Reviewed, UniProtKB/Swiss-Prot Q23977 (HEP_DROME)

Names and origin

Protein names

Recommended name:
    Dual specificity mitogen-activated protein kinase kinase hemipterous
      Short name=MAPKK
    EC=2.7.12.2

Gene names

Name:	hep
Synonyms:	hem, MKK7
ORF Names:	CG4353

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	1178 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for the epithelial cell sheet movement called dorsal closure (DC), which allows establishment of the dorsal epidermis. Controls the expression in the dorsal epithelium edges of another dorsal closure gene, puckered (puc). Phosphorylates and activates the MAP kinase bsk; bsk signal transduction pathway mediates an immune response and morphogenesis. Ref.1 Ref.2 Ref.6
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Post-translational modification	MAPKK is itself dependent on Ser/Thr phosphorylation for activity catalyzed by MAP kinase kinase kinases By similarity. Weakly autophosphorylated. Ref.7
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
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	JNK cascade Traceable author statement. Source: FlyBase actin filament bundle formation Inferred from mutant phenotype. Source: FlyBase axon extension Inferred from mutant phenotype. Source: FlyBase basement membrane disassembly Inferred from mutant phenotype. Source: FlyBase border follicle cell migration Inferred from genetic interaction. Source: FlyBase chorion-containing eggshell pattern formation Inferred from mutant phenotype. Source: FlyBase determination of adult lifespan Inferred from mutant phenotype. Source: FlyBase dorsal appendage formation Inferred from mutant phenotype. Source: FlyBase dorsal closure, spreading of leading edge cells Ref.1 Inferred from mutant phenotype. Source: FlyBase establishment of planar polarity Non-traceable author statement. Source: FlyBase filopodium assembly Inferred from mutant phenotype. Source: FlyBase imaginal disc eversion Inferred from mutant phenotype. Source: FlyBase imaginal disc fusion, thorax closure Traceable author statement. Source: FlyBase lamellipodium assembly Inferred from mutant phenotype. Source: FlyBase micropyle formation Inferred from mutant phenotype. Source: FlyBase positive regulation of JUN kinase activity Inferred from mutant phenotype. Source: FlyBase protein amino acid phosphorylation Traceable author statement. Source: FlyBase regulation of hemocyte differentiation Inferred from mutant phenotype. Source: FlyBase wound healing Inferred from mutant phenotype. Source: FlyBase
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase kinase activity Traceable author statement. Source: FlyBase MAP-kinase scaffold activity Inferred from direct assay. Source: UniProtKB protein kinase binding Inferred from physical interaction. Source: UniProtKB protein tyrosine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW receptor signaling protein serine/threonine kinase activity Non-traceable author statement. Source: FlyBase
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Aplip1	Q9W0K0	2	EBI-74214,EBI-74120
bsk	P92208	1	EBI-74214,EBI-74487

Alternative products

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

Isoform A (identifier: Q23977-1)

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 B (identifier: Q23977-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-621: Missing.
     652-652: G → GGFGSIDLDLEKKKEYSTNSSLAG

Note: No experimental confirmation available.

Isoform C (identifier: Q23977-3)

The sequence of this isoform differs from the canonical sequence as follows:
     489-492: ATAT → LPNS
     493-1178: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1178	1178	Dual specificity mitogen-activated protein kinase kinase hemipterous		PRO_0000085992
Regions
	Domain	197 – 456	260	Protein kinase
	Nucleotide binding	203 – 211	9	ATP By similarity
	Compositional bias	672 – 743	72	Thr-rich
	Compositional bias	768 – 815	48	Gln-rich
Sites
	Active site	320	1	Proton acceptor By similarity
	Binding site	226	1	ATP By similarity
Amino acid modifications
	Modified residue	348	1	Phosphoserine By similarity
	Modified residue	352	1	Phosphothreonine By similarity
	Modified residue	646	1	Phosphoserine Ref.7
	Modified residue	662	1	Phosphoserine Ref.7
	Modified residue	1150	1	Phosphoserine Ref.7
	Modified residue	1154	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 621	621	Missing in isoform B.		VSP_015106
	Alternative sequence	489 – 492	4	ATAT → LPNS in isoform C.		VSP_015107
	Alternative sequence	493 – 1178	686	Missing in isoform C.		VSP_015108
	Alternative sequence	652	1	G → GGFGSIDLDLEKKKEYSTNS SLAG in isoform B.		VSP_015109
Experimental info
	Sequence conflict	71	1	G → S in AAC46944. Ref.1
	Sequence conflict	93 – 97	5	PFGSA → LRSP in AAC46944. Ref.1
	Sequence conflict	106	1	A → R in AAC46944. Ref.1
	Sequence conflict	110	1	A → R in AAC46944. Ref.1
	Sequence conflict	118 – 121	4	TFGG → LRW in AAC46944. Ref.1
	Sequence conflict	147 – 150	4	GLNR → DVEC in AAC46944. Ref.1
	Sequence conflict	477 – 489	13	RLRAN…TLQRA → DCGQWRSNAPEVT Ref.1
	Sequence conflict	927	1	D → G in AAL48832. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified August 16, 2005. Version 2. Checksum: 79A2987068EC1870	FASTA	1,178	125,108
	10 20 30 40 50 60 MSTIEFETIG SRLQSLEAKL QAQNESHDQI VLSGARGPVV SGSVPSARVP PLATSASAAT 70 80 90 100 110 120 SATHAPSLGA GSVSGSGISI AQRPAPPVPH ATPFGSASAS SSSSSASAFA SAAPATGTFG 130 140 150 160 170 180 GTYTPPTTRV SRATPTLPML SSGPGGGLNR TRPVILPLPT PPHPPVSETD MKLKIIMEQT 190 200 210 220 230 240 GKLNINGRQY PTDINDLKHL GDLGNGTSGN VVKMMHLSSN TIIAVKQMRR TGNAEENKRI 250 260 270 280 290 300 LMDLDVVLKS HDCKYIVKCL GCFVRDPDVW ICMELMSMCF DKLLKLSKKP VPEQILGKVT 310 320 330 340 350 360 VATVNALSYL KDKHGVIHRD VKPSNILIDE RGNIKLCDFG ISGRLVDSKA NTRSAGCAAY 370 380 390 400 410 420 MAPERIDPKK PKYDIRADVW SLGITLVELA TARSPYEGCN TDFEVLTKVL DSEPPCLPYG 430 440 450 460 470 480 EGYNFSQQFR DFVIKCLTKN HQDRPKYPEL LAQPFIRIYE SAKVDVPNWF QSIKDNRLRA 490 500 510 520 530 540 NGDPTLQRAT ATGSAIGSGA GSLAGSGSGS AGGAVKYGRA TTYAGQSPTN PQKTIKPTQI 550 560 570 580 590 600 PSYQQQQSQF FMQSATQLPQ TTTTTPTATT NCFGGSGNGN GRGNGSGGSG NGSGSSSSAS 610 620 630 640 650 660 PLSPPSAGIG DLNRLYRKSP FMQRKLSNGS HHPHYKYNDE SPKKESMFSS IGQSILRNLT 670 680 690 700 710 720 TSPFSQKKHN STATTIPLPH NNQTLITDAA TAAAAAATAT TPPNIAATVL TTTPTTTPTW 730 740 750 760 770 780 RLPTENSQAY DSCDSSSNAT TTTLNLGLSS PSPSLPRKQF PTESPTLQLT SQQQQQPQRL 790 800 810 820 830 840 QPGNQSPIVL QRFYHQQNQL REKEAAERYQ QQRQQPPVGV TSTNPFHSNY VPPPPSTHST 850 860 870 880 890 900 SSQSSTQSTC SQIAINPASI SPSSGSGTGN MAGLGIGSAP ASGLGAAGHF GAGGTGEQLQ 910 920 930 940 950 960 YQPLPIAAEA TGTSPTLQSR SPEQQSDYGG NGNMVASKLS KLYARRQLLG QSSSSGASNS 970 980 990 1000 1010 1020 SLDGCSREQH DAGWFNTLAG AMKRQFATYV KTQLNSTATS PVASSMDRDQ EPVHPQPPAY 1030 1040 1050 1060 1070 1080 RSVVNNGSGG KSYYYRTLSA ASSSSNTSQS TSPTTEPLPG GGTSSFLRRY ASSGPGGSIS 1090 1100 1110 1120 1130 1140 TPPSPHILAG LDRRHRSPDP PPRYNRGQSP LLLRKNLLEL SGQPPGSPLL HRRYVSASPP 1150 1160 1170 LPPPRRGSES VPGSPQHFRT RIHYTPEPQR RIYRTIDQ
	Isoform B. Checksum: 9A96898AB57A5F9E	FASTA	580	61,938
	10 20 30 40 50 60 MQRKLSNGSH HPHYKYNDES PKKESMFSSI GGFGSIDLDL EKKKEYSTNS SLAGQSILRN 70 80 90 100 110 120 LTTSPFSQKK HNSTATTIPL PHNNQTLITD AATAAAAAAT ATTPPNIAAT VLTTTPTTTP 130 140 150 160 170 180 TWRLPTENSQ AYDSCDSSSN ATTTTLNLGL SSPSPSLPRK QFPTESPTLQ LTSQQQQQPQ 190 200 210 220 230 240 RLQPGNQSPI VLQRFYHQQN QLREKEAAER YQQQRQQPPV GVTSTNPFHS NYVPPPPSTH 250 260 270 280 290 300 STSSQSSTQS TCSQIAINPA SISPSSGSGT GNMAGLGIGS APASGLGAAG HFGAGGTGEQ 310 320 330 340 350 360 LQYQPLPIAA EATGTSPTLQ SRSPEQQSDY GGNGNMVASK LSKLYARRQL LGQSSSSGAS 370 380 390 400 410 420 NSSLDGCSRE QHDAGWFNTL AGAMKRQFAT YVKTQLNSTA TSPVASSMDR DQEPVHPQPP 430 440 450 460 470 480 AYRSVVNNGS GGKSYYYRTL SAASSSSNTS QSTSPTTEPL PGGGTSSFLR RYASSGPGGS 490 500 510 520 530 540 ISTPPSPHIL AGLDRRHRSP DPPPRYNRGQ SPLLLRKNLL ELSGQPPGSP LLHRRYVSAS 550 560 570 580 PPLPPPRRGS ESVPGSPQHF RTRIHYTPEP QRRIYRTIDQ
	Isoform C. Checksum: 6A16227A5B55F464	FASTA	492	53,132
	10 20 30 40 50 60 MSTIEFETIG SRLQSLEAKL QAQNESHDQI VLSGARGPVV SGSVPSARVP PLATSASAAT 70 80 90 100 110 120 SATHAPSLGA GSVSGSGISI AQRPAPPVPH ATPFGSASAS SSSSSASAFA SAAPATGTFG 130 140 150 160 170 180 GTYTPPTTRV SRATPTLPML SSGPGGGLNR TRPVILPLPT PPHPPVSETD MKLKIIMEQT 190 200 210 220 230 240 GKLNINGRQY PTDINDLKHL GDLGNGTSGN VVKMMHLSSN TIIAVKQMRR TGNAEENKRI 250 260 270 280 290 300 LMDLDVVLKS HDCKYIVKCL GCFVRDPDVW ICMELMSMCF DKLLKLSKKP VPEQILGKVT 310 320 330 340 350 360 VATVNALSYL KDKHGVIHRD VKPSNILIDE RGNIKLCDFG ISGRLVDSKA NTRSAGCAAY 370 380 390 400 410 420 MAPERIDPKK PKYDIRADVW SLGITLVELA TARSPYEGCN TDFEVLTKVL DSEPPCLPYG 430 440 450 460 470 480 EGYNFSQQFR DFVIKCLTKN HQDRPKYPEL LAQPFIRIYE SAKVDVPNWF QSIKDNRLRA 490 NGDPTLQRLP NS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hemipterous encodes a novel Drosophila MAP kinase kinase, required for epithelial cell sheet movement." Glise B., Bourbon H., Noselli S. Cell 83:451-461(1995) [PubMed: 8521475] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), FUNCTION. Strain: Oregon-R.
[2]	"Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase." Tournier C., Whitmarsh A.J., Cavanagh J., Barrett T., Davis R.J. Proc. Natl. Acad. Sci. U.S.A. 94:7337-7342(1997) [PubMed: 9207092] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), FUNCTION.
[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 B). Strain: Berkeley. Tissue: Embryo.
[6]	"A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila." Sluss H.K., Han Z., Barrett T., Davis R.J., Ip Y.T. Genes Dev. 10:2745-2758(1996) [PubMed: 8946915] [Abstract] Cited for: FUNCTION.
[7]	"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-646; SER-662; SER-1150 AND SER-1154, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U05240 mRNA. Translation: AAC46944.1. U93032 mRNA. Translation: AAB63449.1. AE014298 Genomic DNA. Translation: AAF48222.1. AE014298 Genomic DNA. Translation: AAG22351.2. AE014298 Genomic DNA. Translation: AAN09646.1. AY069695 mRNA. Translation: AAL39840.1. AY071210 mRNA. Translation: AAL48832.1.
RefSeq	NP_511142.2. NP_727661.1. NP_727662.1.
UniGene	Dm.5867
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q23977. 5 interactions.
STRING	Q23977.
Genome annotation databases
Ensembl	FBtr0073747; FBpp0073578; FBgn0010303; Drosophila melanogaster. [Genome view]
GeneID	32256.
KEGG	dme:Dmel_CG4353.
NMPDR	fig|7227.3.peg.17639.
Organism-specific databases
CTD	32256.
FlyBase	FBgn0010303. hep.
Phylogenomic databases
OMA	IRIYESA.
Enzyme and pathway databases
BRENDA	2.7.12.2. 48.
Gene expression databases
Bgee	Q23977.
GermOnline	CG4353. 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	777608.
PMAP-CutDB	Q23977.

Entry information

Entry name

HEP_DROME

Accession

Primary (citable) accession number: Q23977
Secondary accession number(s): O18411 , Q8SZ04, Q8SZZ1, Q9I7S3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	August 16, 2005
Last modified:	November 3, 2009
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project