dbPTM

DPOLA_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DPOLA_HUMAN
UniProt AC	P09884
Protein Name	DNA polymerase alpha catalytic subunit
Gene Name	POLA1
Organism	Homo sapiens (Human).
Sequence Length	1462
Subcellular Localization	Nucleus . Cytoplasm, cytosol . In the cytosol, colocalizes with RNA:DNA hybrids with a speckled pattern.
Protein Description	Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses. [PubMed: 27019227]
Protein Sequence	MAPVHGDDSLSDSGSFVSSRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDFTGVYEEVDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDADEKGKDGKARNKDKRNVKKLAVTKPNNIKSMFIACAGKKTADKAVDLSKDGLLGDILQDLNTETPQITPPPVMILKKKRSIGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDDVQVESTEEEQESGAMEFEDGDFDEPMEVEEVDLEPMAAKAWDKESEPAEEVKQEADSGKGTVSYLGSFLPDVSCWDIDQEGDSSFSVQEVQVDSSHLPLVKGADEEQVFHFYWLDAYEDQYNQPGVVFLFGKVWIESAETHVSCCVMVKNIERTLYFLPREMKIDLNTGKETGTPISMKDVYEEFDEKIATKYKIMKFKSKPVEKNYAFEIPDVPEKSEYLEVKYSAEMPQLPQDLKGETFSHVFGTNTSSLELFLMNRKIKGPCWLEVKSPQLLNQPVSWCKVEAMALKPDLVNVIKDVSPPPLVVMAFSMKTMQNAKNHQNEIIAMAALVHHSFALDKAAPKPPFQSHFCVVSKPKDCIFPYAFKEVIEKKNVKVEVAATERTLLGFFLAKVHKIDPDIIVGHNIYGFELEVLLQRINVCKAPHWSKIGRLKRSNMPKLGGRSGFGERNATCGRMICDVEISAKELIRCKSYHLSELVQQILKTERVVIPMENIQNMYSESSQLLYLLEHTWKDAKFILQIMCELNVLPLALQITNIAGNIMSRTLMGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKLGDEDEEIDGDTNKYKKGRKKAAYAGGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASEAQKVTEDGEQEQIPELPDPSLEMGILPREIRKLVERRKQVKQLMKQQDLNPDLILQYDIRQKALKLTANSMYGCLGFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFKLGNKVKSEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYVTKQELKGLDIVRRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALTKDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLTASQRAYAPEQLQKQDNLTIDTQYYLAQQIHPVVARICEPIDGIDAVLIATWLGLDPTQFRVHHYHKDEENDALLGGPAQLTDEEKYRDCERFKCPCPTCGTENIYDNVFDGSGTDMEPSLYRCSNIDCKASPLTFTVQLSNKLIMDIRRFIKKYYDGWLICEEPTCRNRTRHLPLQFSRTGPLCPACMKATLQPEYSDKSLYTQLCFYRYIFDAECALEKLTTDHEKDKLKKQFFTPKVLQDYRKLKNTAEQFLSRSGYSEVNLSKLFAGCAVKS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
9	Phosphorylation	APVHGDDSLSDSGSF CCCCCCCCCCCCCCH	34.22	-
11	Phosphorylation	VHGDDSLSDSGSFVS CCCCCCCCCCCCHHH	33.41	-
49	Phosphorylation	KAGEKYKYEVEDFTG HCCCCEEEEEEECCC	23.32	27251275
55	Phosphorylation	KYEVEDFTGVYEEVD EEEEEECCCCEEECC	37.75	21659604
58	Phosphorylation	VEDFTGVYEEVDEEQ EEECCCCEEECCHHH	14.02	-
66	Phosphorylation	EEVDEEQYSKLVQAR EECCHHHHHHHHHHH	15.85	27251275
67	Phosphorylation	EVDEEQYSKLVQARQ ECCHHHHHHHHHHHC	21.14	27251275
109	Ubiquitination	DALDADEKGKDGKAR CCCCCCCCCCCCCCC	72.33	-
129	Phosphorylation	NVKKLAVTKPNNIKS CCHHEEECCCCCHHH	34.87	19413330
130	Acetylation	VKKLAVTKPNNIKSM CHHEEECCCCCHHHE	38.87	23236377
130	Ubiquitination	VKKLAVTKPNNIKSM CHHEEECCCCCHHHE	38.87	-
135	Acetylation	VTKPNNIKSMFIACA ECCCCCHHHEEEHHH	37.68	25953088
144	Acetylation	MFIACAGKKTADKAV EEEHHHCCCCHHHHH	28.55	25953088
149	Acetylation	AGKKTADKAVDLSKD HCCCCHHHHHHCCCC	48.09	25953088
168	Phosphorylation	DILQDLNTETPQITP HHHHHCCCCCCCCCC	48.83	22210691
170	Phosphorylation	LQDLNTETPQITPPP HHHCCCCCCCCCCCC	20.60	30301811
174	Phosphorylation	NTETPQITPPPVMIL CCCCCCCCCCCEEEE	25.21	25159151
186	Phosphorylation	MILKKKRSIGASPNP EEEEECCCCCCCCCC	33.96	22167270
190	Phosphorylation	KKRSIGASPNPFSVH ECCCCCCCCCCCCCE	21.72	23927012
195	Phosphorylation	GASPNPFSVHTATAV CCCCCCCCCEECEEC	17.78	23927012
198	Phosphorylation	PNPFSVHTATAVPSG CCCCCCEECEECCCC	24.45	23927012
200	Phosphorylation	PFSVHTATAVPSGKI CCCCEECEECCCCCC	29.37	23927012
204	Phosphorylation	HTATAVPSGKIASPV EECEECCCCCCCCCC	46.23	23927012
206	Acetylation	ATAVPSGKIASPVSR CEECCCCCCCCCCCC	39.16	25953088
209	Phosphorylation	VPSGKIASPVSRKEP CCCCCCCCCCCCCCC	29.34	22167270
212	Phosphorylation	GKIASPVSRKEPPLT CCCCCCCCCCCCCCC	40.81	30266825
214	Acetylation	IASPVSRKEPPLTPV CCCCCCCCCCCCCCC	68.04	26051181
219	Phosphorylation	SRKEPPLTPVPLKRA CCCCCCCCCCCCCCC	28.19	26055452
224	Acetylation	PLTPVPLKRAEFAGD CCCCCCCCCCHHCCC	43.42	25953088
271	Acetylation	DLEPMAAKAWDKESE CCHHHHHHCCCCCCC	40.24	18530321
277	Phosphorylation	AKAWDKESEPAEEVK HHCCCCCCCCHHHHH	55.40	25159151
284	Sumoylation	SEPAEEVKQEADSGK CCCHHHHHHHHHCCC	45.78	-
284	Sumoylation	SEPAEEVKQEADSGK CCCHHHHHHHHHCCC	45.78	-
289	Phosphorylation	EVKQEADSGKGTVSY HHHHHHHCCCCCCHH	49.83	-
400	Phosphorylation	EMKIDLNTGKETGTP CEEEECCCCCCCCCC	57.85	29083192
402	Ubiquitination	KIDLNTGKETGTPIS EEECCCCCCCCCCCC	50.49	-
404	Phosphorylation	DLNTGKETGTPISMK ECCCCCCCCCCCCHH	50.25	29083192
406	Phosphorylation	NTGKETGTPISMKDV CCCCCCCCCCCHHHH	25.52	23312004
409	Phosphorylation	KETGTPISMKDVYEE CCCCCCCCHHHHHHH	22.45	29083192
411	Ubiquitination	TGTPISMKDVYEEFD CCCCCCHHHHHHHHH	36.93	-
414	Phosphorylation	PISMKDVYEEFDEKI CCCHHHHHHHHHHHH	21.63	29083192
420	Ubiquitination	VYEEFDEKIATKYKI HHHHHHHHHHHHHHH	39.21	-
449	Ubiquitination	EIPDVPEKSEYLEVK ECCCCCCCCCCEEEE	42.38	-
450	Phosphorylation	IPDVPEKSEYLEVKY CCCCCCCCCCEEEEE	29.79	25072903
452	Phosphorylation	DVPEKSEYLEVKYSA CCCCCCCCEEEEEEC	18.43	25072903
457	Phosphorylation	SEYLEVKYSAEMPQL CCCEEEEEECCCCCC	20.49	25072903
458	Phosphorylation	EYLEVKYSAEMPQLP CCEEEEEECCCCCCC	16.43	25072903
472	Phosphorylation	PQDLKGETFSHVFGT CCCCCCCCCCCCCCC	38.82	22210691
474	Phosphorylation	DLKGETFSHVFGTNT CCCCCCCCCCCCCCC	26.59	22210691
483	Phosphorylation	VFGTNTSSLELFLMN CCCCCCCHHHHHHHC	24.67	21601212
494	Ubiquitination	FLMNRKIKGPCWLEV HHHCCCCCCCEEEEE	60.89	-
503	Phosphorylation	PCWLEVKSPQLLNQP CEEEEECCHHHHCCC	24.05	25159151
515	Ubiquitination	NQPVSWCKVEAMALK CCCCCCHHHHHHCCC	36.53	-
522	Ubiquitination	KVEAMALKPDLVNVI HHHHHCCCHHHHHHH	27.26	-
533	Phosphorylation	VNVIKDVSPPPLVVM HHHHHCCCCCCEEEE	41.65	27499020
543	Phosphorylation	PLVVMAFSMKTMQNA CEEEEEEEHHHHHHH	15.16	24719451
590	Ubiquitination	FCVVSKPKDCIFPYA EEEEECCCCCCCCCC	69.81	-
599	Acetylation	CIFPYAFKEVIEKKN CCCCCCHHHHHHHCC	42.79	20167786
599	Ubiquitination	CIFPYAFKEVIEKKN CCCCCCHHHHHHHCC	42.79	-
604	Ubiquitination	AFKEVIEKKNVKVEV CHHHHHHHCCCEEEE	38.22	-
661	Acetylation	CKAPHWSKIGRLKRS CCCCCHHHHCHHHHC	43.94	25953088
661	Ubiquitination	CKAPHWSKIGRLKRS CCCCCHHHHCHHHHC	43.94	-
829	Ubiquitination	EIDGDTNKYKKGRKK CCCCCCCHHHHCCCC	61.61	-
848	Ubiquitination	GGLVLDPKVGFYDKF CCEEECCCCCCCCCE	55.44	-
930	Ubiquitination	KQVKQLMKQQDLNPD HHHHHHHHCCCCCHH	54.09	-
942	Phosphorylation	NPDLILQYDIRQKAL CHHHHHHHHHHHHHH	15.19	-
952	Phosphorylation	RQKALKLTANSMYGC HHHHHHHHHHHHHHH	23.39	24043423
955	Phosphorylation	ALKLTANSMYGCLGF HHHHHHHHHHHHHCC	15.77	24043423
957	Phosphorylation	KLTANSMYGCLGFSY HHHHHHHHHHHCCCH	12.42	24043423
963	Phosphorylation	MYGCLGFSYSRFYAK HHHHHCCCHHHCCCC	22.02	24043423
964	Phosphorylation	YGCLGFSYSRFYAKP HHHHCCCHHHCCCCC	11.12	24043423
965	Phosphorylation	GCLGFSYSRFYAKPL HHHCCCHHHCCCCCH	18.08	24043423
970	Acetylation	SYSRFYAKPLAALVT CHHHCCCCCHHHHHH	29.23	26051181
970	Succinylation	SYSRFYAKPLAALVT CHHHCCCCCHHHHHH	29.23	-
970	Succinylation	SYSRFYAKPLAALVT CHHHCCCCCHHHHHH	29.23	21890473
970	Ubiquitination	SYSRFYAKPLAALVT CHHHCCCCCHHHHHH	29.23	-
1000	Phosphorylation	KMNLEVIYGDTDSIM HCCCEEEECCCCCEE	17.71	-
1031	Ubiquitination	KVKSEVNKLYKLLEI HHHHHHHHHHHHHCC	59.37	-
1054	Ubiquitination	LLLLKKKKYAALVVE HHHHHCCCEEEEEEE	49.34	-
1055	Phosphorylation	LLLKKKKYAALVVEP HHHHCCCEEEEEEEC	13.14	-
1063	Phosphorylation	AALVVEPTSDGNYVT EEEEEECCCCCCCCC	26.41	24114839
1064	Phosphorylation	ALVVEPTSDGNYVTK EEEEECCCCCCCCCH	54.99	24114839
1071	Ubiquitination	SDGNYVTKQELKGLD CCCCCCCHHHHCCCC	31.56	-
1075	Acetylation	YVTKQELKGLDIVRR CCCHHHHCCCCCCCC	57.59	23236377
1075	Ubiquitination	YVTKQELKGLDIVRR CCCHHHHCCCCCCCC	57.59	-
1089	Ubiquitination	RDWCDLAKDTGNFVI CHHHHHHHHCCCEEH	64.22	-
1107	Phosphorylation	LSDQSRDTIVENIQK HCCCCCHHHHHHHHH	26.30	20068231
1114	Ubiquitination	TIVENIQKRLIEIGE HHHHHHHHHHHHHCH	45.43	-
1141	Ubiquitination	EINKALTKDPQDYPD HHHHHHCCCCCCCCC	69.16	-
1174	Phosphorylation	RKVKAGDTVSYVICQ CEECCCCEEEEEEEC	15.50	21601212
1187	Phosphorylation	CQDGSNLTASQRAYA ECCCCCCCHHHHCCC	28.63	21601212
1189	Phosphorylation	DGSNLTASQRAYAPE CCCCCCHHHHCCCHH	18.24	21601212
1200	Ubiquitination	YAPEQLQKQDNLTID CCHHHHHCCCCCCHH	69.11	21890473
1268	Phosphorylation	LGGPAQLTDEEKYRD CCCCCCCCCHHHHCC	29.32	21815630
1272	Ubiquitination	AQLTDEEKYRDCERF CCCCCHHHHCCHHHC	43.46	-
1327	Phosphorylation	LTFTVQLSNKLIMDI EEEEEEECCHHHHHH	18.15	-
1376	Ubiquitination	PLCPACMKATLQPEY CCCHHHHHCCCCCCC	37.80	-
1407	Acetylation	DAECALEKLTTDHEK CHHHHHHHCCCHHHH	52.57	25953088
1419	Ubiquitination	HEKDKLKKQFFTPKV HHHHHHHHHHCCHHH	63.87	-
1434	Methylation	LQDYRKLKNTAEQFL HHHHHHHHHHHHHHH	56.11	115975233
1434	Ubiquitination	LQDYRKLKNTAEQFL HHHHHHHHHHHHHHH	56.11	-
1436	Phosphorylation	DYRKLKNTAEQFLSR HHHHHHHHHHHHHHH	29.95	29759185
1444	Phosphorylation	AEQFLSRSGYSEVNL HHHHHHHCCCCCCCH	38.41	29759185
1446	Phosphorylation	QFLSRSGYSEVNLSK HHHHHCCCCCCCHHH	11.69	29759185
1447	Phosphorylation	FLSRSGYSEVNLSKL HHHHCCCCCCCHHHH	38.30	29759185
1462	Phosphorylation	FAGCAVKS------- HCCCCCCC-------	38.56	21712546

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
Oops, there are no upstream regulatory protein records of DPOLA_HUMAN !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of DPOLA_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of DPOLA_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RBMS1_HUMAN	RBMS1	physical	10869558
CDC45_HUMAN	CDC45	physical	10518787
RB_HUMAN	RB1	physical	9395244
RBMS1_HUMAN	RBMS1	genetic	10869558
PARP1_HUMAN	PARP1	physical	9518481
P53_HUMAN	TP53	physical	11917009
SLD5_HUMAN	GINS4	physical	21705323
PRI1_HUMAN	PRIM1	physical	22593576
PRI2_HUMAN	PRIM2	physical	22593576
PRI2_HUMAN	PRIM2	physical	22939629
PRI1_HUMAN	PRIM1	physical	22939629
PCNA_HUMAN	PCNA	physical	22939629
MCM3_HUMAN	MCM3	physical	22939629
PURA_HUMAN	PURA	physical	22939629
CCNE1_HUMAN	CCNE1	physical	11259605
CDK2_HUMAN	CDK2	physical	11259605
CCNA2_HUMAN	CCNA2	physical	11259605
PP2AA_HUMAN	PPP2CA	physical	11259605
2AAB_HUMAN	PPP2R1B	physical	11259605
MCM2_HUMAN	MCM2	physical	11259605
DNLI1_HUMAN	LIG1	physical	26344197
DPOE1_HUMAN	POLE	physical	26344197
DPOE4_HUMAN	POLE4	physical	26344197
PRI1_HUMAN	PRIM1	physical	26344197
WDHD1_HUMAN	WDHD1	physical	26344197

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00242	Cladribine
DB00631	Clofarabine
DB01073	Fludarabine
DB01280	Nelarabine

Regulatory Network of DPOLA_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions."; Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.; Sci. Signal. 2:RA46-RA46(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-174 AND SER-186, ANDMASS SPECTROMETRY.	19690332 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-190 ANDSER-209, AND MASS SPECTROMETRY.	18669648 [Abstract]
"Evaluation of the low-specificity protease elastase for large-scalephosphoproteome analysis."; Wang B., Malik R., Nigg E.A., Korner R.; Anal. Chem. 80:9526-9533(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209, AND MASSSPECTROMETRY.	19007248 [Abstract]
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-129 AND THR-219, ANDMASS SPECTROMETRY.	19413330 [Abstract]