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   08-JUN-2016, entry version 56.
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   Cyprinidae; 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
RT   sprouting.";
RL   Nat. Genet. 41:396-398(2009).
CC   -!- FUNCTION: Required for lymphangioblast budding and angiogenic
CC       sprouting from venous endothelium during embryogenesis. Necessary
CC       for lymphangiogenesis, but is probably not part of either the
CC       vegfc-vegfr3 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
CC       endothelial cells, correlating spatially and temporally with the
CC       migration routes of endothelial cells that bud from the PCV,
CC       migrate in association with somite boundaries and seed the
CC       horizontal myoseptum region from where lymphatic precursors later
CC       migrate. {ECO:0000269|PubMed:19287381}.
CC   -!- DEVELOPMENTAL STAGE: Restricted expression during development with
CC       expression in the pronephros and ventral mesenchyme at 24 hours
CC       post fertilization (hpf). By 36 hpf, expression is detected in
CC       discrete zones along each somitic boundary, between the PCV and
CC       the horizontal myoseptum, as well as along the horizontal
CC       myoseptum itself. At 48 hpf, expression is restricted along the
CC       horizontal myoseptum. {ECO:0000269|PubMed:19287381}.
CC   -!- SIMILARITY: Belongs to the CCBE1 family. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 2 collagen-like domains. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 EGF-like domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00076}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAI54644.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; BC154643; AAI54644.1; ALT_INIT; mRNA.
DR   RefSeq; NP_001157395.1; NM_001163923.1.
DR   UniGene; Dr.110996; -.
DR   STRING; 7955.ENSDARP00000078551; -.
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   eggNOG; ENOG410XQWV; LUCA.
DR   GeneTree; ENSGT00390000014907; -.
DR   HOGENOM; HOG000111400; -.
DR   InParanoid; A8WGB1; -.
DR   KO; K19638; -.
DR   OMA; TSNETLC; -.
DR   PhylomeDB; A8WGB1; -.
DR   PRO; PR:A8WGB1; -.
DR   Proteomes; UP000000437; Chromosome 21.
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: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; IPR013032; EGF-like_CS.
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; Complete proteome;
KW   Developmental protein; Disulfide bond; EGF-like domain; Glycoprotein;
KW   Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL        1     22       {ECO:0000255}.
FT   CHAIN        23    401       Collagen and calcium-binding EGF domain-
FT                                containing protein 1.
FT                                /FTId=PRO_0000370636.
FT   DOMAIN      126    167       EGF-like; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      234    276       Collagen-like 1.
FT   DOMAIN      286    319       Collagen-like 2.
FT   COMPBIAS    236    319       Gly-rich.
FT   CARBOHYD    134    134       N-linked (GlcNAc...). {ECO:0000255}.
FT   DISULFID    130    142       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    138    151       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    153    166       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   MUTAGEN     162    162       D->E: In fof(hu3613); lacks the thoracic
FT                                duct and the previously unidentified
FT                                intersegmental (ISLVs) and dorsal
FT                                longitudinal lymphatic vessels (DLLVs)
FT                                but retains a seemingly normal blood
FT                                vasculature. Mutants show edema,
FT                                initiating in the lower intestine and
FT                                around the eyes from 6 dpf. At 36 dpf,
FT                                surviving mutants show severe edema.
FT                                {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
//