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Protein

MAP/microtubule affinity-regulating kinase 4

Gene

Mark4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine-protein kinase (By similarity). Phosphorylates the microtubule-associated protein MAPT (By similarity). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (By similarity). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (By similarity). Required for the initiation of axoneme extension during cilium assembly (By similarity). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (By similarity). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (By similarity). Reduces neuronal cell survival (By similarity). Plays a role in energy homeostasis by regulating satiety and metabolic rate (PubMed:22992738). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (PubMed:24989893). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (By similarity).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation on Thr-214.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei88ATPPROSITE-ProRule annotation1
Active sitei181Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi65 – 73ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Cilium biogenesis/degradation, Mitosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5620912 Anchoring of the basal body to the plasma membrane

Names & Taxonomyi

Protein namesi
Recommended name:
MAP/microtubule affinity-regulating kinase 4 (EC:2.7.11.1By similarity)
Gene namesi
Name:Mark4
Synonyms:Kiaa1860
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1920955 Mark4

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 projection, Cytoplasm, Cytoskeleton

Pathology & Biotechi

Disruption phenotypei

Hyperphagia, hyperactivity and hypermetabolism leading to protection from diet-induced obesity, and improved glucose homeostasis due to up-regulation of AMPK kinase activity.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863081 – 752MAP/microtubule affinity-regulating kinase 4Add BLAST752

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei214Phosphothreonine; by LKB1By similarity1
Modified residuei423PhosphoserineCombined sources1
Modified residuei543PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X (By similarity).By similarity
Phosphorylated at Thr-214 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylated throughout the cell cycle.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8CIP4
PaxDbiQ8CIP4
PeptideAtlasiQ8CIP4
PRIDEiQ8CIP4

PTM databases

iPTMnetiQ8CIP4
PhosphoSitePlusiQ8CIP4

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 show similar expression patterns in the central nervous system and are present in the same subsets of neurons including pyramidal and non-pyramidal neurons in the cerebral cortex and hippocampus, cerebellar Purkinje cells, and interneurons and motor neurons in the spinal cord but not in glial cells (at protein level) (PubMed:16973293). Isoform 2 is the major isoform in brain and cerebellum (PubMed:16973293, PubMed:15009667). Also expressed in spleen, liver, small intestine, colon, kidney, tongue, testis and lung (PubMed:16973293, PubMed:15009667). Isoform 1 and isoform 2 are expressed at similar levels in heart (PubMed:16973293).2 Publications

Gene expression databases

BgeeiENSMUSG00000030397
CleanExiMM_MARK4
ExpressionAtlasiQ8CIP4 baseline and differential
GenevisibleiQ8CIP4 MM

Interactioni

Subunit structurei

Interacts with gamma-tubulin. Interacts with ODF2. Interacts with USP9X.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi231328, 4 interactors
DIPiDIP-60721N
IntActiQ8CIP4, 4 interactors
STRINGi10090.ENSMUSP00000082862

Structurei

3D structure databases

ProteinModelPortaliQ8CIP4
SMRiQ8CIP4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini59 – 310Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini324 – 368UBAPROSITE-ProRule annotationAdd BLAST45
Domaini703 – 752KA1PROSITE-ProRule annotationAdd BLAST50

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0586 Eukaryota
ENOG410XNQ0 LUCA
GeneTreeiENSGT00900000140806
HOGENOMiHOG000233025
HOVERGENiHBG052453
InParanoidiQ8CIP4
KOiK08798
OMAiLAHEATP
OrthoDBiEOG091G0D1E
PhylomeDBiQ8CIP4
TreeFamiTF315213

Family and domain databases

InterProiView protein in InterPro
IPR028375 KA1/Ssp2_C
IPR001772 KA1_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
IPR015940 UBA
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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8CIP4-1) [UniParc]FASTAAdd to basket
Also known as: MARK4L

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
MSSRTALAPG NDRNSDTHGT LGSGRSSDKG PSWSSRSLGA RCRNSIASCP
60 70 80 90 100
EEQPHVGNYR LLRTIGKGNF AKVKLARHIL TGREVAIKII DKTQLNPSSL
110 120 130 140 150
QKLFREVRIM KGLNHPNIVK LFEVIETEKT LYLVMEYASA GEVFDYLVSH
160 170 180 190 200
GRMKEKEARA KFRQIVSAVH YCHQKNIVHR DLKAENLLLD AEANIKIADF
210 220 230 240 250
GFSNEFTLGS KLDTFCGSPP YAAPELFQGK KYDGPEVDIW SLGVILYTLV
260 270 280 290 300
SGSLPFDGHN LKELRERVLR GKYRVPFYMS TDCESILRRF LVLNPAKRCT
310 320 330 340 350
LEQIMKDKWI NIGYEGEELK PYTEPEEDFG DTKRIEVMVG MGYTREEIKE
360 370 380 390 400
ALTNQKYNEV TATYLLLGRK TEEGGDRGAP GLALARVRAP SDTTNGTSSS
410 420 430 440 450
KGSSHNKGQR ASSSTYHRQR RHSDFCGPSP APLHPKRSPT STGDTELKEE
460 470 480 490 500
RMPGRKASCS AVGSGSRGLP PSSPMVSSAH NPNKAEIPER RKDSTSTPNN
510 520 530 540 550
LPPSMMTRRN TYVCTERPGS ERPSLLPNGK ENSSGTSRVP PASPSSHSLA
560 570 580 590 600
PPSGERSRLA RGSTIRSTFH GGQVRDRRAG SGSGGGVQNG PPASPTLAHE
610 620 630 640 650
AAPLPSGRPR PTTNLFTKLT SKLTRRVTDE PERIGGPEVT SCHLPWDKTE
660 670 680 690 700
TAPRLLRFPW SVKLTSSRPP EALMAALRQA TAAARCRCRQ PQPFLLACLH
710 720 730 740 750
GGAGGPEPLS HFEVEVCQLP RPGLRGVLFR RVAGTALAFR TLVTRISNDL

EL
Length:752
Mass (Da):82,644
Last modified:March 1, 2003 - v1
Checksum:i185FDAE3F0D627DD
GO
Isoform 2 (identifier: Q8CIP4-2) [UniParc]FASTAAdd to basket
Also known as: MARK4S

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

Show »
Length:688
Mass (Da):75,415
Checksum:i07BA89EC2926A3B9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti162F → L in AX305103 (PubMed:15009667).Curated1
Sequence conflicti162F → L in AX305104 (PubMed:15009667).Curated1
Sequence conflicti268V → I in AX305103 (PubMed:15009667).Curated1
Sequence conflicti268V → I in AX305104 (PubMed:15009667).Curated1
Sequence conflicti372E → D in AX305103 (PubMed:15009667).Curated1
Sequence conflicti372E → D in AX305104 (PubMed:15009667).Curated1
Sequence conflicti438S → T in AX305103 (PubMed:15009667).Curated1
Sequence conflicti677L → M in AX305103 (PubMed:15009667).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_058199628 – 752TDEPE…NDLEL → TLDPSKRQNSNRCVSGASLP QGSKIRSQTNLRESGDLRSQ VAIYLGIKRKPPPGCSDSPG V in isoform 2. 1 PublicationAdd BLAST125

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY151083 mRNA Translation: AAN60072.1
AX305103 mRNA No translation available.
AX305104 mRNA No translation available.
AK122565 mRNA Translation: BAC65847.2
CCDSiCCDS20903.1 [Q8CIP4-1]
RefSeqiNP_758483.1, NM_172279.1 [Q8CIP4-1]
XP_006539892.1, XM_006539829.3 [Q8CIP4-2]
UniGeneiMm.260504

Genome annotation databases

EnsembliENSMUST00000085715; ENSMUSP00000082862; ENSMUSG00000030397 [Q8CIP4-1]
GeneIDi232944
KEGGimmu:232944
UCSCiuc009flx.1 mouse [Q8CIP4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMARK4_MOUSE
AccessioniPrimary (citable) accession number: Q8CIP4
Secondary accession number(s): Q80T81
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: March 1, 2003
Last modified: May 23, 2018
This is version 128 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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