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Identification
HMDB Protein ID HMDBP07585
Secondary Accession Numbers
  • 13293
Name Cartilage intermediate layer protein 1
Synonyms
  1. CILP-1
  2. Cartilage intermediate layer protein 1 C1
  3. Cartilage intermediate layer protein 1 C2
  4. Cartilage intermediate-layer protein
Gene Name CILP
Protein Type Unknown
Biological Properties
General Function Involved in negative regulation of insulin-like growth
Specific Function Probably plays a role in cartilage scaffolding. May act by antagonizing TGF-beta1 (TGFB1) and IGF1 functions. Has the ability to suppress IGF1-induced proliferation and sulfated proteoglycan synthesis, and inhibits ligand-induced IGF1R autophosphorylation. May inhibit TGFB1-mediated induction of cartilage matrix genes via its interaction with TGFB1. Overexpression may lead to impair chondrocyte growth and matrix repair and indirectly promote inorganic pyrophosphate (PPi) supersaturation in aging and osteoarthritis cartilage
Pathways Not Available
Reactions Not Available
GO Classification Not Available
Cellular Location
  1. Secreted
  2. extracellular space
  3. extracellular matrix
Gene Properties
Chromosome Location Chromosome:1
Locus 15q22
SNPs CILP
Gene Sequence
>3555 bp
ATGGTGGGGACCAAGGCCTGGGTGTTCTCCTTCCTGGTCCTGGAAGTCACATCTGTGTTG
GGGAGACAGACGATGCTCACCCAGTCAGTAAGAAGAGTCCAGCCTGGGAAGAAGAACCCC
AGCATCTTTGCCAAGCCTGCCGACACCCTGGAGAGCCCTGGTGAGTGGACAACATTGTTC
AACATCGACTACCCAGGCGGGAAGGGCGACTATGAGCGGCTGGACGCCATTCGCTTCTAC
TATGGGGACCGTGTATGTGCCCGTCCCCTGCGGCTAGAGGCTCGGACCACTGACTGGACA
CCTGCGGGCAGCACTGGCCAGGTGGTCCATGGTAGTCCCCGTGAGGGTTTCTGGTGCCTC
AACAGGGAGCAGCGGCCTGGCCAGAACTGCTCTAATTACACCGTACGCTTCCTCTGCCCA
CCAGGATCCCTGCGCCGAGACACAGAGCGCATCTGGAGCCCATGGTCTCCCTGGAGCAAG
TGCTCAGCTGCCTGTGGTCAGACTGGGGTCCAGACTCGCACACGCATTTGCTTGGCAGAG
ATGGTGTCGCTGTGCAGTGAGGCCAGCGAAGAGGGTCAGCACTGCATGGGCCAGGACTGT
ACAGCCTGTGACCTGACCTGCCCAATGGGCCAGGTGAATGCTGACTGTGATGCCTGCATG
TGCCAGGACTTCATGCTTCATGGGGCTGTCTCCCTTCCCGGAGGTGCCCCAGCCTCAGGG
GCTGCTATCTACCTCCTGACCAAGACGCCGAAGCTGCTGACCCAGACAGACAGTGATGGG
AGATTCCGAATCCCTGGCTTGTGCCCTGATGGCAAAAGCATCCTGAAGATCACAAAGGTC
AAGTTTGCCCCCATTGTACTCACAATGCCCAAGACTAGCCTGAAGGCAGCCACCATCAAG
GCAGAGTTTGTGAGGGCAGAGACTCCATACATGGTGATGAACCCTGAGACAAAAGCACGG
AGAGCTGGGCAGAGCGTGTCTCTGTGCTGTAAGGCCACAGGGAAGCCCAGGCCAGACAAG
TATTTTTGGTATCATAATGACACATTGCTGGATCCTTCCCTCTACAAGCATGAGAGCAAG
CTGGTGCTGAGGAAACTGCAGCAGCACCAGGCTGGGGAGTACTTTTGCAAGGCCCAGAGT
GATGCTGGGGCTGTGAAGTCCAAGGTTGCCCAGCTGATTGTCACAGCATCTGATGAGACT
CCTTGCAACCCAGTTCCTGAGAGCTATCTTATCCGGCTGCCCCATGATTGCTTTCAGAAT
GCCACCAACTCCTTCTACTATGACGTGGGACGCTGCCCTGTTAAGACTTGTGCAGGGCAG
CAGGATAATGGGATCAGGTGCCGTGATGCTGTGCAGAACTGCTGTGGCATCTCCAAGACA
GAGGAAAGGGAGATCCAGTGCAGTGGCTACACGCTACCCACCAAGGTGGCCAAGGAGTGC
AGCTGCCAGCGGTGTACGGAAACTCGGAGCATCGTGCGGGGCCGTGTCAGTGCTGCTGAC
AATGGGGAGCCCATGCGCTTTGGCCATGTGTACATGGGGAACAGCCGTGTAAGCATGACT
GGCTACAAGGGCACTTTCACCCTCCATGTCCCCCAGGACACTGAGAGGCTGGTGCTCACA
TTTGTGGACAGGCTGCAGAAGTTTGTCAACACCACCAAAGTGCTACCTTTCAACAAGAAG
GGGAGTGCCGTGTTCCATGAAATCAAGATGCTTCGTCGGAAAGAGCCCATCACTTTGGAA
GCCATGGAGACCAACATCATCCCCCTGGGGGAAGTGGTTGGTGAAGACCCCATGGCTGAA
CTGGAGATTCCATCCAGGAGTTTCTACAGGCAGAATGGGGAGCCCTACATAGGAAAAGTG
AAGGCCAGTGTGACCTTCCTGGATCCCCGGAATATTTCCACAGCCACAGCTGCCCAGACT
GACCTGAACTTCATCAATGACGAAGGAGACACTTTCCCCCTTCGGACGTATGGCATGTTC
TCTGTGGACTTCAGAGATGAGGTCACCTCAGAGCCACTTAATGCTGGCAAAGTGAAGGTC
CACCTTGACTCGACCCAGGTCAAGATGCCAGAGCACATATCCACAGTGAAACTCTGGTCA
CTCAATCCAGACACAGGGCTGTGGGAGGAGGAAGGTGATTTCAAATTTGAAAATCAAAGG
AGGAACAAAAGAGAAGACAGAACCTTCCTGGTGGGCAACCTGGAGATTCGTGAGAGGAGG
CTCTTTAACCTGGATGTTCCTGAAAGCAGGCGGTGCTTTGTTAAGGTGAGGGCCTACCGG
AGTGAGAGGTTCTTGCCTAGTGAGCAGATCCAGGGGGTTGTGATCTCCGTGATTAACCTG
GAGCCTAGAACTGGCTTCTTGTCCAACCCTAGGGCCTGGGGCCGCTTTGACAGTGTCATC
ACAGGCCCCAACGGGGCCTGTGTGCCTGCCTTCTGTGATGACCAGTCCCCTGATGCCTAC
TCTGCCTATGTCTTGGCAAGCCTGGCTGGGGAGGAACTGCAAGCAGTGGAGTCTTCTCCT
AAATTCAACCCAAATGCAATTGGCGTCCCTCAGCCCTATCTCAACAAGCTCAACTACCGT
CGGACGGACCATGAGGATCCACGGGTTAAAAAGACAGCTTTCCAGATTAGCATGGCCAAG
CCAAGGCCCAACTCAGCTGAGGAGAGCAATGGGCCCATCTATGCCTTTGAGAACCTCCGG
GCATGTGAAGAGGCACCACCCAGTGCAGCCCACTTCCGGTTCTACCAGATTGAGGGGGAT
CGATATGACTACAACACAGTCCCCTTCAACGAAGATGACCCTATGAGCTGGACTGAAGAC
TATCTGGCATGGTGGCCAAAGCCGATGGAATTCAGGGCCTGCTATATCAAGGTGAAGATT
GTGGGGCCACTGGAAGTGAATGTGCGATCCCGCAACATGGGGGGCACTCATCGGCGGACA
GTGGGGAAGCTGTATGGAATCCGAGATGTGAGGAGCACTCGGGACAGGGACCAGCCCAAT
GTCTCAGCTGCCTGTCTGGAGTTCAAGTGCAGTGGGATGCTCTATGATCAGGACCGTGTG
GACCGCACCCTGGTGAAGGTCATCCCCCAGGGCAGCTGCCGTCGAGCCAGTGTGAACCCC
ATGCTGCATGAGTACCTGGTCAACCACTTGCCACTTGCAGTCAACAACGACACCAGTGAG
TACACCATGCTGGCACCCTTGGACCCACTGGGCCACAACTATGGCATCTACACTGTCACT
GACCAGGACCCTCGCACGGCCAAGGAGATCGCGCTCGGCCGGTGCTTTGATGGCACATCC
GATGGCTCCTCCAGAATCATGAAGAGCAATGTGGGAGTAGCCCTCACCTTCAACTGTGTA
GAGAGGCAAGTAGGCCGCCAGAGTGCCTTCCAGTACCTCCAAAGCACCCCAGCCCAGTCC
CCTGCTGCAGGCACTGTCCAAGGAAGAGTGCCCTCGAGGAGGCAGCAGCGAGCGAGCAGG
GGTGGCCAGCGCCAGAGTGGAGTGGTGGCCTCTCTGAGATTTCCTAGAGTTGCTCAACAG
CCCCTGATCAACTAA
Protein Properties
Number of Residues 1184
Molecular Weight 132622.7
Theoretical pI 8.44
Pfam Domain Function
Signals
  • 1-21
Transmembrane Regions
  • None
Protein Sequence
>Cartilage intermediate layer protein 1
MVGTKAWVFSFLVLEVTSVLGRQTMLTQSVRRVQPGKKNPSIFAKPADTLESPGEWTTWF
NIDYPGGKGDYERLDAIRFYYGDRVCARPLRLEARTTDWTPAGSTGQVVHGSPREGFWCL
NREQRPGQNCSNYTVRFLCPPGSLRRDTERIWSPWSPWSKCSAACGQTGVQTRTRICLAE
MVSLCSEASEEGQHCMGQDCTACDLTCPMGQVNADCDACMCQDFMLHGAVSLPGGAPASG
AAIYLLTKTPKLLTQTDSDGRFRIPGLCPDGKSILKITKVKFAPIVLTMPKTSLKAATIK
AEFVRAETPYMVMNPETKARRAGQSVSLCCKATGKPRPDKYFWYHNDTLLDPSLYKHESK
LVLRKLQQHQAGEYFCKAQSDAGAVKSKVAQLIVIASDETPCNPVPESYLIRLPHDCFQN
ATNSFYYDVGRCPVKTCAGQQDNGIRCRDAVQNCCGISKTEEREIQCSGYTLPTKVAKEC
SCQRCTETRSIVRGRVSAADNGEPMRFGHVYMGNSRVSMTGYKGTFTLHVPQDTERLVLT
FVDRLQKFVNTTKVLPFNKKGSAVFHEIKMLRRKEPITLEAMETNIIPLGEVVGEDPMAE
LEIPSRSFYRQNGEPYIGKVKASVTFLDPRNISTATAAQTDLNFINDEGDTFPLRTYGMF
SVDFRDEVTSEPLNAGKVKVHLDSTQVKMPEHISTVKLWSLNPDTGLWEEEGDFKFENQR
RNKREDRTFLVGNLEIRERRLFNLDVPESRRCFVKVRAYRSERFLPSEQIQGVVISVINL
EPRTGFLSNPRAWGRFDSVITGPNGACVPAFCDDQSPDAYSAYVLASLAGEELQAVESSP
KFNPNAIGVPQPYLNKLNYRRTDHEDPRVKKTAFQISMAKPRPNSAEESNGPIYAFENLR
ACEEAPPSAAHFRFYQIEGDRYDYNTVPFNEDDPMSWTEDYLAWWPKPMEFRACYIKVKI
VGPLEVNVRSRNMGGTHRRTVGKLYGIRDVRSTRDRDQPNVSAACLEFKCSGMLYDQDRV
DRTLVKVIPQGSCRRASVNPMLHEYLVNHLPLAVNNDTSEYTMLAPLDPLGHNYGIYTVT
DQDPRTAKEIALGRCFDGTSDGSSRIMKSNVGVALTFNCVERQVGRQSAFQYLQSTPAQS
PAAGTVQGRVPSRRQQRASRGGQRQSGVVASLRFPRVAQQPLIN
GenBank ID Protein 4587271
UniProtKB/Swiss-Prot ID O75339
UniProtKB/Swiss-Prot Entry Name CILP1_HUMAN
PDB IDs Not Available
GenBank Gene ID AB022430
GeneCard ID CILP
GenAtlas ID CILP
HGNC ID HGNC:1980
References
General References
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  3. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309 ]
  4. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [PubMed:16572171 ]
  5. Lorenzo P, Neame P, Sommarin Y, Heinegard D: Cloning and deduced amino acid sequence of a novel cartilage protein (CILP) identifies a proform including a nucleotide pyrophosphohydrolase. J Biol Chem. 1998 Sep 4;273(36):23469-75. [PubMed:9722584 ]
  6. Nakamura I, Okawa A, Ikegawa S, Takaoka K, Nakamura Y: Genomic organization, mapping, and polymorphisms of the gene encoding human cartilage intermediate layer protein (CILP). J Hum Genet. 1999;44(3):203-5. [PubMed:10319588 ]
  7. Lorenzo P, Aman P, Sommarin Y, Heinegard D: The human CILP gene: exon/intron organization and chromosomal mapping. Matrix Biol. 1999 Oct;18(5):445-54. [PubMed:10601732 ]
  8. Lorenzo P, Bayliss MT, Heinegard D: A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. J Biol Chem. 1998 Sep 4;273(36):23463-8. [PubMed:9722583 ]
  9. Hirose J, Ryan LM, Masuda I: Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum. 2002 Dec;46(12):3218-29. [PubMed:12483726 ]
  10. Tsuruha J, Masuko-Hongo K, Kato T, Sakata M, Nakamura H, Nishioka K: Implication of cartilage intermediate layer protein in cartilage destruction in subsets of patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 2001 Apr;44(4):838-45. [PubMed:11315923 ]
  11. Johnson K, Farley D, Hu SI, Terkeltaub R: One of two chondrocyte-expressed isoforms of cartilage intermediate-layer protein functions as an insulin-like growth factor 1 antagonist. Arthritis Rheum. 2003 May;48(5):1302-14. [PubMed:12746903 ]
  12. Yao Z, Nakamura H, Masuko-Hongo K, Suzuki-Kurokawa M, Nishioka K, Kato T: Characterisation of cartilage intermediate layer protein (CILP)-induced arthropathy in mice. Ann Rheum Dis. 2004 Mar;63(3):252-8. [PubMed:14962958 ]
  13. Du H, Masuko-Hongo K, Nakamura H, Xiang Y, Bao CD, Wang XD, Chen SL, Nishioka K, Kato T: The prevalence of autoantibodies against cartilage intermediate layer protein, YKL-39, osteopontin, and cyclic citrullinated peptide in patients with early-stage knee osteoarthritis: evidence of a variety of autoimmune processes. Rheumatol Int. 2005 Nov;26(1):35-41. Epub 2004 Sep 18. [PubMed:15378262 ]
  14. Seki S, Kawaguchi Y, Chiba K, Mikami Y, Kizawa H, Oya T, Mio F, Mori M, Miyamoto Y, Masuda I, Tsunoda T, Kamata M, Kubo T, Toyama Y, Kimura T, Nakamura Y, Ikegawa S: A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease. Nat Genet. 2005 Jun;37(6):607-12. Epub 2005 May 1. [PubMed:15864306 ]