Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cartilage intermediate layer protein 1

Gene

CILP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Cartilage intermediate layer protein 1
Short name:
CILP-1
Alternative name(s):
Cartilage intermediate-layer protein
Cleaved into the following 2 chains:
Gene namesi
Name:CILP
ORF Names:UNQ602/PRO1188
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:1980. CILP.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • extracellular space Source: BHF-UCL
  • proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Intervertebral disc disease (IDD)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.1 Publication
Disease descriptionA common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain.
See also OMIM:603932

Organism-specific databases

MalaCardsiCILP.
MIMi603932. phenotype.
PharmGKBiPA26518.

Polymorphism and mutation databases

BioMutaiCILP.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 11841163Cartilage intermediate layer protein 1PRO_0000014671Add
BLAST
Chaini22 – ?724703Cartilage intermediate layer protein 1 C1PRO_0000014672Add
BLAST
Chaini?725 – 1184460Cartilage intermediate layer protein 1 C2PRO_0000014673Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi129 – 1291N-linked (GlcNAc...)Sequence analysis
Glycosylationi132 – 1321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi161 ↔ 195By similarity
Disulfide bondi165 ↔ 200By similarity
Disulfide bondi177 ↔ 185By similarity
Disulfide bondi330 ↔ 376By similarity
Glycosylationi346 – 3461N-linked (GlcNAc...)1 Publication
Glycosylationi420 – 4201N-linked (GlcNAc...)Sequence analysis
Glycosylationi550 – 5501N-linked (GlcNAc...)Sequence analysis
Glycosylationi631 – 6311N-linked (GlcNAc...)Sequence analysis
Glycosylationi1000 – 10001N-linked (GlcNAc...)Sequence analysis
Glycosylationi1056 – 10561N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO75339.
PeptideAtlasiO75339.
PRIDEiO75339.

PTM databases

iPTMnetiO75339.
PhosphoSiteiO75339.

Expressioni

Tissue specificityi

Specifically expressed in cartilage. Localizes in the intermediates layer of articular cartilage but neither in the superficial nor in the deepest regions. Specifically and highly expressed in intervertebral disk tissue. Expression increases with aging in hip articular cartilage. Overexpressed in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease (CPPD). Expression in intervertebral disk tissue from individuals with lumbar disk disease increases as disk degeneration progresses.4 Publications

Gene expression databases

BgeeiENSG00000138615.
CleanExiHS_CILP.
GenevisibleiO75339. HS.

Organism-specific databases

HPAiHPA003195.

Interactioni

Subunit structurei

Monomer. Interacts with TGFB1.2 Publications

Protein-protein interaction databases

BioGridi114057. 2 interactions.
IntActiO75339. 1 interaction.
STRINGi9606.ENSP00000261883.

Structurei

3D structure databases

ProteinModelPortaliO75339.
SMRiO75339. Positions 269-394.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini149 – 20153TSP type-1PROSITE-ProRule annotationAdd
BLAST
Domaini309 – 39587Ig-like C2-typeAdd
BLAST

Sequence similaritiesi

Contains 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Signal

Phylogenomic databases

eggNOGiENOG410IJBD. Eukaryota.
ENOG410XXZR. LUCA.
GeneTreeiENSGT00390000008152.
HOGENOMiHOG000111676.
HOVERGENiHBG081175.
InParanoidiO75339.
OMAiYLVNHLP.
OrthoDBiEOG091G010Q.
PhylomeDBiO75339.
TreeFamiTF330132.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR008969. CarboxyPept-like_regulatory.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000884. TSP1_rpt.
IPR025155. WxxW_domain.
[Graphical view]
PfamiPF13330. Mucin2_WxxW. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF49464. SSF49464. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O75339-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVGTKAWVFS FLVLEVTSVL GRQTMLTQSV RRVQPGKKNP SIFAKPADTL
60 70 80 90 100
ESPGEWTTWF NIDYPGGKGD YERLDAIRFY YGDRVCARPL RLEARTTDWT
110 120 130 140 150
PAGSTGQVVH GSPREGFWCL NREQRPGQNC SNYTVRFLCP PGSLRRDTER
160 170 180 190 200
IWSPWSPWSK CSAACGQTGV QTRTRICLAE MVSLCSEASE EGQHCMGQDC
210 220 230 240 250
TACDLTCPMG QVNADCDACM CQDFMLHGAV SLPGGAPASG AAIYLLTKTP
260 270 280 290 300
KLLTQTDSDG RFRIPGLCPD GKSILKITKV KFAPIVLTMP KTSLKAATIK
310 320 330 340 350
AEFVRAETPY MVMNPETKAR RAGQSVSLCC KATGKPRPDK YFWYHNDTLL
360 370 380 390 400
DPSLYKHESK LVLRKLQQHQ AGEYFCKAQS DAGAVKSKVA QLIVIASDET
410 420 430 440 450
PCNPVPESYL IRLPHDCFQN ATNSFYYDVG RCPVKTCAGQ QDNGIRCRDA
460 470 480 490 500
VQNCCGISKT EEREIQCSGY TLPTKVAKEC SCQRCTETRS IVRGRVSAAD
510 520 530 540 550
NGEPMRFGHV YMGNSRVSMT GYKGTFTLHV PQDTERLVLT FVDRLQKFVN
560 570 580 590 600
TTKVLPFNKK GSAVFHEIKM LRRKKPITLE AMETNIIPLG EVVGEDPMAE
610 620 630 640 650
LEIPSRSFYR QNGEPYIGKV KASVTFLDPR NISTATAAQT DLNFINDEGD
660 670 680 690 700
TFPLRTYGMF SVDFRDEVTS EPLNAGKVKV HLDSTQVKMP EHISTVKLWS
710 720 730 740 750
LNPDTGLWEE EGDFKFENQR RNKREDRTFL VGNLEIRERR LFNLDVPESR
760 770 780 790 800
RCFVKVRAYR SERFLPSEQI QGVVISVINL EPRTGFLSNP RAWGRFDSVI
810 820 830 840 850
TGPNGACVPA FCDDQSPDAY SAYVLASLAG EELQAVESSP KFNPNAIGVP
860 870 880 890 900
QPYLNKLNYR RTDHEDPRVK KTAFQISMAK PRPNSAEESN GPIYAFENLR
910 920 930 940 950
ACEEAPPSAA HFRFYQIEGD RYDYNTVPFN EDDPMSWTED YLAWWPKPME
960 970 980 990 1000
FRACYIKVKI VGPLEVNVRS RNMGGTHRQT VGKLYGIRDV RSTRDRDQPN
1010 1020 1030 1040 1050
VSAACLEFKC SGMLYDQDRV DRTLVKVIPQ GSCRRASVNP MLHEYLVNHL
1060 1070 1080 1090 1100
PLAVNNDTSE YTMLAPLDPL GHNYGIYTVT DQDPRTAKEI ALGRCFDGTS
1110 1120 1130 1140 1150
DGSSRIMKSN VGVALTFNCV ERQVGRQSAF QYLQSTPAQS PAAGTVQGRV
1160 1170 1180
PSRRQQRASR GGQRQGGVVA SLRFPRVAQQ PLIN
Length:1,184
Mass (Da):132,565
Last modified:January 11, 2011 - v4
Checksum:i190B0316404D3B84
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541G → M AA sequence (PubMed:9722584).Curated
Sequence conflicti288 – 2881T → D AA sequence (PubMed:9722584).Curated
Sequence conflicti305 – 3051R → D AA sequence (PubMed:9722584).Curated
Sequence conflicti347 – 3471D → T AA sequence (PubMed:9722584).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591W → L.3 Publications
Corresponds to variant rs2585033 [ dbSNP | Ensembl ].
VAR_022768
Natural varianti327 – 3271S → F.1 Publication
VAR_022769
Natural varianti395 – 3951I → T Common polymorphism; associated with susceptibility to lumbar disk disease in Japanese; increases binding and inhibition of TGFB1. 5 Publications
Corresponds to variant rs2073711 [ dbSNP | Ensembl ].
VAR_022770
Natural varianti495 – 4951R → H.1 Publication
Corresponds to variant rs149286218 [ dbSNP | Ensembl ].
VAR_069430
Natural varianti575 – 5751K → E.6 Publications
Corresponds to variant rs2679118 [ dbSNP | Ensembl ].
VAR_022771
Natural varianti895 – 8951A → V.1 Publication
Corresponds to variant rs771628304 [ dbSNP | Ensembl ].
VAR_022772
Natural varianti979 – 9791Q → R.6 Publications
Corresponds to variant rs2679117 [ dbSNP | Ensembl ].
VAR_022773
Natural varianti1032 – 10321S → T.1 Publication
Corresponds to variant rs768702821 [ dbSNP | Ensembl ].
VAR_069431
Natural varianti1101 – 11011D → N.1 Publication
Corresponds to variant rs769023414 [ dbSNP | Ensembl ].
VAR_022774
Natural varianti1166 – 11661G → S.5 Publications
Corresponds to variant rs938952 [ dbSNP | Ensembl ].
VAR_022775
Natural varianti1168 – 11681V → A.1 Publication
Corresponds to variant rs747702148 [ dbSNP | Ensembl ].
VAR_022776

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF035408 mRNA. Translation: AAC33838.1.
AB022430 Genomic DNA. Translation: BAA76692.1.
AF035455
, AF035448, AF035451, AF035453, AF035449 Genomic DNA. Translation: AAF14689.1.
AY358904 mRNA. Translation: AAQ89263.1.
AK313352 mRNA. Translation: BAG36154.1.
AC068213 Genomic DNA. No translation available.
BC035776 mRNA. Translation: AAH35776.1.
CCDSiCCDS10203.1.
PIRiT09484.
RefSeqiNP_003604.3. NM_003613.3.
UniGeneiHs.442180.

Genome annotation databases

EnsembliENST00000261883; ENSP00000261883; ENSG00000138615.
GeneIDi8483.
KEGGihsa:8483.
UCSCiuc002aon.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF035408 mRNA. Translation: AAC33838.1.
AB022430 Genomic DNA. Translation: BAA76692.1.
AF035455
, AF035448, AF035451, AF035453, AF035449 Genomic DNA. Translation: AAF14689.1.
AY358904 mRNA. Translation: AAQ89263.1.
AK313352 mRNA. Translation: BAG36154.1.
AC068213 Genomic DNA. No translation available.
BC035776 mRNA. Translation: AAH35776.1.
CCDSiCCDS10203.1.
PIRiT09484.
RefSeqiNP_003604.3. NM_003613.3.
UniGeneiHs.442180.

3D structure databases

ProteinModelPortaliO75339.
SMRiO75339. Positions 269-394.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114057. 2 interactions.
IntActiO75339. 1 interaction.
STRINGi9606.ENSP00000261883.

PTM databases

iPTMnetiO75339.
PhosphoSiteiO75339.

Polymorphism and mutation databases

BioMutaiCILP.

Proteomic databases

PaxDbiO75339.
PeptideAtlasiO75339.
PRIDEiO75339.

Protocols and materials databases

DNASUi8483.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261883; ENSP00000261883; ENSG00000138615.
GeneIDi8483.
KEGGihsa:8483.
UCSCiuc002aon.3. human.

Organism-specific databases

CTDi8483.
GeneCardsiCILP.
HGNCiHGNC:1980. CILP.
HPAiHPA003195.
MalaCardsiCILP.
MIMi603489. gene.
603932. phenotype.
neXtProtiNX_O75339.
PharmGKBiPA26518.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJBD. Eukaryota.
ENOG410XXZR. LUCA.
GeneTreeiENSGT00390000008152.
HOGENOMiHOG000111676.
HOVERGENiHBG081175.
InParanoidiO75339.
OMAiYLVNHLP.
OrthoDBiEOG091G010Q.
PhylomeDBiO75339.
TreeFamiTF330132.

Miscellaneous databases

ChiTaRSiCILP. human.
GeneWikiiCILP.
GenomeRNAii8483.
PROiO75339.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138615.
CleanExiHS_CILP.
GenevisibleiO75339. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR008969. CarboxyPept-like_regulatory.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003598. Ig_sub2.
IPR000884. TSP1_rpt.
IPR025155. WxxW_domain.
[Graphical view]
PfamiPF13330. Mucin2_WxxW. 1 hit.
PF00090. TSP_1. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
SM00408. IGc2. 1 hit.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF49464. SSF49464. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
PS50092. TSP1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCILP1_HUMAN
AccessioniPrimary (citable) accession number: O75339
Secondary accession number(s): B2R8F7, Q6UW99, Q8IYI5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: January 11, 2011
Last modified: September 7, 2016
This is version 131 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Antibodies against CILP are detected in patients with early-stage knee osteoarthritis and rheumatoid arthritis.

Caution

Was originally thought to constitute the ATP pyrophosphatase enzyme (NTPPH). However, it was later shown (PubMed:12746903 and PubMed:15864306) that it is not the case.Curated

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.