ID   CRDL2_MOUSE             Reviewed;         426 AA.
AC   Q8VEA6; Q925I3;
DT   26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   24-JAN-2024, entry version 119.
DE   RecName: Full=Chordin-like protein 2;
DE   Flags: Precursor;
GN   Name=Chrdl2; Synonyms=Chl2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL
RP   STAGE, AND INTERACTION WITH BMPS; GDF5 AND INHBA.
RX   PubMed=14660436; DOI=10.1242/dev.00901;
RA   Nakayama N., Han C.-Y.E., Cam L., Lee J.I., Pretorius J., Fisher S.,
RA   Rosenfeld R., Scully S., Nishinakamura R., Duryea D., Van G., Bolon B.,
RA   Yokota T., Zhang K.;
RT   "A novel chordin-like BMP inhibitor, CHL2, expressed preferentially in
RT   chondrocytes of developing cartilage and osteoarthritic joint cartilage.";
RL   Development 131:229-240(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J;
RA   Coffinier C.C., De Robertis E.M.;
RL   Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, AND ALTERNATIVE SPLICING.
RX   PubMed=15094188; DOI=10.1016/j.gene.2004.01.029;
RA   Oren A., Toporik A., Biton S., Almogy N., Eshel D., Bernstein J.,
RA   Savitsky K., Rotman G.;
RT   "hCHL2, a novel chordin-related gene, displays differential expression and
RT   complex alternative splicing in human tissues and during myoblast and
RT   osteoblast maturation.";
RL   Gene 331:17-31(2004).
CC   -!- FUNCTION: Implicated in tumor angiogenesis (By similarity). May
CC       inhibits BMPs activity by blocking their interaction with their
CC       receptors. Has a negative regulator effect on the cartilage
CC       formation/regeneration from immature mesenchymal cells, by preventing
CC       or reducing the rate of matrix accumulation. May play a role during
CC       myoblast and osteoblast differentiation, and maturation. {ECO:0000250,
CC       ECO:0000269|PubMed:14660436, ECO:0000269|PubMed:15094188}.
CC   -!- SUBUNIT: Interacts with GDF5. May interact with INHBA, BMP2, BMP4,
CC       BMP5, BMP6, and BMP7. {ECO:0000269|PubMed:14660436}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=1;
CC         Comment=Additional isoforms seem to exist. Differential expression of
CC         isoforms was observed during myoblast and osteoblast differentiation
CC         and maturation.;
CC       Name=1;
CC         IsoId=Q8VEA6-1; Sequence=Displayed;
CC   -!- TISSUE SPECIFICITY: Weakly expressed in the liver and kidney. In
CC       reproductive organs expressed in connective tissues such as ligaments
CC       of the ovary and oviduct in females, and of testis, epididymis and
CC       certain male accessory sex glands in males. Expression was high in
CC       uterine myometrium. Weakly expressed in cartilage of the femoral head,
CC       patella, articular facets of vertebrae, in the annulus fibrosus of
CC       intervertebral disks. In normal cartilage, expression was confined to
CC       articular chondrocytes especially in the superficial zone.
CC       {ECO:0000269|PubMed:14660436}.
CC   -!- DEVELOPMENTAL STAGE: In embryo expressed to the surface chondrocytes of
CC       developing joint cartilage and to the connective tissue of reproductive
CC       organs. {ECO:0000269|PubMed:14660436}.
CC   -!- CAUTION: According to PubMed:14660436 interacts with human BMP2, BMP4,
CC       BMP5, BMP6, BMP7 but not human INHBA. According to PubMed:15094188
CC       interacts with human INHBA but not human BMP2, BMP4 and BMP6.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK50575.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AF338222; AAK50575.1; ALT_FRAME; mRNA.
DR   EMBL; BC019399; AAH19399.1; -; mRNA.
DR   CCDS; CCDS21492.1; -. [Q8VEA6-1]
DR   RefSeq; NP_001278249.1; NM_001291320.1.
DR   RefSeq; NP_598470.3; NM_133709.3.
DR   AlphaFoldDB; Q8VEA6; -.
DR   SMR; Q8VEA6; -.
DR   BioGRID; 213242; 6.
DR   STRING; 10090.ENSMUSP00000102699; -.
DR   GlyCosmos; Q8VEA6; 2 sites, No reported glycans.
DR   GlyGen; Q8VEA6; 2 sites.
DR   PhosphoSitePlus; Q8VEA6; -.
DR   PaxDb; 10090-ENSMUSP00000032977; -.
DR   ProteomicsDB; 284167; -. [Q8VEA6-1]
DR   DNASU; 69121; -.
DR   GeneID; 69121; -.
DR   KEGG; mmu:69121; -.
DR   AGR; MGI:1916371; -.
DR   CTD; 25884; -.
DR   MGI; MGI:1916371; Chrdl2.
DR   eggNOG; ENOG502QQFQ; Eukaryota.
DR   InParanoid; Q8VEA6; -.
DR   OrthoDB; 3670395at2759; -.
DR   PhylomeDB; Q8VEA6; -.
DR   BioGRID-ORCS; 69121; 0 hits in 77 CRISPR screens.
DR   ChiTaRS; Chrdl2; mouse.
DR   PRO; PR:Q8VEA6; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8VEA6; Protein.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0036122; F:BMP binding; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0002062; P:chondrocyte differentiation; IDA:MGI.
DR   GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:MGI.
DR   GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR   Gene3D; 6.20.200.20; -; 1.
DR   Gene3D; 2.10.70.10; Complement Module, domain 1; 2.
DR   InterPro; IPR045717; CHRDL1/2.
DR   InterPro; IPR045716; CHRDL_1/2_C.
DR   InterPro; IPR001007; VWF_dom.
DR   PANTHER; PTHR46303:SF3; CHORDIN-LIKE PROTEIN 2; 1.
DR   PANTHER; PTHR46303; VWFC DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF19548; CHRDL_1_2_C; 1.
DR   Pfam; PF00093; VWC; 3.
DR   SMART; SM00214; VWC; 3.
DR   SUPFAM; SSF57603; FnI-like domain; 3.
DR   PROSITE; PS01208; VWFC_1; 3.
DR   PROSITE; PS50184; VWFC_2; 3.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chondrogenesis; Developmental protein;
KW   Differentiation; Glycoprotein; Osteogenesis; Phosphoprotein;
KW   Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000250"
FT   CHAIN           26..426
FT                   /note="Chordin-like protein 2"
FT                   /id="PRO_0000005372"
FT   DOMAIN          31..96
FT                   /note="VWFC 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          109..175
FT                   /note="VWFC 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   DOMAIN          246..311
FT                   /note="VWFC 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT   REGION          182..216
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         182
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WN34"
FT   CARBOHYD        114
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        26
FT                   /note="R -> L (in Ref. 2; AAK50575)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        335
FT                   /note="H -> Q (in Ref. 2; AAK50575)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   426 AA;  47765 MW;  45BAB7BEE09AFE04 CRC64;
     MVPGVRIIPS LLGLVMFWLP LDSQARSRSG KVCLFGEKIY TPGQSWHPYL EPQGTIYCVR
     CTCSENGHVN CYRLRCPPLH CSQPVMEPQQ CCPRCVDPHV PSGLRVPLKS CQLNETTYQH
     GEIFSAQELF PARLSNQCVL CSCIEGHTYC GLMTCPEPSC PTTLPLPDSC CQTCKDRTTE
     SSTEENLTQL QHGERHSQDP CSERRGPSTP APTSLSSPLG FIPRHFQSVG MGSTTIKIIL
     KEKHKKACTH NGKTYSHGEV WHPTVLSFGP MPCILCTCID GYQDCHRVTC PTQYPCSQPK
     KVAGKCCKIC PEDEAEDDHS EVISTRCPKV PGQFHVYTLA SPSPDSLHRF VLEHEASDQV
     EMYIWKLVKG IYHLVQIKRV RKQDFQKEAQ NFRLLTGTHE GYWTVFLAQT PELKVTASPD
     KVTKTL
//