Q8VHJ5 (MARK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase MARK1
EC=2.7.11.1
EC=2.7.11.26

Alternative name(s):
ELKL motif serine/threonine-protein kinase 3
MAP/microtubule affinity-regulating kinase 1
PAR1 homolog c
Short name=Par-1c
Short name=mPar-1c

Gene names

Name:	Mark1
Synonyms:	Emk3, Kiaa1477

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

General annotation (Comments)

Function	Serine/threonine-protein kinase involved in cell polarity and microtubule dynamics regulation. Phosphorylates DCX, MAP2, MAP4 and MAPT/TAU. Involved in cell polarity by phosphorylating the microtubule-associated proteins MAP2, MAP4 and MAPT/TAU at KXGS motifs, causing detachment from microtubules, and their disassembly. Involved in the regulation of neuronal migration through its dual activities in regulating cellular polarity and microtubule dynamics, possibly by phosphorylating and regulating DCX. Also acts as a positive regulator of the Wnt signaling pathway, probably by mediating phosphorylation of dishevelled proteins (DVL1, DVL2 and/or DVL3) By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. UniProtKB Q9POL2 ATP + [tau protein] = ADP + [tau protein] phosphate.
Cofactor	Magnesium By similarity. UniProtKB Q9POL2
Enzyme regulation	Inhibited by phosphorylation at Ser-219. Activated by phosphorylation on Thr-215 By similarity.
Subcellular location	Cell membrane; Peripheral membrane protein By similarity. Cytoplasm › cytoskeleton By similarity. Note: Appears to localize to an intracellular network By similarity.
Domain	The UBA domain does not seem to bind ubiquitin and ubiquitin-like and might play a role in regulating the enzyme conformation and localization. Activation of the kinase activity following phosphorylation at Thr-208 is accompanied by a conformational change that alters the orientation of the UBA domain with respect to the catalytic domain By similarity. The KA1 domain mediates binding to phospholipids and targeting to membranes. Binds phosphatidic acid (PA), phosphatidylserine (PtdSer) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) By similarity.
Post-translational modification	Phosphorylated at Thr-215 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-215 by TAOK1 activates the kinase activity, leading to phosphorylation and detachment of MAPT/TAU from microtubules. Phosphorylation at Ser-219 by GSK3-beta (GSK3B) inhibits the kinase activity. Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 KA1 (kinase-associated) domain. Contains 1 protein kinase domain. Contains 1 UBA domain.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Ligand	ATP-binding Lipid-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW intracellular protein kinase cascade Inferred from sequence or structural similarity. Source: UniProtKB microtubule cytoskeleton organization Inferred from electronic annotation. Source: Compara neuron migration Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from sequence or structural similarity. Source: UniProtKB phosphatidic acid binding Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Inferred from sequence or structural similarity. Source: UniProtKB phosphatidylserine binding Inferred from sequence or structural similarity. Source: UniProtKB protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB tau-protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 795	795	Serine/threonine-protein kinase MARK1		PRO_0000086299
Regions
	Domain	60 – 311	252	Protein kinase
	Domain	329 – 370	42	UBA
	Domain	746 – 795	50	KA1
	Nucleotide binding	66 – 74	9	ATP By similarity UniProtKB Q9H0K1
Sites
	Active site	182	1	Proton acceptor By similarity UniProtKB Q9H0K1
	Binding site	89	1	ATP By similarity UniProtKB O08678
Amino acid modifications
	Modified residue	5	1	Phosphothreonine By similarity
	Modified residue	215	1	Phosphothreonine; by LKB1 and TAOK1 By similarity UniProtKB O08678
	Modified residue	219	1	Phosphoserine; by GSK3-beta By similarity UniProtKB O08678
	Modified residue	394	1	Phosphoserine Ref.4
	Modified residue	403	1	Phosphoserine Ref.4
	Modified residue	588	1	Phosphoserine By similarity
	Modified residue	613	1	Phosphothreonine; by PKC/PRKCZ By similarity
	Modified residue	666	1	Phosphoserine Ref.4
Experimental info
	Sequence conflict	32	1	A → T in AAL50826. Ref.1
	Sequence conflict	40	1	L → I in AAL50826. Ref.1
	Sequence conflict	110	1	I → T in BAD32459. Ref.3
	Sequence conflict	276	1	I → V in AAL50826. Ref.1
	Sequence conflict	318	1	E → D in BAD32459. Ref.3
	Sequence conflict	331	1	S → N in AAL50826. Ref.1
	Sequence conflict	385	1	S → N in AAL50826. Ref.1
	Sequence conflict	454	1	G → D in AAL50826. Ref.1
	Sequence conflict	579	1	G → GS in BAD32459. Ref.3
	Sequence conflict	630	1	P → R in AAL50826. Ref.1
	Sequence conflict	641	1	F → L in AAL50826. Ref.1
	Sequence conflict	674	1	A → T in AAL50826. Ref.1
	Sequence conflict	683	1	D → E in AAL50826. Ref.1
	Sequence conflict	690	1	D → E in AAL50826. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8VHJ5 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: F43F2B541C346697	FASTA	795	88,335
	10 20 30 40 50 60 MSARTPLPTV NERDTENHTS VDGYTETHIP PAKSSSRQNL PRCRNSITSA TDEQPHIGNY 70 80 90 100 110 120 RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS LQKLFREVRI MKILNHPNIV 130 140 150 160 170 180 KLFEVIETEK TLYLVMEYAS GGEVFDYLVA HGRMKEKEAR AKFRQIVSAV QYCHQKCIVH 190 200 210 220 230 240 RDLKAENLLL DADMNIKIAD FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV 250 260 270 280 290 300 WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM STDCENLLKK LLVLNPIKRG 310 320 330 340 350 360 SLEQIMKDRW MNVGHEEEEL KPYSEPELDL SDAKRIDIMV TMGFARDEIN DALVSQKYDE 370 380 390 400 410 420 VMATYILLGR KPPEFEGGES LSSGSLCQRS RPSSDLNNST LQSPAHLKVQ RSISANQKQR 430 440 450 460 470 480 RFSDHAGPSI PPAVSYTKRP QANSVESEQK EEWGKDTARR LGSTTVGSKS EVTASPLVGP 490 500 510 520 530 540 DRKKSTASPS NNVYSGGSMA RRNTYVCERS TDRYAALQNG RDSSLTEMSA SSMSSAGSTV 550 560 570 580 590 600 ASAGPSARPR HQKSMSTSGH PIKVTLPTIK DGSEAYRPGA AQRVPAASPS AHSISASTPD 610 620 630 640 650 660 RTRFPRGSSS RSTFHGEQLR ERRSAAYNGP PASPSHETGA FAHARRGTST GIISKITSKF 670 680 690 700 710 720 VRRDPSEGEA SGRADTARGS SGDPKERDKD EGKEAKPRSL RFTWSMKTTS SMDPNDMLRE 730 740 750 760 770 780 IRKVLDANTC DYEQKERFLL FCVHGDARQD SLVQWEMEVC KLPRLSLNGV RFKRISGTSI 790 AFKNIASKIA NELKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mus musculus Emk3/Mark1 mRNA." Darmon Y.M., Le Morvan V. Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H. DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 26-795. Tissue: Fetal brain.
[4]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-403 AND SER-666, MASS SPECTROMETRY. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF453686 mRNA. Translation: AAL50826.1. AC117826 Genomic DNA. No translation available. AC131992 Genomic DNA. No translation available. AK173181 mRNA. Translation: BAD32459.1.
IPI	IPI00928064.
RefSeq	NP_663490.2. NM_145515.2.
UniGene	Mm.7445.
3D structure databases
ProteinModelPortal	Q8VHJ5.
SMR	Q8VHJ5. Positions 1-371, 696-795.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8VHJ5. 1 interaction.
PTM databases
PhosphoSite	Q8VHJ5.
Proteomic databases
PaxDb	Q8VHJ5.
PRIDE	Q8VHJ5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000027929; ENSMUSP00000027929; ENSMUSG00000026620.
GeneID	226778.
KEGG	mmu:226778.
Organism-specific databases
CTD	4139.
MGI	MGI:2664902. Mark1.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00690000101885.
HOVERGEN	HBG052453.
InParanoid	Q8VHJ5.
KO	K08798.
OMA	NHTSVDG.
OrthoDB	EOG4C2H8X.
Gene expression databases
Bgee	Q8VHJ5.
CleanEx	MM_MARK1.
Genevestigator	Q8VHJ5.
GermOnline	ENSMUSG00000026620. Mus musculus.
Family and domain databases
InterPro	IPR001772. KA1_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. IPR000449. UBA/transl_elong_EF1B_N. IPR015940. UBA/transl_elong_EF1B_N_euk. [Graphical view]
Pfam	PF02149. KA1. 1 hit. PF00069. Pkinase. 1 hit. PF00627. UBA. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. SM00165. UBA. 1 hit. [Graphical view]
SUPFAM	SSF103243. Kinase-assoc_KA1. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS50032. KA1. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50030. UBA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	378347.
SOURCE	Search...

Entry information

Entry name

MARK1_MOUSE

Accession

Primary (citable) accession number: Q8VHJ5
Secondary accession number(s): E9QL17, Q69ZI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program