CILP

Protein identityUniProt · HPA

UniProt accession

O75339

Gene

CILP

Ensembl

ENSG00000138615

Chromosome

15

Canonical length

1184 aa

Protein class

Disease related genes, Human disease related genes, Predicted secreted proteins

Secretome location

Secreted to extracellular matrix

OverviewNCBI Gene

Major alterations in the composition of the cartilage extracellular matrix occur in joint disease, such as osteoarthrosis. This gene encodes the cartilage intermediate layer protein (CILP), which increases in early osteoarthrosis cartilage. The encoded protein was thought to encode a protein precursor for two different proteins; an N-terminal CILP and a C-terminal homolog of NTPPHase, however, later studies identified no nucleotide pyrophosphatase phosphodiesterase (NPP) activity. The full-length and the N-terminal domain of this protein was shown to function as an IGF-1 antagonist. An allelic variant of this gene has been associated with lumbar disc disease. [provided by RefSeq, Sep 2010]

Canonical amino-acid sequenceUniProt

1184 residues, UniProt reviewed canonical sequence.

>O75339|CILP
     1  MVGTKAWVFS FLVLEVTSVL GRQTMLTQSV RRVQPGKKNP SIFAKPADTL ESPGEWTTWF
    61  NIDYPGGKGD YERLDAIRFY YGDRVCARPL RLEARTTDWT PAGSTGQVVH GSPREGFWCL
   121  NREQRPGQNC SNYTVRFLCP PGSLRRDTER IWSPWSPWSK CSAACGQTGV QTRTRICLAE
   181  MVSLCSEASE EGQHCMGQDC TACDLTCPMG QVNADCDACM CQDFMLHGAV SLPGGAPASG
   241  AAIYLLTKTP KLLTQTDSDG RFRIPGLCPD GKSILKITKV KFAPIVLTMP KTSLKAATIK
   301  AEFVRAETPY MVMNPETKAR RAGQSVSLCC KATGKPRPDK YFWYHNDTLL DPSLYKHESK
   361  LVLRKLQQHQ AGEYFCKAQS DAGAVKSKVA QLIVIASDET PCNPVPESYL IRLPHDCFQN
   421  ATNSFYYDVG RCPVKTCAGQ QDNGIRCRDA VQNCCGISKT EEREIQCSGY TLPTKVAKEC
   481  SCQRCTETRS IVRGRVSAAD NGEPMRFGHV YMGNSRVSMT GYKGTFTLHV PQDTERLVLT
   541  FVDRLQKFVN TTKVLPFNKK GSAVFHEIKM LRRKKPITLE AMETNIIPLG EVVGEDPMAE
   601  LEIPSRSFYR QNGEPYIGKV KASVTFLDPR NISTATAAQT DLNFINDEGD TFPLRTYGMF
   661  SVDFRDEVTS EPLNAGKVKV HLDSTQVKMP EHISTVKLWS LNPDTGLWEE EGDFKFENQR
   721  RNKREDRTFL VGNLEIRERR LFNLDVPESR RCFVKVRAYR SERFLPSEQI QGVVISVINL
   781  EPRTGFLSNP RAWGRFDSVI TGPNGACVPA FCDDQSPDAY SAYVLASLAG EELQAVESSP
   841  KFNPNAIGVP QPYLNKLNYR RTDHEDPRVK KTAFQISMAK PRPNSAEESN GPIYAFENLR
   901  ACEEAPPSAA HFRFYQIEGD RYDYNTVPFN EDDPMSWTED YLAWWPKPME FRACYIKVKI
   961  VGPLEVNVRS RNMGGTHRQT VGKLYGIRDV RSTRDRDQPN VSAACLEFKC SGMLYDQDRV
  1021  DRTLVKVIPQ GSCRRASVNP MLHEYLVNHL PLAVNNDTSE YTMLAPLDPL GHNYGIYTVT
  1081  DQDPRTAKEI ALGRCFDGTS DGSSRIMKSN VGVALTFNCV ERQVGRQSAF QYLQSTPAQS
  1141  PAAGTVQGRV PSRRQQRASR GGQRQGGVVA SLRFPRVAQQ PLIN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CILP can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

48 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CILP.

Disease | AllUniProt

Conditions CILP is implicated in, by any mechanism.

• Intervertebral disc disease (IDD) MIM:603932

Disease | ImmuneIEDB

Conditions an epitope on CILP was assayed in.

• rheumatoid arthritis T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.29

gnomAD pLI

0

gnomAD missense Z

0.17

DepMap mean gene effect

-0.12

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of gene expression
• negative regulation of insulin-like growth factor receptor signaling pathway
• negative regulation of SMAD protein signal transduction
• negative regulation of transforming growth factor beta receptor signaling pathway

Cellular components

• extracellular exosome
• extracellular matrix
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Thrombospondin type-1 (TSP1) repeat
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Carboxypeptidase-like, regulatory domain superfamily
• Immunoglobulin-like fold
• WxxW domain
• Immunoglobulin-like domain superfamily
• Thrombospondin type-1 repeat superfamily
• Cartilage intermediate layer protein 1/2
• Cartilage intermediate layer protein 1/2 domain
• Cartilage intermediate layer protein 1/2, beta-sandwich domain 2
• Cartilage intermediate layer protein 1/2, beta-sandwich domain
• Cartilage intermediate layer protein 1/2, C-terminal
• Thrombospondin type 1 domain
• Mucin-2 protein WxxW repeating region
• Immunoglobulin domain
• Cartilage intermediate layer protein 1-like domain
• Cartilage intermediate layer protein 1-like, C-terminal
• Cartilage intermediate layer protein 1-like domain
• Cartilage intermediate layer protein 1-like domain

KeywordsUniProt

• Cleavage on pair of basic residues
• Disulfide bond
• Extracellular matrix
• Glycoprotein
• Immunoglobulin domain
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of CILP in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TGFB1