Reviewed, UniProtKB/Swiss-Prot P49762 (DOA_DROME)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase Doa
    EC=2.7.12.1
Alternative name(s):
    Protein darkener of apricot

Gene names

Name:	Doa
ORF Names:	CG1658

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	832 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Negative regulator of the copia retrotransposon element of the white (w) gene. In the eye, it is required for normal pigmentation, photoreceptor cell development and for organization of interommatidial bristles. Also essential for embryonic segmentation and differentiation of the nervous system. Functions in the control of alternative splicing by phosphorylating the argine/serine-rich splicing factors, SR proteins. Ref.1 Ref.6 Ref.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Subcellular location	Isoform C: Cytoplasm › cytosol. Ref.7 Isoform A: Nucleus. Note: Mainly nuclear with only low levels present in the cytoplasm. Ref.7
Tissue specificity	Ubiquitous expression in embryos. Stage 17 embryos show elevated expression in CNS and brain. Ubiquitous expression in larval imaginal disks. Increased expression posterior to the eye-antennal disk morphogenetic furrow. Ref.1 Ref.7
Developmental stage	Expressed both maternally (isoform C) and zygotically (isoforms A and C) in all developmental stages. Ref.1 Ref.7
Post-translational modification	Autophosphorylated on serine, threonine and tyrosine residues.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. Lammer subfamily. Contains 1 protein kinase domain.
Sequence caution	The sequence CAA55367.1 differs from that shown. Reason: Miscellaneous discrepancy. Chimera. Chimera of genomic DNA and cDNA.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
muskelin	Q8MR83	2	EBI-198460,EBI-466869
tra2	P19018-2	1	EBI-198486,EBI-198442
Ubp64E	Q24574	1	EBI-198486,EBI-189528

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform C (identifier: P49762-1)

Also known as: 105 kDa isoform;

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.

Note: No experimental confirmation available. May correspond to the described 105kDa isoform although there is no translation sequence evidence for this.

Isoform A (identifier: P49762-2)

Also known as: 55 kDa isoform;

The sequence of this isoform differs from the canonical sequence as follows:
     1-252: Missing.
     253-453: APQQQSKIGY...KSALGLHFIE → MQLPSLKDKL...GRNNRQSQAK
     722-727: Missing.

Note: Mainly nuclear with only low levels present in the cytoplasm. Ref.7

Isoform B (identifier: P49762-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-315: Missing.
     316-453: GMMSRNYYNM...KSALGLHFIE → MPRTRRLHHS...GRNNRQSQAK
     722-727: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 832	832	Serine/threonine-protein kinase Doa		PRO_0000085926
Regions
	Domain	479 – 799	321	Protein kinase
	Nucleotide binding	485 – 493	9	ATP By similarity
Sites
	Active site	605	1	Proton acceptor By similarity
	Binding site	508	1	ATP
Natural variations
	Alternative sequence	1 – 315	315	Missing in isoform B.		VSP_008269
	Alternative sequence	1 – 252	252	Missing in isoform A.		VSP_008268
	Alternative sequence	253 – 453	201	APQQQ…LHFIE → MQLPSLKDKLMPSGSVQQAK ANFSWQSLTQLLSGLWQRLY LPRSPFLALPAPPLATPPAN TTQRRAKKEMPRTRRLHHSR DRSSAGTRDKRRRHDTADHS PPLAEAPSPPRITNTHHTRS AAKRRRHELDAKKAQISKEP TFDDSISTRRRKERSKRSHR KSPAASRRQHKYRYRDETSH SSSRRRHRDRAKDERDSGRN NRQSQAK in isoform A.		VSP_008270
	Alternative sequence	316 – 453	138	GMMSR…LHFIE → MPRTRRLHHSRDRSSAGTRD KRRRHDTADHSPPLAEAPSP PRITNTHHTRSAAKRRRHEL DAKKAQISKEPTFDDSISTR RRKERSKRSHRKSPAASRRQ HKYRYRDETSHSSSRRRHRD RAKDERDSGRNNRQSQAK in isoform B.		VSP_008271
	Alternative sequence	722 – 727	6	Missing in isoform A and isoform B.		VSP_008272
Experimental info
	Mutagenesis	508	1	K → R: Loss of activity. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform C (105 kDa isoform) [UniParc]. Last modified September 19, 2003. Version 2. Checksum: 6EC90CB1A031DD68	FASTA	832	95,723
	10 20 30 40 50 60 MVAANLEVPT SSSSSAATKR QKDVDNKLEK CLNDMLKLKT SSNNNSTSNS NNNAIMSHSL 70 80 90 100 110 120 TGEHKDPKTA LEGPTSSSSS SSSKYIGESQ IPVPVQLYDP QKPLLQQQQQ QQRICYPIGK 130 140 150 160 170 180 SNSTSQLPMG GYQRLLQHQQ QQHHQQQQQQ HQEQQQYPQH KRPFLNWNSF ACSAMNGASD 190 200 210 220 230 240 PFMQQQHMPA HQQQQHLPHK LQQSYSSSHV PKQAPKSGLA MFLQKNTNKE NKFGQPMQQQ 250 260 270 280 290 300 PPGMMPQMYG YQAPQQQSKI GYPRTGAPLT HSASFSSAQR PTALQFHQQH QQQQHLQQQQ 310 320 330 340 350 360 QHPQQQQHQH SSFGVGMMSR NYYNMPKQPE RKPLQTFDPY AYPKPNQMQP VKYQQQQQHP 370 380 390 400 410 420 HTQFQNASAG GGGGGAAGLQ YDPNTNTQLF YASPASSSSN KQPQQPQQQQ QQQQSQLQQS 430 440 450 460 470 480 NSVIFNHSGQ QHQPHQQQQN EMSKSALGLH FIETAKPVIQ DDADGHLIYH TGDILHHRYK 490 500 510 520 530 540 IMATLGEGTF GRVVKVKDME RDYCMALKII KNVEKYREAA KLEINALEKI AQKDPHCDHL 550 560 570 580 590 600 CVKMIDWFDY HGHMCIVFEM LGLSVFDFLR ENNYEPYPLD QVRHMAYQLC YSVKFLHDNR 610 620 630 640 650 660 LTHTDLKPEN ILFVDSDYTS HYNHKINREV RRVKNTDVRL IDFGSATFDH EHHSTIVSTR 670 680 690 700 710 720 HYRAPEVILE LGWSQPCDVW SIGCILFELY LGITLFQTHD NREHLAMMER ILGQIPYRMA 730 740 750 760 770 780 RNHTLYSKTK TKYFYHGKLD WDEKSSAGRY VRDHCKPLFL CQLSDSEDHC ELFSLIKKML 790 800 810 820 830 EYEPSSRITL GEALHHPFFD RLPPHHRVGE VSNKQPLSSG SSSRERSHSL SR
	Isoform A (55 kDa isoform). Checksum: F73AC5B47733AF3A	FASTA	580	67,894
	10 20 30 40 50 60 MQLPSLKDKL MPSGSVQQAK ANFSWQSLTQ LLSGLWQRLY LPRSPFLALP APPLATPPAN 70 80 90 100 110 120 TTQRRAKKEM PRTRRLHHSR DRSSAGTRDK RRRHDTADHS PPLAEAPSPP RITNTHHTRS 130 140 150 160 170 180 AAKRRRHELD AKKAQISKEP TFDDSISTRR RKERSKRSHR KSPAASRRQH KYRYRDETSH 190 200 210 220 230 240 SSSRRRHRDR AKDERDSGRN NRQSQAKTAK PVIQDDADGH LIYHTGDILH HRYKIMATLG 250 260 270 280 290 300 EGTFGRVVKV KDMERDYCMA LKIIKNVEKY REAAKLEINA LEKIAQKDPH CDHLCVKMID 310 320 330 340 350 360 WFDYHGHMCI VFEMLGLSVF DFLRENNYEP YPLDQVRHMA YQLCYSVKFL HDNRLTHTDL 370 380 390 400 410 420 KPENILFVDS DYTSHYNHKI NREVRRVKNT DVRLIDFGSA TFDHEHHSTI VSTRHYRAPE 430 440 450 460 470 480 VILELGWSQP CDVWSIGCIL FELYLGITLF QTHDNREHLA MMERILGQIP YRMARKTKTK 490 500 510 520 530 540 YFYHGKLDWD EKSSAGRYVR DHCKPLFLCQ LSDSEDHCEL FSLIKKMLEY EPSSRITLGE 550 560 570 580 ALHHPFFDRL PPHHRVGEVS NKQPLSSGSS SRERSHSLSR
	Isoform B. Checksum: 8D6366BFDBD8A948	FASTA	511	60,210
	10 20 30 40 50 60 MPRTRRLHHS RDRSSAGTRD KRRRHDTADH SPPLAEAPSP PRITNTHHTR SAAKRRRHEL 70 80 90 100 110 120 DAKKAQISKE PTFDDSISTR RRKERSKRSH RKSPAASRRQ HKYRYRDETS HSSSRRRHRD 130 140 150 160 170 180 RAKDERDSGR NNRQSQAKTA KPVIQDDADG HLIYHTGDIL HHRYKIMATL GEGTFGRVVK 190 200 210 220 230 240 VKDMERDYCM ALKIIKNVEK YREAAKLEIN ALEKIAQKDP HCDHLCVKMI DWFDYHGHMC 250 260 270 280 290 300 IVFEMLGLSV FDFLRENNYE PYPLDQVRHM AYQLCYSVKF LHDNRLTHTD LKPENILFVD 310 320 330 340 350 360 SDYTSHYNHK INREVRRVKN TDVRLIDFGS ATFDHEHHST IVSTRHYRAP EVILELGWSQ 370 380 390 400 410 420 PCDVWSIGCI LFELYLGITL FQTHDNREHL AMMERILGQI PYRMARKTKT KYFYHGKLDW 430 440 450 460 470 480 DEKSSAGRYV RDHCKPLFLC QLSDSEDHCE LFSLIKKMLE YEPSSRITLG EALHHPFFDR 490 500 510 LPPHHRVGEV SNKQPLSSGS SSRERSHSLS R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The Doa locus encodes a member of a new protein kinase family and is essential for eye and embryonic development in Drosophila melanogaster." Yun B., Farkas R., Lee K., Rabinow L. Genes Dev. 8:1160-1173(1994) [PubMed: 7926721] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[2]	Rabinow L. Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[4]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
[5]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND C). Strain: Berkeley. Tissue: Embryo.
[6]	"Activity and autophosphorylation of LAMMER protein kinases." Lee K., Du C., Horn M., Rabinow L. J. Biol. Chem. 271:27299-27303(1996) [PubMed: 8910305] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF LYS-508.
[7]	"The LAMMER protein kinase encoded by the Doa locus of Drosophila is required in both somatic and germline cells and is expressed as both nuclear and cytoplasmic isoforms throughout development." Yun B., Lee K., Farkas R., Hitte C., Rabinow L. Genetics 156:749-761(2000) [PubMed: 11014821] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X78715 Genomic DNA. Translation: CAA55367.1. Sequence problems. AE014297 Genomic DNA. Translation: AAF56832.3. AE014297 Genomic DNA. Translation: AAF56833.2. AE014297 Genomic DNA. Translation: AAN14305.1. AY061474 mRNA. Translation: AAL29022.1. AY069573 mRNA. Translation: AAL39718.1.
PIR	A54099.
RefSeq	NP_001014679.1. NP_001014680.1. NP_001014682.1. NP_001036765.1. NP_001138120.1. NP_001138121.1. NP_001138122.1.
UniGene	Dm.6767
3D structure databases
HSSP	HSSP built from PDB template 1HOW based on UniProtKB Q03656.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49762. 52 interactions.
STRING	P49762.
Genome annotation databases
Ensembl	FBtr0091524; FBpp0084704; FBgn0053553; Drosophila melanogaster. [Genome view]
GeneID	43415.
Organism-specific databases
CTD	43415.
FlyBase	FBgn0259220. Doa.
Phylogenomic databases
OMA	THHTRSA.
Enzyme and pathway databases
BioCyc	DMEL-XXX-02:DMEL-XXX-02-013877-MON.
BRENDA	2.7.11.1. 48. 2.7.12.1. 48.
Gene expression databases
GermOnline	CG33553. Drosophila melanogaster.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	833791.

Entry information

Entry name

DOA_DROME

Accession

Primary (citable) accession number: P49762
Secondary accession number(s): Q8IMM0 , Q8T041, Q95RC9, Q9VAR8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	September 19, 2003
Last modified:	November 3, 2009
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project