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Protein

MAP/microtubule affinity-regulating kinase 3

Gene

MARK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the specific phosphorylation of microtubule-associated proteins for tau, MAP2 and MAP4. Phosphorylates CDC25C on 'Ser-216'. Regulates localization and activity of some histone deacetylases by mediating phosphorylation of HDAC7, promoting subsequent interaction between HDAC7 and 14-3-3 and export from the nucleus (PubMed:16980613). Negatively regulates the Hippo signaling pathway and antagonizes the phosphorylation of LATS1. Cooperates with DLG5 to inhibit the kinase activity of STK3/MST2 toward LATS1 (PubMed:28087714).2 Publications

Caution

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by phosphorylation on Thr-211. Inhibited by phosphorylation on Thr-564.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei85ATPPROSITE-ProRule annotation1
Active sitei178Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi62 – 70ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-5673000 RAF activation
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
SignaLinkiP27448
SIGNORiP27448

Names & Taxonomyi

Protein namesi
Recommended name:
MAP/microtubule affinity-regulating kinase 3 (EC:2.7.11.1)
Alternative name(s):
C-TAK1
Short name:
cTAK1
Cdc25C-associated protein kinase 1
ELKL motif kinase 2
Short name:
EMK-2
Protein kinase STK10
Ser/Thr protein kinase PAR-1
Short name:
Par-1a
Serine/threonine-protein kinase p78
Gene namesi
Name:MARK3
Synonyms:CTAK1, EMK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000075413.17
HGNCiHGNC:6897 MARK3
MIMi602678 gene
neXtProtiNX_P27448

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi211T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication1

Organism-specific databases

DisGeNETi4140
OpenTargetsiENSG00000075413
PharmGKBiPA30640

Chemistry databases

ChEMBLiCHEMBL5600
GuidetoPHARMACOLOGYi2099

Polymorphism and mutation databases

BioMutaiMARK3
DMDMi341941142

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863041 – 753MAP/microtubule affinity-regulating kinase 3Add BLAST753

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphoserineCombined sources1
Modified residuei211Phosphothreonine; by LKB11 Publication1
Modified residuei368PhosphoserineBy similarity1
Modified residuei374PhosphoserineBy similarity1
Modified residuei376PhosphoserineCombined sources1
Modified residuei380PhosphoserineCombined sources1
Modified residuei383PhosphoserineCombined sources1
Modified residuei400PhosphoserineCombined sources1
Modified residuei419PhosphoserineCombined sources1
Modified residuei469PhosphoserineCombined sources1
Modified residuei540PhosphoserineCombined sources1
Modified residuei543PhosphoserineBy similarity1
Modified residuei549PhosphothreonineCombined sources1
Modified residuei564Phosphothreonine; by PKC/PRKCZBy similarity1
Modified residuei583PhosphoserineCombined sources1
Modified residuei598PhosphoserineCombined sources1
Modified residuei601PhosphoserineCombined sources1
Modified residuei643PhosphoserineCombined sources1
Isoform 5 (identifier: P27448-6)
Modified residuei384PhosphoserineCombined sources1
Isoform 6 (identifier: P27448-7)
Modified residuei407PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Thr-211 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-564 by PRKCZ/aPKC inhibits the kinase activity.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP27448
PaxDbiP27448
PeptideAtlasiP27448
PRIDEiP27448

PTM databases

iPTMnetiP27448
PhosphoSitePlusiP27448

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000075413
CleanExiHS_MARK3
ExpressionAtlasiP27448 baseline and differential
GenevisibleiP27448 HS

Organism-specific databases

HPAiHPA024652

Interactioni

Subunit structurei

Interacts with DLG5 (via coiled-coil domain). Interacts with STK3/MST2 and STK4/MST1 in the presence of DLG5 (PubMed:28087714).1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi11031066 interactors.
DIPiDIP-34637N
IntActiP27448 56 interactors.
MINTiP27448
STRINGi9606.ENSP00000411397

Chemistry databases

BindingDBiP27448

Structurei

Secondary structure

1753
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi56 – 64Combined sources9
Beta strandi66 – 75Combined sources10
Turni76 – 78Combined sources3
Beta strandi81 – 88Combined sources8
Helixi89 – 91Combined sources3
Helixi94 – 109Combined sources16
Beta strandi118 – 123Combined sources6
Beta strandi125 – 132Combined sources8
Helixi140 – 147Combined sources8
Helixi152 – 171Combined sources20
Helixi181 – 183Combined sources3
Beta strandi184 – 186Combined sources3
Beta strandi192 – 194Combined sources3
Helixi201 – 203Combined sources3
Beta strandi204 – 206Combined sources3
Helixi208 – 210Combined sources3
Beta strandi213 – 215Combined sources3
Helixi216 – 218Combined sources3
Helixi221 – 225Combined sources5
Helixi232 – 248Combined sources17
Helixi258 – 267Combined sources10
Helixi278 – 287Combined sources10
Turni292 – 294Combined sources3
Helixi298 – 301Combined sources4
Turni305 – 310Combined sources6
Helixi329 – 337Combined sources9
Helixi342 – 350Combined sources9
Helixi356 – 364Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2QNJX-ray2.70A/B48-370[»]
3FE3X-ray1.90A/B41-367[»]
ProteinModelPortaliP27448
SMRiP27448
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27448

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini56 – 307Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini326 – 365UBAPROSITE-ProRule annotationAdd BLAST40
Domaini704 – 753KA1PROSITE-ProRule annotationAdd BLAST50

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0586 Eukaryota
ENOG410XNQ0 LUCA
GeneTreeiENSGT00900000140806
HOGENOMiHOG000233025
HOVERGENiHBG052453
InParanoidiP27448
KOiK08798
TreeFamiTF315213

Family and domain databases

InterProiView protein in InterPro
IPR028375 KA1/Ssp2_C
IPR001772 KA1_dom
IPR011009 Kinase-like_dom_sf
IPR033624 MARK/par1
IPR033628 MARK3
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR015940 UBA
PANTHERiPTHR24346 PTHR24346, 1 hit
PTHR24346:SF1 PTHR24346:SF1, 1 hit
PfamiView protein in Pfam
PF02149 KA1, 1 hit
PF00069 Pkinase, 1 hit
PF00627 UBA, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SM00165 UBA, 1 hit
SUPFAMiSSF103243 SSF103243, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequences (7)i

Sequence statusi: Complete.

This entry describes 7 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27448-5) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSTRTPLPTV NERDTENHTS HGDGRQEVTS RTSRSGARCR NSIASCADEQ
60 70 80 90 100
PHIGNYRLLK TIGKGNFAKV KLARHILTGR EVAIKIIDKT QLNPTSLQKL
110 120 130 140 150
FREVRIMKIL NHPNIVKLFE VIETEKTLYL IMEYASGGEV FDYLVAHGRM
160 170 180 190 200
KEKEARSKFR QIVSAVQYCH QKRIVHRDLK AENLLLDADM NIKIADFGFS
210 220 230 240 250
NEFTVGGKLD TFCGSPPYAA PELFQGKKYD GPEVDVWSLG VILYTLVSGS
260 270 280 290 300
LPFDGQNLKE LRERVLRGKY RIPFYMSTDC ENLLKRFLVL NPIKRGTLEQ
310 320 330 340 350
IMKDRWINAG HEEDELKPFV EPELDISDQK RIDIMVGMGY SQEEIQESLS
360 370 380 390 400
KMKYDEITAT YLLLGRKSSE LDASDSSSSS NLSLAKVRPS SDLNNSTGQS
410 420 430 440 450
PHHKVQRSVS SSQKQRRYSD HAGPAIPSVV AYPKRSQTST ADSDLKEDGI
460 470 480 490 500
SSRKSSGSAV GGKGIAPASP MLGNASNPNK ADIPERKKSS TVPSSNTASG
510 520 530 540 550
GMTRRNTYVC SERTTADRHS VIQNGKENST IPDQRTPVAS THSISSAATP
560 570 580 590 600
DRIRFPRGTA SRSTFHGQPR ERRTATYNGP PASPSLSHEA TPLSQTRSRG
610 620 630 640 650
STNLFSKLTS KLTRRNMSFR FIKRLPTEYE RNGRYEGSSR NVSAEQKDEN
660 670 680 690 700
KEAKPRSLRF TWSMKTTSSM DPGDMMREIR KVLDANNCDY EQRERFLLFC
710 720 730 740 750
VHGDGHAENL VQWEMEVCKL PRLSLNGVRF KRISGTSIAF KNIASKIANE

LKL
Length:753
Mass (Da):84,429
Last modified:March 28, 2018 - v5
Checksum:iB50B3C145E896B0B
GO
Isoform 2 (identifier: P27448-2) [UniParc]FASTAAdd to basket
Also known as: CTAK75a

The sequence of this isoform differs from the canonical sequence as follows:
     161-161: Q → QGCQAGQTIKVQVSFDLLSLMFTF
     615-638: Missing.

Show »
Length:752
Mass (Da):83,955
Checksum:i4577DF508B021FAF
GO
Isoform 3 (identifier: P27448-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     615-638: Missing.

Show »
Length:729
Mass (Da):81,439
Checksum:i0B808DC1BC333C25
GO
Isoform 4 (identifier: P27448-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     615-623: Missing.

Show »
Length:744
Mass (Da):83,248
Checksum:i6FB18E6E4B830D9F
GO
Isoform 5 (identifier: P27448-6) [UniParc]FASTAAdd to basket
Also known as: p58

The sequence of this isoform differs from the canonical sequence as follows:
     371-386: Missing.
     615-638: Missing.

Show »
Length:713
Mass (Da):79,876
Checksum:i74C47366AA34FCF8
GO
Isoform 6 (identifier: P27448-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     161-161: Q → QGCQAGQTIKVQVSFDLLSLMFTF
     371-386: Missing.

Show »
Length:760
Mass (Da):85,381
Checksum:iF5148E18A88C54B7
GO
Isoform 7 (identifier: P27448-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     179-257: Missing.
     624-638: Missing.

Note: No experimental confirmation available.
Show »
Length:659
Mass (Da):74,091
Checksum:iB002CF23F4B21A20
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti125E → Q in AAA59991 (Ref. 5) Curated1
Sequence conflicti139E → K in AAL69982 (Ref. 4) Curated1
Sequence conflicti139E → K in AAA59991 (Ref. 5) Curated1
Sequence conflicti149R → K in AAD48007 (Ref. 2) Curated1
Sequence conflicti425A → G in AAA59991 (Ref. 5) Curated1
Sequence conflicti456S → T in AAA59991 (Ref. 5) Curated1
Sequence conflicti516A → D in AAA59991 (Ref. 5) Curated1
Sequence conflicti603N → T in AAA59991 (Ref. 5) Curated1
Sequence conflicti645E → K in AAA59991 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080189410S → F1 PublicationCorresponds to variant dbSNP:rs10137161Ensembl.1
Natural variantiVAR_040765429V → A1 Publication1
Natural variantiVAR_046763443S → G3 PublicationsCorresponds to variant dbSNP:rs56305318Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041582161Q → QGCQAGQTIKVQVSFDLLSL MFTF in isoform 2 and isoform 6. 1 Publication1
Alternative sequenceiVSP_043197179 – 257Missing in isoform 7. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_004943371 – 386Missing in isoform 5 and isoform 6. 2 PublicationsAdd BLAST16
Alternative sequenceiVSP_004944615 – 638Missing in isoform 2, isoform 3 and isoform 5. 4 PublicationsAdd BLAST24
Alternative sequenceiVSP_004945615 – 623Missing in isoform 4. 1 Publication9
Alternative sequenceiVSP_043198624 – 638Missing in isoform 7. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U64205 mRNA Translation: AAC15093.1
AF159295 mRNA Translation: AAD48007.1
AF387637 mRNA Translation: AAK82367.1
AF465413 mRNA Translation: AAL69982.1
M80359 mRNA Translation: AAA59991.1
BX161395 mRNA Translation: CAD61882.1
AL133367 Genomic DNA No translation available.
KF456011 Genomic DNA No translation available.
CH471061 Genomic DNA Translation: EAW81813.1
CH471061 Genomic DNA Translation: EAW81815.1
CH471061 Genomic DNA Translation: EAW81817.1
BC024773 mRNA Translation: AAH24773.1
AF170723 mRNA Translation: AAD51631.1
CCDSiCCDS41993.1 [P27448-3]
CCDS45165.1 [P27448-5]
CCDS45166.1 [P27448-4]
CCDS45167.1 [P27448-8]
CCDS55947.1 [P27448-6]
PIRiS27966
RefSeqiNP_001122390.2, NM_001128918.2
NP_001122391.2, NM_001128919.2
NP_001122392.2, NM_001128920.2
NP_001122393.2, NM_001128921.2
NP_002367.5, NM_002376.6
UniGeneiHs.35828

Genome annotation databases

EnsembliENST00000216288; ENSP00000216288; ENSG00000075413 [P27448-6]
ENST00000303622; ENSP00000303698; ENSG00000075413 [P27448-3]
ENST00000416682; ENSP00000408092; ENSG00000075413 [P27448-2]
ENST00000429436; ENSP00000411397; ENSG00000075413 [P27448-5]
ENST00000440884; ENSP00000402104; ENSG00000075413 [P27448-8]
ENST00000553942; ENSP00000450772; ENSG00000075413 [P27448-4]
GeneIDi4140
KEGGihsa:4140
UCSCiuc001ymw.5 human [P27448-5]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMARK3_HUMAN
AccessioniPrimary (citable) accession number: P27448
Secondary accession number(s): A0A0A0MQR8
, A0A0A0MST9, A0A0A0MT23, O60219, Q86TT8, Q8TB41, Q8WX83, Q96RG1, Q9UMY9, Q9UN34
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: March 28, 2018
Last modified: April 25, 2018
This is version 185 of the entry and version 5 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome