ID CCBE1_DANRE Reviewed; 401 AA. AC A8WGB1; DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 02-OCT-2024, entry version 93. DE RecName: Full=Collagen and calcium-binding EGF domain-containing protein 1; DE AltName: Full=Full of fluid protein; DE Flags: Precursor; GN Name=ccbe1; Synonyms=fof; OS Danio rerio (Zebrafish) (Brachydanio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Danionidae; Danioninae; Danio. OX NCBI_TaxID=7955; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases. RN [2] RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF RP ASP-162. RX PubMed=19287381; DOI=10.1038/ng.321; RA Hogan B.M., Bos F.L., Bussmann J., Witte M., Chi N.C., Duckers H.J., RA Schulte-Merker S.; RT "ccbe1 is required for embryonic lymphangiogenesis and venous sprouting."; RL Nat. Genet. 41:396-398(2009). RN [3] RP DISRUPTION PHENOTYPE. RX PubMed=28179432; DOI=10.1161/circresaha.116.308813; RA Karpanen T., Padberg Y., van de Pavert S.A., Dierkes C., Morooka N., RA Peterson-Maduro J., van de Hoek G., Adrian M., Mochizuki N., Sekiguchi K., RA Kiefer F., Schulte D., Schulte-Merker S.; RT "An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel RT Formation."; RL Circ. Res. 120:1263-1275(2017). RN [4] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=37097004; DOI=10.7554/elife.82969; RA Hussmann M., Schulte D., Weischer S., Carlantoni C., Nakajima H., RA Mochizuki N., Stainier D.Y.R., Zobel T., Koch M., Schulte-Merker S.; RT "Svep1 is a binding ligand of Tie1 and affects specific aspects of facial RT lymphatic development in a Vegfc-independent manner."; RL Elife 12:0-0(2023). CC -!- FUNCTION: Required for lymphangioblast budding and angiogenic sprouting CC from venous endothelium during embryogenesis. Required for the CC formation of facial lymphatic structures (PubMed:37097004). Necessary CC for lymphangiogenesis, but is probably not part of either the vegfc- CC vegfr3 signaling or sox18-prox1 transcriptional pathways. CC {ECO:0000269|PubMed:19287381, ECO:0000269|PubMed:37097004}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Not expressed in blood or lymphatic endothelial CC cells, correlating spatially and temporally with the migration routes CC of endothelial cells that bud from the PCV, migrate in association with CC somite boundaries and seed the horizontal myoseptum region from where CC lymphatic precursors later migrate. {ECO:0000269|PubMed:19287381}. CC -!- DEVELOPMENTAL STAGE: Restricted expression during development with CC expression in the pronephros and ventral mesenchyme at 24 hours post CC fertilization (hpf). By 36 hpf, expression is detected in discrete CC zones along each somitic boundary, between the PCV and the horizontal CC myoseptum, as well as along the horizontal myoseptum itself. At 48 hpf, CC expression is restricted along the horizontal myoseptum. CC {ECO:0000269|PubMed:19287381}. CC -!- DISRUPTION PHENOTYPE: Significant reduction in phosphorylated mapk/erk CC in the nuclei within the posterior cardinal vein endothelium at 32 hpf CC (PubMed:28179432). Loss of facial lymphatic vessels including; lateral CC facial lymphatic vessel, medial facial lymphatic vessel, facial CC lymphatic branchial arches and otolithic lymphatic vessel at 5 dpf CC (PubMed:37097004). In a svep1 and ccbe1 double knockout model there is CC complete loss of the facial lymphatic architecture at 5 dpf CC (PubMed:37097004). {ECO:0000269|PubMed:28179432, CC ECO:0000269|PubMed:37097004}. CC -!- SIMILARITY: Belongs to the CCBE1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI54644.1; Type=Erroneous initiation; Evidence={ECO:0000305}; 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; BC154643; AAI54644.1; ALT_INIT; mRNA. DR RefSeq; NP_001157395.1; NM_001163923.1. DR AlphaFoldDB; A8WGB1; -. DR STRING; 7955.ENSDARP00000106577; -. DR GlyCosmos; A8WGB1; 1 site, No reported glycans. DR PaxDb; 7955-ENSDARP00000078551; -. DR Ensembl; ENSDART00000127963; ENSDARP00000106577; ENSDARG00000086158. DR GeneID; 555629; -. DR KEGG; dre:555629; -. DR AGR; ZFIN:ZDB-GENE-090506-7; -. DR CTD; 147372; -. DR ZFIN; ZDB-GENE-090506-7; ccbe1. DR eggNOG; KOG1218; Eukaryota. DR HOGENOM; CLU_062964_0_0_1; -. DR InParanoid; A8WGB1; -. DR OMA; SWTYREE; -. DR OrthoDB; 5263252at2759; -. DR PhylomeDB; A8WGB1; -. DR PRO; PR:A8WGB1; -. DR Proteomes; UP000000437; Chromosome 21. DR Bgee; ENSDARG00000086158; Expressed in spleen and 30 other cell types or tissues. DR ExpressionAtlas; A8WGB1; baseline and differential. DR GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0048514; P:blood vessel morphogenesis; IGI:ZFIN. DR GO; GO:0001945; P:lymph vessel development; IMP:ZFIN. DR GO; GO:0001946; P:lymphangiogenesis; IMP:UniProtKB. DR GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB. DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; IGI:ZFIN. DR GO; GO:0048845; P:venous blood vessel morphogenesis; IMP:UniProtKB. DR GO; GO:0060855; P:venous endothelial cell migration involved in lymph vessel development; IMP:ZFIN. DR CDD; cd00054; EGF_CA; 1. DR Gene3D; 2.10.25.10; Laminin; 2. DR InterPro; IPR008160; Collagen. DR InterPro; IPR050751; ECM_structural_protein. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR PANTHER; PTHR24034:SF76; COLLAGEN AND CALCIUM-BINDING EGF DOMAIN-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR24034; EGF-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF01391; Collagen; 1. DR Pfam; PF14670; FXa_inhibition; 1. DR SMART; SM00181; EGF; 2. DR SMART; SM00179; EGF_CA; 2. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS01187; EGF_CA; 1. PE 1: Evidence at protein level; KW Angiogenesis; Calcium; Collagen; Developmental protein; Disulfide bond; KW EGF-like domain; Glycoprotein; Reference proteome; Repeat; Secreted; KW Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..401 FT /note="Collagen and calcium-binding EGF domain-containing FT protein 1" FT /id="PRO_0000370636" FT DOMAIN 126..167 FT /note="EGF-like; calcium-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 234..276 FT /note="Collagen-like 1" FT DOMAIN 286..319 FT /note="Collagen-like 2" FT REGION 229..321 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 344..401 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 130..142 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 138..151 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DISULFID 153..166 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT MUTAGEN 162 FT /note="D->E: In fof(hu3613); lacks the thoracic duct and FT the previously unidentified intersegmental (ISLVs) and FT dorsal longitudinal lymphatic vessels (DLLVs) but retains a FT seemingly normal blood vasculature. Mutants show edema, FT initiating in the lower intestine and around the eyes from FT 6 dpf. At 36 dpf, surviving mutants show severe edema." FT /evidence="ECO:0000269|PubMed:19287381" SQ SEQUENCE 401 AA; 43849 MW; 27F2BB0FF261DCBC CRC64; MIYPGRGASL SVAVALVLFS SGAPWTFREE KEDVDREVCS ESKIATTKYP CVKSTGEVTT CYRKKCCEGF KFVLGQCIPE DYDVCAGAPC EQQCTDHFGR VVCTCYDGYR YDRERHRNRE KPYCLDIDEC ANNNETVCSQ MCVNTPGSYR CDCHSGFYLE DDGKTCTKGE RAPLFEKSDN VMKEGTCSAT CEDFHQMKMT VLQLKQKMSL LSSNTEINKQ MTNEKMMMTT NSFLPGPPGP PGPAGTPGAK GSSGSPGQMG PPGLPGPRGD MGPIGPSPDL SHIKQGRRGP VGPPGAPGRD GMKGERGFPG PSGPPGPPGS FDFLLLMMAD IRNDIAELQS KVFSRPLHSS FEDFPSAPDS WRDTPENLDF GSGEDYKSQS PPKSSRKRKL PRNLKNPDWP V //