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Table 1 Selected candidate proteins for verification of processing by HERV-K(HML-2) Proteasea

From: A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins

Gene/Protein Protein ID Function ver.
C15orf57 (CCDC32; Coiled-Coil Domain Containing 32) Q9BV29 unknown +/+
CALR (Calreticulin) P27797 Prevents binding of glucocorticoid receptor to glucocorticoid response element. Important modulator of gene transcription. AD: Myelofibrosis With Myeloid Metaplasia; Somatic and Essential Thrombocythemia −/n.t.
CIAPIN1 (Cytokine Induced Apoptosis Inhibitor 1) Q6FI81 Cytokine-induced inhibitor of apoptosis. Anti-apoptotic effects in the cell. Negative control of cell death upon cytokine withdrawal +/+
DDX3X (DEAD-Box Helicase 3, X-Linked) O00571 Transcriptional regulation, mRNP assembly, pre-mRNA splicing, mRNA export, translation, cellular signaling, viral replication. Misregulation implicated in tumorigenesis. Cofactor for XPO1-mediated nuclear export of incompletely spliced HIV-1 Rev. RNAs. AD: Mental Retardation, X-Linked 102; Toriello-Carey Syndrome (Corpus Callosum, Agenesis Of, With Facial Anomalies And Robin Sequence) i/n.t.
ENO1 (Enolase 1) P06733 Role in glycolysis, growth control, hypoxia tolerance, allergic responses. Shorter isoform binds to c-myc promoter and functions as a tumor suppressor. Autoantigen in Hashimoto encephalopathy. AD: Cancer-Associated Retinopathy; Non-Herpetic Acute Limbic Encephalitis i/n.t.
HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1) P07900 Proper folding of target proteins, regulation of transcription machinery. AD: Epidermolysis Bullosa Acquisita; Hypersensitivity Vasculitis +/+
HSP90AB1 (Heat Shock Protein 90 Alpha Family Class B Member 1) P08238 Signal transduction, protein folding and degradation; morphological evolution. AD: Bronchitis; Larynx Cancer +/n.t.
MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2) P36507 Critical role in mitogen growth factor signal transduction. AD: Cardiofaciocutaneous Syndrome 4 +/+
PDIA3 (Protein Disulfide Isomerase Family A Member 3) P30101 Modulates folding of newly synthesized glycoproteins. Molecular chaperone preventing protein aggregates. AD: Maxillary Sinus Squamous Cell Carcinoma; Anomalous Left Coronary Artery From The Pulmonary Artery +/n.t.
PSMC4 (Proteasome 26S Subunit, ATPase 4) P43686 26S proteasome assembly. AD: Cystic Fibrosis; Myotonia; Parkinson’s disease(?) −/n.t.
RANBP1 (RAN Binding Protein 1) P43487 Participates in regulation of cell cycle by controlling transport of proteins and nucleic acids into nucleus. May control progression through the cell cycle by regulating transport of protein and nucleic acids across nuclear membrane. +/n.t.
RNASEH2A (Ribonuclease H2 Subunit A) O75792 Component of RNase H2 complex that degrades RNA of RNA:DNA hybrids. Catalytic subunit of RNase H2. Mediates excision of single ribonucleotides from DNA:RNA duplexes. AD: Aicardi-Goutières Syndrome n.t./+
RNASEH2B (Ribonuclease H2 Subunit B) Q5TBB1 Component of RNase H2 complex. Non catalytic subunit of RNase H2. AD: Aicardi-Goutières Syndrome. +/n.t.
S100A4 (S100 Calcium Binding Protein A4) P26447 Regulation of cell cycle progression, differentiation. Altered expression implicated in tumor metastasis. AD: Bile Duct Adenocarcinoma; Pancreatic Cancer −/n.t.
STUB1 (STIP1 Homology And U-Box Containing Protein 1) Q9UNE7 Ubiquitin ligase/cochaperone. Targets misfolded chaperone substrates towards proteasomal degradation. Binds and ubiquitinates Hspa8 and Polb. Negatively regulates suppressive function of regulatory T-cells during inflammation. Negatively regulates TGF-β signaling. AD: Spinocerebellar ataxia, autosomal recessive 16; Gordon Holmes Syndrome n.t./+
TUBA1A (Tubulin Alpha 1a) Q71U36 Major component of microtubules. AD: Lissencephaly 3; Lissencephaly With Cerebellar Hypoplasia +/+
TRIM28 (Tripartite Motif Containing 28) Q13263 Nuclear corepressor for KRAB domain-containing zinc finger proteins. Mediates gene silencing. Important regulator of CDKN1A/p21. Mediates nuclear localization of KOX1, ZNF268, ZNF300. Required to maintain transcriptionally repressive state of genes in undifferentiated embryonic stem cells. n.t./+
  1. aGene/Protein as given by approved gene/protein symbols and full names. A representative protein ID is given. Selected functional characteristics as well as associated diseases (“AD”) for respective genes/proteins were compiled from information provided by GeneCards [55]. Experimental verifications (“ver.”) of processing of particular proteins by HML-2 Pro in vitro and in vivo is indicated as “+/+”, no processing observed as “–”, inconclusive evidence as “i” (see the text), n.t.: not tested in either in vitro or in vitro experiments