Q6UXH8 (CCBE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Angiogenesis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Mental retardation
Domain	Collagen EGF-like domain Repeat Signal
Ligand	Calcium
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	lymphangiogenesis Inferred from mutant phenotype Ref.6. Source: UniProtKB sprouting angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB venous blood vessel morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	collagen Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 34	34	Potential
	Chain	35 – 406	372	Collagen and calcium-binding EGF domain-containing protein 1		PRO_0000279516
Regions
	Domain	134 – 175	42	EGF-like; calcium-binding Potential
	Domain	245 – 290	46	Collagen-like 1
	Domain	300 – 333	34	Collagen-like 2
Amino acid modifications
	Glycosylation	142	1	N-linked (GlcNAc...) Potential
	Glycosylation	182	1	N-linked (GlcNAc...) Potential
	Disulfide bond	138 ↔ 150		By similarity
	Disulfide bond	146 ↔ 159		By similarity
	Disulfide bond	161 ↔ 174		By similarity
Natural variations
	Alternative sequence	1 – 271	271	Missing in isoform 2.		VSP_023470
	Alternative sequence	1 – 191	191	Missing in isoform 3.		VSP_023469
	Alternative sequence	272 – 305	34	MPGPP…RRGPV → MQLTWASISLVTRCWPQTPT FQDLLACLGARALP in isoform 2.		VSP_023471
	Natural variant	75	1	C → S in HLLS. Ref.6 Ref.7 Corresponds to variant rs121908250 [ dbSNP | Ensembl ].		VAR_063746
	Natural variant	102	1	C → S in HLLS. Ref.6 Corresponds to variant rs121908251 [ dbSNP | Ensembl ].		VAR_063747
	Natural variant	158	1	R → C in HLLS. Ref.6 Corresponds to variant rs121908253 [ dbSNP | Ensembl ].		VAR_063748
	Natural variant	174	1	C → R in HLLS. Ref.6 Corresponds to variant rs121908254 [ dbSNP | Ensembl ].		VAR_063749
	Natural variant	193	1	V → G. Corresponds to variant rs11659589 [ dbSNP | Ensembl ].		VAR_048971
	Natural variant	327	1	G → R in HLLS; rs121908252. Ref.6		VAR_063750

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 86BCB49EF2D801F9	FASTA	406	44,103
	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
	Isoform 2 [UniParc]. Checksum: 3E73036EA15B76AD	FASTA	135	14,800
	10 20 30 40 50 60 MQLTWASISL VTRCWPQTPT FQDLLACLGA RALPGPPGAP GRDGSKGERG APGPRGSPGP 70 80 90 100 110 120 PGSFDFLLLM LADIRNDITE LQEKVFGHRT HSSAEEFPLP QEFPSYPEAM DLGSGDDHPR 130 RTETRDLRAP RDFYP
	Isoform 3 [UniParc]. Checksum: A6648F6EE5BFCF05	FASTA	215	22,600
	10 20 30 40 50 60 MVKAGTCCAT CKEFYQMKQT VLQLKQKIAL LPNNAADLGK YITGDKVLAS NTYLPGPPGL 70 80 90 100 110 120 PGGQGPPGSP GPKGSPGFPG MPGPPGQPGP RGSMGPMGPS PDLSHIKQGR RGPVGPPGAP 130 140 150 160 170 180 GRDGSKGERG APGPRGSPGP PGSFDFLLLM LADIRNDITE LQEKVFGHRT HSSAEEFPLP 190 200 210 QEFPSYPEAM DLGSGDDHPR RTETRDLRAP RDFYP

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00152815. IPI00830026. IPI00830123.
RefSeq	NP_597716.1. NM_133459.3.
UniGene	Hs.34333.
3D structure databases
HSSP	HSSP built from PDB template 1APQ based on UniProtKB P00736.
ProteinModelPortal	Q6UXH8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6UXH8. 2 interactions.
STRING	9606.ENSP00000404464.
PTM databases
PhosphoSite	Q6UXH8.
Polymorphism databases
DMDM	74738220.
Proteomic databases
PaxDb	Q6UXH8.
PRIDE	Q6UXH8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000398179; ENSP00000381241; ENSG00000183287. ENST00000439986; ENSP00000404464; ENSG00000183287.
GeneID	147372.
KEGG	hsa:147372.
UCSC	uc002lia.3. human. uc010dpq.3. human.
Organism-specific databases
CTD	147372.
GeneCards	GC18M057101.
HGNC	HGNC:29426. CCBE1.
HPA	HPA041361. HPA041374.
MIM	235510. phenotype. 612753. gene.
neXtProt	NX_Q6UXH8.
Orphanet	2136. Hennekam syndrome.
PharmGKB	PA134880094.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG291472.
HOGENOM	HOG000111400.
HOVERGEN	HBG081035.
InParanoid	Q6UXH8.
OMA	YPNDTGH.
OrthoDB	EOG44BB30.
Gene expression databases
Bgee	Q6UXH8.
CleanEx	HS_CCBE1.
Genevestigator	Q6UXH8.
Family and domain databases
InterPro	IPR008160. Collagen. IPR000742. EG-like_dom. IPR001881. EGF-like_Ca-bd. IPR013032. EGF-like_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_site. IPR018097. EGF_Ca-bd_CS. [Graphical view]
Pfam	PF01391. Collagen. 2 hits. PF07645. EGF_CA. 1 hit. [Graphical view]
SMART	SM00181. EGF. 1 hit. SM00179. EGF_CA. 1 hit. [Graphical view]
PROSITE	PS00010. ASX_HYDROXYL. 1 hit. PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. 1 hit. PS01187. EGF_CA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CCBE1. human.
GenomeRNAi	147372.
NextBio	85596.
SOURCE	Search...

Entry information

Entry name

CCBE1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.