Q8N726

※ Protein Information

Tag	Content
UniProt Accession	ARF_HUMAN; Q8N726;
Entrez ID	1029
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	Tumor suppressor ARF (Alternative reading frame) (ARF) (Cyclin-dependent kinase inhibitor 2A) (p14ARF)
Gene Name	CDKN2A; CDKN2; MLM
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and (view all) Functional Description Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development. Isoform smARF may be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP.
Sequence (Fasta)	MVRRFLVTLR IRRACGPPRV RVFVVHIPRL TGEWAAPGAP AAVALVLMLL RSQRLGQQPL 60 PRRPGHDDGQ RPSGGAAAAP RRGAQLRRPR HSHPTRARRC PGGLPGHAGG AAPGRGAAGR 120 ARCLGPSARG PG 133 Fasta Sequence >Q8N726\|CDKN2A; CDKN2; MLM\|Homo sapiens (Human) MVRRFLVTLRIRRACGPPRVRVFVVHIPRLTGEWAAPGAPAAVALVLMLLRSQRLGQQPLPRRPGHDDGQRPSGGAAAAPRRGAQLRRPRHSHPTRARRCPGGLPGHAGGAAPGRGAAGRARCLGPSARGPG

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Ubiquitination	Gastric cancer		P		23104211
1	[Reference]: Acceleration of gastric tumorigenesis through MKRN1-mediated posttranslational regulation of p14ARF

※ Disease Cross-ref Annotation

Database	Annotation
CTD (Curated) (count: 51) (view all)	MESH:D000230 ; Adenocarcinoma MESH:C562730 ; Adenocarcinoma Of Esophagus MESH:D000310 ; Adrenal Gland Neoplasms MESH:D018268 ; Adrenocortical Carcinoma MESH:D001932 ; Brain Neoplasms MESH:D020295 ; Brain Stem Neoplasms MESH:D001943 ; Breast Neoplasms MESH:D063646 ; Carcinogenesis MESH:D006528 ; Carcinoma, Hepatocellular MESH:D021441 ; Carcinoma, Pancreatic Ductal MESH:D002294 ; Carcinoma, Squamous Cell MESH:C535575 ; Carcinoma, squamous cell of head and neck MESH:D002872 ; Chromosome Deletion MESH:D004938 ; Esophageal Neoplasms MESH:C562729 ; Esophageal Squamous Cell Carcinoma MESH:D005901 ; Glaucoma MESH:D005910 ; Glioma MESH:D008113 ; Liver Neoplasms MESH:D008175 ; Lung Neoplasms MESH:D008223 ; Lymphoma MESH:D016403 ; Lymphoma, Large B-Cell, Diffuse MESH:D016410 ; Lymphoma, T-Cell, Cutaneous MESH:D008545 ; Melanoma MESH:C536149 ; Melanoma astrocytoma syndrome MESH:C562393 ; Melanoma, Cutaneous Malignant OMIM:155601 ; MELANOMA, CUTANEOUS MALIGNANT, SUSCEPTIBILITY TO, 2 MESH:C563985 ; Melanoma-Pancreatic Cancer Syndrome MESH:D008654 ; Mesothelioma MESH:C562839 ; Mesothelioma, Malignant MESH:D048629 ; Micronuclei, Chromosome-Defective MESH:D009062 ; Mouth Neoplasms MESH:D009101 ; Multiple Myeloma MESH:C538339 ; Nasopharyngeal carcinoma MESH:D009361 ; Neoplasm Invasiveness MESH:D009369 ; Neoplasms MESH:D018317 ; Nerve Sheath Neoplasms MESH:D009447 ; Neuroblastoma MESH:D002289 ; Carcinoma, Non-Small-Cell Lung MESH:D010190 ; Pancreatic Neoplasms MESH:D010523 ; Peripheral Nervous System Diseases MESH:D011041 ; Poisoning MESH:D011230 ; Precancerous Conditions MESH:D054198 ; Precursor Cell Lymphoblastic Leukemia-Lymphoma MESH:D012751 ; Sezary Syndrome MESH:D013274 ; Stomach Neoplasms MESH:D013945 ; Thymoma MESH:D014178 ; Translocation, Genetic MESH:D014314 ; Trisomy MESH:D001749 ; Urinary Bladder Neoplasms MESH:D014565 ; Urogenital Neoplasms MESH:D007724 ; Vulvar Lichen Sclerosus
DisGeNet (Curated) (count: 72) (view all)	C0001418; Adenocarcinoma C0001624; Adrenal Gland Neoplasms C0004114; Astrocytoma C0005695; Bladder Neoplasm C0006118; Brain Neoplasms C0007131; Non-Small Cell Lung Carcinoma C0007137; Squamous cell carcinoma C0008628; Chromosome Deletion C0011570; Mental Depression C0011581; Depressive disorder C0014859; Esophageal Neoplasms C0016689; Freckles C0017601; Glaucoma C0017638; Glioma C0022783; Vulvar Lichen Sclerosus C0023903; Liver neoplasms C0024121; Lung Neoplasms C0024228; Lymphatic Diseases C0024299; Lymphoma C0025202; melanoma C0025500; Mesothelioma C0026640; Mouth Neoplasms C0026764; Multiple Myeloma C0027626; Neoplasm Invasiveness C0027819; Neuroblastoma C0027960; Nevus C0027962; Melanocytic nevus C0030297; Pancreatic Neoplasm C0031117; Peripheral Neuropathy C0032927; Precancerous Conditions C0036920; Sezary Syndrome C0038356; Stomach Neoplasms C0040100; Thymoma C0040715; Chromosomal translocation C0041107; Trisomy C0041696; Unipolar Depression C0042065; Genitourinary Neoplasms C0079744; Diffuse Large B-Cell Lymphoma C0079773; Lymphoma, T-Cell, Cutaneous C0151779; Cutaneous Melanoma C0151908; Dry skin C0157733; hair abnormalities (non-specific) C0206686; Adrenocortical carcinoma C0206727; Nerve Sheath Tumors C0259817; Xerosis C0279626; Squamous cell carcinoma of esophagus C0279628; Adenocarcinoma Of Esophagus C0280313; Squamous cell carcinoma of oropharynx C0281361; Adenocarcinoma of pancreas C0345967; Malignant mesothelioma C0596263; Carcinogenesis C0677866; Brain Stem Neoplasms C0751688; Malignant Squamous Cell Neoplasm C0887833; Carcinoma, Pancreatic Ductal C1168401; Squamous cell carcinoma of the head and neck C1261473; Sarcoma C1269683; Major Depressive Disorder C1449861; Micronuclei, Chromosome-Defective C1458155; Mammary Neoplasms C1512419; Hereditary Melanoma C1835042; Melanoma astrocytoma syndrome C1835044; MELANOMA, CUTANEOUS MALIGNANT, 2 C1835047; MELANOMA, CUTANEOUS MALIGNANT, 1 C1835398; LI-FRAUMENI SYNDROME 1 C1838547; MELANOMA-PANCREATIC CANCER SYNDROME C1961102; Precursor Cell Lymphoblastic Leukemia Lymphoma C2239176; Liver carcinoma C2675993; Pancreatic squamous cell carcinoma C2677869; Hair shaft abnormalities C2931038; Pancreatic carcinoma, familial C2931822; Nasopharyngeal carcinoma C4021976; Abnormality of the lymphatic system
HGMD (count: 160) (view all)	CD972118; Melanoma; Small deletions CD951647; Melanoma; Small deletions CD024714; Melanoma; Small deletions CD972119; Melanoma; Small deletions CD951648; Melanoma; Small deletions CD961883; Melanoma; Small deletions CD044135; Melanoma; Small deletions CD062128; Melanoma; Small deletions CD982535; Melanoma; Small deletions CD951646; Melanoma; Small deletions CD994409; Melanoma; Small deletions CD014458; Melanoma; Small deletions CG066463; Melanoma; Gross deletions CG004949; Melanoma; Gross deletions CG024827; Melanoma; Gross deletions CG084371; Melanoma; Gross deletions CG004950; Melanoma; Gross deletions CG962814; Melanoma; Gross deletions CG984263; Melanoma / nervous system tumours; Gross deletions CG984264; Melanoma / nervous system tumours; Gross deletions CN952372; Melanoma; Gross insertions CN984490; Melanoma; Gross insertions CX024722; Squamous cell carcinoma, head and neck; Small indels CX091778; Melanoma; Small indels CX984029; Melanoma; Small indels CX073790; Melanoma; Small indels CI075603; Melanoma ?; Small insertions CI056876; Melanoma ?; Small insertions CI034362; Melanoma ?; Small insertions CI962238; Melanoma; Small insertions CI024720; Pancreatic cancer; Small insertions CI071424; Melanoma; Small insertions CI983050; Melanoma; Small insertions CI044189; Melanoma; Small insertions CI003210; Melanoma; Small insertions CI034363; Melanoma ?; Small insertions CI091777; Melanoma; Small insertions CM061680; Melanoma; Missense/nonsense CM040397; Melanoma ?; Missense/nonsense CM072935; Melanoma ?; Missense/nonsense CM960269; Melanoma; Missense/nonsense CM994496; Melanoma; Missense/nonsense CM980321; Melanoma; Missense/nonsense CM023346; Melanoma; Missense/nonsense CM056560; Melanoma ?; Missense/nonsense CM056561; Melanoma ?; Missense/nonsense CM024657; Melanoma; Missense/nonsense CM980322; Melanoma; Missense/nonsense CM950224; Melanoma; Missense/nonsense CM072932; Melanoma ?; Missense/nonsense CM063892; Melanoma; Missense/nonsense CM024658; Melanoma; Missense/nonsense CM950225; Melanoma; Missense/nonsense CM065062; Melanoma; Missense/nonsense CM950226; Melanoma; Missense/nonsense CM091775; Melanoma; Missense/nonsense CM072934; Melanoma ?; Missense/nonsense CM994497; Melanoma; Missense/nonsense CM065060; Melanoma; Missense/nonsense CM080136; Multiple primary melanomas; Missense/nonsense CM980323; Melanoma; Missense/nonsense CM970251; Melanoma; Missense/nonsense CM003922; Melanoma ?; Missense/nonsense CM950227; Melanoma; Missense/nonsense CM004238; Melanoma; Missense/nonsense CM056554; Melanoma ?; Missense/nonsense CM950228; Melanoma; Missense/nonsense CM023895; Melanoma/Pancreatic cancer; Missense/nonsense CM065063; Melanoma; Missense/nonsense CM014694; Melanoma; Missense/nonsense CM056552; Melanoma ?; Missense/nonsense CM950229; Melanoma; Missense/nonsense CM042317; Melanoma; Missense/nonsense CM970252; Melanoma; Missense/nonsense CM980324; Melanoma; Missense/nonsense CM980325; Melanoma; Missense/nonsense CM940227; Melanoma; Missense/nonsense CM056556; Melanoma ?; Missense/nonsense CM980326; Melanoma; Missense/nonsense CM056558; Melanoma ?; Missense/nonsense CM980327; Melanoma; Missense/nonsense CM070665; Melanoma; Missense/nonsense CM041748; Melanoma; Missense/nonsense CM034775; Sarcoma; Missense/nonsense CM994793; Renal cancer; Missense/nonsense CM013694; Melanoma; Missense/nonsense CM994399; Melanoma; Missense/nonsense CM960270; Melanoma; Missense/nonsense CM065061; Melanoma; Missense/nonsense CM040398; Melanoma; Missense/nonsense CM940228; Melanoma; Missense/nonsense CM983987; Melanoma; Missense/nonsense CM980328; Melanoma; Missense/nonsense CM045607; Melanoma; Missense/nonsense CM040399; Melanoma; Missense/nonsense CM086526; Multiple primary melanomas; Missense/nonsense CM014695; Melanoma; Missense/nonsense CM091776; Multiple primary melanomas; Missense/nonsense CM077178; Melanoma; Missense/nonsense CM080133; Melanoma ?; Missense/nonsense CM950230; Melanoma; Missense/nonsense CM056553; Melanoma ?; Missense/nonsense CM053801; Melanoma; Missense/nonsense CM056557; Melanoma ?; Missense/nonsense CM085316; Melanoma ?; Missense/nonsense CM990358; Melanoma; Missense/nonsense CM014696; Melanoma; Missense/nonsense CM960271; Melanoma; Missense/nonsense CM024659; Melanoma/Pancreatic cancer; Missense/nonsense CM990359; Melanoma; Missense/nonsense CM994780; Renal cancer; Missense/nonsense CM940229; Melanoma; Missense/nonsense CM034218; Melanoma ?; Missense/nonsense CM083605; Melanoma; Missense/nonsense CM035015; Melanoma; Missense/nonsense CM980329; Melanoma; Missense/nonsense CM045408; Melanoma ?; Missense/nonsense CM056555; Melanoma ?; Missense/nonsense CM980330; Melanoma; Missense/nonsense CM940230; Melanoma; Missense/nonsense CM056559; Melanoma ?; Missense/nonsense CM994773; Melanoma; Missense/nonsense CM960272; Melanoma; Missense/nonsense CM973278; Melanoma; Missense/nonsense CM071585; Melanoma; Missense/nonsense CM072933; Melanoma ?; Missense/nonsense CM060208; Melanoma; Missense/nonsense CM013695; Melanoma; Missense/nonsense CM983988; Melanoma; Missense/nonsense CM014526; Melanoma; Missense/nonsense CM004887; Melanoma ?; Missense/nonsense CM080137; Melanoma ?; Missense/nonsense CM970253; Melanoma; Missense/nonsense CM001960; Melanoma; Missense/nonsense CM056562; Melanoma ?; Missense/nonsense CM994498; Melanoma; Missense/nonsense CM940231; Melanoma; Missense/nonsense CM022333; Melanoma/Pancreatic cancer; Missense/nonsense CM023043; Oesophageal tumours; Missense/nonsense CM080134; Melanoma ?; Missense/nonsense CM080135; Melanoma ?; Missense/nonsense CM086527; Multiple primary melanomas; Missense/nonsense CM942292; Oesophageal tumours; Missense/nonsense CM004869; Melanoma, increased risk, association with; Missense/nonsense CM034219; Melanoma ?; Missense/nonsense CR982410; Melanoma; Regulatory CR003345; Melanoma ?; Regulatory CR040566; Melanoma; Regulatory CS014762; Melanoma; Splicing CS054176; Melanoma; Splicing CS067079; Melanoma; Splicing CS971644; Melanoma; Splicing CS014428; Melanoma / nervous system tumours; Splicing CS022094; Melanoma; Splicing CS054177; Melanoma; Splicing CS022093; Melanoma; Splicing CS013625; Melanoma; Splicing CS041518; Melanoma; Splicing CS972842; Pancreatic cancer; Splicing CS941435; Melanoma; Splicing
GWASdb (count: 14) (view all)	rs3731245; Menopause (age at onset); obesity\|type 2 diabetes mellitus\|cardiovascular system disease\|osteoporosis\|breast cancer\|Alzheimer's disease rs3731239; Glaucoma; glaucoma rs3731239; Coronary artery calcification; coronary artery disease rs3731239; Glaucoma (primary open-angle); glaucoma rs36228836; Menopause (age at onset); obesity\|type 2 diabetes mellitus\|cardiovascular system disease\|osteoporosis\|breast cancer\|Alzheimer's disease rs3731236; LDL cholesterol; atherosclerosis\|coronary artery disease rs2811709; Basophils; hematopoietic system disease\|heart disease rs3731217; Acute lymphoblastic leukemia (B-cell precursor); acute lymphocytic leukemia\|acute leukemia rs3731215; Triglycerides; coronary artery disease\|lipid metabolism disorder\|arteriosclerosis rs3731215; Cholesterol, total; coronary artery disease\|lipid metabolism disorder\|arteriosclerosis rs3731215; HDL cholesterol; cholesterol ester storage disease\|cholesterol embolism\|coronary artery disease rs3731215; LDL cholesterol; atherosclerosis\|coronary artery disease rs3731211; Platelet counts; hematopoietic system disease\|Human immunodeficiency virus infectious disease\|coronary artery disease rs3731199; HDL cholesterol; cholesterol ester storage disease\|cholesterol embolism\|coronary artery disease

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 2)	31 VVHIPRLTGEWAAPG dbPAF 8 MVRRFLVTLRIRRAC dbPAF

※ Protein-Protein Interaction

Network

Interaction

Source

E7EX81	Q8N726	HPRD
O00311	Q8N726	HPRD
O43929	Q8N726	HPRD
O75419	Q8N726	HPRD
O75496	Q8N726	HPRD
P01106	Q8N726	HPRD
P02730	Q8N726	HPRD
P04198	Q8N726	MINT
P04637	Q8N726	DIP; IntAct
P06748	Q8N726	IntAct; MINT
P08238	Q8N726	HPRD
P11802	Q8N726	HPRD
P15170	Q8N726	HPRD
P17980	Q8N726	HPRD
P18146	Q8N726	HPRD; MINT
P29590	Q8N726	IntAct
P33992	Q8N726	HPRD
P36873	Q8N726	IntAct
P40855	Q8N726	HPRD
P42773	Q8N726	HPRD
P49459	Q8N726	HPRD; DIP
P49736	Q8N726	HPRD
P51959	Q8N726	HPRD
P60174	Q8N726	HPRD
P62081	Q8N726	HPRD
P62140	Q8N726	IntAct
P62988	Q8N726	DIP
Q00534	Q8N726	HPRD
Q00987	Q8N726	HPRD; DIP; IntAct; MINT
Q01094	Q8N726	HPRD; DIP
Q09666	Q8N726	HPRD
Q14191	Q8N726	HPRD
Q14669	Q8N726	DIP
Q16665	Q8N726	HPRD
Q3YBR2	Q8N726	HPRD
Q5T5S1	Q8N726	HPRD
Q66K89	Q8N726	HPRD
Q6UB98	Q8N726	HPRD
Q7L590	Q8N726	HPRD
Q7Z6Z7	Q8N726	IntAct;HPRD
Q86VK4	Q8N726	HPRD
Q86WZ6	Q8N726	HPRD
Q8N187	Q8N726	HPRD
Q8N726	Q8N726	HPRD
Q8N726	Q96JP5	HPRD
Q8N726	Q96SB3	HPRD
Q8N726	Q99459	HPRD
Q8N726	Q99741	HPRD
Q8N726	Q9NXV6	HPRD; DIP
Q8N726	Q9UER7	IntAct
Q8N726	Q9UHV2	HPRD
Q8N726	RTD	DIP

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction