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Q6UXH8 (CCBE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Collagen and calcium-binding EGF domain-containing protein 1
Alternative name(s):
Full of fluid protein homolog
Gene names
Name:CCBE1
Synonyms:KIAA1983
ORF Names:UNQ1921/PRO4395
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length406 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for lymphangioblast budding and angiogenic sprouting from venous endothelium during embryogenesis. Ref.6

Subcellular location

Secreted Potential.

Tissue specificity

Not expressed in blood or lymphatic endothelial cells. Ref.5

Involvement in disease

Hennekam lymphangiectasia-lymphedema syndrome (HLLS) [MIM:235510]: A generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and severe mental retardation.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.7

Sequence similarities

Belongs to the CCBE1 family.

Contains 2 collagen-like domains.

Contains 1 EGF-like domain.

Sequence caution

The sequence BAB85569.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Mental retardation
   DomainCollagen
EGF-like domain
Repeat
Signal
   LigandCalcium
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processlymphangiogenesis

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein processing

Inferred from direct assay PubMed 24552833. Source: BHF-UCL

positive regulation of vascular endothelial growth factor signaling pathway

Inferred from direct assay PubMed 24552833. Source: BHF-UCL

positive regulation vascular endothelial growth factor production

Inferred from direct assay PubMed 24552833. Source: BHF-UCL

sprouting angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

venous blood vessel morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcollagen trimer

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix

Inferred from direct assay PubMed 21778431. Source: MGI

extracellular space

Inferred from direct assay PubMed 24552833. Source: BHF-UCL

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

collagen binding

Inferred from direct assay PubMed 21778431. Source: MGI

protease binding

Inferred from physical interaction PubMed 24552833. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6UXH8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q6UXH8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-271: Missing.
     272-305: MPGPPGQPGPRGSMGPMGPSPDLSHIKQGRRGPV → MQLTWASISLVTRCWPQTPTFQDLLACLGARALP
Note: No experimental confirmation available.
Isoform 3 (identifier: Q6UXH8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-191: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434 Potential
Chain35 – 406372Collagen and calcium-binding EGF domain-containing protein 1
PRO_0000279516

Regions

Domain134 – 17542EGF-like; calcium-binding Potential
Domain245 – 29046Collagen-like 1
Domain300 – 33334Collagen-like 2

Amino acid modifications

Glycosylation1421N-linked (GlcNAc...) Potential
Glycosylation1821N-linked (GlcNAc...) Potential
Disulfide bond138 ↔ 150 By similarity
Disulfide bond146 ↔ 159 By similarity
Disulfide bond161 ↔ 174 By similarity

Natural variations

Alternative sequence1 – 271271Missing in isoform 2.
VSP_023470
Alternative sequence1 – 191191Missing in isoform 3.
VSP_023469
Alternative sequence272 – 30534MPGPP…RRGPV → MQLTWASISLVTRCWPQTPT FQDLLACLGARALP in isoform 2.
VSP_023471
Natural variant751C → S in HLLS. Ref.6 Ref.7
Corresponds to variant rs121908250 [ dbSNP | Ensembl ].
VAR_063746
Natural variant1021C → S in HLLS. Ref.6
Corresponds to variant rs121908251 [ dbSNP | Ensembl ].
VAR_063747
Natural variant1581R → C in HLLS. Ref.6
Corresponds to variant rs121908253 [ dbSNP | Ensembl ].
VAR_063748
Natural variant1741C → R in HLLS. Ref.6
Corresponds to variant rs121908254 [ dbSNP | Ensembl ].
VAR_063749
Natural variant1931V → G.
Corresponds to variant rs11659589 [ dbSNP | Ensembl ].
VAR_048971
Natural variant3271G → R in HLLS. Ref.6
Corresponds to variant rs121908252 [ dbSNP | Ensembl ].
VAR_063750

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 86BCB49EF2D801F9

FASTA40644,103
        10         20         30         40         50         60 
MVPPPPSRGG AARGQLGRSL GPLLLLLALG HTWTYREEPE DGDREICSES KIATTKYPCL 

        70         80         90        100        110        120 
KSSGELTTCY RKKCCKGYKF VLGQCIPEDY DVCAEAPCEQ QCTDNFGRVL CTCYPGYRYD 

       130        140        150        160        170        180 
RERHRKREKP YCLDIDECAS SNGTLCAHIC INTLGSYRCE CREGYIREDD GKTCTRGDKY 

       190        200        210        220        230        240 
PNDTGHEKSE NMVKAGTCCA TCKEFYQMKQ TVLQLKQKIA LLPNNAADLG KYITGDKVLA 

       250        260        270        280        290        300 
SNTYLPGPPG LPGGQGPPGS PGPKGSPGFP GMPGPPGQPG PRGSMGPMGP SPDLSHIKQG 

       310        320        330        340        350        360 
RRGPVGPPGA PGRDGSKGER GAPGPRGSPG PPGSFDFLLL MLADIRNDIT ELQEKVFGHR 

       370        380        390        400 
THSSAEEFPL PQEFPSYPEA MDLGSGDDHP RRTETRDLRA PRDFYP 

« Hide

Isoform 2 [UniParc].

Checksum: 3E73036EA15B76AD
Show »

FASTA13514,800
Isoform 3 [UniParc].

Checksum: A6648F6EE5BFCF05
Show »

FASTA21522,600

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins."
Nagase T., Kikuno R., Ohara O.
DNA Res. 8:319-327(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Fetal brain.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Lung.
[5]"ccbe1 is required for embryonic lymphangiogenesis and venous sprouting."
Hogan B.M., Bos F.L., Bussmann J., Witte M., Chi N.C., Duckers H.J., Schulte-Merker S.
Nat. Genet. 41:396-398(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans."
Alders M., Hogan B.M., Gjini E., Salehi F., Al-Gazali L., Hennekam E.A., Holmberg E.E., Mannens M.M., Mulder M.F., Offerhaus G.J., Prescott T.E., Schroor E.J., Verheij J.B., Witte M., Zwijnenburg P.J., Vikkula M., Schulte-Merker S., Hennekam R.C.
Nat. Genet. 41:1272-1274(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS HLLS SER-75; SER-102; CYS-158; ARG-174 AND ARG-327.
[7]"Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia."
Connell F., Kalidas K., Ostergaard P., Brice G., Homfray T., Roberts L., Bunyan D.J., Mitton S., Mansour S., Mortimer P., Jeffery S.
Hum. Genet. 127:231-241(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HLLS SER-75.
[8]Erratum
Connell F., Kalidas K., Ostergaard P., Brice G., Homfray T., Roberts L., Bunyan D.J., Mitton S., Mansour S., Mortimer P., Jeffery S.
Hum. Genet. 127:243-243(2010)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB075863 mRNA. Translation: BAB85569.1. Different initiation.
AY358347 mRNA. Translation: AAQ88713.1.
BX640826 mRNA. Translation: CAE45902.1.
BC046645 mRNA. Translation: AAH46645.1.
CCDSCCDS32838.1. [Q6UXH8-1]
RefSeqNP_597716.1. NM_133459.3. [Q6UXH8-1]
XP_005266705.1. XM_005266648.1. [Q6UXH8-1]
XP_005266706.1. XM_005266649.2. [Q6UXH8-3]
XP_006722456.1. XM_006722393.1. [Q6UXH8-1]
UniGeneHs.34333.

3D structure databases

ProteinModelPortalQ6UXH8.
SMRQ6UXH8. Positions 98-207.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127056. 2 interactions.
IntActQ6UXH8. 2 interactions.
STRING9606.ENSP00000404464.

PTM databases

PhosphoSiteQ6UXH8.

Polymorphism databases

DMDM74738220.

Proteomic databases

PaxDbQ6UXH8.
PRIDEQ6UXH8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000398179; ENSP00000381241; ENSG00000183287. [Q6UXH8-2]
ENST00000439986; ENSP00000404464; ENSG00000183287. [Q6UXH8-1]
GeneID147372.
KEGGhsa:147372.
UCSCuc002lia.3. human. [Q6UXH8-1]
uc010dpq.3. human. [Q6UXH8-2]

Organism-specific databases

CTD147372.
GeneCardsGC18M057101.
HGNCHGNC:29426. CCBE1.
HPAHPA041361.
HPA041374.
MIM235510. phenotype.
612753. gene.
neXtProtNX_Q6UXH8.
Orphanet2136. Hennekam syndrome.
PharmGKBPA134880094.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG291472.
HOGENOMHOG000111400.
HOVERGENHBG081035.
InParanoidQ6UXH8.
OMAGRTCTKG.
OrthoDBEOG73BVDG.
PhylomeDBQ6UXH8.
TreeFamTF333138.

Gene expression databases

ArrayExpressQ6UXH8.
BgeeQ6UXH8.
CleanExHS_CCBE1.
GenevestigatorQ6UXH8.

Family and domain databases

InterProIPR008160. Collagen.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
[Graphical view]
PfamPF01391. Collagen. 2 hits.
PF07645. EGF_CA. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 1 hit.
SM00179. EGF_CA. 1 hit.
[Graphical view]
PROSITEPS00010. ASX_HYDROXYL. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS01187. EGF_CA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCCBE1. human.
GeneWikiCCBE1.
GenomeRNAi147372.
NextBio85596.
PROQ6UXH8.
SOURCESearch...

Entry information

Entry nameCCBE1_HUMAN
AccessionPrimary (citable) accession number: Q6UXH8
Secondary accession number(s): Q6MZX5, Q86SS2, Q8TF19
Entry history
Integrated into UniProtKB/Swiss-Prot: March 6, 2007
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM