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Q6WN34 (CRDL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 87. 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:
Chordin-like protein 2
Alternative name(s):
Breast tumor novel factor 1
Short name=BNF-1
Chordin-related protein 2
Gene names
Name:CHRDL2
Synonyms:BNF1, CHL2
ORF Names:UNQ765/PRO1557
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length429 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May inhibit BMPs activity by blocking their interaction with their receptors. Has a negative regulator effect on the cartilage formation/regeneration from immature mesenchymal cells, by preventing or reducing the rate of matrix accumulation By similarity. Implicated in tumor angiogenesis. May play a role during myoblast and osteoblast differentiation, and maturation. Ref.1 Ref.2

Subunit structure

Interacts with GDF5 By similarity. May interact with BMP2, BMP4, BMP5, BMP6, BMP7 and INHBA. Ref.2 Ref.3

Subcellular location

Isoform 1: Secreted Potential Ref.2.

Isoform 2: Secreted Potential Ref.2.

Isoform 3: Cytoplasm Potential Ref.2.

Isoform 4: Cytoplasm Potential Ref.2.

Isoform 5: Cytoplasm Potential Ref.2.

Tissue specificity

Highly expressed in uterus. Moderately expressed in heart, liver, prostate, testis and ovary. Weakly expressed in skeletal muscle, kidney, spleen, small intestine and colon. Expressed in the secretory epithelial cells of uterine endometrium, fallopian tubes, endocervical glands, bladder and prostate, as well as the transitional epithelium of the urinary bladder, and in bone osteoblasts (at protein level). In normal cartilage, expression was confined in a few chondrocytes in the superficial zone as well as in the middle zone. In diseased cartilage coming from osteoarthritic patients, expression was limited to the middle zone of chondrocytes. Isoform 1 and isoform 2 are expressed in fetal cerebellum and heart, while only isoform 2 is detected in fetal spleen. Isoform 2 present in plasma. Ref.1 Ref.2 Ref.3

Induction

Up-regulated in breast tumors but also in lung and colon tumors. Ref.1

Post-translational modification

Phosphorylation sites are present in the extracellular medium. Isoform 2 is phosphorylated on Ser-402.

Sequence similarities

Contains 3 VWFC domains.

Caution

According to Ref.3, interacts with BMP2, BMP4, BMP5, BMP6, BMP7 but not INHBA. According to Ref.2, interacts with INHBA but not BMP2, BMP4 and BMP6.

Ontologies

Keywords
   Biological processChondrogenesis
Differentiation
Osteogenesis
   Cellular componentCytoplasm
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
   Molecular functionDevelopmental protein
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcartilage development

Inferred from electronic annotation. Source: UniProtKB-KW

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

ossification

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Five additional mRNAs also exist. Differential expression of isoforms was observed during myoblast and osteoblast differentiation and maturation.
Isoform 1 (identifier: Q6WN34-1)

Also known as: I;

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: Q6WN34-2)

Also known as: II;

The sequence of this isoform differs from the canonical sequence as follows:
     374-426: GIFHLTQIKK...LKVTASPDKV → DEETEAQRGE...GQSRQSDQDI
Isoform 3 (identifier: Q6WN34-3)

Also known as: VII;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-28: LDSHARAR → MALVGLPG
     66-162: GAHVSCYRLH...TTCPEPGCPA → NLTLPLDSGP...KRTVCSRSMG
     163-429: Missing.
Isoform 4 (identifier: Q6WN34-4)

Also known as: VIII;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-28: LDSHARAR → MALVGLPG
     145-162: EGQIYCGLTTCPEPGCPA → MRQVSNRMKRTVCSRSMG
     163-429: Missing.
Isoform 5 (identifier: Q6WN34-5)

Also known as: IX;

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.
     21-28: LDSHARAR → MALVGLPG
     66-113: GAHVSCYRLH...LRAPPKSCQH → NLTLPLDSGP...PTSVSSAAAQ
     114-429: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Ref.6
Chain26 – 429404Chordin-like protein 2
PRO_0000005371

Regions

Domain31 – 9666VWFC 1
Domain109 – 17567VWFC 2
Domain250 – 31566VWFC 3

Amino acid modifications

Glycosylation1141N-linked (GlcNAc...) Ref.7

Natural variations

Alternative sequence1 – 2020Missing in isoform 3, isoform 4 and isoform 5.
VSP_013512
Alternative sequence21 – 288LDSHARAR → MALVGLPG in isoform 3, isoform 4 and isoform 5.
VSP_013513
Alternative sequence66 – 16297GAHVS…PGCPA → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQRARSTAASQPAP NQAAQHPSRCQTPAAKPAKM RQVSNRMKRTVCSRSMG in isoform 3.
VSP_013514
Alternative sequence66 – 11348GAHVS…KSCQH → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQ in isoform 5.
VSP_013515
Alternative sequence114 – 429316Missing in isoform 5.
VSP_013516
Alternative sequence145 – 16218EGQIY…PGCPA → MRQVSNRMKRTVCSRSMG in isoform 4.
VSP_013517
Alternative sequence163 – 429267Missing in isoform 3 and isoform 4.
VSP_013518
Alternative sequence374 – 42653GIFHL…SPDKV → DEETEAQRGEVPGPRPHSQN LPLDSDQESQEARLPERGTA LPTARWPPRRSLERLPSPDP GAEGHGQSRQSDQDI in isoform 2.
VSP_013519
Natural variant3351P → L.
Corresponds to variant rs35903991 [ dbSNP | Ensembl ].
VAR_055651

Experimental info

Sequence conflict1871S → R in AX140199. Ref.2
Sequence conflict2311R → I in AX140199. Ref.2

Sequences

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

Last modified July 5, 2004. Version 1.
Checksum: A8111F26B2EF96A4

FASTA42947,495
        10         20         30         40         50         60 
MVPEVRVLSS LLGLALLWFP LDSHARARPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR 

        70         80         90        100        110        120 
CTCSEGAHVS CYRLHCPPVH CPQPVTEPQQ CCPKCVEPHT PSGLRAPPKS CQHNGTMYQH 

       130        140        150        160        170        180 
GEIFSAHELF PSRLPNQCVL CSCTEGQIYC GLTTCPEPGC PAPLPLPDSC CQACKDEASE 

       190        200        210        220        230        240 
QSDEEDSVQS LHGVRHPQDP CSSDAGRKRG PGTPAPTGLS APLSFIPRHF RPKGAGSTTV 

       250        260        270        280        290        300 
KIVLKEKHKK ACVHGGKTYS HGEVWHPAFR AFGPLPCILC TCEDGRQDCQ RVTCPTEYPC 

       310        320        330        340        350        360 
RHPEKVAGKC CKICPEDKAD PGHSEISSTR CPKAPGRVLV HTSVSPSPDN LRRFALEHEA 

       370        380        390        400        410        420 
SDLVEIYLWK LVKGIFHLTQ IKKVRKQDFQ KEAQHFRLLA GPHEGHWNVF LAQTLELKVT 


ASPDKVTKT 

« Hide

Isoform 2 (II) [UniParc].

Checksum: CFBF0BFA7D58CFE3
Show »

FASTA45149,675
Isoform 3 (VII) [UniParc].

Checksum: 66564AA513E1D2E7
Show »

FASTA14215,136
Isoform 4 (VIII) [UniParc].

Checksum: 577245066155CBC1
Show »

FASTA14215,922
Isoform 5 (IX) [UniParc].

Checksum: 9DFEC54E7C1EF6CE
Show »

FASTA939,846

References

« Hide 'large scale' references
[1]"BNF-1, a novel gene encoding a putative extracellular matrix protein, is overexpressed in tumor tissues."
Wu I., Moses M.A.
Gene 311:105-110(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, INDUCTION.
[2]"hCHL2, a novel chordin-related gene, displays differential expression and complex alternative splicing in human tissues and during myoblast and osteoblast maturation."
Oren A., Toporik A., Biton S., Almogy N., Eshel D., Bernstein J., Savitsky K., Rotman G.
Gene 331:17-31(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), FUNCTION, INTERACTION WITH BMPS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
[3]"A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in chondrocytes of developing cartilage and osteoarthritic joint cartilage."
Nakayama N., Han C.-Y.E., Cam L., Lee J.I., Pretorius J., Fisher S., Rosenfeld R., Scully S., Nishinakamura R., Duryea D., Van G., Bolon B., Yokota T., Zhang K.
Development 131:229-240(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH BMPS.
[4]"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 2).
[5]"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 1).
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 26-40.
[7]"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry."
Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.
Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-114.
Tissue: Milk.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY163868 mRNA. Translation: AAO31809.1.
AY279090 mRNA. Translation: AAQ19179.1.
AY279092 mRNA. Translation: AAQ19181.1.
AY279093 mRNA. Translation: AAQ19182.1.
AY279094 mRNA. Translation: AAQ19183.1.
AX140199 mRNA. No translation available.
AY358522 mRNA. Translation: AAQ88886.1.
BC142623 mRNA. Translation: AAI42624.1.
CCDSCCDS60893.1. [Q6WN34-1]
CCDS8234.1. [Q6WN34-2]
RefSeqNP_001265402.1. NM_001278473.1. [Q6WN34-1]
NP_056239.3. NM_015424.4. [Q6WN34-2]
UniGeneHs.432379.

3D structure databases

ProteinModelPortalQ6WN34.
SMRQ6WN34. Positions 251-319.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117395. 1 interaction.
STRING9606.ENSP00000263671.

PTM databases

PhosphoSiteQ6WN34.

Polymorphism databases

DMDM62900089.

Proteomic databases

PaxDbQ6WN34.
PRIDEQ6WN34.

Protocols and materials databases

DNASU25884.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263671; ENSP00000263671; ENSG00000054938. [Q6WN34-2]
ENST00000376332; ENSP00000365510; ENSG00000054938. [Q6WN34-1]
ENST00000528471; ENSP00000434589; ENSG00000054938. [Q6WN34-5]
ENST00000534276; ENSP00000432055; ENSG00000054938. [Q6WN34-4]
GeneID25884.
KEGGhsa:25884.
UCSCuc001ovg.3. human. [Q6WN34-1]
uc001ovh.3. human. [Q6WN34-2]

Organism-specific databases

CTD25884.
GeneCardsGC11M074407.
HGNCHGNC:24168. CHRDL2.
HPAHPA021771.
MIM613127. gene.
neXtProtNX_Q6WN34.
PharmGKBPA134883081.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147797.
HOGENOMHOG000049211.
HOVERGENHBG051113.
KOK17280.
OMAPEDKADP.
PhylomeDBQ6WN34.
TreeFamTF106451.

Gene expression databases

ArrayExpressQ6WN34.
BgeeQ6WN34.
CleanExHS_CHRDL2.
GenevestigatorQ6WN34.

Family and domain databases

InterProIPR001007. VWF_C.
[Graphical view]
PfamPF00093. VWC. 3 hits.
[Graphical view]
SMARTSM00214. VWC. 3 hits.
[Graphical view]
PROSITEPS01208. VWFC_1. 3 hits.
PS50184. VWFC_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi25884.
NextBio47300.
PROQ6WN34.
SOURCESearch...

Entry information

Entry nameCRDL2_HUMAN
AccessionPrimary (citable) accession number: Q6WN34
Secondary accession number(s): A5PKU9 expand/collapse secondary AC list , Q6WN30, Q6WN31, Q6WN32, Q7Z5J3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 87 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 11

Human chromosome 11: entries, gene names and cross-references to MIM