Q96L34 (MARK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	752 AA.
Sequence status	Complete.
Protein existence	Evidence 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 diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	microtubule bundle formation Inferred from expression pattern 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
Cellular_component	centrosome Inferred from direct assay PubMed 14594945. Source: UniProtKB neuron projection Inferred from direct assay PubMed 14594945. Source: UniProtKB
Molecular_function	ATP 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...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953	2	EBI-302319,EBI-81752
PARD6G	Q9BYG4	2	EBI-302319,EBI-295417
PNMA1	Q8ND90	2	EBI-302319,EBI-302345
PRKCI	P41743	2	EBI-302319,EBI-286199
STK11	Q15831	2	EBI-302319,EBI-306838
TUBG1	P23258	4	EBI-302319,EBI-302589
YWHAH	Q04917	6	EBI-302319,EBI-306940

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 752	752	MAP/microtubule affinity-regulating kinase 4		PRO_0000086307
Regions
	Domain	59 – 310	252	Protein kinase
	Domain	324 – 368	45	UBA
	Domain	703 – 752	50	KA1
	Nucleotide binding	65 – 73	9	ATP By similarity
Sites
	Active site	181	1	Proton acceptor By similarity
	Binding site	88	1	ATP By similarity
Amino acid modifications
	Modified residue	214	1	Phosphothreonine; by LKB1 Ref.6
Natural variations
	Alternative sequence	628 – 752	125	ADEPE…NDLEL → TLDPSKRQNSNRCVSGASLP QGSKIRSQTNLRESGDLRSQ VAIYLGIKRKPPPGCSDSPG V in isoform 2.		VSP_004946
	Natural variant	377	1	R → Q. Ref.9 Corresponds to variant rs35070611 [ dbSNP | Ensembl ].		VAR_040766
	Natural variant	418	1	R → C in a colorectal adenocarcinoma sample; somatic mutation. Ref.9		VAR_040767
Experimental info
	Mutagenesis	214	1	T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.6
	Mutagenesis	214	1	T → E: Mimicks phosphorylation state, leading to increased activity. Ref.6
	Sequence conflict	70	1	F → S in BAB39380. Ref.2
	Sequence conflict	70	1	F → S in BAC03375. Ref.2
	Sequence conflict	518	1	P → L in BAB55238. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 4B430FFD2B150E7A	FASTA	752	82,520
	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
	Isoform 2 (MARKL1S) [UniParc]. Checksum: A49143B34FDDD086	FASTA	688	75,321
	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 SKLTRRVTLD PSKRQNSNRC VSGASLPQGS KIRSQTNLRE 670 680 SGDLRSQVAI YLGIKRKPPP GCSDSPGV

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00064797. IPI00297959.
RefSeq	NP_001186796.1. NM_001199867.1. NP_113605.2. NM_031417.3.
UniGene	Hs.34314.
3D structure databases
ProteinModelPortal	Q96L34.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96L34. 28 interactions.
STRING	9606.ENSP00000300843.
PTM databases
PhosphoSite	Q96L34.
Polymorphism databases
DMDM	29840797.
Proteomic databases
PaxDb	Q96L34.
PRIDE	Q96L34.
Protocols and materials databases
DNASU	57787.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000262891; ENSP00000262891; ENSG00000007047. ENST00000300843; ENSP00000300843; ENSG00000007047.
GeneID	57787.
KEGG	hsa:57787.
UCSC	uc002pba.2. human. uc002pbb.2. human.
Organism-specific databases
CTD	57787.
GeneCards	GC19P045754.
HGNC	HGNC:13538. MARK4.
HPA	HPA039186.
MIM	606495. gene.
neXtProt	NX_Q96L34.
PharmGKB	PA30641.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233025.
HOVERGEN	HBG052453.
InParanoid	Q96L34.
KO	K08798.
OMA	KDSMSTP.
OrthoDB	EOG4TB49R.
PhylomeDB	Q96L34.
Gene expression databases
ArrayExpress	Q96L34.
Bgee	Q96L34.
CleanEx	HS_MARK4.
Genevestigator	Q96L34.
GermOnline	ENSG00000007047. 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. 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
BindingDB	Q96L34.
ChEMBL	CHEMBL5754.
GenomeRNAi	57787.
NextBio	64721.
SOURCE	Search...

Entry information

Entry name

MARK4_HUMAN

Accession

Primary (citable) accession number: Q96L34
Secondary accession number(s): Q8NG37 , Q96JG7, Q96SQ2, Q9BYD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 121 of the entry and version 1 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.