Cardiac-enriched FHL2-interacting protein (CEFIP) is a protein encoded by the gene C10orf71 on chromosome 10 open reading frame 71. It is primarily understood that this gene is moderately expressed in muscle tissue and cardiac tissue.
Gene
The cytogenic locus is found at 10q11.23. C10orf71 encodes 28294 base pairs (bp) within chromosome 10 at 49299193-49327487 bp. It is located on the plus strand and is flanked by several other genes.
mRNA
The mRNA sequence of C10orf71 has 3 exons and 10 stop codons in the favorable splice form. The two alternative splice forms had 47 and 75 stop codons interspersed throughout the sequence so they were not utilized to obtain further sequence information. The main splice form that was analyzed had the ten stop codons interspersed throughout the 5' and 3' UTR, which was why this splice form was utilized to further analyze. The mRNA of the Homo sapiens ortholog of C10orf71was 5286 bp in length. +Alternative splice forms of C10orf7Splice 1Stop Codons found starting at bp: 4, 150, 247, 310, 4645, 4774, 4783, 4855, 4986, and 5250
Exons found between bp: 431/432, 544/545, and 5285/5286
Kozak site found at bp 332-334Splice 247 Stop Codons found interspersed throughout the entire sequenceSplice 375 stop codons found interspersed throughout the entire sequence The three alternative splice forms found of C10orf71 mRNA sequence and the locations stop codons, exons and the Kozak site found in Splice 1. Splice 1 was utilized to analyze and obtain information about as all of the stop codons found in this splice form were found in the 5' and 3' UTR regions of the sequence. There were three exons found in Splice 1 with a Kozak consensus sequence in the overall sequence as well.
Protein
The mature Homo sapiens homolog of the CEFIP protein encoded by C10orf71 is 1435 amino acids (aa) in length and weighs approximately 156.5 kDa. This homolog has an isoelectric point of 5.94. The range of pH values from Homo sapiens to the latest ortholog analyzed, Rhincodon types, ranged from 5.94-6.93, with it gradually increasing as it went later in the divergence of the ortholog. Species Length (aa) Molecular Weight (kDa) Isoelectric pointHomo sapiens1,435156.55.94Gorilla gorilla1,435156.25.91Mus muculus1,412154.55.81Gallus gallus1,521167.76.15Rhincodon typus1,253138.86.93 Comparison of some of the orthologs analyzed when compared to Homo sapiens. The orthologs are arranged from species that are most closely related to the Homo sapiens ortholog to least closely related (top to bottom respectively).
Composition of protein
CEFIP is predicted to be a non-transmembrane, soluble protein. It is predicted to be a nuclear protein with 91.3% confidence with it being fairly confident to be a nuclear protein throughout the orthologs. There was one positive charge cluster found in CEFIP protein sequence, that is located from amino acids 1165–1193. This cluster was moderately conserved throughout the orthologs analyzed. There was also a mixed charge cluster found in the Homo sapiens' sequence of this protein, located from amino acid 750–778, although this cluster was not highly conserved throughout the analyzed orthologs. There was one repeat sequence found as well, TASKPPA, located at amino acids 163-169 and 116–1172. This protein is Proline and Serine rich as well.
+Predicted C10orf71 location in orthologs. Species Nuclear Cytoplasmic CytoskeletalHomo sapiens91.3%4.3%4.3%Gorilla gorilla91.3%4.3%4.3%Mus musculus82.6%13.0%—Gallus gallus69.6%17.4%4.3%Rhincodon typus69.6%21.7%—
Domains and motifs
One confirmed domain of unknown function (DUF) was found within the CEFIP protein sequence, DUF4585. DUF4585 is located on the Homo sapiens protein sequence from amino acid 311–334. DUF4585 was highly conserved throughout the orthologs that were analyzed. There was also a small vacuolar targeting motif (VAC) found within the analyzed protein sequence spanning amino acids 543–546.
Protein structure
The mature CEFIP protein contains nuclear localization signals (NLS), pat4 (RKPK at aa 382, RPRK at aa 640, KRRK at aa 1190) and pat7 (PPWRKPK at aa 379 and PWRKPKT at aa 380) with an NLS score of 0.94. A secondary structure was constructed with a 6.1% confidence level.
Post-translational modifications
There were seven GlcNAc O-glycosylation sites predicted within the protein sequence found at amino acids 116, 120, 139, 165, 468, 470, and 844. There were also several phosphorylation sites found interspersed throughout the sequence. One propeptide cleavage site was predicted at amino acid 38. There were three predicted sumoylation sites found at amino acids 599, 890, and 1176.
Expression
The C10orf71 mRNA was found to be highly expressed in cardiac, muscle, and liver tissue (biology).
Regulation of expression
There were 6 possible promoters found in the sequence. Promoter GXP_6729162 is 1403 bp in length. This promoter had several transcription factors of interest including those involved with myocytes.
Function
There is little scientific information known about the function of CEFIP.
Interacting proteins
There was a total of 25 proteins generated that were predicted to interact with CEFIP (Homo sapiens ortholog). Most of the interactions predicted were physical interactions with CEFIP. These interactions were discovered through a variety of mechanisms including, but not limited to: affinity chromatography, microarray analysis, and tandem mass spectrometry among others. Refer to table for details about the interacting proteins of CEFIP. Interacting Protein Name of Protein Known Function Location Expressed or Associated DiseasesC20orf78Chromosome 20 Open Reading Frame 78UnknownUnconfirmedBPIFA2BPI Fold Containing Family A Member 2Plays a role in antibacterial resistance in upper respiratory pathwayExpressed in salivary glandsPPIL6Peptidyl Prolyl Isomerase Like 6Accelerates folding of proteinsUnconfirmedKIF17Kinesin Family Member 17Transports vesicles containing NMDA receptor 2BExpressed in microtubulesKRT78Keratin 78Forms cytoplasmic network; encodes proteins with intermediate filament domainsExpressed in intermediate filamentsTBX4T-box4 Transcription FactorEncode transcription factors involved in regulation of developmental processes; assists with regulation of mesoderm differentiation; could play a role in limb pattern formationAssociated with Small Patella Syndrome and Heritable Pulmonary Arterial HypertensionDNAH8Dynein Axonemal Heavy Chain 8heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility.Associated with Colchicine Resistance and Mitochondrial Complex V Deficiency, Nuclear Type 1TSPAN17Tetraspanin 17Predicted to regulate ADAM10 maturationUnconfirmedC14orf80Chromosome 14 Open Reading Frame 80UnknownUnconfirmedSLC35F4Solute Carrier Family 35 Member F4Solute transporterUnconfirmedLHX4LIM Homeobox 4Predicted to play a role in maturing lungs, development of respiratory mechanisms, and development of the pituitary glandAssociated with Pituitary Hormone Deficiency, Combined 4 and Lhx4=Related Combined Pituitary HormoneFAM53AFamily With Sequence Similarity 53 Member APlays a role in neural developmentPossibly expressed in ventricle tissueGRIK5Glutamate Ionotropic Receptor Kainase Type Subunit 5Forms functional heteromeric kainite-preferring ionic channelsAssociated with SchizophreniaFADS2Fatty Acid Denaturase 2Regulates unsaturation of fatty acids through introduction of double bonds between define Cysteines of the fatty acid chainsAssociated with Best Vitelliform Macular DystrophyGDF2Growth Differentiation Factor 2Regulates cartilage and bone development; differentiation of cholinergic receptors in CNSUnconfirmedC17orf77Chromosome 17 Open Reading Frame 77UnknownUnconfirmedCFAP45 (CCDC19)Cilia And Flagella Associated Protein 45Associated with pharynx cancerUnconfirmedDCST2DC-STAMP Domain Containing 2UnknownUnconfirmedCTXN1Cortexin 1Predicted to play a role in IC or EC signaling of the cortical neurons during the development of the forebrain.UnconfirmedC19orf68Chromosome 19 Open Reading Frame 68UnknownUnconfirmedDCAF7DDB1 And CUL4 Associated Factor 7It's been shown to function as a scaffold protein in kinase signaling. It's also been known to be involved with craniofacial developmentUnconfirmedDYRK1ADual Specificity YAK1-Related KinaseMay play a role in brain development and cell proliferation; nuclear localized proteinAssociated with Mental Retardation, Autosomal Dominant 7 and MicrocephalyDYRK1BDual Specificity Tyrosine-(Y)-Phosphorylation Regulated Kinase 1BPlays a role in the cell cycle; nuclear-localized proteinAssociated with Abdominal Obesity-Metabolic Syndrome 3 and Abdominal Obesity-Metabolic SyndromeFNTAProtein Farnesyltransferase/Geranylgeranyltransferase Type-1 Subunit AlphaHelps regulate neuromuscular junction developmentUnconfirmedFNTBProtein Farnesyltransferase Subunit BetaCatalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteineUnconfirmed Interacting proteins, their function if known, and any tissues they have been found or predicted to be expressed in and any diseases they have been associated with.
Homologs
Paralogs There are currently no known paralogs to the C10orf71 gene.
Orthologs
C10orf71 is known to have 68 orthologs in various species including primates (11 species), rodents (8 species), Laurasiatheria carnivores (14 species), Placental mammals (38 species), Sauropsida birds and reptiles (7 species), and fish (11 species). The highly conserved sequences are primarily from primates with the identity percentage of these species being >90%, whereas species such as reptiles, birds, and fish had an identity percentage ≤30%. Refer to table for additional information on dates of divergence, sequence length, and sequence identity and similarity for orthologs. C10orf71 is not present in prokaryotes, archaea, or fungi. Abbreviation (for Phylogenetic Tree) Species Common Name Protein Accession # Estimated Date of Divergence (MYA) Sequence length (aa) Sequence identity to Human mRNA/protein (%) Sequence similarity to Human mRNA/protein (%)HomSHomo sapienshumanNP_001128668.11435100100GorGGorilla gorillawestern gorillaXP_018889898.19.06143598.398.7RhiRRhinopithecus roxellanaGolden snub-nosed monkeyXP_010381152.129.44143593.495.3OtoGOtolemur garnettiismall-eared galagoXP_003801705.174141974.981.5TupCTupaia chinensisChinese tree shrewXP_014439281.182118661.567.8MusMMus musculushouse mouseNP_001182026.190141265.474.3OctDOctodon degusCommon deguXP_004647022.190140763.373.1HetGHeterocephalus glaberNaked mole-ratXP_004874589.190141163.273.3CerSCeratotherium simum simumSouthern white rhinocerosXP_004432504.19614367481OrcOOrcinus orcakiller whaleXP_00428643696143372.679.4LoxALoxodonta AfricanaAfrican bush elephantXP_003408977.1105143865.574.5SarHSarcophilus harrisiiTasmanian devilXP_003755230.2159147049.062.5GavGGavialis gangeticuscrocodileXP_019358113.1312153832.846.7TinGTinamus guttatusWhite-throated tinamouXP_010216992.1312152932.446.3PelSPelodiscus sinensisturtleXP_006118195.1312150532.046.2GalGGallus galluschickenXP_421655.3312152130.544.7MelUMelopsittacus undulatesparrotXP_005153970312153830.345.1OreNOreochromis niloticusNile tilapiaXP_019221822 43566112.018.7SclFScleropages formosusAsian arowanaXP_018580403435312511.517.9DanRDanio rerioZebrafishXP_005157004.143535919.216.0CluHClupea harengusAtlantic herringXP_012687674.143536339.113.8RhiTRhincodon typuswhale sharkXP_020385611.1473125340.024.8 Ortholog table in descending order to latest ortholog diverged. This table compares the orthologs analyzed, their species names, common names, dates of divergence from Homo sapiens ortholog (MYA), length (aa), and percentage of similarity and identity.
Phylogeny
A phylogenetic tree was constructed for the orthologs that were analyzed in comparison to Homo sapiens. With the species of latest divergence being Rhincodon types, or the whale shark.
Evolutionary rate