CNMD_HUMAN
ID CNMD_HUMAN Reviewed; 334 AA.
AC O75829; Q5TAM4; Q8TAY6; Q9UM18;
DT 29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Leukocyte cell-derived chemotaxin 1 {ECO:0000305};
DE AltName: Full=Chondromodulin {ECO:0000312|HGNC:HGNC:17005};
DE Contains:
DE RecName: Full=Chondrosurfactant protein;
DE Short=CH-SP;
DE Contains:
DE RecName: Full=Chondromodulin-1;
DE AltName: Full=Chondromodulin-I;
DE Short=ChM-I;
DE Flags: Precursor;
GN Name=CNMD {ECO:0000312|HGNC:HGNC:17005};
GN Synonyms=CHMI {ECO:0000312|HGNC:HGNC:17005},
GN LECT1 {ECO:0000312|HGNC:HGNC:17005}, MYETS1 {ECO:0000312|HGNC:HGNC:17005};
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 1).
RC TISSUE=Chondrosarcoma;
RX PubMed=9731231; DOI=10.1006/bbrc.1998.9233;
RA Shukunami C., Hiraki Y.;
RT "Expression of cartilage-specific functional matrix chondromodulin-I mRNA
RT in rabbit growth plate chondrocytes and its responsiveness to growth
RT stimuli in vitro.";
RL Biochem. Biophys. Res. Commun. 249:885-890(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Chondrosarcoma;
RX PubMed=10103018; DOI=10.1046/j.1432-1327.1999.00227.x;
RA Hiraki Y., Mitsui K., Endo N., Takahashi K., Hayami T., Inoue H.,
RA Shukunami C., Tokunaga K., Kono T., Yamada M., Takahashi H.E., Kondo J.;
RT "Molecular cloning of human chondromodulin-I, a cartilage-derived growth
RT modulating factor, and its expression in Chinese hamster ovary cells.";
RL Eur. J. Biochem. 260:869-878(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20.
RA Ozono K.;
RT "Human chondromodulin-1 gene promoter.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 215-334 (ISOFORM 1).
RX PubMed=10570955; DOI=10.1016/s0014-5793(99)01201-6;
RA Hayami T., Shukunami C., Mitsui K., Endo N., Tokunaga K., Kondo J.,
RA Takahashi H.E., Hiraki Y.;
RT "Specific loss of chondromodulin-I gene expression in chondrosarcoma and
RT the suppression of tumor angiogenesis and growth by its recombinant protein
RT in vivo.";
RL FEBS Lett. 458:436-440(1999).
RN [8]
RP REVIEW.
RX PubMed=10912526; DOI=10.1007/s004670000339;
RA Hiraki Y., Shukunami C.;
RT "Chondromodulin-I as a novel cartilage-specific growth-modulating factor.";
RL Pediatr. Nephrol. 14:602-605(2000).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16980969; DOI=10.1038/nm1476;
RA Yoshioka M., Yuasa S., Matsumura K., Kimura K., Shiomi T., Kimura N.,
RA Shukunami C., Okada Y., Mukai M., Shin H., Yozu R., Sata M., Ogawa S.,
RA Hiraki Y., Fukuda K.;
RT "Chondromodulin-I maintains cardiac valvular function by preventing
RT angiogenesis.";
RL Nat. Med. 12:1151-1159(2006).
CC -!- FUNCTION: Bifunctional growth regulator that stimulates the growth of
CC cultured chondrocytes in the presence of basic fibroblast growth factor
CC (FGF) but inhibits the growth of cultured vascular endothelial cells.
CC May contribute to the rapid growth of cartilage and vascular invasion
CC prior to the replacement of cartilage by bone during endochondral bone
CC development. Inhibits in vitro tube formation and mobilization of
CC endothelial cells. Plays a role as antiangiogenic factor in cardiac
CC valves to suppress neovascularization. {ECO:0000269|PubMed:16980969}.
CC -!- INTERACTION:
CC O75829-2; Q95HB9: HLA-DPA1; NbExp=3; IntAct=EBI-10696063, EBI-17686856;
CC O75829-2; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-10696063, EBI-10243654;
CC -!- SUBCELLULAR LOCATION: [Chondromodulin-1]: Secreted, extracellular
CC space, extracellular matrix. Note=Accumulated in the inter-territorial
CC matrix of cartilage.
CC -!- SUBCELLULAR LOCATION: [Chondrosurfactant protein]: Endomembrane system
CC {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75829-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75829-2; Sequence=VSP_038380;
CC -!- TISSUE SPECIFICITY: Detected in cartilage and cardiac valves (at
CC protein level). Detected in the laminae fibrosa, spongiosa and
CC ventricularis layers of normal cardiac valves (at protein level).
CC Expression is decreased cardiac valves of patients with valvular heart
CC disease (at protein level). Weakly expressed in chondrosarcoma.
CC {ECO:0000269|PubMed:16980969}.
CC -!- DEVELOPMENTAL STAGE: Expressed at 9 weeks in developing cartilagenous
CC bone rudiments.
CC -!- PTM: After cleavage, the post-translationally modified ChM-I is
CC secreted as a glycoprotein.
CC -!- SIMILARITY: Belongs to the chondromodulin-1 family. {ECO:0000305}.
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DR EMBL; AB006000; BAA33443.1; -; mRNA.
DR EMBL; AF050147; AAC98971.1; -; Genomic_DNA.
DR EMBL; CR541910; CAG46708.1; -; mRNA.
DR EMBL; AL139085; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139089; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025659; AAH25659.1; -; mRNA.
DR EMBL; AB021290; BAA77384.1; -; Genomic_DNA.
DR EMBL; AB005999; BAA86262.1; -; mRNA.
DR CCDS; CCDS45051.1; -. [O75829-2]
DR CCDS; CCDS9437.1; -. [O75829-1]
DR RefSeq; NP_001011705.1; NM_001011705.1. [O75829-2]
DR RefSeq; NP_008946.1; NM_007015.2. [O75829-1]
DR AlphaFoldDB; O75829; -.
DR BioGRID; 116245; 7.
DR IntAct; O75829; 7.
DR STRING; 9606.ENSP00000367198; -.
DR GlyGen; O75829; 1 site.
DR iPTMnet; O75829; -.
DR PhosphoSitePlus; O75829; -.
DR BioMuta; CNMD; -.
DR EPD; O75829; -.
DR jPOST; O75829; -.
DR MassIVE; O75829; -.
DR PaxDb; O75829; -.
DR PeptideAtlas; O75829; -.
DR PRIDE; O75829; -.
DR ProteomicsDB; 50217; -. [O75829-1]
DR ProteomicsDB; 50218; -. [O75829-2]
DR Antibodypedia; 24240; 204 antibodies from 28 providers.
DR DNASU; 11061; -.
DR Ensembl; ENST00000377962.8; ENSP00000367198.3; ENSG00000136110.13. [O75829-1]
DR Ensembl; ENST00000448904.6; ENSP00000388576.2; ENSG00000136110.13. [O75829-2]
DR GeneID; 11061; -.
DR KEGG; hsa:11061; -.
DR MANE-Select; ENST00000377962.8; ENSP00000367198.3; NM_007015.3; NP_008946.1.
DR UCSC; uc001vhf.4; human. [O75829-1]
DR CTD; 11061; -.
DR DisGeNET; 11061; -.
DR GeneCards; CNMD; -.
DR HGNC; HGNC:17005; CNMD.
DR HPA; ENSG00000136110; Tissue enhanced (brain, retina, salivary gland).
DR MIM; 605147; gene.
DR neXtProt; NX_O75829; -.
DR OpenTargets; ENSG00000136110; -.
DR PharmGKB; PA134897668; -.
DR VEuPathDB; HostDB:ENSG00000136110; -.
DR eggNOG; ENOG502QVPC; Eukaryota.
DR GeneTree; ENSGT00480000042679; -.
DR HOGENOM; CLU_071852_0_0_1; -.
DR InParanoid; O75829; -.
DR OMA; GNLPIFW; -.
DR OrthoDB; 1308600at2759; -.
DR PhylomeDB; O75829; -.
DR TreeFam; TF329712; -.
DR PathwayCommons; O75829; -.
DR SignaLink; O75829; -.
DR BioGRID-ORCS; 11061; 9 hits in 1057 CRISPR screens.
DR ChiTaRS; CNMD; human.
DR GeneWiki; LECT1; -.
DR GenomeRNAi; 11061; -.
DR Pharos; O75829; Tbio.
DR PRO; PR:O75829; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; O75829; protein.
DR Bgee; ENSG00000136110; Expressed in tibia and 61 other tissues.
DR ExpressionAtlas; O75829; baseline and differential.
DR Genevisible; O75829; HS.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:0006029; P:proteoglycan metabolic process; TAS:ProtInc.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR InterPro; IPR007084; BRICHOS_dom.
DR InterPro; IPR043405; Chondromodulin/Tenomodulin.
DR PANTHER; PTHR14064; PTHR14064; 1.
DR Pfam; PF04089; BRICHOS; 1.
DR SMART; SM01039; BRICHOS; 1.
DR PROSITE; PS50869; BRICHOS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chondrogenesis; Cleavage on pair of basic residues;
KW Developmental protein; Differentiation; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Membrane; Reference proteome; Secreted;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..210
FT /note="Chondrosurfactant protein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000005346"
FT PROPEP 211..214
FT /evidence="ECO:0000255"
FT /id="PRO_0000005347"
FT CHAIN 215..334
FT /note="Chondromodulin-1"
FT /id="PRO_0000005348"
FT TRANSMEM 45..65
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 104..201
FT /note="BRICHOS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00255"
FT REGION 218..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 243
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 131..193
FT /evidence="ECO:0000250"
FT DISULFID 282..286
FT /evidence="ECO:0000250"
FT DISULFID 283..323
FT /evidence="ECO:0000250"
FT DISULFID 293..317
FT /evidence="ECO:0000250"
FT DISULFID 297..313
FT /evidence="ECO:0000250"
FT VAR_SEQ 264
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038380"
FT VARIANT 116
FT /note="F -> L (in dbSNP:rs3742298)"
FT /id="VAR_048719"
FT VARIANT 175
FT /note="V -> I (in dbSNP:rs7330220)"
FT /id="VAR_024413"
SQ SEQUENCE 334 AA; 37102 MW; 9E2393111F9D4FE5 CRC64;
MTENSDKVPI ALVGPDDVEF CSPPAYATLT VKPSSPARLL KVGAVVLISG AVLLLFGAIG
AFYFWKGSDS HIYNVHYTMS INGKLQDGSM EIDAGNNLET FKMGSGAEEA IAVNDFQNGI
TGIRFAGGEK CYIKAQVKAR IPEVGAVTKQ SISSKLEGKI MPVKYEENSL IWVAVDQPVK
DNSFLSSKVL ELCGDLPIFW LKPTYPKEIQ RERREVVRKI VPTTTKRPHS GPRSNPGAGR
LNNETRPSVQ EDSQAFNPDN PYHQQEGESM TFDPRLDHEG ICCIECRRSY THCQKICEPL
GGYYPWPYNY QGCRSACRVI MPCSWWVARI LGMV
