Q7T2V3 (M3K10_XENLA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase 10
EC=2.7.11.25

Alternative name(s):
Mixed lineage kinase 2
Short name=xMLK2

Gene names

Name:	map3k10
Synonyms:	mlk2

Organism

Xenopus laevis (African clawed frog)

Taxonomic identifier

8355 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amphibia › Batrachia › Anura › Pipoidea › Pipidae › Xenopodinae › Xenopus › Xenopus

Protein attributes

Sequence length	1005 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Activates the JUN N-terminal pathway. Essential for pronephros and cement gland development. Ref.1 Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation By similarity.
Subunit structure	Homodimer. Binds to the GTPase rac1 but not cdc42 or rhoA. Interacts (via kinase domain) with pak1 (via kinase domain). Interacts with the ubiquitin-conjugating enzyme ube2d4. Ref.1 Ref.2 Ref.3
Tissue specificity	In adults, strongly expressed in the brain and spleen with lower levels in pancreas, heart, muscle and kidney (at protein level). In the developing embryo, expressed at stage 22 in the cement gland. Weakly expressed in the pronephros from stage 24 or 25, with expression increasing in strength by stage 30 and continuing at least until stage 37. Expression in the developing pronephros correlates with epithelialization of the proximal pronephric tubules. Ref.1
Developmental stage	Expressed zygotically from stages 12 to 14 (late gastrula to early neurula), increasing in concentration up to stages 40 to 45 (late tadpole). Expression continues through to adults. Ref.1
Post-translational modification	Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation By similarity. Mono- and poly-ubiquitinated.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain. Contains 1 SH3 domain.

Ontologies

Keywords
Domain	Repeat SH3 domain
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Ubl conjugation
Gene Ontology (GO)
Biological_process	cement gland development Inferred from mutant phenotype Ref.1. Source: UniProtKB positive regulation of JNK cascade Inferred from direct assay Ref.1Ref.2. Source: UniProtKB pronephros development Inferred from mutant phenotype Ref.1. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW JUN kinase kinase kinase activity Inferred from direct assay Ref.2. Source: UniProtKB Rac GTPase binding Inferred from direct assay Ref.1. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.3. Source: UniProtKB protein tyrosine kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1005	1005	Mitogen-activated protein kinase kinase kinase 10		PRO_0000277827
Regions
	Domain	32 – 96	65	SH3
	Domain	118 – 380	263	Protein kinase
	Nucleotide binding	124 – 132	9	ATP By similarity
	Region	404 – 425	22	Leucine-zipper 1
	Region	439 – 460	22	Leucine-zipper 2
	Compositional bias	724 – 765	42	Ser-rich
Sites
	Active site	242	1	Proton acceptor By similarity
	Binding site	145	1	ATP By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q7T2V3 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: B406102A77244309	FASTA	1,005	111,875
	10 20 30 40 50 60 MDGLPKDEAF LWQSSKDNKE NGVWSDVQSY GVSNPLWMAV FDYEPTAEEE LTLRRGDLVE 70 80 90 100 110 120 ILSKDSTVSG DEGWWTGKIK DKVGIFPSNY VVSDDKYTTL TGAPKQCPLP LEIEFDELNL 130 140 150 160 170 180 DEIIGVGGFG KVYKGLWRDE EVAVKAVRHD PDEDINVTAE NVRQEAKIFC MLCHPNIIAL 190 200 210 220 230 240 TGVCLKPPHL CLVMEYARGG PLHRALAGKK VPAHVLVNWA VQIAKGMTYL HNEAIVPIIH 250 260 270 280 290 300 RDLGSSNILI LEKAENDDLF NKTLNITDFG LAREWQKTTK MSAAGTYAWM APEVIRLSLF 310 320 330 340 350 360 SKSSDVWSFG VLLWELLTGE VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFVRILEACW 370 380 390 400 410 420 DPDPHSRPTF SCILEQLTTI EQSAMFQMPL ESFHSLQEDW RLEIQQMFDE LRTKEKELRS 430 440 450 460 470 480 REEELVRAAE EQRILEDLLK RREQELAERE IDIVERELNI IMYQMYQEKP KVKKRKGNFK 490 500 510 520 530 540 KSRLKLKDGN RISLPSGFEH KITVQASPML DKCKGQGTSS YSPPGSPLII PRLRAIRLTP 550 560 570 580 590 600 VDGSKTWGRS SVLKKEEVTT SNKKKGRTWG PSSTQQKERV GGEERLKTLG EGNKQWSSSA 610 620 630 640 650 660 PNLGKSPKHT PISVGFASLT EMEEYADSDG SVPQSPYSQS YLTLPVQSDH RSHPEDTAHA 670 680 690 700 710 720 GAPSSDSPKR GSQSRRKSEL VLLGCASLLA AVALGSDLSE LVPQEEKRKG IFQWAGRGPR 730 740 750 760 770 780 RRASSPSRSM SYGEDSVIPS SSVTLISLSS ISDCNSTRSL IRSDSDDIGL DHDNVSSGRG 790 800 810 820 830 840 VKEDRGQQPN VGSNPLVDYK VESFKRDPKQ SLTPTHVTVG RNNTTETRGH RRTPSDGAIR 850 860 870 880 890 900 QVTQGHKRSP SDGSTPYQCE PEPSPFPRLP DPHFVFPPPV RRKDTGVERP TSLEFAPRPR 910 920 930 940 950 960 PSSNRPRMDP WKFVSLSQTH SSSPSSGGGD ACSSGSAEGA QVADVEETLL DMEVEGQRLD 970 980 990 1000 STVPLCGLGL RPTTDPFFKY GNRRVLMKEL SISLLQYKVE SGVLL

References

[1]	"A tissue restricted role for the Xenopus Jun N-terminal kinase kinase kinase MLK2 in cement gland and pronephric tubule differentiation." Poitras L., Bisson N., Islam N., Moss T. Dev. Biol. 254:200-214(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH RAC1, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Tail bud.
[2]	"PAK interacts with NCK and MLK2 to regulate the activation of jun N-terminal kinase." Poitras L., Jean S., Islam N., Moss T. FEBS Lett. 543:129-135(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WTIH PAK1.
[3]	"A ubiquitin-conjugating enzyme, ube2d3.2, regulates xMLK2 and pronephros formation in Xenopus." Jean S., Moss T. Differentiation 76:431-441(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBE2D4, HOMODIMERIZATION, UBIQUITINATION.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF510499 mRNA. Translation: AAP46399.1.
RefSeq	NP_001082629.1. NM_001089160.1.
UniGene	Xl.26500.
3D structure databases
ProteinModelPortal	Q7T2V3.
SMR	Q7T2V3. Positions 33-91.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	398612.
KEGG	xla:398612.
Organism-specific databases
CTD	4294.
Xenbase	XB-GENE-920952. map3k10.
Phylogenomic databases
HOVERGEN	HBG067662.
KO	K04418.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR016231. MAPKKK9/10/11. IPR015785. MAPKKK9/10/11-like. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR001452. SH3_domain. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
PANTHER	PTHR23257:SF87. PTHR23257:SF87. 1 hit.
Pfam	PF07714. Pkinase_Tyr. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
PIRSF	PIRSF000556. MAPKKK9_11. 1 hit.
PRINTS	PR00452. SH3DOMAIN. PR00109. TYRKINASE.
SMART	SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

M3K10_XENLA

Accession

Primary (citable) accession number: Q7T2V3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 20, 2007
Last sequence update:	October 1, 2003
Last modified:	May 29, 2013
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program