Q8BPM2 (M4K5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase kinase kinase kinase 5
EC=2.7.11.1

Alternative name(s):
MAPK/ERK kinase kinase kinase 5
Short name=MEK kinase kinase 5
Short name=MEKKK 5

Gene names

Name:

Map4k5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	847 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway By similarity. UniProtKB Q9Y4K4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9Y4K4
Cofactor	Magnesium By similarity. UniProtKB Q9Y4K4
Subunit structure	Interacts with both SH3 domains of the adapter proteins CRK and CRKL By similarity. UniProtKB Q9Y4K4
Subcellular location	Cytoplasm By similarity UniProtKB Q9Y4K4.
Sequence similarities	Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily. Contains 1 CNH domain. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	intracellular protein kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB response to stress Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB small GTPase regulator activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8BPM2-1)

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: Q8BPM2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     294-312: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 847	847	Mitogen-activated protein kinase kinase kinase kinase 5		PRO_0000086283
Regions
	Domain	20 – 277	258	Protein kinase
	Domain	507 – 820	314	CNH
	Nucleotide binding	26 – 34	9	ATP By similarity UniProtKB O00506
Sites
	Active site	140	1	Proton acceptor By similarity UniProtKB O00506
	Binding site	49	1	ATP By similarity UniProtKB Q9Y4K4
Natural variations
	Alternative sequence	294 – 312	19	Missing in isoform 2.		VSP_050478
Experimental info
	Sequence conflict	79	1	A → P in BAC35517. Ref.1
	Sequence conflict	103	1	Q → H in BAC35517. Ref.1
	Sequence conflict	118	1	A → P in BAC35517. Ref.1
	Sequence conflict	441	1	A → V in AAH40381. Ref.2
	Sequence conflict	727	1	L → Q in BAB31739. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 30, 2003. Version 2. Checksum: 377F0EFFC6EECFA3	FASTA	847	95,045
	10 20 30 40 50 60 MEAPLRPAAD ILRRNPQHDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI IKLEPGDDFS 70 80 90 100 110 120 LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG SLQDIYHVTG PLSEMQIAYV 130 140 150 160 170 180 CRETLQGLAY LHTKGKMHRD IKGANILLTD HGDVKLADFG VAAKITATIA KRKSFIGTPY 190 200 210 220 230 240 WMAPEVAAVE KNGGYNQLCD IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL 250 260 270 280 290 300 KDKTKWSSTF HNFVKIALTK NPKKRPTAER LLTHTFVGQP GLSRALAVEL LDKVSNPDNH 310 320 330 340 350 360 APYSEGDEDD LEPHAIIRHT IRSTNRNSRA ERTASEINFD KLQFEPPLRK ETEARDEMGL 370 380 390 400 410 420 SSEPNFILHW NPFVDGANTG RSTSKRAIPP PLPPKPRVNT YPEDSLPDEE KSSTIKRCPD 430 440 450 460 470 480 LEARAPQVLR RQSSPSCVPV AETSSSIGNG DGISKLISEN TEGSAQAPQL PRKKDKRDFP 490 500 510 520 530 540 KPTINGLPPT PKVLMGACFS KVFDGCPLKI NCATSWIHPD TKDQYIIFGT EDGIYTLNLN 550 560 570 580 590 600 ELHEATMEQL FPRKCTWLYV INNTLMSLSE GKTFQLYSHN LIALFEQAKK PGLAAHIQTH 610 620 630 640 650 660 RFPDRILPRK FALTTKIPDT KGCHKCCIVR NPYTGHKYLC GALQSGIVLL QWYEPMQKFM 670 680 690 700 710 720 LIKHFDFPLP SPLNVFEMLV IPEQEYPMVC VAISKGSDSS QVVQFETINL NSASSWFTEI 730 740 750 760 770 780 GAGSQQLDSI HVTQLERDTV LVCLDKFVKI VNLQGKLKSS KKLASELSFD FRIESVVCLQ 790 800 810 820 830 840 DSVLAFWKHG MQGKSFKSDE VTQEISDETR VFRLLGSDRV VVLESRPTEN PAAHSNLYIL AGHENSY
	Isoform 2 [UniParc]. Checksum: 53F3939E68AEA591	FASTA	828	92,960
	10 20 30 40 50 60 MEAPLRPAAD ILRRNPQHDY ELVQRVGSGT YGDVYKARNV HTGELAAVKI IKLEPGDDFS 70 80 90 100 110 120 LIQQEIFMVK ECKHCNIVAY FGSYLSREKL WICMEYCGGG SLQDIYHVTG PLSEMQIAYV 130 140 150 160 170 180 CRETLQGLAY LHTKGKMHRD IKGANILLTD HGDVKLADFG VAAKITATIA KRKSFIGTPY 190 200 210 220 230 240 WMAPEVAAVE KNGGYNQLCD IWAVGITAIE LGELQPPMFD LHPMRALFLM SKSNFQPPKL 250 260 270 280 290 300 KDKTKWSSTF HNFVKIALTK NPKKRPTAER LLTHTFVGQP GLSRALAVEL LDKPHAIIRH 310 320 330 340 350 360 TIRSTNRNSR AERTASEINF DKLQFEPPLR KETEARDEMG LSSEPNFILH WNPFVDGANT 370 380 390 400 410 420 GRSTSKRAIP PPLPPKPRVN TYPEDSLPDE EKSSTIKRCP DLEARAPQVL RRQSSPSCVP 430 440 450 460 470 480 VAETSSSIGN GDGISKLISE NTEGSAQAPQ LPRKKDKRDF PKPTINGLPP TPKVLMGACF 490 500 510 520 530 540 SKVFDGCPLK INCATSWIHP DTKDQYIIFG TEDGIYTLNL NELHEATMEQ LFPRKCTWLY 550 560 570 580 590 600 VINNTLMSLS EGKTFQLYSH NLIALFEQAK KPGLAAHIQT HRFPDRILPR KFALTTKIPD 610 620 630 640 650 660 TKGCHKCCIV RNPYTGHKYL CGALQSGIVL LQWYEPMQKF MLIKHFDFPL PSPLNVFEML 670 680 690 700 710 720 VIPEQEYPMV CVAISKGSDS SQVVQFETIN LNSASSWFTE IGAGSQQLDS IHVTQLERDT 730 740 750 760 770 780 VLVCLDKFVK IVNLQGKLKS SKKLASELSF DFRIESVVCL QDSVLAFWKH GMQGKSFKSD 790 800 810 820 EVTQEISDET RVFRLLGSDR VVVLESRPTE NPAAHSNLYI LAGHENSY

References

[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Fetal eye, Fetal liver and Fetal lung.
[2]	"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] (ISOFORM 1). Strain: Czech II. Tissue: Mammary gland.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK019468 mRNA. Translation: BAB31739.1. AK053775 mRNA. Translation: BAC35517.1. AK084891 mRNA. Translation: BAC39305.1. BC002309 mRNA. Translation: AAH02309.1. BC040381 mRNA. Translation: AAH40381.2. BC057930 mRNA. Translation: AAH57930.1.
IPI	IPI00225230. IPI00276646.
RefSeq	NP_958927.2. NM_201519.2.
UniGene	Mm.291936.
3D structure databases
ProteinModelPortal	Q8BPM2.
SMR	Q8BPM2. Positions 13-293.
ModBase	Search...
PTM databases
PhosphoSite	Q8BPM2.
Proteomic databases
PaxDb	Q8BPM2.
PRIDE	Q8BPM2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000110567; ENSMUSP00000106196; ENSMUSG00000034761. ENSMUST00000110570; ENSMUSP00000106199; ENSMUSG00000034761.
GeneID	399510.
KEGG	mmu:399510.
UCSC	uc007nsu.1. mouse. uc011yne.1. mouse.
Organism-specific databases
CTD	11183.
MGI	MGI:1925503. Map4k5.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00690000101936.
HOGENOM	HOG000230824.
HOVERGEN	HBG036702.
InParanoid	Q8BPM2.
KO	K08833.
OMA	YKARNVH.
OrthoDB	EOG483D3W.
Gene expression databases
ArrayExpress	Q8BPM2.
Bgee	Q8BPM2.
Genevestigator	Q8BPM2.
GermOnline	ENSMUSG00000034761. Mus musculus.
Family and domain databases
InterPro	IPR001180. Citron. IPR011009. Kinase-like_dom. IPR021160. MAPKKKK. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. [Graphical view]
Pfam	PF00780. CNH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF038172. MAPKKKK. 1 hit.
SMART	SM00036. CNH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50219. CNH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MAP4K5. mouse.
NextBio	406008.
SOURCE	Search...

Entry information

Entry name

M4K5_MOUSE

Accession

Primary (citable) accession number: Q8BPM2
Secondary accession number(s): Q6PEQ2 , Q8C3U5, Q8CGF3, Q99LM7, Q9CX73

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 30, 2003
Last sequence update:	April 30, 2003
Last modified:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program