P06400

PTMD Annotation Information


※ Protein Information

Tag Content
UniProt Accession RB_HUMAN; P06400;
Entrez ID 5925
GenBank Protein ID
GenBank Nucleotide ID
Protein Name Retinoblastoma-associated protein (p105-Rb) (pRb) (Rb) (pp110)
Gene Name RB1
Organism Homo sapiens
NCBI Taxa ID 9606
Functional DescriptionKey regulator of entry into cell division that acts as a tumor suppressor. Promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. Acts as a transcription repressor of E2F1 target genes. The underphosphorylated, active form of RB1 interacts with E2F1 and represses its transcription activity, leading to cell cycle arrest. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methylt(view all)
Sequence
(Fasta)
MPPKTPRKTA ATAAAAAAEP PAPPPPPPPE EDPEQDSGPE DLPLVRLEFE ETEEPDFTAL 60
CQKLKIPDHV RERAWLTWEK VSSVDGVLGG YIQKKKELWG ICIFIAAVDL DEMSFTFTEL 120
QKNIEISVHK FFNLLKEIDT STKVDNAMSR LLKKYDVLFA LFSKLERTCE LIYLTQPSSS 180
ISTEINSALV LKVSWITFLL AKGEVLQMED DLVISFQLML CVLDYFIKLS PPMLLKEPYK 240
TAVIPINGSP RTPRRGQNRS ARIAKQLEND TRIIEVLCKE HECNIDEVKN VYFKNFIPFM 300
NSLGLVTSNG LPEVENLSKR YEEIYLKNKD LDARLFLDHD KTLQTDSIDS FETQRTPRKS 360
NLDEEVNVIP PHTPVRTVMN TIQQLMMILN SASDQPSENL ISYFNNCTVN PKESILKRVK 420
DIGYIFKEKF AKAVGQGCVE IGSQRYKLGV RLYYRVMESM LKSEEERLSI QNFSKLLNDN 480
IFHMSLLACA LEVVMATYSR STSQNLDSGT DLSFPWILNV LNLKAFDFYK VIESFIKAEG 540
NLTREMIKHL ERCEHRIMES LAWLSDSPLF DLIKQSKDRE GPTDHLESAC PLNLPLQNNH 600
TAADMYLSPV RSPKKKGSTT RVNSTANAET QATSAFQTQK PLKSTSLSLF YKKVYRLAYL 660
RLNTLCERLL SEHPELEHII WTLFQHTLQN EYELMRDRHL DQIMMCSMYG ICKVKNIDLK 720
FKIIVTAYKD LPHAVQETFK RVLIKEEEYD SIIVFYNSVF MQRLKTNILQ YASTRPPTLS 780
PIPHIPRSPY KFPSSPLRIP GGNIYISPLK SPYKISEGLP TPTKMTPRSR ILVSIGESFG 840
TSEKFQKINQ MVCNSDRVLK RSAEGSNPPK PLKKLRFDIE GSDEADGSKH LPGESKFQQK 900
LAEMTSTRTR MQKQKMNDSM DTSNKEEK 929

※ PTM-Disease Association

NumPTMDiseaseCell TypeTypePTM SitePMID
1PhosphorylationColon cancer/carcinomaD11032757
[Reference]: There was a 2.4-fold decrease in the ratio of hyperphosphorylated pRb (ppRb) to hypophosphorylated pRb, as well as a 60-75% decrease in cdk 2- and cdk 4-specific phosphorylated pRb proteins.
2PhosphorylationHead and neck squamous cell carcinomaP23414419
[Reference]: P276-00 treatment suppressed cell proliferation through inhibition of CCND1 expression, reduced phosphorylation of retinoblastoma protein and abrogative transcription of E2F1 gene targets
3PhosphorylationLung cancer/carcinomaP9393586
[Reference]: The positive correlation between the expressions of RB protein and cyclin A suggests that RB protein in most RB(+) lung cancer cell lines is a target of cyclin-A-dependent kinase and that the tumor-suppressor function may be inactivated by phosphorylation.
4PhosphorylationBreast cancer/tumor/carcinomaU10860819; 23686806
[Reference]: Bone morphogenetic protein-2 blocks MDA MB 231 human breast cancer cell proliferation by inhibiting cyclin-dependent kinase-mediated retinoblastoma protein phosphorylation.
5PhosphorylationPancreatic cancer/carcinoma/adenocarcinomaU24107447; 24334458
[Reference]: Here, we found that proliferating pancreatic cancer cells (PCCs) from human PDAC patients and multiple murine models of PDAC (mPDAC) often exhibit abundant levels of phosphorylated retinoblastoma 1 (RB) and Smad2
6PhosphorylationAcute lymphoblastic leukaemiaU11380466
[Reference]: In p15- and p16-null K562 cells transfected with a tetracycline-inducible p15 cDNA construct, induction of p15 transcripts and protein was accompanied by decreased growth rates, decreased S-phase fraction, decreased retinoblastoma protein phosphorylation, and markedly reduced levels of DHFR transcripts and protein.
7PhosphorylationNeuroblastomaU16824683; 10644979
[Reference]: Membrane depolarization stimulates the proliferation of SH-SY5Y human neuroblastoma cells by increasing retinoblastoma protein (RB) phosphorylation through the activation of cyclin-dependent kinase 2 (Cdk2).
8PhosphorylationRetinoblastomaU11900540
[Reference]: Overexpression of gankyrin not only led to increased phosphorylation of Rb and activation of E2F-1 in U2-OS cells but also caused cell transformation in NIH3T3 cells.
9PhosphorylationUlcerative colitisU23967107
[Reference]: RB phosphorylation was significantly greater in colon samples from patients with CD compared with UC (p<0.005).
10PhosphorylationCrohn's diseaseU23967107
[Reference]: RB phosphorylation was significantly greater in colon samples from patients with CD compared with UC (p<0.005).
11PhosphorylationNasopharyngeal carcinomaU18697201
[Reference]: While LTF treatment downregulated expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), expression of p21 and p27 in 5-8F NPC cells was enhanced.
12Serine PhosphorylationBreast cancer/tumor/carcinomaUS24917599043
[Reference]: This was accompanied by the sustained expression of cyclin D1 despite progestin treatment, and increased levels of retinoblastoma (Rb) phosphorylation at sites targeted by cyclin D1-Cdk4 (Ser249/Thr252).
13Threonine PhosphorylationBreast cancer/tumor/carcinomaUT25217599043
[Reference]: MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts.
14Threonine PhosphorylationOvarian cancer/carcinomaUT35628319064
[Reference]: OCT4 controls mitotic stability and inactivates the RB tumor suppressor pathway to enhance ovarian cancer aggressiveness.
15Threonine PhosphorylationSquamous cell carcinomaUT35626265441
[Reference]: these data suggest such agents may merit evaluation in HPV-negative SCCHN, specifically in cases associated with high pT356RB1.
16Serine PhosphorylationPancreatic cancer/carcinoma/adenocarcinomatumor tissuePS78023408967
[Reference]: Consistent with previous studies (reviewed in [2]), pancreatic cancer cells showed phosphorylation of Rb protein (p-RbS780, p-RbS807/811
17Serine PhosphorylationProstate cancer/carcinoma/adenocarcinomaPS78016648554
[Reference]: Oral intake of apigenin resulted in dose-dependent (a) increase in the protein expression of WAF1/p21, KIP1/p27, INK4a/p16, and INK4c/p18; (b) down-modulation of the protein expression of cyclins D1, D2, and E; and cyclin-dependent kinases (cdk), cdk2, cdk4, and cdk6; (c) decrease in retinoblastoma phosphorylation at serine 780; (d) increase in the binding of cyclin D1 toward WAF1/p21 and KIP1/p27; and (e) decrease in the binding of cyclin E toward cdk2 in both types of tumors.
18Serine PhosphorylationHepatocellular carcinoma/Hepatocarcinoma/HepatomaUS78015349907
[Reference]: pRb phosphorylated at serine(Ser) 780 was detected more frequently in p18INK4C - negative than in p18INK4C - positive HCCs.
19Serine PhosphorylationSkin cancerAS79523888052
[Reference]: It caused loss of retinoblastoma phosphorylation at both Ser-795 and Ser-807/811, the preferred sites phosphorylated by Cdk4/6 and Cdk2, respectively.
20Serine PhosphorylationMelanomaUS79515502804
[Reference]: phosphorylation increases as goes from melanocytic nevus to metastatic tumor; increased p-Rb correlates with a worse prognosis
21Tyrosine PhosphorylationChronic myelogenous leukemia/Chronic myeloid leukemiaPY80516158058
[Reference]: We also show that ectopic expression of Rb induces apoptosis in Abl-dependent tumor cells by inhibiting the Abl tyrosine kinase activity, and that Rb-induced apoptosis is compromised by Abl-catalysed phosphorylation of Rb at Y805.?
22Serine PhosphorylationSkin cancerAS807/81123888052
[Reference]: It caused loss of retinoblastoma phosphorylation at both Ser-795 and Ser-807/811, the preferred sites phosphorylated by Cdk4/6 and Cdk2, respectively.
23Serine PhosphorylationPancreatic cancer/carcinoma/adenocarcinomatumor tissuePS807/81123408967
[Reference]: Consistent with previous studies (reviewed in [2]), pancreatic cancer cells showed phosphorylation of Rb protein (p-RbS780, p-RbS807/811
24Serine PhosphorylationNeuroendocrine cancer/carcinomaPS80724135281
[Reference]: Prevention of Rb phosphorylation at Ser807/Ser811 attenuated MTC proliferation
25Serine PhosphorylationBladder cancerPS807/81122787429
[Reference]: RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation
26Serine PhosphorylationOvarian cancer/carcinomaUS80728319064
[Reference]: OCT4 controls mitotic stability and inactivates the RB tumor suppressor pathway to enhance ovarian cancer aggressiveness.
27Serine PhosphorylationMelanomaUS80710969768; 15502804
[Reference]: Phosphorylation increases as goes from melanocytic nevus to metastatic tumor; increased p-Rb correlates with a worse prognosis
28Lysine MethylationBladder cancerPK81022787429
[Reference]: SMYD2 is an important oncoprotein in various types of cancer, and SMYD2-dependent RB1 methylation at lysine 810 promotes cell cycle progression of cancer cells
29Serine PhosphorylationNeuroendocrine cancer/carcinomaPS81124135281
[Reference]: Prevention of Rb phosphorylation at Ser807/Ser811 attenuated MTC proliferation
30DephosphorylationBreast cancer/tumor/carcinomacell lineUT82110353599; 22895174
[Reference]: Dephosphorylation of threonine-821 of the retinoblastoma tumor suppressor protein (Rb) is required for apoptosis induced by UV and Cdk inhibition

※ Disease Cross-ref Annotation

DatabaseAnnotation
Cancer Gene Census
retinoblastoma, sarcoma, breast, small cell lung carcinoma retinoblastoma, sarcoma, breast, small cell lung carcinoma familial retinoblastoma
CTD (Curated)
(count: 24)
(view all)
MESH:D000310 ; Adrenal Gland Neoplasms
MESH:D018268 ; Adrenocortical Carcinoma
MESH:D002545 ; Brain Ischemia
MESH:D001943 ; Breast Neoplasms
MESH:D002277 ; Carcinoma
MESH:D002280 ; Carcinoma, Basal Cell
HGMD
(count: 620)
(view all)
CP044537; Retinoblastoma; Complex rearrangements
CP044538; Retinoblastoma; Complex rearrangements
CP084624; Retinoblastoma; Complex rearrangements
CX941940; Retinoblastoma; Complex rearrangements
CD050472; Retinoblastoma; Small deletions
CD931046; Retinoblastoma; Small deletions
GWASdb
(count: 2)
rs2804085; Multiple complex diseases; Null
rs4151601; Multiple complex diseases; Null

※ PTM Sites

PTM Modification Sites
Phosphorylation
(count: 62)
(view all)
140       NLLKEIDTSTKVDNA     dbPAF
149       TKVDNAMSRLLKKYD     dbPAF
163       DVLFALFSKLERTCE     dbPAF
230       LDYFIKLSPPMLLKE     dbPAF
239       PMLLKEPYKTAVIPI     dbPAF
241       LLKEPYKTAVIPING     dbPAF
Acetylation
(count: 18)
(view all)
265       NRSARIAKQLENDTR     PLMD
279       RIIEVLCKEHECNID     PLMD
289       ECNIDEVKNVYFKNF     PLMD
341       RLFLDHDKTLQTDSI     PLMD
427       KDIGYIFKEKFAKAV     PLMD
548       NLTREMIKHLERCEH     PLMD
Ubiquitination
(count: 25)
(view all)
143       KEIDTSTKVDNAMSR     PLMD
265       NRSARIAKQLENDTR     PLMD
279       RIIEVLCKEHECNID     PLMD
289       ECNIDEVKNVYFKNF     PLMD
319       PEVENLSKRYEEIYL     PLMD
327       RYEEIYLKNKDLDAR     PLMD
Sumoylation
(count: 1)
720       KVKNIDLKFKIIVTA     PLMD
Glycation
(count: 1)
847       GTSEKFQKINQMVCN     PLMD
Methylation
(count: 3)
810       NIYISPLKSPYKISE     PLMD
860       CNSDRVLKRSAEGSN     PLMD
873       SNPPKPLKKLRFDIE     PLMD

※ Protein-Protein Interaction

NetworkInteraction
ABSource
A6H8Y1P06400HPRD
A6NJZ3P06400MINT
E7ENZ3P06400MINT
E9PFC7P06400HPRD
G3V1C4P06400HPRD
G3V1K3P06400IntAct
H7BYL5P06400MINT
O00257P06400HPRD
O00716P06400HPRD; DIP; IntAct; MINT
O14682P06400HPRD
O14757P06400MINT
O14777P06400HPRD
O15151P06400HPRD; MINT
O15379P06400HPRD
O43236P06400IntAct
O43463P06400HPRD
O60381P06400HPRD
O60583P06400HPRD
O75150P06400HPRD
O75569P06400HPRD
O75629P06400HPRD
O75717P06400MINT
O75832P06400HPRD; IntAct
O75884P06400HPRD
O94921P06400HPRD
O96017P06400MINT
P00390P06400IntAct
P00519P06400HPRD
P01100P06400HPRD
P01106P06400HPRD
P01308P06400HPRD
P03255P06400MINT
P03256P06400MINT
P04049P06400HPRD; IntAct
P04637P06400IntAct
P05120P06400HPRD
P05412P06400HPRD
P05549P06400HPRD
P05771P06400HPRD
P06400P06400HPRD; MINT
P06400P06493HPRD
P06400P07197IntAct
P06400P08047HPRD
P06400P09429HPRD
P06400P09884HPRD
P06400P10275HPRD
P06400P11142HPRD
P06400P11388HPRD
P06400P11802HPRD
P06400P14373HPRD
P06400P15172HPRD
P06400P15336HPRD
P06400P15976DIP
P06400P17480HPRD; DIP
P06400P17542DIP
P06400P17676HPRD
P06400P17947DIP;HPRD
P06400P19338IntAct
P06400P20226HPRD
P06400P21675DIP; IntAct;HPRD
P06400P21980HPRD
P06400P24385HPRD; IntAct
P06400P24941HPRD; IntAct
P06400P26358HPRD
P06400P27986HPRD
P06400P28482HPRD
P06400P29374DIP
P06400P29375HPRD; DIP
P06400P29590HPRD
P06400P30279HPRD
P06400P32519HPRD; DIP
P06400P33993HPRD; MINT
P06400P35232HPRD
P06400P35869HPRD; IntAct
P06400P36873HPRD
P06400P38936HPRD
P06400P39880HPRD; MINT
P06400P40337IntAct
P06400P41218HPRD; MINT
P06400P42166HPRD
P06400P42574HPRD
P06400P42575HPRD
P06400P42685HPRD; IntAct
P06400P43686DIP
P06400P45984HPRD
P06400P49715HPRD
P06400P49716HPRD
P06400P50750HPRD
P06400P51948HPRD
P06400P55210HPRD
P06400P55211HPRD
P06400P55212HPRD
P06400P55345HPRD; IntAct
P06400P62136IntAct;HPRD
P06400P62140HPRD
P06400P62805IntAct
P06400P62937HPRD
P06400P63244HPRD
P06400P67775MINT
P06400P78396HPRD
P06400Q00534HPRD; DIP; IntAct
P06400Q00577HPRD; IntAct
P06400Q00987HPRD; DIP; IntAct; MINT
P06400Q01094HPRD; DIP; IntAct; MINT
P06400Q01892HPRD
P06400Q02363HPRD
P06400Q02447HPRD
P06400Q02548HPRD
P06400Q02962HPRD
P06400Q05516HPRD
P06400Q06587HPRD
P06400Q06710IntAct
P06400Q07161DIP; MINT
P06400Q09028HPRD
P06400Q09472HPRD; IntAct
P06400Q12824HPRD
P06400Q12931HPRD
P06400Q13029HPRD; DIP
P06400Q13107HPRD
P06400Q13309HPRD
P06400Q13363HPRD
P06400Q13547HPRD; DIP; IntAct; MINT
P06400Q13573HPRD
P06400Q13574HPRD;IntAct
P06400Q14186DIP
P06400Q14188DIP
P06400Q14209HPRD; DIP; MINT
P06400Q14686HPRD; IntAct
P06400Q14790HPRD
P06400Q15014HPRD; IntAct
P06400Q15291HPRD
P06400Q15643HPRD
P06400Q15744HPRD
P06400Q16254HPRD; DIP
P06400Q16533HPRD
P06400Q16539IntAct; MINT
P06400Q16576HPRD; DIP
P06400Q5SVQ8MINT
P06400Q5T802HPRD
P06400Q5TKA1HPRD
P06400Q63HQ0IntAct
P06400Q66K89HPRD
P06400Q6PEW1MINT
P06400Q6UWW7MINT
P06400Q6UYC3HPRD
P06400Q6ZN30HPRD
P06400Q86U42IntAct
P06400Q86Y97HPRD
P06400Q8IVW6HPRD
P06400Q8IY32MINT
P06400Q8IZL8HPRD
P06400Q8N201MINT
P06400Q8WTS6MINT
P06400Q8WUA4HPRD
P06400Q92569HPRD
P06400Q92769DIP; MINT
P06400Q92831IntAct
P06400Q92851HPRD
P06400Q92966HPRD
P06400Q92994HPRD
P06400Q96EB6IntAct
P06400Q96FV9HPRD
P06400Q96PU4IntAct
P06400Q99708DIP; MINT;HPRD
P06400Q99933HPRD
P06400Q9BV86DIP
P06400Q9BZM1IntAct
P06400Q9HBD4HPRD
P06400Q9NY61HPRD
P06400Q9NYW8HPRD
P06400Q9UBU8HPRD
P06400Q9UGL1HPRD
P06400Q9UQ80HPRD; IntAct
P06400Q9Y276MINT
P06400Q9Y468IntAct;HPRD
P06400Q9Y676DIP
P06400Q9Y6B2HPRD