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Q96L34 (MARK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
MAP/microtubule affinity-regulating kinase 4

EC=2.7.11.1
Alternative name(s):
MAP/microtubule affinity-regulating kinase-like 1
Gene names
Name:MARK4
Synonyms:KIAA1860, MARKL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length752 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activated by phosphorylation on Thr-214. Ref.6

Tissue specificity

Ubiquitous. Isoform 2 is brain-specific. Ref.2

Post-translational modification

Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X. Ref.7

Phosphorylated at Thr-214 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Ref.6

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 BAB47489.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAB55238.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processmicrotubule bundle formation

Inferred from expression pattern PubMed 14594945. Source: UniProtKB

microtubule cytoskeleton organization

Inferred from mutant phenotype PubMed 14594945. Source: UniProtKB

nervous system development

Inferred from direct assay PubMed 14594945. Source: UniProtKB

positive regulation of programmed cell death

Non-traceable author statement PubMed 15009667. Source: UniProtKB

protein phosphorylation

Traceable author statement PubMed 14594945. Source: UniProtKB

   Cellular_componentcentrosome

Inferred from direct assay PubMed 14594945. Source: UniProtKB

microtubule cytoskeleton

Inferred from direct assay PubMed 14594945. Source: UniProtKB

microtubule organizing center

Inferred from direct assay PubMed 14594945. Source: UniProtKB

neuron projection

Inferred from direct assay PubMed 14594945. Source: UniProtKB

   Molecular_functionATP binding

Non-traceable author statement PubMed 15009667. Source: UniProtKB

gamma-tubulin binding

Inferred from direct assay PubMed 14594945. Source: UniProtKB

microtubule binding

Inferred from direct assay PubMed 14594945. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay PubMed 15009667. Source: UniProtKB

tau-protein kinase activity

Inferred from direct assay PubMed 14594945. Source: UniProtKB

ubiquitin binding

Non-traceable author statement PubMed 14594945. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96L34-1)

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: Q96L34-2)

Also known as: MARKL1S;

The sequence of this isoform differs from the canonical sequence as follows:
     628-752: ADEPERIGGP...VTRISNDLEL → TLDPSKRQNS...PPGCSDSPGV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 752752MAP/microtubule affinity-regulating kinase 4
PRO_0000086307

Regions

Domain59 – 310252Protein kinase
Domain324 – 36845UBA
Domain703 – 75250KA1
Nucleotide binding65 – 739ATP By similarity

Sites

Active site1811Proton acceptor By similarity
Binding site881ATP By similarity

Amino acid modifications

Modified residue2141Phosphothreonine; by LKB1 Ref.6

Natural variations

Alternative sequence628 – 752125ADEPE…NDLEL → TLDPSKRQNSNRCVSGASLP QGSKIRSQTNLRESGDLRSQ VAIYLGIKRKPPPGCSDSPG V in isoform 2.
VSP_004946
Natural variant3771R → Q. Ref.9
Corresponds to variant rs35070611 [ dbSNP | Ensembl ].
VAR_040766
Natural variant4181R → C in a colorectal adenocarcinoma sample; somatic mutation. Ref.9
VAR_040767

Experimental info

Mutagenesis2141T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.6
Mutagenesis2141T → E: Mimicks phosphorylation state, leading to increased activity. Ref.6
Sequence conflict701F → S in BAB39380. Ref.2
Sequence conflict701F → S in BAC03375. Ref.2
Sequence conflict5181P → L in BAB55238. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 4B430FFD2B150E7A

FASTA75282,520
        10         20         30         40         50         60 
MSSRTVLAPG NDRNSDTHGT LGSGRSSDKG PSWSSRSLGA RCRNSIASCP EEQPHVGNYR 

        70         80         90        100        110        120 
LLRTIGKGNF AKVKLARHIL TGREVAIKII DKTQLNPSSL QKLFREVRIM KGLNHPNIVK 

       130        140        150        160        170        180 
LFEVIETEKT LYLVMEYASA GEVFDYLVSH GRMKEKEARA KFRQIVSAVH YCHQKNIVHR 

       190        200        210        220        230        240 
DLKAENLLLD AEANIKIADF GFSNEFTLGS KLDTFCGSPP YAAPELFQGK KYDGPEVDIW 

       250        260        270        280        290        300 
SLGVILYTLV SGSLPFDGHN LKELRERVLR GKYRVPFYMS TDCESILRRF LVLNPAKRCT 

       310        320        330        340        350        360 
LEQIMKDKWI NIGYEGEELK PYTEPEEDFG DTKRIEVMVG MGYTREEIKE SLTSQKYNEV 

       370        380        390        400        410        420 
TATYLLLGRK TEEGGDRGAP GLALARVRAP SDTTNGTSSS KGTSHSKGQR SSSSTYHRQR 

       430        440        450        460        470        480 
RHSDFCGPSP APLHPKRSPT STGEAELKEE RLPGRKASCS TAGSGSRGLP PSSPMVSSAH 

       490        500        510        520        530        540 
NPNKAEIPER RKDSTSTPNN LPPSMMTRRN TYVCTERPGA ERPSLLPNGK ENSSGTPRVP 

       550        560        570        580        590        600 
PASPSSHSLA PPSGERSRLA RGSTIRSTFH GGQVRDRRAG GGGGGGVQNG PPASPTLAHE 

       610        620        630        640        650        660 
AAPLPAGRPR PTTNLFTKLT SKLTRRVADE PERIGGPEVT SCHLPWDQTE TAPRLLRFPW 

       670        680        690        700        710        720 
SVKLTSSRPP EALMAALRQA TAAARCRCRQ PQPFLLACLH GGAGGPEPLS HFEVEVCQLP 

       730        740        750 
RPGLRGVLFR RVAGTALAFR TLVTRISNDL EL 

« Hide

Isoform 2 (MARKL1S) [UniParc].

Checksum: A49143B34FDDD086
Show »

FASTA68875,321

References

« Hide 'large scale' references
[1]"MARK4, homologue of MARK1, MARK2 and MARK3."
Drewes G., Mandelkow E.M.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis."
Kato T., Satoh S., Okabe H., Kitahara O., Ono K., Kihara C., Tanaka T., Tsunoda T., Yamaoka Y., Nakamura Y., Furukawa Y.
Neoplasia 3:4-9(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Tissue: Brain.
[3]"Neural progenitor-restricted isoform of MARKL1 gene is upregulated by 19q13 amplification in human glioblastoma."
Beghini A., Magnani I., Roversi G., Piepoli T., DiTerlizzi S., Pollo B., Conti A.M.F., Cowell J.K., Finocchiaro G., Larizza L.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.
DNA Res. 8:85-95(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[5]"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. expand/collapse author list , 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 1).
Tissue: Thyroid.
[6]"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: ENZYME REGULATION, PHOSPHORYLATION AT THR-214, MUTAGENESIS OF THR-214.
[7]"Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains."
Al-Hakim A.K., Zagorska A., Chapman L., Deak M., Peggie M., Alessi D.R.
Biochem. J. 411:249-260(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP9X.
[8]"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].
[9]"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. expand/collapse author list , 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] GLN-377 AND CYS-418.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY057448 mRNA. Translation: AAL23683.1.
AB049127 mRNA. Translation: BAB39380.1.
AB088047 mRNA. Translation: BAC03375.1.
AY120867 mRNA. Translation: AAM55491.1.
AB058763 mRNA. Translation: BAB47489.1. Different initiation.
AK027619 mRNA. Translation: BAB55238.1. Different initiation.
AK075272 mRNA. Translation: BAC11510.1.
RefSeqNP_001186796.1. NM_001199867.1.
NP_113605.2. NM_031417.3.
UniGeneHs.34314.

3D structure databases

ProteinModelPortalQ96L34.
SMRQ96L34. Positions 53-369, 653-752.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121760. 40 interactions.
IntActQ96L34. 28 interactions.
MINTMINT-6425023.
STRING9606.ENSP00000300843.

Chemistry

BindingDBQ96L34.
ChEMBLCHEMBL5754.
GuidetoPHARMACOLOGY2100.

PTM databases

PhosphoSiteQ96L34.

Polymorphism databases

DMDM29840797.

Proteomic databases

PaxDbQ96L34.
PRIDEQ96L34.

Protocols and materials databases

DNASU57787.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000262891; ENSP00000262891; ENSG00000007047. [Q96L34-1]
ENST00000300843; ENSP00000300843; ENSG00000007047. [Q96L34-2]
GeneID57787.
KEGGhsa:57787.
UCSCuc002pba.2. human. [Q96L34-2]
uc002pbb.2. human. [Q96L34-1]

Organism-specific databases

CTD57787.
GeneCardsGC19P045583.
HGNCHGNC:13538. MARK4.
HPAHPA039186.
MIM606495. gene.
neXtProtNX_Q96L34.
PharmGKBPA30641.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233025.
HOVERGENHBG052453.
InParanoidQ96L34.
KOK08798.
OMADSMSTPN.
OrthoDBEOG79CXXX.
PhylomeDBQ96L34.
TreeFamTF315213.

Enzyme and pathway databases

SignaLinkQ96L34.

Gene expression databases

ArrayExpressQ96L34.
BgeeQ96L34.
CleanExHS_MARK4.
GenevestigatorQ96L34.

Family and domain databases

Gene3D3.30.310.80. 1 hit.
InterProIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_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.
IPR000449. UBA/Ts_N.
[Graphical view]
PfamPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50032. 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]
ProtoNetSearch...

Other

GeneWikiMARK4.
GenomeRNAi57787.
NextBio64721.
PROQ96L34.
SOURCESearch...

Entry information

Entry nameMARK4_HUMAN
AccessionPrimary (citable) accession number: Q96L34
Secondary accession number(s): Q8NG37 expand/collapse secondary AC list , Q96JG7, Q96SQ2, Q9BYD8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 28, 2003
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM