ISG15_BOVIN
ID ISG15_BOVIN Reviewed; 154 AA.
AC O02741; Q3T0N6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Ubiquitin-like protein ISG15;
DE AltName: Full=Interferon-stimulated gene product 17;
DE AltName: Full=Ubiquitin cross-reactive protein;
DE Short=BoUCRP;
GN Name=ISG15; Synonyms=G1P2, ISG17, UCRP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Endometrium;
RA Austin K.J., Pru J.K., Hansen T.R.;
RT "Complementary deoxyribonucleic acid sequence encoding bovine ubiquitin
RT cross-reactive protein: a comparison with ubiquitin and a 15-kDa ubiquitin
RT homolog.";
RL Endocrine 5:191-197(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=10406469; DOI=10.1210/mend.13.7.0294;
RA Perry D.J., Austin K.J., Hansen T.R.;
RT "Cloning of interferon-stimulated gene 17: the promoter and nuclear
RT proteins that regulate transcription.";
RL Mol. Endocrinol. 13:1197-1206(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION.
RX PubMed=8835381; DOI=10.1095/biolreprod54.3.600;
RA Austin K.J., Ward S.K., Teixeira M.G., Dean V.C., Moore D.W., Hansen T.R.;
RT "Ubiquitin cross-reactive protein is released by the bovine uterus in
RT response to interferon during early pregnancy.";
RL Biol. Reprod. 54:600-606(1996).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9348245; DOI=10.1210/endo.138.11.5655;
RA Hansen T.R., Austin K.J., Johnson G.A.;
RT "Transient ubiquitin cross-reactive protein gene expression in the bovine
RT endometrium.";
RL Endocrinology 138:5079-5082(1997).
RN [6]
RP FUNCTION.
RX PubMed=9546718; DOI=10.1095/biolreprod58.4.898;
RA Johnson G.A., Austin K.J., Van Kirk E.A., Hansen T.R.;
RT "Pregnancy and interferon-tau induce conjugation of bovine ubiquitin cross-
RT reactive protein to cytosolic uterine proteins.";
RL Biol. Reprod. 58:898-904(1998).
CC -!- FUNCTION: Ubiquitin-like protein which plays a key role in the innate
CC immune response to viral infection either via its conjugation to a
CC target protein (ISGylation) or via its action as a free or unconjugated
CC protein. ISGylation involves a cascade of enzymatic reactions involving
CC E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a
CC lysine residue in the target protein. Exhibits antiviral activity
CC towards both DNA and RNA viruses. The secreted form of ISG15 can:
CC induce natural killer cell proliferation, augment lymphokine-activated-
CC killer (LAK) activity, induce dendritic cell maturation, act as a
CC chemotactic factor for neutrophils and act as a IFN-gamma-inducing
CC cytokine playing an essential role in antimycobacterial immunity (By
CC similarity). The secreted form acts through the integrin ITGAL/ITGB2
CC receptor to initiate activation of SRC family tyrosine kinases
CC including LYN, HCK and FGR which leads to secretion of IFNG and IL10;
CC the interaction is mediated by ITGAL (By similarity). In response to
CC IFN-tau secreted by the conceptus, may ligate to and regulate proteins
CC involved in the release of prostaglandin F2-alpha (PGF), and thus
CC prevent lysis of the corpus luteum and maintain the pregnancy
CC (PubMed:9546718). {ECO:0000250|UniProtKB:P05161,
CC ECO:0000250|UniProtKB:Q64339, ECO:0000269|PubMed:9546718}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with,
CC and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2
CC (E2 enzyme) (By similarity). Interacts with NEDD4 (By similarity).
CC {ECO:0000250|UniProtKB:P05161}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P05161}.
CC Secreted {ECO:0000250|UniProtKB:P05161}. Note=Exists in three distinct
CC states: free within the cell, released into the extracellular space, or
CC conjugated to target proteins. {ECO:0000250|UniProtKB:P05161}.
CC -!- TISSUE SPECIFICITY: Expressed in endometrium and uterine flushings of
CC pregnant cow. Also secreted. Not detected in spleen, liver, corpus
CC luteum or muscle. {ECO:0000269|PubMed:10406469,
CC ECO:0000269|PubMed:9348245}.
CC -!- DEVELOPMENTAL STAGE: Follows the pattern of expression of interferon
CC tau by the conceptus. First appears on day 15 of pregnancy in
CC endometrium of cows, reaches a maximum on day 18 and remains high
CC through day 26. {ECO:0000269|PubMed:9348245}.
CC -!- INDUCTION: By type I interferons.
CC -!- DOMAIN: Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are
CC required for its efficient conjugation to cellular proteins. The two
CC domains play different roles in the ISGylation pathway: Ubiquitin-like
CC 2 domain is necessary for the first two steps allowing the linking of
CC ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is
CC essential for the final, E3-mediated transfer of ISG15, from the E2 to
CC the Lys of the target protein. {ECO:0000250|UniProtKB:P05161}.
CC -!- PTM: S-nitrosylation decreases its dimerization, thereby increasing the
CC availability as well as the solubility of monomeric ISG15 for its
CC conjugation to cellular proteins. {ECO:0000250|UniProtKB:P05161}.
CC -!- PTM: Induced as an inactive, precursor protein that is cleaved by
CC specific proteases to expose the C-terminal diglycine (LRLRGG) motif.
CC This motif is essential not only for its conjugation to substrates but
CC also for its recognition by the relevant processing proteases.
CC {ECO:0000250|UniProtKB:P05161}.
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DR EMBL; U96014; AAB57687.1; -; mRNA.
DR EMBL; AF069133; AAD56716.1; -; Genomic_DNA.
DR EMBL; BC102318; AAI02319.1; -; mRNA.
DR RefSeq; NP_776791.1; NM_174366.1.
DR PDB; 6JH1; X-ray; 3.00 A; C/D=1-154.
DR PDBsum; 6JH1; -.
DR AlphaFoldDB; O02741; -.
DR SMR; O02741; -.
DR IntAct; O02741; 1.
DR STRING; 9913.ENSBTAP00000019573; -.
DR PaxDb; O02741; -.
DR PRIDE; O02741; -.
DR Ensembl; ENSBTAT00000019573; ENSBTAP00000019573; ENSBTAG00000014707.
DR GeneID; 281871; -.
DR KEGG; bta:281871; -.
DR CTD; 9636; -.
DR VEuPathDB; HostDB:ENSBTAG00000014707; -.
DR VGNC; VGNC:30293; ISG15.
DR eggNOG; KOG0001; Eukaryota.
DR GeneTree; ENSGT00940000162007; -.
DR HOGENOM; CLU_010412_4_2_1; -.
DR InParanoid; O02741; -.
DR OMA; QCTVFMN; -.
DR OrthoDB; 1367357at2759; -.
DR TreeFam; TF338379; -.
DR Reactome; R-BTA-1169408; ISG15 antiviral mechanism.
DR Reactome; R-BTA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-BTA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000014707; Expressed in anterior segment of eyeball and 107 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0031386; F:protein tag; IBA:GO_Central.
DR GO; GO:0003735; F:structural constituent of ribosome; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0032020; P:ISG15-protein conjugation; ISS:UniProtKB.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISS:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IEA:Ensembl.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032461; P:positive regulation of protein oligomerization; IEA:Ensembl.
DR GO; GO:0070585; P:protein localization to mitochondrion; IEA:Ensembl.
DR GO; GO:0032649; P:regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; ISS:UniProtKB.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR019956; Ubiquitin_dom.
DR Pfam; PF00240; ubiquitin; 2.
DR PRINTS; PR00348; UBIQUITIN.
DR SMART; SM00213; UBQ; 2.
DR SUPFAM; SSF54236; SSF54236; 2.
DR PROSITE; PS50053; UBIQUITIN_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Cytoplasm; Disulfide bond;
KW Isopeptide bond; Reference proteome; Repeat; S-nitrosylation; Secreted;
KW Ubl conjugation pathway.
FT CHAIN 1..154
FT /note="Ubiquitin-like protein ISG15"
FT /id="PRO_0000114913"
FT DOMAIN 2..78
FT /note="Ubiquitin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 79..154
FT /note="Ubiquitin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT REGION 150..154
FT /note="Involved in the ligation of specific target
FT proteins"
FT MOTIF 149..154
FT /note="LRLRGG"
FT /evidence="ECO:0000250"
FT SITE 150
FT /note="Interacts with activating enzyme"
FT /evidence="ECO:0000250"
FT MOD_RES 78
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P05161"
FT MOD_RES 143
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q64339"
FT CROSSLNK 154
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-? in acceptor proteins)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 14..17
FT /evidence="ECO:0007829|PDB:6JH1"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:6JH1"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:6JH1"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:6JH1"
FT TURN 60..64
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 90..100
FT /evidence="ECO:0007829|PDB:6JH1"
FT HELIX 101..111
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 120..123
FT /evidence="ECO:0007829|PDB:6JH1"
FT HELIX 134..137
FT /evidence="ECO:0007829|PDB:6JH1"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:6JH1"
SQ SEQUENCE 154 AA; 17310 MW; 3FF8284C6438F44B CRC64;
MGGDLTVKML GGQEILVPLR DSMTVSELKQ FIAQKINVPA FQQRLAHLDS REVLQEGVPL
VLQGLRAGST VLLVVQNCIS ILVRNDKGRS SPYEVQLKQT VAELKQQVCQ KERVQADQFW
LSFEGRPMDD EHPLEEYGLM KGCTVFMNLR LRGG
