P46527

※ Protein Information

Tag	Content
UniProt Accession	CDN1B_HUMAN; P46527;
Entrez ID	1027
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	Cyclin-dependent kinase inhibitor 1B (Cyclin-dependent kinase inhibitor p27) (p27Kip1)
Gene Name	CDKN1B; KIP1
Organism	Homo sapiens
NCBI Taxa ID	9606
Functional Description	Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry. Functional Description Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA (PubMed:28666995). Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.
Sequence (Fasta)	MSNVRVSNGS PSLERMDARQ AEHPKPSACR NLFGPVDHEE LTRDLEKHCR DMEEASQRKW 60 NFDFQNHKPL EGKYEWQEVE KGSLPEFYYR PPRPPKGACK VPAQESQDVS GSRPAAPLIG 120 APANSEDTHL VDPKTDPSDS QTGLAEQCAG IRKRPATDDS STQNKRANRT EENVSDGSPN 180 AGSVEQTPKK PGLRRRQT 199 Fasta Sequence >P46527\|CDKN1B; KIP1\|Homo sapiens (Human) MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFGPVDHEELTRDLEKHCRDMEEASQRKWNFDFQNHKPLEGKYEWQEVEKGSLPEFYYRPPRPPKGACKVPAQESQDVSGSRPAAPLIGAPANSEDTHLVDPKTDPSDSQTGLAEQCAGIRKRPATDDSSTQNKRANRTEENVSDGSPNAGSVEQTPKKPGLRRRQT

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Phosphorylation	Corticotroph tumor		U		12050228
1	[Reference]: Our findings suggest that in corticotroph tumors there is an accentuated phosphorylation of p27 into P-p27, possibly related to increased cyclin E expression, whereas both p27 and P-p27 are subject to increased degradation in pituitary carcinomas.
2	Serine Phosphorylation	Epithelial ovarian cancer		P	S10	24018641
2	[Reference]: indicating that CRM1 and pSer10p27 expression was significantly higher in grade II or III EOC tissues than in grade I tissues
3	Serine Phosphorylation	Non-alcoholic steatohepatitis		P	S10	24351862
3	[Reference]: indicating that the phosphorylation of p27 at S10 is significantly correlated with cell proliferation in NASH-related HCC; however, phosphorylation of p27 at S10 was observed to be significantly correlated with the prognosis of the patients
4	Serine Phosphorylation	Breast cancer/tumor/carcinoma	MCF7	P	S10	21216562; 21067268
4	[Reference]: Microarray analysis showing that S10A, then abrogation of Ser(10) phosphorylation, result in important changes in a large number of genes involved in the control of cell cycle, cell differentiation, metabolism, immune response and signal transduction.
5	Serine Phosphorylation	Atherosclerosis		P	S10	21885849
5	[Reference]: Scarce phosphorylation of p27 at Ser10 is a hallmark of human and mouse atherosclerosis and promotes disease progression in mice.
6	Serine Phosphorylation	Chronic myelogenous leukemia/Chronic myeloid leukemia		U	S10	24098519
6	[Reference]: Therefore, cells expressing greater levels of phosphorylated p27kip1 and hence having increased cytosolic p27kip1 should have lower RhoA activity and hence lower RhoA membrane retention
7	Tyrosine Phosphorylation	Breast cancer/tumor/carcinoma		U	Y74	17254967
7	[Reference]: p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2.
8	Threonine Phosphorylation	Breast cancer/tumor/carcinoma		D	T157	26701207
8	[Reference]: Protein expression data of The Cancer Genome Atlas breast invasive carcinoma set revealed significantly lower Myc protein levels in tumors with highly expressed p27 lacking phosphorylation at Thr-157--a marker for active p27 localized in the nucleus.
9	Threonine Phosphorylation	Oral squamous cell carcinoma	cell line	P	T157	23106397
9	[Reference]: T157 phosphorylation contributes to cytoplasmic localization of p27 where it can promote cell proliferation and cell motility
10	Threonine Phosphorylation	Ovarian cancer/carcinoma	SKOV-3 cell line	P	T157	23339869
10	[Reference]: The LIM1 domain and pre-LIM region of TRIP6 regulate its function in AKT-mediated T157 phosphorylation of p27KIP1 and ovarian cancer cell proliferation
11	Threonine Phosphorylation	Thyroid cancer/carcinoma		U	T157	15743786
11	[Reference]: Finally, we evaluated whether these results were applicable to human tumors. Analysis of 100 thyroid carcinomas indicated that p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K/AKT pathway.?
12	Threonine Phosphorylation	Renal cancer/carcinoma		U	T157	19118035
12	[Reference]: In RCC, p27 is phosphorylated at T157 of the NLS, with increasing tumor grade associated with cytoplasmic p27.
13	Threonine Phosphorylation	Breast cancer/tumor/carcinoma	MCF7 cell line	P	T187	23769441
13	[Reference]: Expression of SKP2 and Thr187 phosphorylated p27(kip1) proteins in human breast carcinoma and their prognostic significance
14	Threonine Phosphorylation	B-cell lymphoma		P	T187	21338280
14	[Reference]: Overall, our results suggest that high levels of pThr187-p27(Kip1) may predict a worse clinical outcome in patients with aggressive lymphomas
15	Threonine Phosphorylation	Lymphoma		P	T187	22492278
15	[Reference]: Spy1 and pThr187-p27 express and Spy1/pThr187-p27 complex involves in proliferating lymphoma cells
16	Threonine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma		U	T187	23707764
16	[Reference]: The elevated p27(kip1) expression levels were concurrent with the decrease of its phosphorylation at threonine 187 through suppression of CDK2 kinase activity and the reduced phosphorylation of Akt at Serine 473 by diminishing the kinase activity of the mammalian target of rapamycin (mTOR)
17	Threonine Phosphorylation	Renal cancer/carcinoma		D	T198	19118035
17	[Reference]: Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.
18	Threonine Phosphorylation	Melanoma	cell line	P	T198	19470470
18	[Reference]: RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility
19	Threonine Phosphorylation	Thyroid cancer/carcinoma		U	T198	15743786
19	[Reference]: Analysis of 100 thyroid carcinomas indicated that p27(kip1) phosphorylation at T157/T198 and cytoplasmic mislocalization were preferentially associated with activation of the PI3K/AKT pathway.

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	breast, small intestine neuroendocrine tumours pituitary, parathyroid multiple endocrine neoplasia type IV
CTD (Curated) (count: 20) (view all)	MESH:D018248 ; Adenoma, Liver Cell MESH:D001943 ; Breast Neoplasms MESH:D006528 ; Carcinoma, Hepatocellular MESH:D054506 ; Chloracne MESH:D016481 ; Helicobacter Infections MESH:D007414 ; Intestinal Neoplasms MESH:D007680 ; Kidney Neoplasms MESH:D008113 ; Liver Neoplasms MESH:D008175 ; Lung Neoplasms MESH:D008654 ; Mesothelioma MESH:C567059 ; Multiple Endocrine Neoplasia, Type IV MESH:D018358 ; Neuroendocrine Tumors MESH:D010051 ; Ovarian Neoplasms MESH:D010911 ; Pituitary Neoplasms MESH:D019048 ; Prostatic Intraepithelial Neoplasia MESH:D011471 ; Prostatic Neoplasms MESH:D012004 ; Rectal Neoplasms MESH:D012751 ; Sezary Syndrome MESH:D013274 ; Stomach Neoplasms MESH:D014594 ; Uterine Neoplasms
DisGeNet (Curated) (count: 47) (view all)	C0001206; Acromegaly C0007095; Carcinoid Tumor C0011991; Diarrhea C0014868; Esophagitis C0020437; Hypercalcemia C0020502; Hyperparathyroidism C0021670; insulinoma C0021841; Intestinal Neoplasms C0022665; Kidney Neoplasm C0023903; Liver neoplasms C0024121; Lung Neoplasms C0025267; Multiple Endocrine Neoplasia Type 1 C0025500; Mesothelioma C0030920; Peptic Ulcer C0032000; Pituitary Adenoma C0032019; Pituitary Neoplasms C0033375; Prolactinoma C0033578; Prostatic Neoplasms C0034885; Rectal Neoplasms C0036920; Sezary Syndrome C0038356; Stomach Neoplasms C0042138; Uterine Neoplasms C0043515; Zollinger-Ellison syndrome C0079487; Helicobacter Infections C0151468; Thyroid Gland Follicular Adenoma C0206667; Adrenal Cortical Adenoma C0206669; Hepatocellular Adenoma C0206731; Angiofibroma C0206754; Neuroendocrine Tumors C0235986; Growth hormone excess C0241961; Angiomyolipoma of kidney C0262527; intermittent abdominal pain C0262587; Parathyroid Adenoma C0263454; Chloracne C0271844; Parathyroid hyperplasia C0282612; Prostatic Intraepithelial Neoplasias C0338078; Non-Functioning Pituitary Gland Neoplasm C0857973; Increased serum parathyroid hormone C0919267; ovarian neoplasm C1403035; Subcutaneous lipomas C1458155; Mammary Neoplasms C1864903; Hyperinsulinaemic hypoglycaemia C1864954; Hyperinsulinemia, fasting C1970712; Multiple Endocrine Neoplasia, Type IV C2239176; Liver carcinoma C3808022; Abdominal pain, episodic C4018860; Pituitary growth hormone cell adenoma
HGMD (count: 10) (view all)	CI073740; Multiple endocrine neoplasia 1; Small insertions CM065059; Pituitary and parathyroid tumours; Missense/nonsense CM092605; Multiple endocrine neoplasia 1; Missense/nonsense CM033961; Prostate cancer, reduced risk, association with; Missense/nonsense CM054649; Myeloproliferative syndrome; Missense/nonsense CM023042; Acute lymphoblastic leukaemia; Missense/nonsense CM092606; Multiple endocrine neoplasia 1; Missense/nonsense CR040861; Prostate cancer, increased risk, association with; Regulatory CR092607; Multiple endocrine neoplasia 1; Regulatory CR045877; Myocardial infarction, increased risk, association; Regulatory
GWASdb (count: 2)	rs34330; Systemic lupus erythematosus; systemic lupus erythematosus rs7330; Type 2 diabetes; type 2 diabetes mellitus

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 15) (view all)	10 NVRVSNGSPSLERMD dbPAF 12 RVSNGSPSLERMDAR dbPAF 140 PKTDPSDSQTGLAEQ dbPAF 157 GIRKRPATDDSSTQN dbPAF 175 NRTEENVSDGSPNAG dbPAF 178 EENVSDGSPNAGSVE dbPAF 183 DGSPNAGSVEQTPKK dbPAF 187 NAGSVEQTPKKPGLR dbPAF 198 PGLRRRQT***** dbPAF 2 ***MSNVRVSNG dbPAF 7 MSNVRVSNGSPSLE dbPAF 74 HKPLEGKYEWQEVEK dbPAF 83 WQEVEKGSLPEFYYR dbPAF 88 KGSLPEFYYRPPRPP dbPAF 89 GSLPEFYYRPPRPPK dbPAF
Acetylation (count: 1)	100 RPPKGACKVPAQESQ PLMD
Ubiquitination (count: 3)	100 RPPKGACKVPAQESQ PLMD 134 DTHLVDPKTDPSDSQ PLMD 165 DDSSTQNKRANRTEE PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

A8K107	P46527	MINT
O00505	P46527	HPRD; IntAct
O14980	P46527	HPRD
O15131	P46527	HPRD; IntAct
O96020	P46527	HPRD; IntAct
P00519	P46527	HPRD
P07947	P46527	HPRD; IntAct
P07948	P46527	HPRD; IntAct
P09936	P46527	HPRD; IntAct
P0CG47	P46527	HPRD
P10914	P46527	IntAct
P11802	P46527	HPRD; DIP; IntAct; MINT
P12931	P46527	HPRD; IntAct
P14635	P46527	HPRD; IntAct
P16949	P46527	IntAct;HPRD
P20248	P46527	HPRD; DIP; IntAct
P22314	P46527	IntAct
P24385	P46527	HPRD; IntAct
P24864	P46527	DIP; IntAct
P24941	P46527	HPRD; DIP; IntAct; MINT
P27348	P46527	HPRD; MINT
P30279	P46527	HPRD; DIP; IntAct; MINT
P30281	P46527	HPRD; IntAct
P31749	P46527	HPRD; MINT
P31946	P46527	HPRD; IntAct
P33993	P46527	HPRD; MINT
P46527	P49815	HPRD
P46527	P52292	MINT
P46527	P52565	HPRD; IntAct; MINT
P46527	P61024	HPRD; IntAct
P46527	P61586	DIP
P46527	P61970	IntAct
P46527	P61981	HPRD; IntAct
P46527	P62258	HPRD; IntAct
P46527	P62826	IntAct
P46527	P62837	IntAct
P46527	P62877	IntAct
P46527	P62993	HPRD; DIP; MINT
P46527	P78396	HPRD; IntAct
P46527	Q00526	HPRD
P46527	Q00534	DIP
P46527	Q00535	HPRD; IntAct
P46527	Q04917	HPRD
P46527	Q12933	HPRD; IntAct
P46527	Q13309	HPRD; IntAct
P46527	Q13616	IntAct
P46527	Q13619	HPRD
P46527	Q14790	HPRD
P46527	Q15078	IntAct
P46527	Q15418	DIP
P46527	Q5MJ70	HPRD
P46527	Q5T8J1	MINT
P46527	Q92905	HPRD; IntAct
P46527	Q9UKX7	HPRD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction