CFC1_HUMAN
ID CFC1_HUMAN Reviewed; 223 AA.
AC P0CG37; B2RCY0; B9EJD3; Q53T05; Q9GZR3;
DT 13-JUL-2010, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Cryptic protein;
DE AltName: Full=Cryptic family protein 1;
DE Flags: Precursor;
GN Name=CFC1;
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 [GENOMIC DNA / MRNA], FUNCTION, VARIANT HTX2 CYS-112,
RP CHARACTERIZATION OF VARIANT HTX2 CYS-112, AND VARIANTS TRP-78 AND CYS-189.
RX PubMed=11062482; DOI=10.1038/81695;
RA Bamford R.N., Roessler E., Burdine R.D., Saplakoglu U., dela Cruz J.,
RA Splitt M., Towbin J., Bowers P., Marino B., Schier A.F., Shen M.M.,
RA Muenke M., Casey B.;
RT "Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with
RT human left-right laterality defects.";
RL Nat. Genet. 26:365-369(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
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 SUBCELLULAR LOCATION, GPI-ANCHOR AT ASP-158, AND MUTAGENESIS OF
RP 151-GLY--LEU-223.
RX PubMed=18930707; DOI=10.1016/j.bbamem.2008.09.011;
RA Watanabe K., Nagaoka T., Strizzi L., Mancino M., Gonzales M., Bianco C.,
RA Salomon D.S.;
RT "Characterization of the glycosylphosphatidylinositol-anchor signal
RT sequence of human Cryptic with a hydrophilic extension.";
RL Biochim. Biophys. Acta 1778:2671-2681(2008).
RN [6]
RP VARIANT TRP-78, AND INVOLVEMENT IN HTX2.
RX PubMed=11799476; DOI=10.1086/339079;
RA Goldmuntz E., Bamford R., Karkera J.D., dela Cruz J., Roessler E.,
RA Muenke M.;
RT "CFC1 mutations in patients with transposition of the great arteries and
RT double-outlet right ventricle.";
RL Am. J. Hum. Genet. 70:776-780(2002).
CC -!- FUNCTION: NODAL coreceptor involved in the correct establishment of the
CC left-right axis. May play a role in mesoderm and/or neural patterning
CC during gastrulation. {ECO:0000269|PubMed:11062482}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18930707};
CC Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:18930707}. Secreted
CC {ECO:0000269|PubMed:18930707}. Note=Does not exhibit a typical GPI-
CC signal sequence. The C-ter hydrophilic extension of the GPI-signal
CC sequence reduces the efficiency of processing and could lead to the
CC production of an secreted unprocessed form. This extension is found
CC only in primates.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- DISEASE: Heterotaxy, visceral, 2, autosomal (HTX2) [MIM:605376]: A form
CC of visceral heterotaxy, a complex disorder due to disruption of the
CC normal left-right asymmetry of the thoracoabdominal organs. Visceral
CC heterotaxy or situs ambiguus results in randomization of the placement
CC of visceral organs, including the heart, lungs, liver, spleen, and
CC stomach. The organs are oriented randomly with respect to the left-
CC right axis and with respect to one another. It can be associated with a
CC variety of congenital defects including cardiac malformations.
CC {ECO:0000269|PubMed:11062482, ECO:0000269|PubMed:11799476}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.
CC {ECO:0000305}.
CC -!- CAUTION: This gene differs from CFC1B by only one residue at position
CC 78:R -> W. R78W is also thought to be a CFC1 polymorphism which has
CC been shown to lead to a different cell surface distribution and
CC activity (PubMed:11799476 and PubMed:11062482). {ECO:0000305}.
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DR EMBL; AF312769; AAG30294.1; -; mRNA.
DR EMBL; AF312925; AAG42475.1; -; Genomic_DNA.
DR EMBL; AK315326; BAG37727.1; -; mRNA.
DR EMBL; AC140481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069508; AAH69508.1; -; mRNA.
DR EMBL; BC074825; AAH74825.1; -; mRNA.
DR EMBL; BC074826; AAH74826.1; -; mRNA.
DR EMBL; BC110080; AAI10081.1; -; mRNA.
DR EMBL; BC146897; AAI46898.1; -; mRNA.
DR CCDS; CCDS2162.1; -.
DR RefSeq; NP_001257349.1; NM_001270420.1.
DR RefSeq; NP_001257350.1; NM_001270421.1.
DR RefSeq; NP_115934.1; NM_032545.3.
DR AlphaFoldDB; P0CG37; -.
DR BioGRID; 121022; 151.
DR STRING; 9606.ENSP00000259216; -.
DR GlyGen; P0CG37; 1 site.
DR iPTMnet; P0CG37; -.
DR PhosphoSitePlus; P0CG37; -.
DR BioMuta; CFC1; -.
DR DMDM; 300680886; -.
DR MassIVE; P0CG37; -.
DR PaxDb; P0CG37; -.
DR PeptideAtlas; P0CG37; -.
DR PRIDE; P0CG37; -.
DR ProteomicsDB; 52467; -.
DR ABCD; P0CG37; 8 sequenced antibodies.
DR Antibodypedia; 33508; 244 antibodies from 30 providers.
DR DNASU; 55997; -.
DR Ensembl; ENST00000259216.6; ENSP00000259216.5; ENSG00000136698.10.
DR GeneID; 55997; -.
DR KEGG; hsa:55997; -.
DR MANE-Select; ENST00000259216.6; ENSP00000259216.5; NM_032545.4; NP_115934.1.
DR UCSC; uc002tro.3; human.
DR CTD; 55997; -.
DR DisGeNET; 55997; -.
DR GeneCards; CFC1; -.
DR HGNC; HGNC:18292; CFC1.
DR HPA; ENSG00000136698; Tissue enhanced (brain, pancreas, pituitary gland).
DR MalaCards; CFC1; -.
DR MIM; 605194; gene.
DR MIM; 605376; phenotype.
DR neXtProt; NX_P0CG37; -.
DR OpenTargets; ENSG00000136698; -.
DR Orphanet; 244283; Biliary atresia with splenic malformation syndrome.
DR Orphanet; 216729; Congenitally uncorrected transposition of the great arteries with cardiac malformation.
DR Orphanet; 99042; Congenitally uncorrected transposition of the great arteries with coarctation.
DR Orphanet; 216718; Isolated congenitally uncorrected transposition of the great arteries.
DR Orphanet; 157769; Situs ambiguus.
DR PharmGKB; PA134916180; -.
DR VEuPathDB; HostDB:ENSG00000136698; -.
DR eggNOG; KOG1217; Eukaryota.
DR GeneTree; ENSGT00940000162302; -.
DR HOGENOM; CLU_092661_0_0_1; -.
DR InParanoid; P0CG37; -.
DR OMA; VFGALHC; -.
DR OrthoDB; 1387592at2759; -.
DR PhylomeDB; P0CG37; -.
DR TreeFam; TF333187; -.
DR PathwayCommons; P0CG37; -.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1433617; Regulation of signaling by NODAL.
DR BioGRID-ORCS; 55997; 26 hits in 975 CRISPR screens.
DR ChiTaRS; CFC1; human.
DR GenomeRNAi; 55997; -.
DR Pharos; P0CG37; Tbio.
DR PRO; PR:P0CG37; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P0CG37; protein.
DR Bgee; ENSG00000136698; Expressed in islet of Langerhans and 60 other tissues.
DR ExpressionAtlas; P0CG37; baseline and differential.
DR Genevisible; P0CG37; HS.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070697; F:activin receptor binding; IBA:GO_Central.
DR GO; GO:0038100; F:nodal binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IBA:GO_Central.
DR GO; GO:0007368; P:determination of left/right symmetry; IBA:GO_Central.
DR GO; GO:0007369; P:gastrulation; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IBA:GO_Central.
DR GO; GO:0038092; P:nodal signaling pathway; IMP:UniProtKB.
DR InterPro; IPR019011; Cryptic/Cripto_CFC-dom.
DR InterPro; IPR000742; EGF-like_dom.
DR Pfam; PF09443; CFC; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Disease variant; Disulfide bond;
KW EGF-like domain; Gastrulation; Glycoprotein; GPI-anchor; Heterotaxy;
KW Lipoprotein; Membrane; Reference proteome; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..158
FT /note="Cryptic protein"
FT /id="PRO_0000044630"
FT PROPEP 159..223
FT /note="Removed in mature form"
FT /id="PRO_0000395407"
FT DOMAIN 86..115
FT /note="EGF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT LIPID 158
FT /note="GPI-anchor amidated aspartate"
FT /evidence="ECO:0000269|PubMed:18930707"
FT CARBOHYD 52
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 90..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 91..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 105..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VARIANT 78
FT /note="R -> W (in dbSNP:rs2579433)"
FT /evidence="ECO:0000269|PubMed:11062482,
FT ECO:0000269|PubMed:11799476"
FT /id="VAR_024322"
FT VARIANT 112
FT /note="R -> C (in HTX2; complete loss of activity; abnormal
FT cell surface localization; dbSNP:rs104893611)"
FT /evidence="ECO:0000269|PubMed:11062482"
FT /id="VAR_024323"
FT VARIANT 189
FT /note="R -> C (in dbSNP:rs1350439781)"
FT /evidence="ECO:0000269|PubMed:11062482"
FT /id="VAR_024324"
FT MUTAGEN 191..223
FT /note="LRPDAPAHPRSLVPSVLQRERRPCGRPGLGHRL->VVVVV: Does not
FT affect the cellular localization and the biological
FT activity."
FT MUTAGEN 191..223
FT /note="Missing: Increased NODAL dependent signaling."
SQ SEQUENCE 223 AA; 24612 MW; B52852A00ABCF1A3 CRC64;
MTWRHHVRLL FTVSLALQII NLGNSYQREK HNGGREEVTK VATQKHRQSP LNWTSSHFGE
VTGSAEGWGP EEPLPYSRAF GEGASARPRC CRNGGTCVLG SFCVCPAHFT GRYCEHDQRR
SECGALEHGA WTLRACHLCR CIFGALHCLP LQTPDRCDPK DFLASHAHGP SAGGAPSLLL
LLPCALLHRL LRPDAPAHPR SLVPSVLQRE RRPCGRPGLG HRL
