a CFC1 polymorphism which has been shown to lead to a different cell surface distribution and activity (Ref.6 and Ref.1).

Ontologies

Keywords
Biological process	Gastrulation
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation Heterotaxy
Domain	EGF-like domain Signal
Molecular function	Developmental protein
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	determination of left/right symmetry Non-traceable author statement Ref.1. Source: UniProtKB gastrulation Inferred from electronic annotation. Source: UniProtKB-KW nodal signaling pathway Inferred from mutant phenotype PubMed 12052855. Source: UniProtKB
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 158	133	Cryptic protein		PRO_0000044630
	Propeptide	159 – 223	65	Removed in mature form		PRO_0000395407
Regions
	Domain	86 – 115	30	EGF-like
Amino acid modifications
	Lipidation	158	1	GPI-anchor amidated aspartate Ref.5
	Glycosylation	52	1	N-linked (GlcNAc...) Potential
	Disulfide bond	90 ↔ 97		By similarity
	Disulfide bond	91 ↔ 103		By similarity
	Disulfide bond	105 ↔ 114		By similarity
Natural variations
	Natural variant	78	1	R → W. Ref.1 Ref.6 Corresponds to variant rs2579433 [ dbSNP | Ensembl ].		VAR_024322
	Natural variant	112	1	R → C in HTX2; complete loss of activity; abnormal cell surface localization. Ref.1		VAR_024323
	Natural variant	189	1	R → C. Ref.1		VAR_024324
Experimental info
	Mutagenesis	191 – 223	33	LRPDA…LGHRL → VVVVV: Does not affect the cellular localization and the biological activity.
	Mutagenesis	191 – 223	33	Missing: Increased NODAL dependent signaling.

Sequences

	Sequence		Length	Mass (Da)
	P0CG37 [UniParc]. Last modified July 13, 2010. Version 1. Checksum: B52852A00ABCF1A3	FASTA	223	24,612
	10 20 30 40 50 60 MTWRHHVRLL FTVSLALQII NLGNSYQREK HNGGREEVTK VATQKHRQSP LNWTSSHFGE 70 80 90 100 110 120 VTGSAEGWGP EEPLPYSRAF GEGASARPRC CRNGGTCVLG SFCVCPAHFT GRYCEHDQRR 130 140 150 160 170 180 SECGALEHGA WTLRACHLCR CIFGALHCLP LQTPDRCDPK DFLASHAHGP SAGGAPSLLL 190 200 210 220 LLPCALLHRL LRPDAPAHPR SLVPSVLQRE RRPCGRPGLG HRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects." Bamford R.N., Roessler E., Burdine R.D., Saplakoglu U., dela Cruz J., Splitt M., Towbin J., Bowers P., Marino B., Schier A.F., Shen M.M., Muenke M., Casey B. Nat. Genet. 26:365-369(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, VARIANT HTX2 CYS-112, CHARACTERIZATION OF VARIANT HTX2 CYS-112, VARIANTS TRP-78 AND CYS-189.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Subthalamic nucleus.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Lung.
[5]	"Characterization of the glycosylphosphatidylinositol-anchor signal sequence of human Cryptic with a hydrophilic extension." Watanabe K., Nagaoka T., Strizzi L., Mancino M., Gonzales M., Bianco C., Salomon D.S. Biochim. Biophys. Acta 1778:2671-2681(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, GPI-ANCHOR, MUTAGENESIS OF 151-GLY--LEU-223.
[6]	"CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle." Goldmuntz E., Bamford R., Karkera J.D., dela Cruz J., Roessler E., Muenke M. Am. J. Hum. Genet. 70:776-780(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TRP-78, INVOLVEMENT IN DTGA2 AND CTHM.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF312769 mRNA. Translation: AAG30294.1. AF312925 Genomic DNA. Translation: AAG42475.1. AK315326 mRNA. Translation: BAG37727.1. AC140481 Genomic DNA. No translation available. BC069508 mRNA. Translation: AAH69508.1. BC074825 mRNA. Translation: AAH74825.1. BC074826 mRNA. Translation: AAH74826.1. BC110080 mRNA. Translation: AAI10081.1. BC146897 mRNA. Translation: AAI46898.1.
IPI	IPI00969174.
RefSeq	NP_001257349.1. NM_001270420.1. NP_001257350.1. NM_001270421.1. NP_115934.1. NM_032545.3.
UniGene	Hs.567542.
3D structure databases
ProteinModelPortal	P0CG37.
SMR	P0CG37. Positions 89-144.
ModBase	Search...
Polymorphism databases
DMDM	300680886.
Proteomic databases
PRIDE	P0CG37.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000259216; ENSP00000259216; ENSG00000136698.
GeneID	55997.
KEGG	hsa:55997.
UCSC	uc002trl.1. human.
Organism-specific databases
CTD	55997.
GeneCards	GC02M131350.
HGNC	HGNC:18292. CFC1.
HPA	HPA041773.
MIM	217095. phenotype. 605194. gene. 605376. phenotype. 613853. phenotype.
neXtProt	NX_P0CG37.
PharmGKB	PA134916180.
GenAtlas	Search...
Phylogenomic databases
OMA	PRCCENG.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology.
Gene expression databases
Bgee	P0CG37.
GermOnline	ENSG00000136698. Homo sapiens.
Family and domain databases
InterPro	IPR019011. Cryptic/Cripto_CFC-dom. IPR000742. EG-like_dom. IPR013032. EGF-like_CS. [Graphical view]
Pfam	PF09443. CFC. 1 hit. [Graphical view]
SMART	SM00181. EGF. 1 hit. [Graphical view]
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. False negative. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	55997.
NextBio	61435.
SOURCE	Search...

Entry information

Entry name

CFC1_HUMAN

Accession

Primary (citable) accession number: P0CG37
Secondary accession number(s): B2RCY0 , B9EJD3, Q53T05, Q9GZR3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 13, 2010
Last sequence update:	July 13, 2010
Last modified:	May 1, 2013
This is version 27 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.