Disease relevance of CRIP1

• By somatic cell hybrid analysis and radiation hybrid mapping, we have located the gene CRIP1 (HGMW-approved symbol) on the subcentromeric region of the q arm of human chromosome 7, flanking a deletion associated with Williams syndrome [1].
• We have expressed hCRHP in E. coli using pAED4 as the vector and the cDNA was engineered so that the authentic protein is produced [2].
• Recombinant FNs and fragments were generated by baculovirus expression of cysteine-rich domains and by bacterial expression of type III repeats as fusion proteins with maltose binding protein [3].
• Trigramin, a cysteine-rich, RGD-containing peptide isolated from the venom of the Trimeresurus gramineus snake, inhibited the adhesion of human melanoma cells to fibronectin and fibrinogen [4].
• The resulting vectors were transfected into retroviral producer cell lines, psi CRE and psi CRIP, and stable recombinant retrovirus producers were isolated [5].

High impact information on CRIP1

• In mouse there are 14.5 cysteine-rich repeats with similarity to the EGF repeat, followed by several repeats with similarity to the type III repeat of fibronectin [6].
• PINCH is a widely expressed and evolutionarily conserved protein comprising primarily five LIM domains, which are cysteine-rich consensus sequences implicated in mediating protein-protein interactions [7].
• Tat proteins containing mutations in the Arg-Gly-Asp (RGD) cell adhesion motif or a deletion of the cysteine-rich domain had no effect on neuronal morphology [8].
• These point mutations map to both the N- and C-terminal cysteine-rich regions, implicating both domains in Argos function [9].
• We have recently identified the cysteine-rich interdomain region 1alpha (CIDR1alpha) of the Plasmodium falciparum erythrocyte membrane protein 1 as a T cell-independent polyclonal B cell activator and Ig binding protein [10].

Biological context of CRIP1

• Cysteine-rich intestinal protein (CRIP) is a small, 8.5-kDa protein with one double zinc-finger motif called a LIM domain [11].
• Southern analysis suggests that there are three copies of the CRIP gene in the human genome. hCRIP mRNA was detected by RT-PCR in human monocytes purified from peripheral blood and THP-1 cells, a human monocytic cell line [11].
• The deduced amino acid sequence of this protein has an overall 82% homology with the human mannose receptor and as such, the ectodomain contains an N-terminus that is cysteine-rich followed by a fibronectin type II domain and eight carbohydrate recognition domains (CRDs) [12].
• Glycoprotein IIIa consists of a long amino-terminal extracellular domain with several potential N-linked glycosylation sites and four cysteine-rich tandem repeats, a 29-residue hydrophobic transmembrane segment, and a short carboxyl-terminal cytoplasmic domain [13].
• We propose that the cysteine-rich repeats contain a regulatory region that is distinct from those previously described in the integrin beta1 chain [14].

Anatomical context of CRIP1

• We have cloned a human CRIP cDNA from human small intestine poly(A)+ RNA by RT-PCR [11].
• Incubation of THP-1 cells with 65Zn and chromatography of the cytosol show that a significant amount of the radioactivity is associated with CRIP as was shown previously for rat intestine [11].
• Recently, we have shown that adhesion of primary human fibroblasts to immobilized Cyr61 is mediated through integrin alpha(6)beta(1) and cell surface heparan sulfate proteoglycans (HSPGs) (Chen, N., Chen, C.-C., and Lau, L.F. (2000) J [15].
• The tissue concentration of CRIP is of the order of 15-20 micrograms/g of mucosal tissue, suggesting that the protein is more abundant than zinc-finger-containing transcription factors [16].
• beta-Microseminoprotein (MSP) is a small cysteine-rich protein (molecular mass about 10 kDa) first isolated from human seminal plasma and later identified in several other organisms [17].

Associations of CRIP1 with chemical compounds

• A novel activating anti-beta1 integrin monoclonal antibody binds to the cysteine-rich repeats in the beta1 chain [14].
• ADAM13 disintegrin and cysteine-rich domains bind to the second heparin-binding domain of fibronectin [18].
• The three genes encode putative type I transmembrane proteins, each containing 10 leucine-rich repeats flanked by N-terminal and C-terminal cysteine-rich regions, a fibronectin/collagen-like domain, and an intracellular tail [19].
• The IGFBP-1 protein sequence contains 12 N-terminal and 6 C-terminal cysteine residues which are conserved in other mammalian IGFBP-1 sequences and amongst other IGFBPs; both of the cysteine-rich regions are required for optimal IGF binding [20].
• The NH(2) terminal cysteine-rich and fibronectin type II domains were expressed and used to immunize mice [21].

Physical interactions of CRIP1

• Mutation of the syndecan-binding site (PPRR --> PPTM) within this domain abolishes binding of the recombinant disintegrin and cysteine-rich domains of ADAM13 [18].

Other interactions of CRIP1

• Members of the IGFBP family share conserved cysteine-rich amino- and carboxyl-terminal regions [22].
• The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts [15].
• The duplication of nucleotides in exon 1 is located in the conserved cysteine-rich N-terminal region that corresponds to the whey acidic protein motif, affecting the KAL1 protein either by interrupting the normal transcription or stopping the translation at the stop codon [23].
• Structure and sequence comparisons have revealed an evolutionary relationship between the N-terminal sub-domain of the CR module and the fibronectin type 1 domain, suggesting that these domains share a common ancestry [24].
• ADAM 9 is a member of the cellular metalloprotease/disintegrin/cysteine-rich (MDC) gene family, related to soluble snake venom metalloproteases (SVMP) [25].

Analytical, diagnostic and therapeutic context of CRIP1

• Sequence analysis has shown that this human cysteine-rich heart protein (hCRHP) is a protein of 77 amino acids and possesses a LIM motif which is considered to be able to bind zinc [2].
• Through sequencing, we found that the human intestinal CRIP protein (hCRIP) differed from the previously cloned rat CRIP by two amino acids (residues 8 and 58). hCRIP was expressed with the pET vector/bacterial system and isolated by gel filtration and ion-exchange chromatography [11].
• Using surface plasmon resonance, the PIII SVMP jararhagin and a recombinant cysteine-rich domain from a PIII SVMP were demonstrated to bind to collagen XIV, collagen XII, and matrilins 1, 3, and 4 [26].

References