Q9NSU2

PTMD Annotation Information

※ Protein Information

Tag	Content
UniProt Accession	TREX1_HUMAN; Q9NSU2;
Entrez ID	11277
GenBank Protein ID	NM_007248.3; NM_016381.5; NM_033629.4;
GenBank Nucleotide ID	NP_009179.2; NP_057465.1; NP_338599.1;
Protein Name	Three-prime repair exonuclease 1 (EC 3.1.11.2) (3'-5' exonuclease TREX1) (Deoxyribonuclease III) (DNase III)
Gene Name	TREX1
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. Prevents cell-intrinsic initiation of autoimmunity. Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements. Unless degraded, these DNA fragments accumulate in the cytosol and activate the IFN-stimulatory DNA (ISD) response and innate immune signaling. Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates. Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light. During GZMA-mediated cell death, contributes to DNA damage in concert with NME1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair. Functional Description Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. Prevents cell-intrinsic initiation of autoimmunity. Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements. Unless degraded, these DNA fragments accumulate in the cytosol and activate the IFN-stimulatory DNA (ISD) response and innate immune signaling. Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates. Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light. During GZMA-mediated cell death, contributes to DNA damage in concert with NME1. NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair.
Sequence (Fasta)	MGSQALPPGP MQTLIFFDME ATGLPFSQPK VTELCLLAVH RCALESPPTS QGPPPTVPPP 60 PRVVDKLSLC VAPGKACSPA ASEITGLSTA VLAAHGRQCF DDNLANLLLA FLRRQPQPWC 120 LVAHNGDRYD FPLLQAELAM LGLTSALDGA FCVDSITALK ALERASSPSE HGPRKSYSLG 180 SIYTRLYGQS PPDSHTAEGD VLALLSICQW RPQALLRWVD AHARPFGTIR PMYGVTASAR 240 TKPRPSAVTT TAHLATTRNT SPSLGESRGT KDLPPVKDPG ALSREGLLAP LGLLAILTLA 300 VATLYGLSLA TPGE 315 Fasta Sequence >Q9NSU2\|TREX1\|Homo sapiens (Human) MGSQALPPGPMQTLIFFDMEATGLPFSQPKVTELCLLAVHRCALESPPTSQGPPPTVPPPPRVVDKLSLCVAPGKACSPAASEITGLSTAVLAAHGRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSALDGAFCVDSITALKALERASSPSEHGPRKSYSLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWRPQALLRWVDAHARPFGTIRPMYGVTASARTKPRPSAVTTTAHLATTRNTSPSLGESRGTKDLPPVKDPGALSREGLLAPLGLLAILTLAVATLYGLSLATPGE

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Ubiquitination	Autoimmune disease		P		23979357
1	[Reference]: TREX1 post-translational modification indicates an additional mechanism by which mutations disrupt TREX1 biology, leading to human autoimmune disease

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 7) (view all)	MESH:C535607 ; Aicardi-Goutieres syndrome MESH:D001927 ; Brain Diseases MESH:C535924 ; Chilblain lupus 1 MESH:D007249 ; Inflammation MESH:D007251 ; Influenza, Human MESH:D008180 ; Lupus Erythematosus, Systemic MESH:C566007 ; Vasculopathy, Retinal, With Cerebral Leukodystrophy
DisGeNet (Curated) (count: 100) (view all)	C0003635; Apraxias C0003862; Arthralgia C0006111; Brain Diseases C0013362; Dysarthria C0013421; Dystonia C0014544; Epilepsy C0015371; Extrapyramidal Disorders C0015967; Fever C0018965; Hematuria C0018989; Hemiparesis C0019214; Hepatosplenomegaly C0020796; Profound Mental Retardation C0021368; Inflammation C0021400; Influenza C0022353; Neonatal Jaundice C0023520; Leukodystrophy C0024141; Lupus Erythematosus, Systemic C0024145; Chilblain lupus 1 C0026838; Muscle Spasticity C0028738; Nystagmus C0030196; Pain in limb C0031256; Petechiae C0033687; Proteinuria C0034150; Purpura C0035309; Retinal Diseases C0035317; Retinal Hemorrhage C0036572; Seizures C0037299; Skin Ulcer C0038379; Strabismus C0038454; Cerebrovascular accident C0039446; Telangiectasis C0040034; Thrombocytopenia C0042798; Low Vision C0078982; Arhinencephaly C0086565; Liver Dysfunction C0149931; Migraine Disorders C0151632; ESR raised C0151766; Liver function tests abnormal finding C0154671; Degenerative brain disorder C0221347; Acrocyanosis C0233514; Abnormal behavior C0234133; Extrapyramidal sign C0234985; Mental deterioration C0235946; Cerebral atrophy C0235996; Hepatic enzyme increased C0236048; Polyposis, Gastric C0240897; Retinal exudates C0262988; Vasculitis of the skin C0270612; Leukoencephalopathies C0271051; Macular retinal edema C0375206; Hemiplegia and hemiparesis C0392386; Decreased platelet count C0393591; AICARDI-GOUTIERES SYNDROME C0438237; Liver enzymes abnormal C0438717; Transaminases increased C0497327; Dementia C0521573; Coloboma of eyelid C0557874; Global developmental delay C0744641; Intermittent migraine headaches C0796126; AICARDI-GOUTIERES SYNDROME 1 C0877359; Liver function test increased C1138421; Spider Veins C1389280; Basal ganglia calcification C1833999; Pigmentary retinal degeneration C1836038; Poor head control C1836696; Lower limb hyperreflexia C1838578; Encephalopathy, progressive C1839364; Progressive visual loss C1842003; Subclinical abnormal liver function tests C1848701; Elevated hepatic transaminases C1850456; Progressive microcephaly C1853562; Adult onset C1853743; Axial hypotonia C1856979; Deep white matter hypodensities C1856983; Increased CSF alpha-interferon C1859236; Prolonged neonatal jaundice C1860518; Vasculopathy, Retinal, With Cerebral Leukodystrophy C1864897; Cognitive delay C1864985; Progressive disorder C2673431; Periventricular white matter abnormalities C2674608; Feeding difficulties in infancy C3161330; Profound intellectual disabilities C3277687; Central nervous system degeneration C3277688; Progressive forgetfulness C3277693; Punctate vasculitis skin lesions C3277697; Decreased visual acuity, progressive C3665347; Visual Impairment C4020859; Pyramidal tract disease C4020860; Supratentorial atrophy C4020871; Dystonic disease C4020875; Mental and motor retardation C4020899; Autosomal recessive predisposition C4021761; Morphological abnormality of the pyramidal tract C4024224; Chilblain lesions C4024229; Chronic CSF lymphocytosis C4024753; Abnormality of the retinal vasculature C4024946; Focal white matter lesions C4025784; Abnormality of the musculature of the lower limbs C4082173; Porencephaly C4280575; Progressive brain disease
HGMD (count: 32) (view all)	CD075572; Systemic lupus erythematosus; Small deletions CD075573; Aicardi-Goutieres syndrome; Small deletions CD075574; Aicardi-Goutieres syndrome; Small deletions CD075575; Aicardi-Goutieres syndrome; Small deletions CN075898; Aicardi-Goutieres syndrome; Gross insertions CI075705; Systemic lupus erythematosus; Small insertions CI075706; Aicardi-Goutieres syndrome; Small insertions CI075707; Retinal vasculopathy with cerebral leukodystrophy; Small insertions CI075708; Aicardi-Goutieres syndrome; Small insertions CI075709; Retinal vasculopathy with cerebral leukodystrophy; Small insertions CI075710; Aicardi-Goutieres syndrome; Small insertions CI075711; Aicardi-Goutieres syndrome; Small insertions CI071463; Chilblain lupus, familial; Small insertions CI075712; Retinal vasculopathy with cerebral leukodystrophy; Small insertions CI075713; Retinal vasculopathy with cerebral leukodystrophy; Small insertions CI075714; Retinal vasculopathy with cerebral leukodystrophy; Small insertions CI063732; Aicardi-Goutieres syndrome; Small insertions CI063733; Aicardi-Goutieres syndrome; Small insertions CM071115; Chilblain lupus, familial; Missense/nonsense CM072095; Chilblain lupus, familial; Missense/nonsense CM063221; Aicardi-Goutieres syndrome; Missense/nonsense CM074611; Aicardi-Goutieres syndrome; Missense/nonsense CM074609; Systemic lupus erythematosus; Missense/nonsense CM063222; Aicardi-Goutieres syndrome; Missense/nonsense CM071114; Aicardi-Goutieres syndrome; Missense/nonsense CM063223; Aicardi-Goutieres syndrome; Missense/nonsense CM074606; Systemic lupus erythematosus; Missense/nonsense CM074613; Systemic lupus erythematosus; Missense/nonsense CM074608; Systemic lupus erythematosus; Missense/nonsense CM074607; Aicardi-Goutieres syndrome; Missense/nonsense CM074612; Systemic lupus erythematosus; Missense/nonsense CM074610; Systemic lupus erythematosus; Missense/nonsense
GWASdb (count: 1)	rs3135940; Obesity-related traits; obesity

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 7) (view all)	133 VAPGKACSPAASEIT dbPAF 221 LKALERASSPSEHGP dbPAF 222 KALERASSPSEHGPR dbPAF 224 LERASSPSEHGPRKS dbPAF 238 SYSLGSIYTRLYGQS dbPAF 261 GDVLALLSICQWRPQ dbPAF 316 LATTRNTSPSLGESR dbPAF
Methylation (count: 1)	332 TKDLPPVKDPGALSR PLMD

※ Protein-Protein Interaction

Network

Interaction

A

B

Source

MINT