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Q6WN34

- CRDL2_HUMAN

UniProt

Q6WN34 - CRDL2_HUMAN

Protein

Chordin-like protein 2

Gene

CHRDL2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 89 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
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    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.By similarity2 Publications

    GO - Biological processi

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

    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

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Secreted

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134883081.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 25251 PublicationAdd
    BLAST
    Chaini26 – 429404Chordin-like protein 2PRO_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.By similarity2 Publications

    Protein-protein interaction databases

    BioGridi117395. 1 interaction.
    STRINGi9606.ENSP00000263671.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6WN34.
    SMRiQ6WN34. Positions 251-319.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

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

    Sequence similaritiesi

    Contains 3 VWFC domains.PROSITE-ProRule annotation

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti187 – 1871S → R in AX140199. (PubMed:15094188)Curated
    Sequence conflicti231 – 2311R → I in AX140199. (PubMed:15094188)Curated

    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. 1 PublicationVSP_013512Add
    BLAST
    Alternative sequencei21 – 288LDSHARAR → MALVGLPG in isoform 3, isoform 4 and isoform 5. 1 PublicationVSP_013513
    Alternative sequencei66 – 16297GAHVS…PGCPA → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQRARSTAASQPAP NQAAQHPSRCQTPAAKPAKM RQVSNRMKRTVCSRSMG in isoform 3. 1 PublicationVSP_013514Add
    BLAST
    Alternative sequencei66 – 11348GAHVS…KSCQH → NLTLPLDSGPHQSPASTTGP CTNTERSSVPMSCSPPACPT SVSSAAAQ in isoform 5. 1 PublicationVSP_013515Add
    BLAST
    Alternative sequencei114 – 429316Missing in isoform 5. 1 PublicationVSP_013516Add
    BLAST
    Alternative sequencei145 – 16218EGQIY…PGCPA → MRQVSNRMKRTVCSRSMG in isoform 4. 1 PublicationVSP_013517Add
    BLAST
    Alternative sequencei163 – 429267Missing in isoform 3 and isoform 4. 1 PublicationVSP_013518Add
    BLAST
    Alternative sequencei374 – 42653GIFHL…SPDKV → DEETEAQRGEVPGPRPHSQN LPLDSDQESQEARLPERGTA LPTARWPPRRSLERLPSPDP GAEGHGQSRQSDQDI in isoform 2. 3 PublicationsVSP_013519Add
    BLAST

    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...
    MobiDBi 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

    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: October 1, 2014
    This is version 89 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 PubMed:14660436, interacts with BMP2, BMP4, BMP5, BMP6, BMP7 but not INHBA. According to PubMed:15094188, interacts with INHBA but not BMP2, BMP4 and BMP6.Curated

    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