Q9P0L2 (MARK1_HUMAN) 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):
MAP/microtubule affinity-regulating kinase 1
PAR1 homolog c
Short name=Par-1c
Short name=Par1c

Gene names

Name:	MARK1
Synonyms:	KIAA1477, MARK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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). Ref.10 Ref.11
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1 ATP + [tau protein] = ADP + [tau protein] phosphate.
Cofactor	Magnesium By similarity. Ref.1
Enzyme regulation	Inhibited by phosphorylation at Ser-219 By similarity. Activated by phosphorylation on Thr-215. Ref.1 Ref.11
Subcellular location	Cell membrane; Peripheral membrane protein. Cytoplasm › cytoskeleton By similarity. Note: Appears to localize to an intracellular network By similarity. Ref.22
Tissue specificity	Highly expressed in heart, skeletal muscle, brain, fetal brain and fetal kidney. Ref.8
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. Ref.22 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). Ref.22
Post-translational modification	Phosphorylation at Thr-613 by PRKCZ/aPKC in polarized epithelial cells inhibits the kinase activity By similarity. 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. Ref.1 Ref.11
Involvement in disease	Genetic variations in MARK1 may be associated with susceptibility to autism. MARK1 is overexpressed in the prefrontal cortex of patients with autism and causes changes in the function of cortical dendrites.
Miscellaneous	Phosphorylation of MAPT/tau by MARK1 could play a role in early steps of Alzheimer disease. Pathological aggregation of MAPT/tau to neurofibrillary tangles, filamentous structures consisting of paired helical filaments (PHFs), is one of the hallmarks of Alzheimer disease. Hyperphosphorylation by MARK1 could be the initial step for this abnormal aggregation of tau in Alzheimer disease and animal models of tauopathy (Ref.9).
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.
Sequence caution	The sequence BAA96001.1 differs from that shown. Reason: Erroneous initiation. The sequence BAB55152.1 differs from that shown. Reason: Frameshift at position 763.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Lipid-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB intracellular protein kinase cascade Inferred from direct assay Ref.1. 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 sequence or structural similarity. Source: UniProtKB microtubule cytoskeleton Traceable author statement Ref.8. Source: ProtInc plasma membrane Inferred from direct assay Ref.22. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.1. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.1. Source: UniProtKB phosphatidic acid binding Inferred from direct assay Ref.22. Source: UniProtKB phosphatidylinositol-4,5-bisphosphate binding Inferred from direct assay Ref.22. Source: UniProtKB phosphatidylserine binding Inferred from direct assay Ref.22. Source: UniProtKB protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: UniProtKB tau-protein kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 Ref.22 (identifier: Q9P0L2-1)

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: Q9P0L2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-135: Missing.
     663-677: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9P0L2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     120-141: Missing.
     663-677: Missing.

Note: No experimental confirmation available.

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_0000086298

Regions

Domain

60 – 311

252

Protein kinase

Domain

325 – 370

46

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 Ref.14

Modified residue

215

1

Phosphothreonine; by LKB1 and TAOK1 Ref.1

Modified residue

219

1

Phosphoserine; by GSK3-beta UniProtKB O08678

Modified residue

394

1

Phosphoserine By similarity

Modified residue

403

1

Phosphoserine Ref.14

Modified residue

588

1

Phosphoserine Ref.15

Modified residue

613

1

Phosphothreonine; by PKC/PRKCZ By similarity

Modified residue

666

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 135

135

Missing in isoform 2.

VSP_051702

Alternative sequence

120 – 141

22

Missing in isoform 3.

VSP_051703

Alternative sequence

663 – 677

15

Missing in isoform 2 and isoform 3.

VSP_051704

Natural variant

233

1

Y → C in a gastric adenocarcinoma sample; somatic mutation. Ref.23

VAR_040760

Natural variant

355

1

N → T in an ovarian serous carcinoma sample; somatic mutation. Ref.23

VAR_040761

Natural variant

530

1

V → M. Ref.23
Corresponds to variant rs56212551 [ dbSNP | Ensembl ].

VAR_040762

Natural variant

578

1

P → L. Ref.23
Corresponds to variant rs55691439 [ dbSNP | Ensembl ].

VAR_040763

Natural variant

645

1

R → G.
Corresponds to variant rs12123778 [ dbSNP | Ensembl ].

VAR_030018

Natural variant

691

1

E → G. Ref.23
Corresponds to variant rs55688276 [ dbSNP | Ensembl ].

VAR_040764

Experimental info

Mutagenesis

215

1

T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.1

Mutagenesis

215

1

T → E: Constitutively active. Ref.1

Mutagenesis

698

1

R → S: Impairs phospholipid-binding, targeting to membrane and vesicle-binding; when associated with S-701. Ref.22

Mutagenesis

701

1

R → S: Impairs phospholipid-binding, targeting to membrane and vesicle-binding; when associated with S-698. Ref.22

Mutagenesis

771 – 773

3

RFK → AFA: Impairs phospholipid-binding. Ref.22

Sequence conflict

16

1

E → V in AAF72103. Ref.2

Sequence conflict

20

1

S → T in AAF72103. Ref.2

Sequence conflict

522

1

D → N in BAB55152. Ref.4

Sequence conflict

544

1

V → A in BAB55152. Ref.4

Sequence conflict

763

1

P → A in BAB55152. Ref.4

Sequence conflict

794

1

K → M in BAA96001. Ref.3

Secondary structure

1

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795

Helix Strand Turn

Details...

Beta strand

60 – 68

9

Beta strand

70 – 79

10

Turn

80 – 82

3

Beta strand

85 – 92

8

Helix

98 – 113

16

Beta strand

122 – 127

6

Beta strand

129 – 136

8

Helix

144 – 151

8

Helix

156 – 176

21

Helix

185 – 187

3

Beta strand

188 – 190

3

Beta strand

196 – 198

3

Beta strand

221 – 223

3

Helix

225 – 229

5

Helix

236 – 252

17

Helix

262 – 271

10

Helix

282 – 291

10

Helix

296 – 298

3

Helix

302 – 306

5

Helix

309 – 312

4

Beta strand

316 – 318

3

Helix

333 – 342

10

Helix

346 – 354

9

Helix

360 – 367

8

Helix

714 – 727

14

Beta strand

731 – 736

6

Beta strand

739 – 745

7

Turn

747 – 750

4

Beta strand

753 – 762

10

Helix

763 – 765

3

Beta strand

767 – 777

11

Helix

779 – 792

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 71BF6EB76912631B	FASTA	795	89,003
	10 20 30 40 50 60 MSARTPLPTV NERDTENHTS VDGYTEPHIQ PTKSSSRQNI 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 QYCHQKYIVH 190 200 210 220 230 240 RDLKAENLLL DGDMNIKIAD FGFSNEFTVG NKLDTFCGSP PYAAPELFQG KKYDGPEVDV 250 260 270 280 290 300 WSLGVILYTL VSGSLPFDGQ NLKELRERVL RGKYRIPFYM STDCENLLKK LLVLNPIKRG 310 320 330 340 350 360 SLEQIMKDRW MNVGHEEEEL KPYTEPDPDF NDTKRIDIMV TMGFARDEIN DALINQKYDE 370 380 390 400 410 420 VMATYILLGR KPPEFEGGES LSSGNLCQRS RPSSDLNNST LQSPAHLKVQ RSISANQKQR 430 440 450 460 470 480 RFSDHAGPSI PPAVSYTKRP QANSVESEQK EEWDKDVARK LGSTTVGSKS EMTASPLVGP 490 500 510 520 530 540 ERKKSSTIPS NNVYSGGSMA RRNTYVCERT TDRYVALQNG KDSSLTEMSV SSISSAGSSV 550 560 570 580 590 600 ASAVPSARPR HQKSMSTSGH PIKVTLPTIK DGSEAYRPGT TQRVPAASPS AHSISTATPD 610 620 630 640 650 660 RTRFPRGSSS RSTFHGEQLR ERRSVAYNGP PASPSHETGA FAHARRGTST GIISKITSKF 670 680 690 700 710 720 VRRDPSEGEA SGRTDTSRST SGEPKERDKE EGKDSKPRSL RFTWSMKTTS SMDPNDMMRE 730 740 750 760 770 780 IRKVLDANNC DYEQKERFLL FCVHGDARQD SLVQWEMEVC KLPRLSLNGV RFKRISGTSI 790 AFKNIASKIA NELKL
	Isoform 2 [UniParc]. Checksum: 7AE395507519DCF6	FASTA	645	72,073
	10 20 30 40 50 60 MEYASGGEVF DYLVAHGRMK EKEARAKFRQ IVSAVQYCHQ KYIVHRDLKA ENLLLDGDMN 70 80 90 100 110 120 IKIADFGFSN EFTVGNKLDT FCGSPPYAAP ELFQGKKYDG PEVDVWSLGV ILYTLVSGSL 130 140 150 160 170 180 PFDGQNLKEL RERVLRGKYR IPFYMSTDCE NLLKKLLVLN PIKRGSLEQI MKDRWMNVGH 190 200 210 220 230 240 EEEELKPYTE PDPDFNDTKR IDIMVTMGFA RDEINDALIN QKYDEVMATY ILLGRKPPEF 250 260 270 280 290 300 EGGESLSSGN LCQRSRPSSD LNNSTLQSPA HLKVQRSISA NQKQRRFSDH AGPSIPPAVS 310 320 330 340 350 360 YTKRPQANSV ESEQKEEWDK DVARKLGSTT VGSKSEMTAS PLVGPERKKS STIPSNNVYS 370 380 390 400 410 420 GGSMARRNTY VCERTTDRYV ALQNGKDSSL TEMSVSSISS AGSSVASAVP SARPRHQKSM 430 440 450 460 470 480 STSGHPIKVT LPTIKDGSEA YRPGTTQRVP AASPSAHSIS TATPDRTRFP RGSSSRSTFH 490 500 510 520 530 540 GEQLRERRSV AYNGPPASPS HETGAFAHAR RGTSTGIISK ITSKFVRRST SGEPKERDKE 550 560 570 580 590 600 EGKDSKPRSL RFTWSMKTTS SMDPNDMMRE IRKVLDANNC DYEQKERFLL FCVHGDARQD 610 620 630 640 SLVQWEMEVC KLPRLSLNGV RFKRISGTSI AFKNIASKIA NELKL
	Isoform 3 [UniParc]. Checksum: D6F1BCD8E884661D	FASTA	758	84,911
	10 20 30 40 50 60 MSARTPLPTV NERDTENHTS VDGYTEPHIQ PTKSSSRQNI PRCRNSITSA TDEQPHIGNY 70 80 90 100 110 120 RLQKTIGKGN FAKVKLARHV LTGREVAVKI IDKTQLNPTS LQKLFREVRI MKILNHPNIG 130 140 150 160 170 180 EVFDYLVAHG RMKEKEARAK FRQIVSAVQY CHQKYIVHRD LKAENLLLDG DMNIKIADFG 190 200 210 220 230 240 FSNEFTVGNK LDTFCGSPPY AAPELFQGKK YDGPEVDVWS LGVILYTLVS GSLPFDGQNL 250 260 270 280 290 300 KELRERVLRG KYRIPFYMST DCENLLKKLL VLNPIKRGSL EQIMKDRWMN VGHEEEELKP 310 320 330 340 350 360 YTEPDPDFND TKRIDIMVTM GFARDEINDA LINQKYDEVM ATYILLGRKP PEFEGGESLS 370 380 390 400 410 420 SGNLCQRSRP SSDLNNSTLQ SPAHLKVQRS ISANQKQRRF SDHAGPSIPP AVSYTKRPQA 430 440 450 460 470 480 NSVESEQKEE WDKDVARKLG STTVGSKSEM TASPLVGPER KKSSTIPSNN VYSGGSMARR 490 500 510 520 530 540 NTYVCERTTD RYVALQNGKD SSLTEMSVSS ISSAGSSVAS AVPSARPRHQ KSMSTSGHPI 550 560 570 580 590 600 KVTLPTIKDG SEAYRPGTTQ RVPAASPSAH SISTATPDRT RFPRGSSSRS TFHGEQLRER 610 620 630 640 650 660 RSVAYNGPPA SPSHETGAFA HARRGTSTGI ISKITSKFVR RSTSGEPKER DKEEGKDSKP 670 680 690 700 710 720 RSLRFTWSMK TTSSMDPNDM MREIRKVLDA NNCDYEQKER FLLFCVHGDA RQDSLVQWEM 730 740 750 EVCKLPRLSL NGVRFKRISG TSIAFKNIAS KIANELKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1." Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R. EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ENZYME REGULATION, PHOSPHORYLATION AT THR-215, MUTAGENESIS OF THR-215.
[2]	"Cloning and isolating human MARK." Zhou H.J., Huang X.W., Zhou Y., Hu S.L., Yuan J.G., Qiang B.Q. Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O. DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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).
[8]	"MARK - a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption." Drewes G., Ebneth A., Preuss U., Mandelkow E.-M., Mandelkow E. Cell 89:297-308(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Microtubule-affinity regulating kinase (MARK) is tightly associated with neurofibrillary tangles in Alzheimer brain: a fluorescence resonance energy transfer study." Chin J.Y., Knowles R.B., Schneider A., Drewes G., Mandelkow E.M., Hyman B.T. J. Neuropathol. Exp. Neurol. 59:966-971(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NEUROFIBRILLARY TANGLES IN ALZHEIMER BRAIN.
[10]	"PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling." Sun T.-Q., Lu B., Feng J.-J., Reinhard C., Jan Y.N., Fantl W.J., Williams L.T. Nat. Cell Biol. 3:628-636(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Suppression of tubulin polymerization by the LKB1-microtubule-associated protein/microtubule affinity-regulating kinase signaling." Kojima Y., Miyoshi H., Clevers H.C., Oshima M., Aoki M., Taketo M.M. J. Biol. Chem. 282:23532-23540(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-208, ENZYME REGULATION, FUNCTION.
[12]	"Convergent evidence identifying MAP/microtubule affinity-regulating kinase 1 (MARK1) as a susceptibility gene for autism." Maussion G., Carayol J., Lepagnol-Bestel A.M., Tores F., Loe-Mie Y., Milbreta U., Rousseau F., Fontaine K., Renaud J., Moalic J.M., Philippi A., Chedotal A., Gorwood P., Ramoz N., Hager J., Simonneau M. Hum. Mol. Genet. 17:2541-2551(2008) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN AUTISM.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-5 AND SER-403, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-588, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"The tau of MARK: a polarized view of the cytoskeleton." Matenia D., Mandelkow E.M. Trends Biochem. Sci. 34:332-342(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[18]	"Structure and function of polarity-inducing kinase family MARK/Par-1 within the branch of AMPK/Snf1-related kinases." Marx A., Nugoor C., Panneerselvam S., Mandelkow E. FASEB J. 24:1637-1648(2010) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[19]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"Structural variations in the catalytic and ubiquitin-associated domains of microtubule-associated protein/microtubule affinity regulating kinase (MARK) 1 and MARK2." Marx A., Nugoor C., Muller J., Panneerselvam S., Timm T., Bilang M., Mylonas E., Svergun D.I., Mandelkow E.M., Mandelkow E. J. Biol. Chem. 281:27586-27599(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 45-371.
[22]	"Kinase associated-1 domains drive MARK/PAR1 kinases to membrane targets by binding acidic phospholipids." Moravcevic K., Mendrola J.M., Schmitz K.R., Wang Y.H., Slochower D., Janmey P.A., Lemmon M.A. Cell 143:966-977(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 683-795, DOMAIN KA1, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-698; ARG-701; 771-ARG--LYS-773 AND 773-LYS-ARG-774.
[23]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-233; THR-355; MET-530; LEU-578 AND GLY-691.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF154845 mRNA. Translation: AAF72103.1.
AB040910 mRNA. Translation: BAA96001.1. Different initiation.
AK027493 mRNA. Translation: BAB55152.1. Frameshift.
AL592406, AC096640 Genomic DNA. Translation: CAH72462.1.
AL592406, AC096640 Genomic DNA. Translation: CAH72463.1.
CH471100 Genomic DNA. Translation: EAW93299.1.
CH471100 Genomic DNA. Translation: EAW93300.1.
CH471100 Genomic DNA. Translation: EAW93302.1.
BC113869 mRNA. Translation: AAI13870.1.
BC114478 mRNA. Translation: AAI14479.1.

IPI

IPI00185037.
IPI00292809.
IPI00555711.

RefSeq

NP_061120.3. NM_018650.3.

UniGene

Hs.497806.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HAK	X-ray	2.60	A/B/C/D/E/F/G/H	45-371	[»]
3OSE	X-ray	1.70	A	683-795	[»]

ProteinModelPortal

Q9P0L2.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9P0L2. 6 interactions.

MINT

MINT-3975018.

STRING

9606.ENSP00000355884.

PTM databases

PhosphoSite

Q9P0L2.

Polymorphism databases

DMDM

124056494.

Proteomic databases

PaxDb

Q9P0L2.

PRIDE

Q9P0L2.

Protocols and materials databases

DNASU

4139.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366917; ENSP00000355884; ENSG00000116141.
ENST00000366918; ENSP00000355885; ENSG00000116141.
ENST00000402574; ENSP00000386017; ENSG00000116141.

GeneID

4139.

KEGG

hsa:4139.

UCSC

uc001hmm.4. human.
uc001hmn.4. human.

Organism-specific databases

CTD

4139.

GeneCards

GC01P220701.

HGNC

HGNC:6896. MARK1.

HPA

HPA007421.
HPA008061.

MIM

606511. gene.

neXtProt

NX_Q9P0L2.

PharmGKB

PA30639.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOVERGEN

HBG052453.

InParanoid

Q9P0L2.

KO

K08798.

OMA

NHTSVDG.

OrthoDB

EOG4C2H8X.

Gene expression databases

ArrayExpress

Q9P0L2.

Bgee

Q9P0L2.

CleanEx

HS_MARK1.

Genevestigator

Q9P0L2.

GermOnline

ENSG00000116141. Homo sapiens.

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.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]

Pfam

PF02149. KA1. 1 hit.
PF00069. Pkinase. 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

BindingDB

Q9P0L2.

ChEMBL

CHEMBL5940.

ChiTaRS

MARK1. human.

EvolutionaryTrace

Q9P0L2.

GenomeRNAi

4139.

NextBio

16256.

SOURCE

Search...

Entry information

Entry name

MARK1_HUMAN

Accession

Primary (citable) accession number: Q9P0L2
Secondary accession number(s): D3DTB0 , D3DTB1, Q2HIY1, Q5VTF9, Q5VTG0, Q96SW9, Q9P251

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.