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 23-FEB-2022, entry version 112. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 SMR; Q8VEA6; -. DR BioGRID; 213242; 6. DR STRING; 10090.ENSMUSP00000032977; -. DR GlyGen; Q8VEA6; 2 sites. DR PhosphoSitePlus; Q8VEA6; -. DR PaxDb; Q8VEA6; -. DR PRIDE; Q8VEA6; -. DR ProteomicsDB; 284167; -. [Q8VEA6-1] DR DNASU; 69121; -. DR GeneID; 69121; -. DR KEGG; mmu:69121; -. DR CTD; 25884; -. DR MGI; MGI:1916371; Chrdl2. DR eggNOG; ENOG502QQFQ; Eukaryota. DR InParanoid; Q8VEA6; -. DR OrthoDB; 454087at2759; -. DR PhylomeDB; Q8VEA6; -. DR BioGRID-ORCS; 69121; 0 hits in 64 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:0051216; P:cartilage development; IEA:UniProtKB-KW. DR GO; GO:0030154; P:cell 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 InterPro; IPR030117; Chordin-like_2. DR InterPro; IPR045717; CHRDL1/2. DR InterPro; IPR045716; CHRDL_1/2_C. DR InterPro; IPR001007; VWF_dom. DR PANTHER; PTHR46303; PTHR46303; 1. DR PANTHER; PTHR46303:SF3; PTHR46303:SF3; 1. DR Pfam; PF19548; CHRDL_1_2_C; 1. DR Pfam; PF00093; VWC; 3. DR SMART; SM00214; VWC; 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 //