Exosomal polycystin-1-interacting protein is a protein that, in humans, is encoded by the EPCIP gene. EPCIP is found on human chromosome 21, and it is thought to be expressed in tissues of the brain and reproductive organs. Additionally, EPCIP is highly expressed in ovarian surface epithelial cells during normal regulation, but is not expressed in cancerous ovarian surface epithelial cells.
Gene Common aliases of EPCIP are C21orf62, C21orf120, PRED81, and B37. EPCIP is located on chromosome 21 in humans, and is specifically at the q22.11 position. The EPCIP gene is 4132 base pairs in length and contains five exons.
mRNA The mRNA sequence of EPCIP in humans has one known isoform. This isoform is called uncharacterized protein C21orf62 isoform X1. This isoform is 458 base pairs, or 104 amino acids, in length, and it is significantly shorter than the most observed sequence of EPCIP in humans. In addition to having an isoform, EPCIP also has splice variants. All splice variants encode the same gene, but the differences in splice variant sequences occur in the 5' untranslated region of the mRNA sequence.
Protein
General protein characteristics
The EPCIP protein in humans has a sequence that is 219 amino acids in length. The primary sequence of EPCIP in humans has a molecular weight of 24.9 kDa and an isoelectric point of 8. When it's cleavable signal peptide, which spans amino acids 1-19, is removed, it has a molecular weight of 22.8 kDa and an isoelectric point of 7.8.
Protein composition
EPCIP in humans has higher cysteine and lower valine concentrations than expected compared to other human proteins. This trend, as showed in Table 1, is the same for other mammals. It does not, however, occur in taxa other than mammalia. +Table 1. Unusual amino acid concentrations of EPCIP in humans and orthologs.Genus and speciesCommon nameOrganism Clade% CysteineAmino Acid Concentration of Cysteine Compared to Expected% ValineAmino Acid Concentration of Valine Compared to ExpectedOther Amino Acids with High or Low Concentration Compared to ExpectedHomo sapiensHumanMammalia4.6%High3.2%Low -Mus musculusHouse MouseMammalia4.3%High3.5%LowGlutamic Acid (1.7%, low)Canis lupus familiarisDogMammalia4.1%High2.7%LowLeucine (14.2%, high)Physeter catodonSperm WhaleMammalia4.6%High4.1%ExpectedSerine (11.9%, high)Gallus gallusChickenAves3.1%Expected6.7%ExpectedAlanine (2.2%, low) Glycine (3.1%, low)
Proline (1.8%, low)
Phenylalanine (7.1%, high)
Serine (12.4%, high)
Threonine (9.8%)Chelonia mydasGreen Sea TurtleReptilia3.6%Expected5.8%ExpectedAlanine (1.8%, low) Serine (11.2%, high)
Protein structure
The protein structure of EPCIP in humans consists of a combination of alpha helices and beta sheets. Figure 1 shows a predicted structure of the protein.
Post-translational modifications
EPCIP has a myristoylation site from amino acid 26–31. It has a sumoylation site from amino acid 132–135. Additionally, it has a nuclear export signal from amino acid 98-104.
Expression
Tissue expression
EPCIP is expressed in human tissues of the brain and reproductive organs.
Expression level
EPCIP in humans is moderately expressed in the brain, kidneys, pancreas, prostate, testes, and ovaries.
Regulation of expression
EPCIP is expressed during blastocyst, fetus, and adult states of human development. It is overexpressed during some tumor states, including pancreatic, gastrointestinal, germ cell, and glioma tumors.
Function The specific function of EPCIP in humans is not yet well understood.
Interacting proteins EPCIP is thought to potentially interact with nine other proteins. These interactions are shown in Table 2, and they were found through text mining. +Table 2. Proteins with Evidence of Interaction with EPCIPProtein Full NameProtein Name SymbolBrief Protein DescriptionBCL2 Interacting Protein LikeBNIPLMay function as a bridge molecule that promotes cell death.Thymosin Beta 4, X-linked Pseudogene 4TMSB4XP4Potentially influences actin polymerization.Synovial Sarcoma X Family Member 4SSX4May function as a repressor of transcription, and can be useful targets in cancer vaccine-based immunotherapy.Crystallin Beta A2CRYBA2A major protein in vertebrate eyes that maintains lens transparency and reflective index.Oral Cancer Overexpressed 1ORAOV1A gene that is frequently overexpressed in esophageal squamous cell cancer.Oligodendrocyte Transcription Factor 1OLIG1May be expressed during the time from process extension through membrane maintenance in oligodendrocytes.PAX3 and PAX7 Binding Protein 1GCFC1 (PAXBP1)The encoded protein potentially binds to GC-rich DNA sequences. It is suggested that this gene is involved in the regulation of transcription.Relaxin/Insulin Like Family Peptide Receptor 1 and 2RXFP1 and RXFP2Encoded protein is a receptor for the protein hormone relaxin that influences sperm motility and pregnancy.
Clinical significance EPCIP over or under expression is linked to some types of cancerous cells and tumors.
Homology
Paralogs
There are no known paralogs of EPCIP in humans at this time.
Orthologs
There are currently 193 organisms that are known to be orthologs of EPCIP. The orthologs of EPCIP are deuterostome animals in the clade Chordata. Table 3 shows a range of EPCIP orthologs, their NCBI accession numbers, sequence lengths, and sequence identity to the EPCIP human protein. At this time, EPCIP is not known to have any protostome or invertebrate orthologs. +Table 3. Orthologs of Human Protein EPCIPGenus and speciesCommon nameOrganism CladeEstimated Date of Divergence from Humans (Millions of Years Ago)Accession numberAmino Acid Sequence LengthCorrected Sequence Identity to Human ProteinHomo sapiensHumanmammalia0NP_001155967.2219100%Mus musculusHouse Mousemammalia90NP_083181.123068.2%Meleagris gallopavoWild Turkeyaves312XP_010721230.122556.4%Chelonia mydasGreen Sea Turtlereptilia312XP_007063646.122460.8%Xenopus tropicalisWestern Clawed Frogtetrapoda352NP_001004889.120748.9%Latimeria chalumnaeWest Indian Ocean Coelacanthsarcopterygii413XP_005993681.223745.0%Ictalurus punctatusChannel Catfishactinopterygii435XP_017326002.121429.6%Callorhinchus miliiAustralian Ghostsharkcondrichthyes473XP_007904174.122240.4%
Evolution rate
EPCIP has an evolution rate that is faster than cytochrome C and fibrinogen. Figure 2 shows the rate of evolution of the EPCIP gene over the past 473 million years.
External links
References