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   03-AUG-2022, entry version 84.
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).
CC   -!- FUNCTION: Required for lymphangioblast budding and angiogenic sprouting
CC       from venous endothelium during embryogenesis. Necessary for
CC       lymphangiogenesis, but is probably not part of either the vegfc-vegfr3
CC       signaling or sox18-prox1 transcriptional pathways.
CC       {ECO:0000269|PubMed:19287381}.
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   -!- 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   PaxDb; A8WGB1; -.
DR   Ensembl; ENSDART00000127963; ENSDARP00000106577; ENSDARG00000086158.
DR   GeneID; 555629; -.
DR   KEGG; dre:555629; -.
DR   CTD; 147372; -.
DR   ZFIN; ZDB-GENE-090506-7; ccbe1.
DR   eggNOG; KOG1218; Eukaryota.
DR   GeneTree; ENSGT00390000014907; -.
DR   HOGENOM; CLU_062964_0_0_1; -.
DR   InParanoid; A8WGB1; -.
DR   OMA; EDYDVCS; -.
DR   OrthoDB; 1174178at2759; -.
DR   PhylomeDB; A8WGB1; -.
DR   PRO; PR:A8WGB1; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 21.
DR   Bgee; ENSDARG00000086158; Expressed in spleen and 30 other tissues.
DR   ExpressionAtlas; A8WGB1; baseline.
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   InterPro; IPR008160; Collagen.
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   Pfam; PF01391; Collagen; 1.
DR   SMART; SM00181; EGF; 2.
DR   SMART; SM00179; EGF_CA; 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