CCBE1_HUMAN
ID CCBE1_HUMAN Reviewed; 406 AA.
AC Q6UXH8; Q6MZX5; Q86SS2; Q8TF19;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Collagen and calcium-binding EGF domain-containing protein 1;
DE AltName: Full=Full of fluid protein homolog;
DE Flags: Precursor;
GN Name=CCBE1; Synonyms=KIAA1983; ORFNames=UNQ1921/PRO4395;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11853319; DOI=10.1093/dnares/8.6.319;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXII. The
RT complete sequences of 50 new cDNA clones which code for large proteins.";
RL DNA Res. 8:319-327(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=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 TISSUE SPECIFICITY.
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 [6]
RP FUNCTION, AND VARIANTS HKLLS1 SER-75; SER-102; CYS-158; ARG-174 AND
RP ARG-327.
RX PubMed=19935664; DOI=10.1038/ng.484;
RA Alders M., Hogan B.M., Gjini E., Salehi F., Al-Gazali L., Hennekam E.A.,
RA Holmberg E.E., Mannens M.M., Mulder M.F., Offerhaus G.J., Prescott T.E.,
RA Schroor E.J., Verheij J.B., Witte M., Zwijnenburg P.J., Vikkula M.,
RA Schulte-Merker S., Hennekam R.C.;
RT "Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans.";
RL Nat. Genet. 41:1272-1274(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP VARIANT HKLLS1 SER-75.
RX PubMed=19911200; DOI=10.1007/s00439-009-0766-y;
RA Connell F., Kalidas K., Ostergaard P., Brice G., Homfray T., Roberts L.,
RA Bunyan D.J., Mitton S., Mansour S., Mortimer P., Jeffery S.;
RT "Linkage and sequence analysis indicate that CCBE1 is mutated in
RT recessively inherited generalised lymphatic dysplasia.";
RL Hum. Genet. 127:231-241(2010).
RN [9]
RP ERRATUM OF PUBMED:19911200.
RA Connell F., Kalidas K., Ostergaard P., Brice G., Homfray T., Roberts L.,
RA Bunyan D.J., Mitton S., Mansour S., Mortimer P., Jeffery S.;
RL Hum. Genet. 127:243-243(2010).
CC -!- FUNCTION: Required for lymphangioblast budding and angiogenic sprouting
CC from venous endothelium during embryogenesis.
CC {ECO:0000269|PubMed:19935664}.
CC -!- INTERACTION:
CC Q6UXH8; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-3923278, EBI-747776;
CC Q6UXH8; Q53G59: KLHL12; NbExp=3; IntAct=EBI-3923278, EBI-740929;
CC Q6UXH8; O75558: STX11; NbExp=3; IntAct=EBI-3923278, EBI-714135;
CC Q6UXH8-3; Q53EZ4: CEP55; NbExp=3; IntAct=EBI-12013534, EBI-747776;
CC Q6UXH8-3; Q7L5N1: COPS6; NbExp=3; IntAct=EBI-12013534, EBI-486838;
CC Q6UXH8-3; Q0VD86: INCA1; NbExp=3; IntAct=EBI-12013534, EBI-6509505;
CC Q6UXH8-3; Q53G59: KLHL12; NbExp=3; IntAct=EBI-12013534, EBI-740929;
CC Q6UXH8-3; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-12013534, EBI-3044087;
CC Q6UXH8-3; O76013-2: KRT36; NbExp=3; IntAct=EBI-12013534, EBI-11958506;
CC Q6UXH8-3; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-12013534, EBI-739832;
CC Q6UXH8-3; D3DTS7: PMP22; NbExp=3; IntAct=EBI-12013534, EBI-25882629;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q6UXH8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6UXH8-2; Sequence=VSP_023470, VSP_023471;
CC Name=3;
CC IsoId=Q6UXH8-3; Sequence=VSP_023469;
CC -!- TISSUE SPECIFICITY: Not expressed in blood or lymphatic endothelial
CC cells. {ECO:0000269|PubMed:19287381}.
CC -!- DISEASE: Hennekam lymphangiectasia-lymphedema syndrome 1 (HKLLS1)
CC [MIM:235510]: A form of Hennekam lymphangiectasia-lymphedema syndrome,
CC a generalized lymph-vessels dysplasia characterized by intestinal
CC lymphangiectasia with severe lymphedema of the limbs, genitalia and
CC face. In addition, affected individuals have unusual facies and some
CC manifest intellectual disability. HKLLS1 inheritance is autosomal
CC recessive. {ECO:0000269|PubMed:19911200, ECO:0000269|PubMed:19935664}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the CCBE1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB85569.1; 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; AB075863; BAB85569.1; ALT_INIT; mRNA.
DR EMBL; AY358347; AAQ88713.1; -; mRNA.
DR EMBL; BX640826; CAE45902.1; -; mRNA.
DR EMBL; BC046645; AAH46645.1; -; mRNA.
DR CCDS; CCDS32838.1; -. [Q6UXH8-1]
DR RefSeq; NP_597716.1; NM_133459.3. [Q6UXH8-1]
DR AlphaFoldDB; Q6UXH8; -.
DR BioGRID; 127056; 19.
DR IntAct; Q6UXH8; 13.
DR MINT; Q6UXH8; -.
DR STRING; 9606.ENSP00000404464; -.
DR GlyGen; Q6UXH8; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q6UXH8; -.
DR PhosphoSitePlus; Q6UXH8; -.
DR BioMuta; CCBE1; -.
DR DMDM; 74738220; -.
DR EPD; Q6UXH8; -.
DR jPOST; Q6UXH8; -.
DR MassIVE; Q6UXH8; -.
DR PaxDb; Q6UXH8; -.
DR PeptideAtlas; Q6UXH8; -.
DR PRIDE; Q6UXH8; -.
DR ProteomicsDB; 67622; -. [Q6UXH8-1]
DR ProteomicsDB; 67623; -. [Q6UXH8-2]
DR ProteomicsDB; 67624; -. [Q6UXH8-3]
DR Antibodypedia; 22986; 190 antibodies from 28 providers.
DR DNASU; 147372; -.
DR Ensembl; ENST00000439986.9; ENSP00000404464.2; ENSG00000183287.14. [Q6UXH8-1]
DR Ensembl; ENST00000649564.1; ENSP00000497183.1; ENSG00000183287.14. [Q6UXH8-1]
DR GeneID; 147372; -.
DR KEGG; hsa:147372; -.
DR MANE-Select; ENST00000439986.9; ENSP00000404464.2; NM_133459.4; NP_597716.1.
DR UCSC; uc002lib.4; human. [Q6UXH8-1]
DR CTD; 147372; -.
DR DisGeNET; 147372; -.
DR GeneCards; CCBE1; -.
DR HGNC; HGNC:29426; CCBE1.
DR HPA; ENSG00000183287; Tissue enhanced (ovary).
DR MalaCards; CCBE1; -.
DR MIM; 235510; phenotype.
DR MIM; 612753; gene.
DR neXtProt; NX_Q6UXH8; -.
DR OpenTargets; ENSG00000183287; -.
DR Orphanet; 2136; Hennekam syndrome.
DR PharmGKB; PA134880094; -.
DR VEuPathDB; HostDB:ENSG00000183287; -.
DR eggNOG; KOG1218; Eukaryota.
DR GeneTree; ENSGT00390000014907; -.
DR InParanoid; Q6UXH8; -.
DR OMA; EDYDVCS; -.
DR OrthoDB; 1011346at2759; -.
DR PhylomeDB; Q6UXH8; -.
DR TreeFam; TF333138; -.
DR PathwayCommons; Q6UXH8; -.
DR SignaLink; Q6UXH8; -.
DR BioGRID-ORCS; 147372; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; CCBE1; human.
DR GeneWiki; CCBE1; -.
DR GenomeRNAi; 147372; -.
DR Pharos; Q6UXH8; Tbio.
DR PRO; PR:Q6UXH8; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q6UXH8; protein.
DR Bgee; ENSG00000183287; Expressed in secondary oocyte and 135 other tissues.
DR ExpressionAtlas; Q6UXH8; baseline and differential.
DR Genevisible; Q6UXH8; HS.
DR GO; GO:0005581; C:collagen trimer; IEA:UniProtKB-KW.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0005518; F:collagen binding; IDA:MGI.
DR GO; GO:0002020; F:protease binding; IPI:BHF-UCL.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0001946; P:lymphangiogenesis; IMP:UniProtKB.
DR GO; GO:1904977; P:lymphatic endothelial cell migration; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IEA:Ensembl.
DR GO; GO:1901492; P:positive regulation of lymphangiogenesis; IEA:Ensembl.
DR GO; GO:0010954; P:positive regulation of protein processing; IDA:BHF-UCL.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IDA:BHF-UCL.
DR GO; GO:1900748; P:positive regulation of vascular endothelial growth factor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0003016; P:respiratory system process; IEA:Ensembl.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0048845; P:venous blood vessel morphogenesis; ISS:UniProtKB.
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 Pfam; PF07645; EGF_CA; 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 Alternative splicing; Angiogenesis; Calcium; Collagen;
KW Developmental protein; Disease variant; Disulfide bond; EGF-like domain;
KW Glycoprotein; Intellectual disability; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..34
FT /evidence="ECO:0000255"
FT CHAIN 35..406
FT /note="Collagen and calcium-binding EGF domain-containing
FT protein 1"
FT /id="PRO_0000279516"
FT DOMAIN 134..175
FT /note="EGF-like; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 245..290
FT /note="Collagen-like 1"
FT DOMAIN 300..333
FT /note="Collagen-like 2"
FT REGION 244..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..286
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 384..406
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 182
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 138..150
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 146..159
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 161..174
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT VAR_SEQ 1..271
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_023470"
FT VAR_SEQ 1..191
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023469"
FT VAR_SEQ 272..305
FT /note="MPGPPGQPGPRGSMGPMGPSPDLSHIKQGRRGPV -> MQLTWASISLVTRC
FT WPQTPTFQDLLACLGARALP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_023471"
FT VARIANT 75
FT /note="C -> S (in HKLLS1; dbSNP:rs121908250)"
FT /evidence="ECO:0000269|PubMed:19911200,
FT ECO:0000269|PubMed:19935664"
FT /id="VAR_063746"
FT VARIANT 102
FT /note="C -> S (in HKLLS1; dbSNP:rs121908251)"
FT /evidence="ECO:0000269|PubMed:19935664"
FT /id="VAR_063747"
FT VARIANT 158
FT /note="R -> C (in HKLLS1; dbSNP:rs121908253)"
FT /evidence="ECO:0000269|PubMed:19935664"
FT /id="VAR_063748"
FT VARIANT 174
FT /note="C -> R (in HKLLS1; dbSNP:rs121908254)"
FT /evidence="ECO:0000269|PubMed:19935664"
FT /id="VAR_063749"
FT VARIANT 193
FT /note="V -> G (in dbSNP:rs11659589)"
FT /id="VAR_048971"
FT VARIANT 327
FT /note="G -> R (in HKLLS1; dbSNP:rs121908252)"
FT /evidence="ECO:0000269|PubMed:19935664"
FT /id="VAR_063750"
SQ SEQUENCE 406 AA; 44103 MW; 86BCB49EF2D801F9 CRC64;
MVPPPPSRGG AARGQLGRSL GPLLLLLALG HTWTYREEPE DGDREICSES KIATTKYPCL
KSSGELTTCY RKKCCKGYKF VLGQCIPEDY DVCAEAPCEQ QCTDNFGRVL CTCYPGYRYD
RERHRKREKP YCLDIDECAS SNGTLCAHIC INTLGSYRCE CREGYIREDD GKTCTRGDKY
PNDTGHEKSE NMVKAGTCCA TCKEFYQMKQ TVLQLKQKIA LLPNNAADLG KYITGDKVLA
SNTYLPGPPG LPGGQGPPGS PGPKGSPGFP GMPGPPGQPG PRGSMGPMGP SPDLSHIKQG
RRGPVGPPGA PGRDGSKGER GAPGPRGSPG PPGSFDFLLL MLADIRNDIT ELQEKVFGHR
THSSAEEFPL PQEFPSYPEA MDLGSGDDHP RRTETRDLRA PRDFYP
