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Q6WN34

- CRDL2_HUMAN

UniProt

Q6WN34 - CRDL2_HUMAN

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Protein
Chordin-like protein 2
Gene
CHRDL2, BNF1, CHL2, UNQ765/PRO1557
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

  1. cartilage development Source: UniProtKB-KW
  2. cell differentiation Source: UniProtKB-KW
  3. ossification Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Chondrogenesis, Differentiation, Osteogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Chordin-like protein 2
Alternative name(s):
Breast tumor novel factor 1
Short name:
BNF-1
Chordin-related protein 2
Gene namesi
Name:CHRDL2
Synonyms:BNF1, CHL2
ORF Names:UNQ765/PRO1557
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:24168. CHRDL2.

Subcellular locationi

Isoform 1 : Secreted Reviewed prediction 1 Publication
Isoform 2 : Secreted Reviewed prediction 1 Publication
Isoform 3 : Cytoplasm Reviewed prediction 1 Publication
Isoform 4 : Cytoplasm Reviewed prediction 1 Publication
Isoform 5 : Cytoplasm Reviewed prediction 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. extracellular space Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134883081.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 25251 Publication
Add
BLAST
Chaini26 – 429404Chordin-like protein 2
PRO_0000005371Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi114 – 1141N-linked (GlcNAc...)1 Publication

Post-translational modificationi

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

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ6WN34.
PRIDEiQ6WN34.

PTM databases

PhosphoSiteiQ6WN34.

Expressioni

Tissue specificityi

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.3 Publications

Inductioni

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

Gene expression databases

ArrayExpressiQ6WN34.
BgeeiQ6WN34.
CleanExiHS_CHRDL2.
GenevestigatoriQ6WN34.

Organism-specific databases

HPAiHPA021771.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi117395. 1 interaction.
STRINGi9606.ENSP00000263671.

Structurei

3D structure databases

ProteinModelPortaliQ6WN34.
SMRiQ6WN34. Positions 251-319.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini31 – 9666VWFC 1
Add
BLAST
Domaini109 – 17567VWFC 2
Add
BLAST
Domaini250 – 31566VWFC 3
Add
BLAST

Sequence similaritiesi

Contains 3 VWFC domains.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG147797.
HOGENOMiHOG000049211.
HOVERGENiHBG051113.
KOiK17280.
OMAiPEDKADP.
PhylomeDBiQ6WN34.
TreeFamiTF106451.

Family and domain databases

InterProiIPR001007. VWF_C.
[Graphical view]
PfamiPF00093. VWC. 3 hits.
[Graphical view]
SMARTiSM00214. VWC. 3 hits.
[Graphical view]
PROSITEiPS01208. VWFC_1. 3 hits.
PS50184. VWFC_2. 3 hits.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. Align

Note: Five additional mRNAs also exist. Differential expression of isoforms was observed during myoblast and osteoblast differentiation and maturation.

Isoform 1 (identifier: Q6WN34-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MVPEVRVLSS LLGLALLWFP LDSHARARPD MFCLFHGKRY SPGESWHPYL    50
EPQGLMYCLR CTCSEGAHVS CYRLHCPPVH CPQPVTEPQQ CCPKCVEPHT 100
PSGLRAPPKS CQHNGTMYQH GEIFSAHELF PSRLPNQCVL CSCTEGQIYC 150
GLTTCPEPGC PAPLPLPDSC CQACKDEASE QSDEEDSVQS LHGVRHPQDP 200
CSSDAGRKRG PGTPAPTGLS APLSFIPRHF RPKGAGSTTV KIVLKEKHKK 250
ACVHGGKTYS HGEVWHPAFR AFGPLPCILC TCEDGRQDCQ RVTCPTEYPC 300
RHPEKVAGKC CKICPEDKAD PGHSEISSTR CPKAPGRVLV HTSVSPSPDN 350
LRRFALEHEA SDLVEIYLWK LVKGIFHLTQ IKKVRKQDFQ KEAQHFRLLA 400
GPHEGHWNVF LAQTLELKVT ASPDKVTKT 429
Length:429
Mass (Da):47,495
Last modified:July 5, 2004 - v1
Checksum:iA8111F26B2EF96A4
GO
Isoform 2 (identifier: Q6WN34-2) [UniParc]FASTAAdd to Basket

Also known as: II

The sequence of this isoform differs from the canonical sequence as follows:
     374-426: GIFHLTQIKK...LKVTASPDKV → DEETEAQRGE...GQSRQSDQDI

Show »
Length:451
Mass (Da):49,675
Checksum:iCFBF0BFA7D58CFE3
GO
Isoform 3 (identifier: Q6WN34-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:142
Mass (Da):15,136
Checksum:i66564AA513E1D2E7
GO
Isoform 4 (identifier: Q6WN34-4) [UniParc]FASTAAdd to Basket

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.

Show »
Length:142
Mass (Da):15,922
Checksum:i577245066155CBC1
GO
Isoform 5 (identifier: Q6WN34-5) [UniParc]FASTAAdd to Basket

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.

Show »
Length:93
Mass (Da):9,846
Checksum:i9DFEC54E7C1EF6CE
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti335 – 3351P → L.
Corresponds to variant rs35903991 [ dbSNP | Ensembl ].
VAR_055651

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2020Missing in isoform 3, isoform 4 and isoform 5.
VSP_013512Add
BLAST
Alternative sequencei21 – 288LDSHARAR → MALVGLPG in isoform 3, isoform 4 and isoform 5.
VSP_013513
Alternative sequencei66 – 16297GAHVS…PGCPA → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQRARSTAASQPAP NQAAQHPSRCQTPAAKPAKM RQVSNRMKRTVCSRSMG in isoform 3.
VSP_013514Add
BLAST
Alternative sequencei66 – 11348GAHVS…KSCQH → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQ in isoform 5.
VSP_013515Add
BLAST
Alternative sequencei114 – 429316Missing in isoform 5.
VSP_013516Add
BLAST
Alternative sequencei145 – 16218EGQIY…PGCPA → MRQVSNRMKRTVCSRSMG in isoform 4.
VSP_013517Add
BLAST
Alternative sequencei163 – 429267Missing in isoform 3 and isoform 4.
VSP_013518Add
BLAST
Alternative sequencei374 – 42653GIFHL…SPDKV → DEETEAQRGEVPGPRPHSQN LPLDSDQESQEARLPERGTA LPTARWPPRRSLERLPSPDP GAEGHGQSRQSDQDI in isoform 2.
VSP_013519Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti187 – 1871S → R in AX140199. 1 Publication
Sequence conflicti231 – 2311R → I in AX140199. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS60893.1. [Q6WN34-1]
CCDS8234.1. [Q6WN34-2]
RefSeqiNP_001265402.1. NM_001278473.1. [Q6WN34-1]
NP_056239.3. NM_015424.4. [Q6WN34-2]
UniGeneiHs.432379.

Genome annotation databases

EnsembliENST00000263671; ENSP00000263671; ENSG00000054938. [Q6WN34-2]
ENST00000376332; ENSP00000365510; ENSG00000054938. [Q6WN34-1]
ENST00000528471; ENSP00000434589; ENSG00000054938. [Q6WN34-5]
ENST00000534276; ENSP00000432055; ENSG00000054938. [Q6WN34-4]
GeneIDi25884.
KEGGihsa:25884.
UCSCiuc001ovg.3. human. [Q6WN34-1]
uc001ovh.3. human. [Q6WN34-2]

Polymorphism databases

DMDMi62900089.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS60893.1. [Q6WN34-1 ]
CCDS8234.1. [Q6WN34-2 ]
RefSeqi NP_001265402.1. NM_001278473.1. [Q6WN34-1 ]
NP_056239.3. NM_015424.4. [Q6WN34-2 ]
UniGenei Hs.432379.

3D structure databases

ProteinModelPortali Q6WN34.
SMRi Q6WN34. Positions 251-319.
ModBasei Search...

Protein-protein interaction databases

BioGridi 117395. 1 interaction.
STRINGi 9606.ENSP00000263671.

PTM databases

PhosphoSitei Q6WN34.

Polymorphism databases

DMDMi 62900089.

Proteomic databases

PaxDbi Q6WN34.
PRIDEi Q6WN34.

Protocols and materials databases

DNASUi 25884.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000263671 ; ENSP00000263671 ; ENSG00000054938 . [Q6WN34-2 ]
ENST00000376332 ; ENSP00000365510 ; ENSG00000054938 . [Q6WN34-1 ]
ENST00000528471 ; ENSP00000434589 ; ENSG00000054938 . [Q6WN34-5 ]
ENST00000534276 ; ENSP00000432055 ; ENSG00000054938 . [Q6WN34-4 ]
GeneIDi 25884.
KEGGi hsa:25884.
UCSCi uc001ovg.3. human. [Q6WN34-1 ]
uc001ovh.3. human. [Q6WN34-2 ]

Organism-specific databases

CTDi 25884.
GeneCardsi GC11M074407.
HGNCi HGNC:24168. CHRDL2.
HPAi HPA021771.
MIMi 613127. gene.
neXtProti NX_Q6WN34.
PharmGKBi PA134883081.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG147797.
HOGENOMi HOG000049211.
HOVERGENi HBG051113.
KOi K17280.
OMAi PEDKADP.
PhylomeDBi Q6WN34.
TreeFami TF106451.

Miscellaneous databases

GenomeRNAii 25884.
NextBioi 47300.
PROi Q6WN34.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q6WN34.
Bgeei Q6WN34.
CleanExi HS_CHRDL2.
Genevestigatori Q6WN34.

Family and domain databases

InterProi IPR001007. VWF_C.
[Graphical view ]
Pfami PF00093. VWC. 3 hits.
[Graphical view ]
SMARTi SM00214. VWC. 3 hits.
[Graphical view ]
PROSITEi PS01208. VWFC_1. 3 hits.
PS50184. VWFC_2. 3 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

Entry informationi

Entry nameiCRDL2_HUMAN
AccessioniPrimary (citable) accession number: Q6WN34
Secondary accession number(s): A5PKU9
, Q6WN30, Q6WN31, Q6WN32, Q7Z5J3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: July 5, 2004
Last modified: September 3, 2014
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

According to 1 Publication, interacts with BMP2, BMP4, BMP5, BMP6, BMP7 but not INHBA. According to 1 Publication, interacts with INHBA but not BMP2, BMP4 and BMP6.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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