P49643 (PRI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA primase large subunit
EC=2.7.7.-

Alternative name(s):
DNA primase 58 kDa subunit
Short name=p58

Gene names

Name:	PRIM2
Synonyms:	PRIM2A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication.
Cofactor	Binds 1 4Fe-4S cluster. Ref.4
Subunit structure	Heterodimer of a small subunit and a large subunit.
Sequence similarities	Belongs to the eukaryotic-type primase large subunit family.

Ontologies

Keywords
Biological process	DNA replication Transcription
Cellular component	DNA-directed RNA polymerase Primosome
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	4Fe-4S DNA-binding Iron Iron-sulfur Metal-binding
Molecular function	Nucleotidyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication initiation Traceable author statement. Source: Reactome DNA strand elongation involved in DNA replication Traceable author statement. Source: Reactome G1/S transition of mitotic cell cycle Traceable author statement. Source: Reactome M/G1 transition of mitotic cell cycle Traceable author statement. Source: Reactome S phase of mitotic cell cycle Traceable author statement. Source: Reactome telomere maintenance via recombination Traceable author statement. Source: Reactome telomere maintenance via semi-conservative replication Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome replisome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA primase activity Traceable author statement Ref.1. Source: ProtInc metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49643-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P49643-2)

The sequence of this isoform differs from the canonical sequence as follows:
     154-158: ISDEE → VSIFL
     159-509: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 509

509

DNA primase large subunit

PRO_0000046768

Sites

Metal binding

287

1

Iron-sulfur (4Fe-4S)

Metal binding

367

1

Iron-sulfur (4Fe-4S)

Metal binding

384

1

Iron-sulfur (4Fe-4S)

Metal binding

424

1

Iron-sulfur (4Fe-4S)

Natural variations

Alternative sequence

154 – 158

5

ISDEE → VSIFL in isoform 2.

VSP_015111

Alternative sequence

159 – 509

351

Missing in isoform 2.

VSP_015112

Natural variant

181

1

E → K.
Corresponds to variant rs5011403 [ dbSNP | Ensembl ].

VAR_059742

Natural variant

204

1

D → G.
Corresponds to variant rs6913546 [ dbSNP | Ensembl ].

VAR_059743

Natural variant

259

1

G → S.
Corresponds to variant rs927192 [ dbSNP | Ensembl ].

VAR_059744

Natural variant

265

1

Q → L.
Corresponds to variant rs3763183 [ dbSNP | Ensembl ].

VAR_051506

Natural variant

287

1

C → Y.
Corresponds to variant rs9476080 [ dbSNP | Ensembl ].

VAR_059745

Natural variant

435

1

D → G.
Corresponds to variant rs4307164 [ dbSNP | Ensembl ].

VAR_059746

Natural variant

446

1

Q → H.
Corresponds to variant rs4294007 [ dbSNP | Ensembl ].

VAR_059747

Natural variant

465

1

P → S. Ref.8
Corresponds to variant rs4294008 [ dbSNP | Ensembl ].

VAR_059748

Experimental info

Sequence conflict

8

1

W → R in CAA52378. Ref.1

Sequence conflict

40

1

I → T in CAA52378. Ref.1

Sequence conflict

88

1

N → K in CAA52378. Ref.1

Secondary structure

1

.

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509

Helix Strand Turn

Details...

Helix

273 – 276

4

Helix

277 – 283

7

Helix

286 – 298

13

Helix

303 – 316

14

Beta strand

318 – 324

7

Turn

333 – 335

3

Helix

338 – 344

7

Beta strand

345 – 351

7

Helix

367 – 372

6

Helix

385 – 388

4

Helix

391 – 400

10

Helix

405 – 416

12

Helix

420 – 432

13

Helix

444 – 455

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 16, 2004. Version 2. Checksum: 80195D48103F87A7	FASTA	509	58,806
	10 20 30 40 50 60 MEFSGRKWRK LRLAGDQRNA SYPHCLQFYL QPPSENISLI EFENLAIDRV KLLKSVENLG 70 80 90 100 110 120 VSYVKGTEQY QSKLESELRK LKFSYRENLE DEYEPRRRDH ISHFILRLAY CQSEELRRWF 130 140 150 160 170 180 IQQEMDLLRF RFSILPKDKI QDFLKDSQLQ FEAISDEEKT LREQEIVASS PSLSGLKLGF 190 200 210 220 230 240 ESIYKIPFAD ALDLFRGRKV YLEDGFAYVP LKDIVAIILN EFRAKLSKAL ALTARSLPAV 250 260 270 280 290 300 QSDERLQPLL NHLSHSYTGQ DYSTQGNVGK ISLDQIDLLS TKSFPPCMRQ LHKALRENHH 310 320 330 340 350 360 LRHGGRMQYG LFLKGIGLTL EQALQFWKQE FIKGKMDPDK FDKGYSYNIR HSFGKEGKRT 370 380 390 400 410 420 DYTPFSCLKI ILSNPPSQGD YHGCPFRHSD PELLKQKLQS YKISPGGISQ ILDLVKGTHY 430 440 450 460 470 480 QVACQKYFEM IHNVDDCGFS LNHPNQFFCE SQRILNGGKD IKKEPIQPET PQPKPSVQKT 490 500 KDASSALASL NSSLEMDMEG LEDYFSEDS
	Isoform 2 [UniParc]. Checksum: BF57630E126F1D14	FASTA	158	19,144
	10 20 30 40 50 60 MEFSGRKWRK LRLAGDQRNA SYPHCLQFYL QPPSENISLI EFENLAIDRV KLLKSVENLG 70 80 90 100 110 120 VSYVKGTEQY QSKLESELRK LKFSYRENLE DEYEPRRRDH ISHFILRLAY CQSEELRRWF 130 140 150 IQQEMDLLRF RFSILPKDKI QDFLKDSQLQ FEAVSIFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA replication in vitro by recombinant DNA-polymerase-alpha-primase." Stadlbauer F., Brueckner A., Rehfuess C., Eckerskorn C., Lottspeich F., Foerster V., Tseng B.Y., Nasheuer H.-P. Eur. J. Biochem. 222:781-793(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Skin.
[4]	"An iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase." Weiner B.E., Huang H., Dattilo B.M., Nilges M.J., Fanning E., Chazin W.J. J. Biol. Chem. 282:33444-33451(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IRON-SULFUR CLUSTER, COFACTOR.
[5]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-465, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X74331 mRNA. Translation: CAA52378.1.
AL121975, AL162579 Genomic DNA. Translation: CAI20534.1.
AL162579, AL121975 Genomic DNA. Translation: CAH73686.1.
BC017833 mRNA. Translation: AAH17833.1.
BC064931 mRNA. Translation: AAH64931.1.

IPI

IPI00027705.
IPI00644817.

PIR

S45631.

RefSeq

NP_000938.2. NM_000947.2.

UniGene

Hs.654580.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3L9Q	X-ray	1.70	A/B	272-464	[»]
3Q36	X-ray	2.50	A/B	266-457	[»]

ProteinModelPortal

P49643.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36438N.

IntAct

P49643. 3 interactions.

MINT

MINT-3017566.

STRING

9606.ENSP00000402620.

PTM databases

PhosphoSite

P49643.

Polymorphism databases

DMDM

51338777.

Proteomic databases

PaxDb

P49643.

PRIDE

P49643.

Protocols and materials databases

DNASU

5558.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

5558.

KEGG

hsa:5558.

UCSC

uc003pdv.1. human.
uc003pdx.3. human.

Organism-specific databases

CTD

5558.

GeneCards

GC06P057179.

HGNC

HGNC:9370. PRIM2.

MIM

176636. gene.

neXtProt

NX_P49643.

PharmGKB

PA162400108.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2219.

HOGENOM

HOG000212154.

HOVERGEN

HBG008257.

InParanoid

P49643.

KO

K02685.

Enzyme and pathway databases

Reactome

REACT_115566. Cell Cycle.
REACT_21300. Mitotic M-M/G1 phases.
REACT_383. DNA Replication.

Gene expression databases

CleanEx

HS_PRIM2.

Genevestigator

P49643.

GermOnline

ENSG00000146143. Homo sapiens.

Family and domain databases

InterPro

IPR016558. DNA_primase_lsu_euk.
IPR007238. DNA_primase_lsu_euk/arc.
[Graphical view]

PANTHER

PTHR10537. PTHR10537. 1 hit.

Pfam

PF04104. DNA_primase_lrg. 1 hit.
[Graphical view]

PIRSF

PIRSF009449. DNA_primase_large_subunit. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P49643.

GenomeRNAi

5558.

NextBio

21538.

SOURCE

Search...

Entry information

Entry name

PRI2_HUMAN

Accession

Primary (citable) accession number: P49643
Secondary accession number(s): Q53FJ8 , Q6P1Q7, Q8WVL2, Q9H413

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	August 16, 2004
Last modified:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.