P31749

※ Protein Information

Tag	Content
UniProt Accession	AKT1_HUMAN; P31749;
Entrez ID	207
GenBank Protein ID	NM_001014431.1; NM_001014432.1; NM_005163.2; XM_005267401.1;
GenBank Nucleotide ID	NP_001014431.1; NP_001014432.1; NP_005154.2; XP_005267458.1;
Protein Name	RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha)
Gene Name	AKT1; PKB; RAC
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the (view all) Functional Description AKT1 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development. Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3. Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation. Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation. Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity. Phosphorylation of BAD stimulates its pro-apoptotic activity. Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53.;AKT1-specific substrates have been recently identified, including palladin (PALLD), which phosphorylation modulates cytoskeletal organization and cell motility; prohibitin (PHB), playing an important role in cell metabolism and proliferation; and CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization. These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation. Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation.
Sequence (Fasta)	MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA PLNNFSVAQC 60 QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KKQEEEEMDF 120 RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI 180 LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS 240 RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI 300 KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL 360 ILMEEIRFPR TLGPEAKSLL SGLLKKDPKQ RLGGGSEDAK EIMQHRFFAG IVWQHVYEKK 420 LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA 480 481 Fasta Sequence >P31749\|AKT1; PKB; RAC\|Homo sapiens (Human) MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Phosphorylation	Laryngeal cancer		D		23886414
1	[Reference]: Low phosphorylated AKT expression in laryngeal cancer: indications for a higher metastatic risk
2	Phosphorylation	Oral squamous cell carcinoma		D		23723304
2	[Reference]: Survival curves show that the survival of patients with high Id-1, p-Akt, p-GSK3? and p-HSF1 expression was significantly worse than those with low Id-1, p-Akt, p-GSK3? and p-HSF1 expression (p=0.000)
3	Phosphorylation	Myelodysplasia		D		12529294
3	[Reference]: We demonstrated higher protein levels of the PI3K subunit p110 in neutrophils from MDS patients and found that though the fMLP-induced phosphorylation of PKB/Akt and ERK1/2 could also be enhanced by pretreatment with GM-CSF in these patients, the degree and kinetics of PKB/Akt and ERK1/2 phosphorylation were significantly disturbed.
4	Phosphorylation	Glioma/Adult gliomas		D		12839945
4	[Reference]: We show that PTEN reconstitution diminished phosphorylation of AKT, induced the transactivation of p53 (7.5-fold induction) and increased the expression of p53 target genes, p21(waf-1) and insulin-like growth factor binding protein 3 in glioma cells.
5	Phosphorylation	Acute monocytic leukemia		P		24422998
5	[Reference]: a human monocytic cell line derived from an acute monocytic leukemia patient, resulted in an increase of AKT phoshorylation
6	SUMOylation	Cancers		P		23884910
6	[Reference]: Akt SUMOylation regulates cell proliferation and tumorigenesis
7	Phosphorylation	Glioblastoma	cell line	P		23262078
7	[Reference]: Similar to the results in Fig. 3, cell invasion suppression coincided with decreased Akt phosphorylation
8	Phosphorylation	Brain cancer/tumor		P		12388552
8	[Reference]: The CXCR4 on glioma lines is a signaling receptor in that its agonist, stromal cell-derived factor-1 (SDF-1; CXCL12), produced rapid phosphorylation of mitogen-activated protein kinases. Furthermore, SDF-1 induced the phosphorylation of Akt (protein kinase B), a kinase associated with survival, and prevented the apoptosis of glioma cells when serum was withdrawn from the culture medium.
9	Phosphorylation	Embryonal central nervous system tumor		P		16230398
9	[Reference]: Treatment of medulloblastoma cells with SF/HGF activates c-Met and downstream signal transduction as evidenced by c-Met, mitogen-activated protein kinase, and Akt phosphorylation.
10	Serine Phosphorylation	Colon cancer/carcinoma		P	S	24464560
10	[Reference]: We found that AOM/DSS treatment induced Akt phosphorylation both in tumor and stromal cells; Colon cancer cells overexpressing miR-223 also displayed increased levels of phosphorylated Akt
11	Phosphorylation	Endometrial cancer/carcinoma		U		12888921
11	[Reference]: As hypothesised, results showed high levels of Akt1/2 mRNAs and protein phosphorylation in the two mutated PTEN human endometrial cancer cells.;Akt phosphorylation decreased and apoptosis was strongly increased in mutated PTEN human endometrial cancer cells in the presence of PI 3-K inhibitor (Wortmannin) which was accompanied by a down-regulation of cIAP-1 protein.
12	Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma		U		10853013; 23785446
12	[Reference]: Elevated phosphorylation of AKT and Stat3 in prostate, breast, and cervical cancer cells.
13	Phosphorylation	Cervical cancer/carcinoma		U		10853013
13	[Reference]: Elevated phosphorylation of AKT and Stat3 in prostate, breast, and cervical cancer cells.
14	Phosphorylation	Gastric cancer		U		23898095
14	[Reference]: Increased phosphorylation of AKT in high-risk gastric mucosa
15	Phosphorylation	Thyroid cancer/carcinoma		U		12788904
15	[Reference]: RNase-triggered apoptosis and caspase activation were accompanied by reduced phosphorylation of Akt/protein kinase B (PKB), a serine-threonine kinase that when phosphorylated is able to deliver survival signals to cancer cells.
16	Phosphorylation	Ovarian clear cell carcinoma		C		24299208
16	[Reference]: One novel mutation T544P was identified in exon 9 which can increase AKT phosphorylation in cell culture
17	Serine Phosphorylation	Lung cancer/carcinoma		P	S129	24008396
17	[Reference]: e found that in lung cancer cells, hematein inhibited cancer cell growth, Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increased apoptosis.
18	Tyrosine Phosphorylation	Pancreatic cancer/carcinoma/adenocarcinoma		P	Y176	22322295
18	[Reference]: Ack1 activates AKT directly in pancreatic and other cancer cell lines by phosphorylating AKT at Tyr176 to promote cell survival
19	Tyrosine Phosphorylation	Breast cancer/tumor/carcinoma		U	Y176	20333297
19	[Reference]: Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation.
20	Threonine Phosphorylation	Ovarian cancer/carcinoma	tumor tissue	D	T308	20153512
20	[Reference]: Higher phospho-AKT Thr308/pan-AKT ratio by Western blotting was associated with more advanced International Federation of Gynecology and Obstetrics stage (P = .018) and a trend for poor response to chemotherapy at first disease recurrence (P = .051).?
21	Threonine Phosphorylation	Diabetes mellitus	cell line	D	T308	17272402; 15919790; 20938636
21	[Reference]: Impaired AS160 phosphorylation was related to aberrant Akt signaling; insulin action on Akt Ser(473) phosphorylation was not significantly reduced in type 2 diabetic compared with control subjects, whereas Thr(308) phosphorylation was impaired 51% (P < 0.05).?
22	Threonine Phosphorylation	Non-small cell lung cancer/carcinoma		P	T308	23091605
22	[Reference]: Vapor of volatile oils from Litsea cubeba seed induces apoptosis and causes cell cycle arrest in lung cancer cells
23	Threonine Phosphorylation	Melanoma	tumor tissue	U	T308	19996208
23	[Reference]: BRAF-mutant tumors had higher levels of P-AKT-Ser473 (P = 0.01), P-AKT-Thr308 (P = 0.002), and P-GSK3alpha/beta (P = 0.08) than NRAS-mutant tumors.?
24	Threonine Phosphorylation	Pancreatic cancer/carcinoma/adenocarcinoma	cell line	U	T308	26676747
24	[Reference]: HEATR1 silencing in PDAC cells increased resistance to gemcitabine and other chemotherapeutics, where this effect was associated with increased AKT kinase phosphorylation at the Thr308 regulatory site.
25	Threonine Phosphorylation	Neuroblastoma	tumor tissue	U	T308	17234785
25	[Reference]: Here, we provide for the first time evidence that phosphorylation of Akt at serine 473 (S473) and/or threonine 308 (T308), S6 ribosomal protein, and ERK frequently occurs in primary neuroblastoma.
26	Threonine Phosphorylation	Lymphocytic leukemia		U	T308	20576813
26	[Reference]: high amounts of total Akt1, Akt1??Ser-473, and Akt??Thr 308 were detected in most CLL samples compared with samples from healthy persons.
27	Threonine Phosphorylation	Rhabdomyosarcoma	cell lines	U	T308	17848913
27	[Reference]: Our results showed phospho-AKT(Thr308) level is elevated 42 and 35% in ARMS and ERMS, respectively.?
28	Threonine Phosphorylation	Chronic lymphocytic leukemia	cell line	U	T308	16940331
28	[Reference]: PMA induced the phosphorylation of Akt at Ser-473 and Thr-308 and the phosphorylation of Akt substrates, independently of PI-3K in B-CLL cells.
29	Threonine Phosphorylation	Acute myeloid leukaemia/Acute myelogenous leukemia		U	T308	12750723
29	[Reference]: The constitutive phosphorylation of Ser473 and Thr308 were both observed in 44 cases (72.1%)
30	Serine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma	cell line	P	S473	23732709
30	[Reference]: AC and phosphorylation of Akt correlate in prostate adenocarcinoma
31	Serine Phosphorylation	Bladder cancer		P	S473	23799035
31	[Reference]: CSTP1, a novel protein phosphatase, blocks cell cycle, promotes cell apoptosis, and suppresses tumor growth of bladder cancer by directly dephosphorylating Akt at Ser473 site
32	Serine Phosphorylation	Acute myeloid leukaemia/Acute myelogenous leukemia		P	S473	15289327; 18056483
32	[Reference]: Cytoplasmic mislocalization of p27Kip1 was significantly associated with the constitutive serine(473) Akt/PKB phosphorylation in AML cells (P < 0.05).;
33	Serine Phosphorylation	Esophageal squamous cell carcinoma	tumor tissue	P	S473	23510069
33	[Reference]: Effects of SOX2 knockdown, including reduced levels of phosphorylated AKT and decreased ESCC cell proliferation, were reversed with constitutive activation of AKT with knockdown of phosphatase and tensin homolog.
34	Serine Phosphorylation	Lung cancer/carcinoma	A549 cell line	P	S473	23149922
34	[Reference]: Furthermore, MIG-7 protein inhibited protein phosphatase 2A to sustain Akt/GSK3? phosphorylation and cancer-cell migration/invasion
35	Serine Phosphorylation	Gastric cancer		P	S473	23440515; 23969493
35	[Reference]: In 40 gastric cancer tissues, significant correlations were found among the levels of phosphorylated AKT (pAKT), hTERT expression, and telomer length
36	Serine Phosphorylation	Ovarian cancer/carcinoma		P	S473	23877012
36	[Reference]: Phospho-AKT (serine473) expression correlated with survival from OVCA (P<0.05) and platinum-response (P=0.004)
37	Serine Phosphorylation	Anaplastic astrocytoma	SW1783 cell line	P	S473	23596468
37	[Reference]: PODXL overexpression in SW1783 cells significantly increased cell invasion, matrix metalloproteinase-9 (MMP-9) expression, cell survival against temozolomide-induced apoptotic stress, and phosphorylation of Akt at serine 473 (ser473), which was abolished by the selective phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (LY)
38	Serine Phosphorylation	Non-small cell lung cancer/carcinoma	A549 cell line	P	S473	23091605
38	[Reference]: Vapor of volatile oils from Litsea cubeba seed induces apoptosis and causes cell cycle arrest in lung cancer cells
39	Serine Phosphorylation	Parkinson's disease		U	S473	19800394
39	[Reference]: Here, double immunofluorescence microscopy found Akt and phospho(Ser473)-Akt to be expressed at high levels in tyrosine hydroxylase (TH) immunopositive dopaminergic neurons in control human brain.
40	Serine Phosphorylation	Neuroblastoma		U	S473	17234785
40	[Reference]: Here, we provide for the first time evidence that phosphorylation of Akt at serine 473 (S473) and/or threonine 308 (T308), S6 ribosomal protein, and ERK frequently occurs in primary neuroblastoma.
41	Serine Phosphorylation	Lymphocytic leukemia		U	S473	20576813
41	[Reference]: high amounts of total Akt1, Akt1??Ser-473, and Akt??Thr 308 were detected in most CLL samples compared with samples from healthy persons.
42	Serine Phosphorylation	Rhabdomyosarcoma		U	S473	17848913
42	[Reference]: Phospho-AKT(Ser473) level is also increased 43% in ARMS and 55% in ERMS. Furthermore, we showed that OSU-03012 inhibits cell viability and induces apoptosis in ARMS and ERMS cell lines (RH30, SMS-CTR), which express elevated phospho-AKT levels.
43	Serine Phosphorylation	Chronic lymphocytic leukemia		U	S473	16940331
43	[Reference]: PMA induced the phosphorylation of Akt at Ser-473 and Thr-308 and the phosphorylation of Akt substrates, independently of PI-3K in B-CLL cells.
44	Serine Phosphorylation	Systemic lupus erythematosus		U	S473	23735868
44	[Reference]: Pretreatment with NaHS decreased PHA-induced expression of CDK2, phosphorylation levels of AKT (ser473) and GSK3? (ser9) and increased the expression of p27(Kip1) and p21(WAF1/CIP1)
45	Serine Phosphorylation	Renal cancer/carcinoma		U	S473	12649200; 16247451; 19118035
45	[Reference]: siRNAs targeting casein kinase I gamma 3 (CSNK1G3) or the inositol polyphosphate multikinase (IPMK) significantly enhanced A-443654-mediated cell killing, and caused decreases in Akt Ser-473 and ribosomal protein S6 phosphorylation.
46	Serine Phosphorylation	Pancreatic cancer/carcinoma/adenocarcinoma		U	S473	15467756; 21474066; 28363942
46	[Reference]: The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells.
47	Serine Phosphorylation	Colon cancer/carcinoma		U	S473	22975685
47	[Reference]: Using anti PHF20 and anti pPKB (S473) antibodies, these events were mapped in various human cancer tissues. Taken together, these data suggest that PHF20 is a novel substrate for PKB and its phosphorylation by PKB plays an important role in tumorigenesis via regulating of p53 mediated signaling.
48	Serine Phosphorylation	Urethral cancer		U	S473	22975685
48	[Reference]: Using anti PHF20 and anti pPKB (S473) antibodies, these events were mapped in various human cancer tissues. Taken together, these data suggest that PHF20 is a novel substrate for PKB and its phosphorylation by PKB plays an important role in tumorigenesis via regulating of p53 mediated signaling.
49	Serine Phosphorylation	Breast cancer/tumor/carcinoma		U	S473	22476852; 12244301; 17545609
49	[Reference]: We demonstrated that inhibition of mTORC1/2 by mTOR kinase inhibitors PP242 and OSI-027 effectively suppress phosphorylation of Akt (S473) and breast cancer cell proliferation.;Expression of phosphorylated S473 in invasive breast carcinomas correlates with cytosolic p27. ;
50	Serine Phosphorylation	Melanoma		U	S473	12499277; 19996208
50	[Reference]: we evaluated Akt activation by immunohistochemistry in a series of pigmented skin lesions using an antibody specific for phospho-Akt Ser-473. Normal and slightly dysplastic nevi exhibited no significant Akt expression, in marked contrast to the dramatic Akt immunoreactivity seen in severely dysplastic nevi and melanomas (66.3% positive).?

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	breast, colorectal, ovarian, NSCLC
CTD (Curated) (count: 30) (view all)	MESH:D011125 ; Adenomatous Polyposis Coli MESH:D019969 ; Amphetamine-Related Disorders MESH:C562942 ; Aortic Valve, Calcification of MESH:D001943 ; Breast Neoplasms MESH:D002294 ; Carcinoma, Squamous Cell MESH:C535575 ; Carcinoma, squamous cell of head and neck MESH:D006332 ; Cardiomegaly MESH:D009202 ; Cardiomyopathies MESH:D015179 ; Colorectal Neoplasms MESH:C567337 ; Cowden-Like Syndrome MESH:D004195 ; Disease Models, Animal MESH:D004827 ; Epilepsy MESH:D005355 ; Fibrosis MESH:D006965 ; Hyperplasia MESH:D007249 ; Inflammation MESH:D008175 ; Lung Neoplasms MESH:D016399 ; Lymphoma, T-Cell MESH:D002189 ; Marijuana Abuse MESH:D008579 ; Meningioma MESH:D009133 ; Muscular Atrophy MESH:D015473 ; Leukemia, Promyelocytic, Acute MESH:D009765 ; Obesity MESH:D010051 ; Ovarian Neoplasms MESH:D010146 ; Pain MESH:D011230 ; Precancerous Conditions MESH:D011471 ; Prostatic Neoplasms MESH:D016715 ; Proteus Syndrome MESH:D011605 ; Psychoses, Substance-Induced MESH:D012559 ; Schizophrenia MESH:D012878 ; Skin Neoplasms
DisGeNet (Curated) (count: 210) (view all)	C0002982; Angioid Streaks C0003706; Arachnodactyly C0003857; Congenital arteriovenous malformation C0005586; Bipolar Disorder C0005745; Blepharoptosis C0006142; Malignant neoplasm of breast C0006281; Congenital bronchogenic cyst C0006625; Cachexia C0007134; Renal Cell Carcinoma C0007137; Squamous cell carcinoma C0007222; Cardiovascular Diseases C0007758; Cerebellar Ataxia C0009404; Colorectal Neoplasms C0011053; Deafness C0011570; Mental Depression C0011581; Depressive disorder C0012811; Colon diverticulum anatomic structure C0012819; Diverticular disease of colon C0013377; Dysgerminoma C0014544; Epilepsy C0016059; Fibrosis C0018021; Goiter C0018418; Gynecomastia C0018553; Hamartoma Syndrome, Multiple C0018772; Hearing Loss, Partial C0018800; Cardiomegaly C0018916; Hemangioma C0018920; Hemangioma, Cavernous C0020507; Hyperplasia C0020534; Orbital separation excessive C0020550; Hyperthyroidism C0020676; Hypothyroidism C0021368; Inflammation C0022596; Palmoplantar Keratosis C0022821; Kyphosis deformity of spine C0023221; Leg Length Inequality C0023487; Acute Promyelocytic Leukemia C0023798; Lipoma C0024121; Lung Neoplasms C0024221; Lymphangioma C0024236; Lymphedema C0024421; Macroglossia C0024809; Marijuana Abuse C0025286; Meningioma C0025362; Mental Retardation C0025990; Micrognathism C0026034; Microstomia C0026351; Moderate mental retardation (I.Q. 35-49) C0026846; Muscular Atrophy C0027092; Myopia C0027960; Nevus C0027962; Melanocytic nevus C0028754; Obesity C0029422; Osteochondrodysplasias C0029927; Ovarian Cysts C0030193; Pain C0030354; Papilloma C0032580; Adenomatous Polyposis Coli C0033578; Prostatic Neoplasms C0033941; Psychoses, Substance-Induced C0034065; Pulmonary Embolism C0036341; Schizophrenia C0036572; Seizures C0037286; Skin Neoplasms C0037293; Skin tag C0037926; Compression of spinal cord C0037932; Curvature of spine C0038002; Splenomegaly C0038356; Stomach Neoplasms C0040046; Thrombophlebitis C0040147; Thyroiditis C0040412; Fissured tongue C0042341; Varicocele C0079772; T-Cell Lymphoma C0085261; Proteus Syndrome C0086543; Cataract C0149871; Deep Vein Thrombosis C0151468; Thyroid Gland Follicular Adenoma C0151811; Subcutaneous nodule C0152421; Macrotia C0162819; Skin Diseases, Vascular C0178421; Fibroadenoma of breast C0206733; Strawberry nevus of skin C0221352; Syndactyly of fingers C0221358; Long narrow head C0234376; Action Tremor C0236733; Amphetamine-Related Disorders C0239479; Round face C0240278; Lymphatic obstruction C0240295; Mandibular hypoplasia C0240310; Hypoplasia of the maxilla C0240379; Open mouth C0240635; Byzanthine arch palate C0243050; Cardiovascular Abnormalities C0265319; Fibrous skin tumor of tuberous sclerosis C0265552; Congenital macrodactylia C0279680; Transitional cell carcinoma of bladder C0280631; Leiomyosarcoma of uterus C0332563; Papule C0332573; Macule C0332890; Congenital hemihypertrophy C0334082; NEVUS, EPIDERMAL (disorder) C0334092; Hamartomatous polyp C0338656; Impaired cognition C0339789; Congenital deafness C0423110; Downward slant of palpebral fissure C0423903; Low intelligence C0428791; Aortic valve calcification C0496897; Benign neoplasm of eye, unspecified C0525045; Mood Disorders C0544886; Somatic mutation C0554972; Large auricle C0557874; Global developmental delay C0575158; Kyphoscoliosis deformity of spine C0678222; Breast Carcinoma C0683322; Mental impairment C0685695; Abnormal lung lobation C0700208; Acquired scoliosis C0745730; Multiple lipomata C0746926; Multiple, subcutaneous nodules C0870082; Hyperkeratosis C0878544; Cardiomyopathies C0917816; Mental deficiency C0919267; ovarian neoplasm C0949059; Polyp of large intestine C1168401; Squamous cell carcinoma of the head and neck C1368816; Sebaceous adenoma C1384666; hearing impairment C1403035; Subcutaneous lipomas C1458155; Mammary Neoplasms C1510497; Lens Opacities C1720771; Testicular Hydrocele C1833325; Thin bony cortex C1835229; Onset of lymphedema around puberty C1835581; Large protruding ears C1836047; Long face C1836542; Depressed nasal bridge C1836996; Marfanoid body habitus C1837108; Decreased muscle mass C1839326; Abnormally-shaped vertebrae C1842892; Vascular abnormalities restricted to skin C1843367; Poor school performance C1845112; Hyperkyphosis C1848570; Large, floppy ears C1848924; Infantile onset C1850189; Large pinnae C1853237; Isolated cases C1853562; Adult onset C1855062; Large dysplastic ears C1856468; Round, full face C1857130; Hypoplastic mandible condyle C1857501; Hyperostosis of facial bones C1858033; Asymmetric chest C1859347; Abnormal subcutaneous fat tissue distribution C1859896; Progressive macrocephaly C1860236; Irregular hyperpigmentation C1860838; Large prominent ears C1861329; Spinal canal stenosis C1861975; Cafe au lait spots, multiple C1863351; Calvarial hyperostosis C1864897; Cognitive delay C1864985; Progressive disorder C1867616; Dermoid choristoma of eye proper C1867617; Hypertrophy of skin of soles C1969913; Hyperkeratosis, generalized C2051831; Pectus excavatum C2676676; BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1 C2937220; Congenital abnormality of vein C3277418; Gastrointestinal hamartomatous polyps C3550546; Depressed nasal root/bridge C3554519; COWDEN SYNDROME 6 C3714756; Intellectual Disability C4020813; Increased gastric cancer C4020856; Terminal tremor C4020875; Mental and motor retardation C4020876; Dull intelligence C4021768; Abnormality of metabolism/homeostasis C4021849; Conjunctival hamartoma C4021977; Visceral angiomatosis C4022020; Mucosal telangiectasiae C4022024; Upper limb asymmetry C4024864; Depigmentation/hyperpigmentation of skin C4024979; Ovarian papillary adenocarcinoma C4024989; Hereditary nonpolyposis colorectal carcinoma C4025321; Mandibular hyperostosis C4025896; Abnormality of the penis C4082243; Maxillary retrognathia C4083076; Increased head circumference C4255213; Increased size of skull C4280269; Noncancerous mole C4280485; Increased ossification of facial bones C4280486; Hypertrophy of facial bones C4280487; Enlargement of facial bones C4280495; Concave bridge of nose C4280519; Increased ossification of calvarial bones C4280520; Enlargement of calvarial bones C4280521; Thick lower jaw bone C4280522; Excessive growth of mandibular bone C4280523; Increased ossification of lower jaw C4280567; Abnormal skeletal development C4280640; Retrusion of upper jaw bones C4280641; Hypotrophic maxilla C4280642; Deficiency of upper jaw bones C4280643; Decreased projection of maxilla C4280653; Turridolichocephaly C4280654; Narrow skull shape C4280655; Narrow head shape C4280656; Narrow cranium shape C4280663; Increased size of cranium C4280664; Big calvaria
HGMD (count: 1)	CM081515; Schizophrenia, familial, association with; Missense/nonsense
GWASdb (count: 3)	rs2494731; Multiple complex diseases; Null rs2494731; Serum metabolites; Null rs2494732; Drug response to Risperidone; Null

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 33) (view all)	122 EEEMDFRSGSPSDNS dbPAF 124 EMDFRSGSPSDNSGA dbPAF 126 DFRSGSPSDNSGAEE dbPAF 129 SGSPSDNSGAEEMEV dbPAF 137 GAEEMEVSLAKPKHR dbPAF 146 AKPKHRVTMNEFEYL dbPAF 176 EKATGRYYAMKILKK dbPAF 211 NSRHPFLTALKYSFQ dbPAF 246 LSRERVFSEDRARFY dbPAF 291 KDGHIKITDFGLCKE dbPAF 305 EGIKDGATMKTFCGT dbPAF 308 KDGATMKTFCGTPEY dbPAF 312 TMKTFCGTPEYLAPE dbPAF 315 TFCGTPEYLAPEVLE dbPAF 326 EVLEDNDYGRAVDWW dbPAF 378 TLGPEAKSLLSGLLK dbPAF 396 KQRLGGGSEDAKEIM dbPAF 417 GIVWQHVYEKKLSPP dbPAF 435 QVTSETDTRYFDEEF dbPAF 437 TSETDTRYFDEEFTA dbPAF 443 RYFDEEFTAQMITIT dbPAF 448 EFTAQMITITPPDQD dbPAF 450 TAQMITITPPDQDDS dbPAF 457 TPPDQDDSMECVDSE dbPAF 473 RPHFPQFSYSASGTA dbPAF 474 PHFPQFSYSASGTA* dbPAF 475 HFPQFSYSASGTA dbPAF 477 PQFSYSASGTA dbPAF 479 FSYSASGTA**** dbPAF 65 AQCQLMKTERPRPNT dbPAF 72 TERPRPNTFIIRCLQ dbPAF 87 WTTVIERTFHVETPE dbPAF 92 ERTFHVETPEEREEW dbPAF
Ubiquitination (count: 12) (view all)	14 VKEGWLHKRGEYIKT PLMD 140 EMEVSLAKPKHRVTM PLMD 158 EYLKLLGKGTFGKVI PLMD 268 LDYLHSEKNVVYRDL PLMD 276 NVVYRDLKLENLMLD PLMD 297 ITDFGLCKEGIKDGA PLMD 30 RPRYFLLKNDGTFIG PLMD 301 GLCKEGIKDGATMKT PLMD 377 RTLGPEAKSLLSGLL PLMD 39 DGTFIGYKERPQDVD PLMD 400 GGGSEDAKEIMQHRF PLMD 8 MSDVAIVKEGWLHKR PLMD
Sumoylation (count: 2)	276 NVVYRDLKLENLMLD PLMD 301 GLCKEGIKDGATMKT PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

E7ETT5	P31749	BioGRID
E9PB61	P31749	DIP
E9PFC7	P31749	HPRD
F5GXF0	P31749	HPRD
F8W9H1	P31749	HPRD
O14492	P31749	HPRD
O14746	P31749	HPRD; MINT
O14757	P31749	HPRD
O14788	P31749	HPRD
O14920	P31749	HPRD
O15105	P31749	HPRD; MINT
O15111	P31749	HPRD
O15151	P31749	HPRD
O15360	P31749	HPRD
O15530	P31749	HPRD; IntAct; MINT
O43521	P31749	HPRD;IntAct
O43524	P31749	HPRD
O60437	P31749	HPRD; IntAct
O60825	P31749	HPRD
O94875	P31749	HPRD; MINT
O95716	P31749	HPRD
O95759	P31749	BioGRID
O95988	P31749	HPRD
O95999	P31749	HPRD; IntAct
P02749	P31749	IntAct
P02765	P31749	IntAct
P03165	P31749	MINT
P03372	P31749	HPRD
P04049	P31749	HPRD; MINT
P05106	P31749	HPRD
P07738	P31749	IntAct
P07900	P31749	HPRD
P07951	P31749	IntAct
P08238	P31749	HPRD
P08670	P31749	IntAct
P09601	P31749	HPRD; MINT
P10275	P31749	HPRD
P10636	P31749	DIP;MINT
P12268	P31749	HPRD
P12931	P31749	HPRD
P13645	P31749	HPRD
P13727	P31749	HPRD
P14598	P31749	HPRD
P15056	P31749	HPRD
P15692	P31749	HPRD
P15976	P31749	HPRD
P16220	P31749	HPRD
P17844	P31749	IntAct
P18031	P31749	HPRD; MINT
P19174	P31749	MINT
P21453	P31749	HPRD
P23443	P31749	HPRD; MINT
P23769	P31749	HPRD
P25685	P31749	IntAct
P26641	P31749	MINT
P27986	P31749	HPRD
P29474	P31749	HPRD
P30153	P31749	MINT
P31749	P31749	HPRD; IntAct
P31749	P31751	HPRD
P31749	P32927	MINT
P31749	P35568	HPRD
P31749	P35813	HPRD
P31749	P38398	IntAct
P31749	P38646	IntAct
P31749	P38936	HPRD
P31749	P41279	HPRD
P31749	P42224	HPRD
P31749	P42345	HPRD; MINT
P31749	P42574	HPRD; MINT
P31749	P42858	HPRD
P31749	P45985	HPRD
P31749	P46527	HPRD; MINT
P31749	P46937	HPRD
P31749	P49137	HPRD
P31749	P49815	HPRD
P31749	P49840	HPRD
P31749	P49841	DIP; IntAct;HPRD
P31749	P51617	HPRD
P31749	P54253	HPRD
P31749	P55211	HPRD
P31749	P56278	HPRD
P31749	P56279	HPRD
P31749	P60484	HPRD; MINT
P31749	P60709	IntAct
P31749	P62136	MINT
P31749	P62140	MINT
P31749	P62988	DIP
P31749	P63000	HPRD
P31749	P63104	HPRD
P31749	P67775	HPRD; MINT
P31749	P67809	HPRD
P31749	P67936	IntAct
P31749	P68371	IntAct
P31749	P78527	HPRD
P31749	P84022	HPRD; MINT
P31749	P98170	HPRD
P31749	P98177	HPRD
P31749	Q00987	HPRD; DIP; IntAct; MINT
P31749	Q01362	HPRD
P31749	Q04759	HPRD
P31749	Q04912	HPRD
P31749	Q05195	DIP
P31749	Q05513	HPRD; MINT
P31749	Q06481	HPRD
P31749	Q09472	HPRD; IntAct
P31749	Q09666	HPRD
P31749	Q12778	HPRD; DIP
P31749	Q13043	MINT
P31749	Q13153	HPRD
P31749	Q13322	HPRD
P31749	Q13362	MINT
P31749	Q13370	HPRD
P31749	Q13418	HPRD
P31749	Q13485	HPRD; MINT
P31749	Q13541	HPRD
P31749	Q13772	IntAct
P31749	Q14203	MINT
P31749	Q14643	DIP
P31749	Q15047	IntAct
P31749	Q15119	HPRD
P31749	Q15121	HPRD
P31749	Q15257	MINT
P31749	Q15796	HPRD; MINT
P31749	Q15910	HPRD
P31749	Q16513	HPRD
P31749	Q16543	IntAct
P31749	Q16584	HPRD
P31749	Q16778	HPRD
P31749	Q3SXZ7	HPRD
P31749	Q3V6T2	HPRD
P31749	Q5S007	MINT
P31749	Q5T1C6	HPRD; MINT
P31749	Q5T653	BioGRID
P31749	Q71DI3	BioGRID
P31749	Q7Z6J0	IntAct
P31749	Q86YN6	HPRD
P31749	Q8BUB4	MINT
P31749	Q8IXJ9	IntAct
P31749	Q8N668	IntAct
P31749	Q8NBZ7	HPRD
P31749	Q8TAI7	HPRD
P31749	Q8TCG2	IntAct
P31749	Q92547	HPRD; MINT
P31749	Q92574	HPRD
P31749	Q92731	HPRD;BioGRID
P31749	Q92831	IntAct
P31749	Q92934	HPRD
P31749	Q92945	DIP
P31749	Q96B36	HPRD
P31749	Q96EB6	IntAct
P31749	Q96QB1	HPRD
P31749	Q96RU7	HPRD
P31749	Q96S96	MINT
P31749	Q99623	HPRD
P31749	Q99683	HPRD; IntAct
P31749	Q9H4A3	HPRD
P31749	Q9H8T0	HPRD
P31749	Q9NPC1	MINT
P31749	Q9NPG2	BioGRID
P31749	Q9NUC0	IntAct
P31749	Q9UBP6	HPRD
P31749	Q9UIW2	HPRD
P31749	Q9UKG1	HPRD
P31749	Q9UKU6	IntAct
P31749	Q9UKY1	MINT
P31749	Q9UNE7	DIP
P31749	Q9UQC2	HPRD
P31749	Q9UQF2	HPRD
P31749	Q9Y6K9	IntAct

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction