CRDL2_HUMAN
ID CRDL2_HUMAN Reviewed; 429 AA.
AC Q6WN34; A5PKU9; Q6WN30; Q6WN31; Q6WN32; Q7Z5J3;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Chordin-like protein 2;
DE AltName: Full=Breast tumor novel factor 1;
DE Short=BNF-1;
DE AltName: Full=Chordin-related protein 2;
DE Flags: Precursor;
GN Name=CHRDL2; Synonyms=BNF1, CHL2; ORFNames=UNQ765/PRO1557;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, AND
RP INDUCTION.
RX PubMed=12853144; DOI=10.1016/s0378-1119(03)00563-8;
RA Wu I., Moses M.A.;
RT "BNF-1, a novel gene encoding a putative extracellular matrix protein, is
RT overexpressed in tumor tissues.";
RL Gene 311:105-110(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), FUNCTION,
RP INTERACTION WITH BMPS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP 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).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND INTERACTION
RP WITH BMPS.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [6]
RP PROTEIN SEQUENCE OF 26-40.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-114.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [8]
RP PHOSPHORYLATION AT SER-182.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
CC -!- FUNCTION: May inhibit BMPs activity by blocking their interaction with
CC their 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 (By similarity). Implicated
CC in tumor angiogenesis. May play a role during myoblast and osteoblast
CC differentiation, and maturation. {ECO:0000250,
CC ECO:0000269|PubMed:12853144, ECO:0000269|PubMed:15094188}.
CC -!- SUBUNIT: Interacts with GDF5 (By similarity). May interact with BMP2,
CC BMP4, BMP5, BMP6, BMP7 and INHBA. {ECO:0000250,
CC ECO:0000269|PubMed:14660436, ECO:0000269|PubMed:15094188}.
CC -!- INTERACTION:
CC Q6WN34-2; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-12593838, EBI-11524452;
CC Q6WN34-2; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-12593838, EBI-947551;
CC Q6WN34-2; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-12593838, EBI-744099;
CC Q6WN34-2; P16930: FAH; NbExp=3; IntAct=EBI-12593838, EBI-4397076;
CC Q6WN34-2; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-12593838, EBI-6658203;
CC Q6WN34-2; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-12593838, EBI-347538;
CC Q6WN34-2; P49639: HOXA1; NbExp=3; IntAct=EBI-12593838, EBI-740785;
CC Q6WN34-2; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-12593838, EBI-726739;
CC Q6WN34-2; P32242: OTX1; NbExp=3; IntAct=EBI-12593838, EBI-740446;
CC Q6WN34-2; Q92569: PIK3R3; NbExp=3; IntAct=EBI-12593838, EBI-79893;
CC Q6WN34-2; Q12837: POU4F2; NbExp=3; IntAct=EBI-12593838, EBI-17236143;
CC Q6WN34-2; O75093: SLIT1; NbExp=3; IntAct=EBI-12593838, EBI-947791;
CC Q6WN34-2; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-12593838, EBI-740727;
CC Q6WN34-2; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-12593838, EBI-6427977;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Five additional mRNAs also exist. Differential expression of
CC isoforms was observed during myoblast and osteoblast differentiation
CC and maturation.;
CC Name=1; Synonyms=I;
CC IsoId=Q6WN34-1; Sequence=Displayed;
CC Name=2; Synonyms=II;
CC IsoId=Q6WN34-2; Sequence=VSP_013519;
CC Name=3; Synonyms=VII;
CC IsoId=Q6WN34-3; Sequence=VSP_013512, VSP_013513, VSP_013514,
CC VSP_013518;
CC Name=4; Synonyms=VIII;
CC IsoId=Q6WN34-4; Sequence=VSP_013512, VSP_013513, VSP_013517,
CC VSP_013518;
CC Name=5; Synonyms=IX;
CC IsoId=Q6WN34-5; Sequence=VSP_013512, VSP_013513, VSP_013515,
CC VSP_013516;
CC -!- TISSUE SPECIFICITY: Highly expressed in uterus. Moderately expressed in
CC heart, liver, prostate, testis and ovary. Weakly expressed in skeletal
CC muscle, kidney, spleen, small intestine and colon. Expressed in the
CC secretory epithelial cells of uterine endometrium, fallopian tubes,
CC endocervical glands, bladder and prostate, as well as the transitional
CC epithelium of the urinary bladder, and in bone osteoblasts (at protein
CC level). In normal cartilage, expression was confined in a few
CC chondrocytes in the superficial zone as well as in the middle zone. In
CC diseased cartilage coming from osteoarthritic patients, expression was
CC limited to the middle zone of chondrocytes. Isoform 1 and isoform 2 are
CC expressed in fetal cerebellum and heart, while only isoform 2 is
CC detected in fetal spleen. Isoform 2 present in plasma.
CC {ECO:0000269|PubMed:12853144, ECO:0000269|PubMed:14660436,
CC ECO:0000269|PubMed:15094188}.
CC -!- INDUCTION: Up-regulated in breast tumors but also in lung and colon
CC tumors. {ECO:0000269|PubMed:12853144}.
CC -!- PTM: Phosphorylated by FAM20C in the extracellular medium.
CC {ECO:0000269|PubMed:26091039}.
CC -!- CAUTION: According to PubMed:14660436, interacts with BMP2, BMP4, BMP5,
CC BMP6, BMP7 but not INHBA. According to PubMed:15094188, interacts with
CC INHBA but not BMP2, BMP4 and BMP6. {ECO:0000305}.
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DR EMBL; AY163868; AAO31809.1; -; mRNA.
DR EMBL; AY279090; AAQ19179.1; -; mRNA.
DR EMBL; AY279092; AAQ19181.1; -; mRNA.
DR EMBL; AY279093; AAQ19182.1; -; mRNA.
DR EMBL; AY279094; AAQ19183.1; -; mRNA.
DR EMBL; AX140199; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY358522; AAQ88886.1; -; mRNA.
DR EMBL; BC142623; AAI42624.1; -; mRNA.
DR CCDS; CCDS60893.1; -. [Q6WN34-1]
DR CCDS; CCDS8234.1; -. [Q6WN34-2]
DR RefSeq; NP_001265402.1; NM_001278473.2. [Q6WN34-1]
DR RefSeq; NP_001291319.1; NM_001304390.1.
DR RefSeq; NP_001291320.1; NM_001304391.1.
DR RefSeq; NP_001291344.1; NM_001304415.1.
DR RefSeq; NP_001291345.1; NM_001304416.1.
DR RefSeq; NP_001291346.1; NM_001304417.1.
DR RefSeq; NP_056239.3; NM_015424.5. [Q6WN34-2]
DR AlphaFoldDB; Q6WN34; -.
DR SMR; Q6WN34; -.
DR BioGRID; 117395; 114.
DR CORUM; Q6WN34; -.
DR IntAct; Q6WN34; 15.
DR STRING; 9606.ENSP00000263671; -.
DR GlyConnect; 2935; 23 N-Linked glycans (1 site).
DR GlyGen; Q6WN34; 2 sites, 24 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q6WN34; -.
DR PhosphoSitePlus; Q6WN34; -.
DR BioMuta; CHRDL2; -.
DR DMDM; 62900089; -.
DR jPOST; Q6WN34; -.
DR MassIVE; Q6WN34; -.
DR PeptideAtlas; Q6WN34; -.
DR PRIDE; Q6WN34; -.
DR ProteomicsDB; 67768; -. [Q6WN34-1]
DR ProteomicsDB; 67769; -. [Q6WN34-2]
DR ProteomicsDB; 67770; -. [Q6WN34-3]
DR ProteomicsDB; 67771; -. [Q6WN34-4]
DR ProteomicsDB; 67772; -. [Q6WN34-5]
DR Antibodypedia; 17275; 155 antibodies from 22 providers.
DR DNASU; 25884; -.
DR Ensembl; ENST00000263671.9; ENSP00000263671.5; ENSG00000054938.17. [Q6WN34-2]
DR Ensembl; ENST00000376332.8; ENSP00000365510.3; ENSG00000054938.17. [Q6WN34-1]
DR Ensembl; ENST00000528471.1; ENSP00000434589.1; ENSG00000054938.17. [Q6WN34-5]
DR Ensembl; ENST00000534276.5; ENSP00000432055.1; ENSG00000054938.17. [Q6WN34-4]
DR GeneID; 25884; -.
DR KEGG; hsa:25884; -.
DR MANE-Select; ENST00000376332.8; ENSP00000365510.3; NM_001278473.3; NP_001265402.1.
DR UCSC; uc001ovh.5; human. [Q6WN34-1]
DR CTD; 25884; -.
DR DisGeNET; 25884; -.
DR GeneCards; CHRDL2; -.
DR HGNC; HGNC:24168; CHRDL2.
DR HPA; ENSG00000054938; Tissue enhanced (endometrium, gallbladder, lymphoid tissue, smooth muscle).
DR MIM; 613127; gene.
DR neXtProt; NX_Q6WN34; -.
DR OpenTargets; ENSG00000054938; -.
DR PharmGKB; PA134883081; -.
DR VEuPathDB; HostDB:ENSG00000054938; -.
DR GeneTree; ENSGT00940000161241; -.
DR HOGENOM; CLU_048288_1_1_1; -.
DR InParanoid; Q6WN34; -.
DR OMA; TNEGHWN; -.
DR OrthoDB; 454087at2759; -.
DR PhylomeDB; Q6WN34; -.
DR TreeFam; TF106451; -.
DR PathwayCommons; Q6WN34; -.
DR SignaLink; Q6WN34; -.
DR BioGRID-ORCS; 25884; 16 hits in 1071 CRISPR screens.
DR ChiTaRS; CHRDL2; human.
DR GenomeRNAi; 25884; -.
DR Pharos; Q6WN34; Tbio.
DR PRO; PR:Q6WN34; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q6WN34; protein.
DR Bgee; ENSG00000054938; Expressed in smooth muscle tissue and 104 other tissues.
DR ExpressionAtlas; Q6WN34; baseline and differential.
DR Genevisible; Q6WN34; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0036122; F:BMP binding; IBA:GO_Central.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IBA:GO_Central.
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; Cytoplasm; Developmental protein;
KW Differentiation; Direct protein sequencing; Glycoprotein; Osteogenesis;
KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 26..429
FT /note="Chordin-like protein 2"
FT /id="PRO_0000005371"
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 250..315
FT /note="VWFC 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT REGION 182..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 182
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18780401"
FT VAR_SEQ 1..20
FT /note="Missing (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013512"
FT VAR_SEQ 21..28
FT /note="LDSHARAR -> MALVGLPG (in isoform 3, isoform 4 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013513"
FT VAR_SEQ 66..162
FT /note="GAHVSCYRLHCPPVHCPQPVTEPQQCCPKCVEPHTPSGLRAPPKSCQHNGTM
FT YQHGEIFSAHELFPSRLPNQCVLCSCTEGQIYCGLTTCPEPGCPA -> NLTLPLDSGP
FT HQSPASTTGPCTNTERSSVPMSCSPPACPTSVSSAAAQRARSTAASQPAPNQAAQHPSR
FT CQTPAAKPAKMRQVSNRMKRTVCSRSMG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013514"
FT VAR_SEQ 66..113
FT /note="GAHVSCYRLHCPPVHCPQPVTEPQQCCPKCVEPHTPSGLRAPPKSCQH ->
FT NLTLPLDSGPHQSPASTTGPCTNTERSSVPMSCSPPACPTSVSSAAAQ (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013515"
FT VAR_SEQ 114..429
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013516"
FT VAR_SEQ 145..162
FT /note="EGQIYCGLTTCPEPGCPA -> MRQVSNRMKRTVCSRSMG (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013517"
FT VAR_SEQ 163..429
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15094188"
FT /id="VSP_013518"
FT VAR_SEQ 374..426
FT /note="GIFHLTQIKKVRKQDFQKEAQHFRLLAGPHEGHWNVFLAQTLELKVTASPDK
FT V -> DEETEAQRGEVPGPRPHSQNLPLDSDQESQEARLPERGTALPTARWPPRRSLER
FT LPSPDPGAEGHGQSRQSDQDI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12853144,
FT ECO:0000303|PubMed:12975309, ECO:0000303|PubMed:15094188"
FT /id="VSP_013519"
FT VARIANT 335
FT /note="P -> L (in dbSNP:rs35903991)"
FT /id="VAR_055651"
FT CONFLICT 187
FT /note="S -> R (in Ref. 2; AX140199)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="R -> I (in Ref. 2; AX140199)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 429 AA; 47495 MW; A8111F26B2EF96A4 CRC64;
MVPEVRVLSS LLGLALLWFP LDSHARARPD MFCLFHGKRY SPGESWHPYL EPQGLMYCLR
CTCSEGAHVS CYRLHCPPVH CPQPVTEPQQ CCPKCVEPHT PSGLRAPPKS CQHNGTMYQH
GEIFSAHELF PSRLPNQCVL CSCTEGQIYC GLTTCPEPGC PAPLPLPDSC CQACKDEASE
QSDEEDSVQS LHGVRHPQDP CSSDAGRKRG PGTPAPTGLS APLSFIPRHF RPKGAGSTTV
KIVLKEKHKK ACVHGGKTYS HGEVWHPAFR AFGPLPCILC TCEDGRQDCQ RVTCPTEYPC
RHPEKVAGKC CKICPEDKAD PGHSEISSTR CPKAPGRVLV HTSVSPSPDN LRRFALEHEA
SDLVEIYLWK LVKGIFHLTQ IKKVRKQDFQ KEAQHFRLLA GPHEGHWNVF LAQTLELKVT
ASPDKVTKT
