P11346 (KRAF1_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Raf homolog serine/threonine-protein kinase phl
Short name=D-Raf
Short name=dRAF-1
EC=2.7.11.1

Alternative name(s):
Protein pole-hole

Gene names

Name:	phl
Synonyms:	ph
ORF Names:	CG2845

Organism

Drosophila melanogaster (Fruit fly)

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	782 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine kinase required in the early embryo for the formation of terminal structure. Also required during the proliferation of imaginal cells. May act downstream of ras1 in the sev signal transduction pathway. Ref.1 Ref.8
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Binds 2 zinc ions per subunit By similarity.
Developmental stage	Expressed both maternally and zygotically. Zygotically expressed throughout embryogenesis. Ref.1 Ref.8
Post-translational modification	Extensively phosphorylated 1 to 2 hours after egg laying. Ref.8 Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain. Contains 1 RBD (Ras-binding) domain.
Sequence caution	The sequence CAA30166.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAB72239.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	border follicle cell migration Inferred from genetic interaction. Source: FlyBase dorsal/ventral axis specification, ovarian follicular epithelium Inferred from mutant phenotype. Source: FlyBase epidermal growth factor receptor signaling pathway Inferred from genetic interaction. Source: FlyBase gastrulation Inferred from mutant phenotype. Source: FlyBase imaginal disc-derived wing morphogenesis Inferred from mutant phenotype. Source: FlyBase instar larval development Inferred from mutant phenotype. Source: FlyBase intracellular signal transduction Inferred from electronic annotation. Source: InterPro lamellocyte differentiation Inferred from mutant phenotype. Source: FlyBase positive regulation of cell proliferation Inferred from mutant phenotype. Source: FlyBase positive regulation of photoreceptor cell differentiation Inferred from mutant phenotype. Source: FlyBase primary branching, open tracheal system Traceable author statement. Source: FlyBase protein autophosphorylation Inferred from direct assay Ref.8. Source: FlyBase regulation of multicellular organism growth Inferred from mutant phenotype. Source: FlyBase spermatogenesis Inferred from mutant phenotype. Source: FlyBase terminal region determination Inferred from mutant phenotype. Source: FlyBase torso signaling pathway Inferred from mutant phenotype. Source: FlyBase wing and notum subfield formation Inferred from genetic interaction. Source: FlyBase
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: FlyBase protein serine/threonine kinase activity Inferred from direct assay Ref.8. Source: FlyBase receptor signaling protein activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform B (identifier: P11346-1)

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.

Note: No experimental confirmation available.

Isoform A (identifier: P11346-2)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     55-97: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 782	782	Raf homolog serine/threonine-protein kinase phl		PRO_0000086194
Regions
	Domain	184 – 255	72	RBD
	Domain	472 – 733	262	Protein kinase
	Zinc finger	265 – 311	47	Phorbol-ester/DAG-type
	Nucleotide binding	478 – 486	9	ATP By similarity
	Compositional bias	346 – 370	25	Ser-rich
Sites
	Active site	591	1	Proton acceptor By similarity
	Metal binding	263	1	Zinc 1 By similarity
	Metal binding	279	1	Zinc 2 By similarity
	Metal binding	282	1	Zinc 2 By similarity
	Metal binding	292	1	Zinc 1 By similarity
	Metal binding	295	1	Zinc 1 By similarity
	Metal binding	300	1	Zinc 2 By similarity
	Metal binding	303	1	Zinc 2 By similarity
	Metal binding	311	1	Zinc 1 By similarity
	Binding site	498	1	ATP By similarity
Amino acid modifications
	Modified residue	389	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	55 – 97	43	Missing in isoform A.		VSP_035659
	Natural variant	365	1	P → L in strain: AA1. Ref.6
	Natural variant	370	1	S → T in strain: KLH4 and KLH6. Ref.6
	Natural variant	403	1	S → R in strain: Reids2. Ref.6
	Natural variant	508	1	A → T in strain: 5-17-88b#5.
Experimental info
	Sequence conflict	161	1	N → T in CAA30166. Ref.1
	Sequence conflict	496	1	A → P in CAA30166. Ref.1
	Sequence conflict	521 – 523	3	KKT → RKA in M16598. Ref.7
	Sequence conflict	572	1	G → R in M16598. Ref.7
	Sequence conflict	701 – 704	4	PQAL → RRHS in CAA30166. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform B [UniParc]. Last modified November 4, 2008. Version 5. Checksum: A0C8C051D455D662	FASTA	782	88,634
	10 20 30 40 50 60 MSSESSTEGD SDLYDPLAEE LHNVQLVKHV TRENIDALNA KFANLQEPPA MYLIGESSKA 70 80 90 100 110 120 ELNTTWVLGN PTPTSKLFIK YPTYVYVCIS RLWFLPTEYQ ELTSKLHELE AKEQELMERL 130 140 150 160 170 180 NSQDQQEDSS LVERFKEQPH YQNQTQILQQ QRQLARVHHG NDLTDSLGSQ PGSQCGTLTR 190 200 210 220 230 240 QPKILLRAHL PNQQRTSVEV ISGVRLCDAL MKALKLRQLT PDMCEVSTTH SGRHIIPWHT 250 260 270 280 290 300 DIGTLHVEEI FVRLLDKFPI RTHIKHQIIR KTFFSLVFCE GCRRLLFTGF YCSQCNFRFH 310 320 330 340 350 360 QRCANRVPML CQPFPMDSYY QLLLAENPDN GVGFPGRGTA VRFNMSSRSR SRRCSSSGSS 370 380 390 400 410 420 SSSKPPSSSS GNHRQGRPPR ISQDDRSNSA PNVCINNIRS VTSEVQRSLI MQARPPLPHP 430 440 450 460 470 480 CTDHSNSTQA SPTSTLKHNR PRARSADESN KNLLLRDAKS SEENWNILAE EILIGPRIGS 490 500 510 520 530 540 GSFGTVYRAH WHGPVAVKTL NVKTPSPAQL QAFKNEVAML KKTRHCNILL FMGCVSKPSL 550 560 570 580 590 600 AIVTQWCEGS SLYKHVHVSE TKFKLNTLID IGRQVAQGMD YLHAKNIIHR DLKSNNIFLH 610 620 630 640 650 660 EDLSVKIGDF GLATAKTRWS GEKQANQPTG SILWMAPEVI RMQELNPYSF QSDVYAFGIV 670 680 690 700 710 720 MYELLAECLP YGHISNKDQI LFMVGRGLLR PDMSQVRSDA PQALKRLAED CIKYTPKDRP 730 740 750 760 770 780 LFRPLLNMLE NMLRTLPKIH RSASEPNLTQ SQLQNDEFLY LPSPKTPVNF NNFQFFGSAG NI
	Isoform A (C) [UniParc]. Checksum: B685A895D05048C1	FASTA	739	83,729
	10 20 30 40 50 60 MSSESSTEGD SDLYDPLAEE LHNVQLVKHV TRENIDALNA KFANLQEPPA MYLIEYQELT 70 80 90 100 110 120 SKLHELEAKE QELMERLNSQ DQQEDSSLVE RFKEQPHYQN QTQILQQQRQ LARVHHGNDL 130 140 150 160 170 180 TDSLGSQPGS QCGTLTRQPK ILLRAHLPNQ QRTSVEVISG VRLCDALMKA LKLRQLTPDM 190 200 210 220 230 240 CEVSTTHSGR HIIPWHTDIG TLHVEEIFVR LLDKFPIRTH IKHQIIRKTF FSLVFCEGCR 250 260 270 280 290 300 RLLFTGFYCS QCNFRFHQRC ANRVPMLCQP FPMDSYYQLL LAENPDNGVG FPGRGTAVRF 310 320 330 340 350 360 NMSSRSRSRR CSSSGSSSSS KPPSSSSGNH RQGRPPRISQ DDRSNSAPNV CINNIRSVTS 370 380 390 400 410 420 EVQRSLIMQA RPPLPHPCTD HSNSTQASPT STLKHNRPRA RSADESNKNL LLRDAKSSEE 430 440 450 460 470 480 NWNILAEEIL IGPRIGSGSF GTVYRAHWHG PVAVKTLNVK TPSPAQLQAF KNEVAMLKKT 490 500 510 520 530 540 RHCNILLFMG CVSKPSLAIV TQWCEGSSLY KHVHVSETKF KLNTLIDIGR QVAQGMDYLH 550 560 570 580 590 600 AKNIIHRDLK SNNIFLHEDL SVKIGDFGLA TAKTRWSGEK QANQPTGSIL WMAPEVIRMQ 610 620 630 640 650 660 ELNPYSFQSD VYAFGIVMYE LLAECLPYGH ISNKDQILFM VGRGLLRPDM SQVRSDAPQA 670 680 690 700 710 720 LKRLAEDCIK YTPKDRPLFR PLLNMLENML RTLPKIHRSA SEPNLTQSQL QNDEFLYLPS 730 PKTPVNFNNF QFFGSAGNI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Proliferation of both somatic and germ cells is affected in the Drosophila mutants of raf proto-oncogene." Nishida Y., Hata M., Ayaki T., Ryo H., Yamagata M., Shimizu K., Nishizuka Y. EMBO J. 7:775-781(1988) [PubMed: 3135183] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DEVELOPMENTAL STAGE.
[2]	"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.
[3]	"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. Strain: Berkeley.
[4]	"From sequence to chromosome: the tip of the X chromosome of D. melanogaster." Benos P.V., Gatt M.K., Ashburner M., Murphy L., Harris D., Barrell B.G., Ferraz C., Vidal S., Brun C., Demailles J., Cadieu E., Dreano S., Gloux S., Lelaure V., Mottier S., Galibert F., Borkova D., Minana B. , Kafatos F.C., Louis C., Siden-Kiamos I., Bolshakov S., Papagiannakis G., Spanos L., Cox S., Madueno E., de Pablos B., Modolell J., Peter A., Schoettler P., Werner M., Mourkioti F., Beinert N., Dowe G., Schaefer U., Jaeckle H., Bucheton A., Callister D.M., Campbell L.A., Darlamitsou A., Henderson N.S., McMillan P.J., Salles C., Tait E.A., Valenti P., Saunders R.D.C., Glover D.M. Science 287:2220-2222(2000) [PubMed: 10731137] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Oregon-R.
[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] (ISOFORM A). Strain: Berkeley. Tissue: Head.
[6]	"Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila." Riley R.M., Jin W., Gibson G. Mol. Ecol. 12:1315-1323(2003) [PubMed: 12694293] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 108-782, VARIANTS LEU-365; THR-370; ARG-403 AND THR-508. Strain: 5-17-88b#5, AA1, AA16, AA18, AA20, AA3, AM2, CA2, G5b, JS, KK1, KK2, KK3, KK4, KKb2, KLGC5, KLH4, KLH6, KM1, KMb1, PYR2 and Reids2.
[7]	"Drosophila melanogaster homologs of the raf oncogene." Mark G.E., Macintyre R.J., Digan M.E., Ambrosio L., Perrimon N. Mol. Cell. Biol. 7:2134-2140(1987) [PubMed: 3037346] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 466-754.
[8]	"Biochemical analysis of torso and D-raf during Drosophila embryogenesis: implications for terminal signal transduction." Sprenger F., Torsoclair M.M., Morrison D.K. Mol. Cell. Biol. 13:1163-1172(1993) [PubMed: 8423783] [Abstract] Cited for: FUNCTION, DEVELOPMENTAL STAGE, PHOSPHORYLATION.
[9]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed: 18327897] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X07181 Genomic DNA. Translation: CAA30166.1. Sequence problems. AE014298 Genomic DNA. Translation: AAF45774.1. AE014298 Genomic DNA. Translation: ABI30965.1. AE014298 Genomic DNA. Translation: ABW09328.1. AL133503 Genomic DNA. Translation: CAB72239.1. Sequence problems. AY089490 mRNA. Translation: AAL90228.1. AY135031 Genomic DNA. Translation: AAN17541.1. AY135032 Genomic DNA. Translation: AAN17542.1. AY135033 Genomic DNA. Translation: AAN17543.1. AY135034 Genomic DNA. Translation: AAN17544.1. AY135035 Genomic DNA. Translation: AAN17545.1. AY135036 Genomic DNA. Translation: AAN17546.1. AY135037 Genomic DNA. Translation: AAN17547.1. AY135038 Genomic DNA. Translation: AAN17548.1. AY135039 Genomic DNA. Translation: AAN17549.1. AY135040 Genomic DNA. Translation: AAN17550.1. AY135041 Genomic DNA. Translation: AAN17551.1. AY135042 Genomic DNA. Translation: AAN17552.1. AY135043 Genomic DNA. Translation: AAN17553.1. AY135044 Genomic DNA. Translation: AAN17554.1. AY135045 Genomic DNA. Translation: AAN17555.1. AY135046 Genomic DNA. Translation: AAN17556.1. AY135047 Genomic DNA. Translation: AAN17557.1. AY135048 Genomic DNA. Translation: AAN17558.1. AY135049 Genomic DNA. Translation: AAN17559.1. AY135050 Genomic DNA. Translation: AAN17560.1. AY135051 Genomic DNA. Translation: AAN17561.1. AY135052 Genomic DNA. Translation: AAN17562.1. M16598 Genomic DNA. No translation available.
PIR	TVFFDF. S00393.
RefSeq	NP_001036258.1. NM_001042793.1. NP_001096867.1. NM_001103397.1. NP_525047.1. NM_080308.2.
UniGene	Dm.39.
3D structure databases
ProteinModelPortal	P11346.
SMR	P11346. Positions 184-256, 265-314, 463-738.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29769N.
IntAct	P11346. 2 interactions.
MINT	MINT-296874.
STRING	P11346.
Proteomic databases
PRIDE	P11346.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0111025; FBpp0110324; FBgn0003079.
GeneID	31221.
KEGG	dme:Dmel_CG2845.
NMPDR	fig|7227.3.peg.16234.
Organism-specific databases
CTD	31221.
FlyBase	FBgn0003079. phl.
Phylogenomic databases
eggNOG	inNOG05988.
GeneTree	EMGT00050000001111.
InParanoid	P11346.
OMA	IEDWEIP.
OrthoDB	EOG49ZW49.
PhylomeDB	P11346.
Enzyme and pathway databases
BRENDA	2.7.10.2. 1994.
Gene expression databases
ArrayExpress	P11346.
Bgee	P11346.
GermOnline	CG2845. Drosophila melanogaster.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR003116. Raf-like_ras-bd. IPR001245. Ser-Thr/Tyr_kinase. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
KO	K02644.
Pfam	PF00130. C1_1. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF02196. RBD. 1 hit. [Graphical view]
SMART	SM00109. C1. 1 hit. SM00455. RBD. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50898. RBD. 1 hit. PS00479. ZF_DAG_PE_1. 1 hit. PS50081. ZF_DAG_PE_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	772524.

Entry information

Entry name

KRAF1_DROME

Accession

Primary (citable) accession number: P11346
Secondary accession number(s): A8JUV5 , Q0KHW7, Q8I086, Q8I0D9, Q8ISE1, Q8ISE2, Q8ISE3, Q9NEH9, Q9W4Z3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	November 4, 2008
Last modified:	January 25, 2012
This is version 131 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project