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Protein

MAP/microtubule affinity-regulating kinase 4

Gene

Mark4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei88 – 881ATPPROSITE-ProRule annotation
Active sitei181 – 1811Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi65 – 739ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Cilium biogenesis/degradation, Mitosis

Keywords - Ligandi

ATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1920955. Mark4.

Subcellular locationi

  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing center By similarity
  • Cytoplasmcytoskeletoncilium axoneme By similarity
  • Cytoplasmcytoskeletoncilium basal body By similarity
  • Cytoplasm By similarity

  • Note: Localized at the tips of neurite-like processes in differentiated neuroblast cells. Detected in the cytoplasm and neuropil of the hippocampus.By similarity

GO - Cellular componenti

Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 752752MAP/microtubule affinity-regulating kinase 4PRO_0000086308Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei214 – 2141Phosphothreonine; by LKB1By similarity
Modified residuei423 – 4231PhosphoserineCombined sources
Modified residuei543 – 5431PhosphoserineBy similarity

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.
PhosphoSiteiQ8CIP4.

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.
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 interactions.
DIPiDIP-60721N.
STRINGi10090.ENSMUSP00000082862.

Structurei

3D structure databases

ProteinModelPortaliQ8CIP4.
SMRiQ8CIP4. Positions 11-369, 653-752.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini59 – 310252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini324 – 36845UBAPROSITE-ProRule annotationAdd
BLAST
Domaini703 – 75250KA1PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 KA1 (kinase-associated) domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00790000122947.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiQ8CIP4.
KOiK08798.
OMAiLAHEATP.
OrthoDBiEOG091G0D1E.
PhylomeDBiQ8CIP4.
TreeFamiTF315213.

Family and domain databases

Gene3Di3.30.310.80. 1 hit.
InterProiIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR033624. MARK/par1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PANTHERiPTHR24346. PTHR24346. 1 hit.
PfamiPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50032. 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]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti162 – 1621F → L in AX305103 (PubMed:15009667).Curated
Sequence conflicti162 – 1621F → L in AX305104 (PubMed:15009667).Curated
Sequence conflicti268 – 2681V → I in AX305103 (PubMed:15009667).Curated
Sequence conflicti268 – 2681V → I in AX305104 (PubMed:15009667).Curated
Sequence conflicti372 – 3721E → D in AX305103 (PubMed:15009667).Curated
Sequence conflicti372 – 3721E → D in AX305104 (PubMed:15009667).Curated
Sequence conflicti438 – 4381S → T in AX305103 (PubMed:15009667).Curated
Sequence conflicti677 – 6771L → M in AX305103 (PubMed:15009667).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei628 – 752125TDEPE…NDLEL → TLDPSKRQNSNRCVSGASLP QGSKIRSQTNLRESGDLRSQ VAIYLGIKRKPPPGCSDSPG V in isoform 2. 1 PublicationVSP_058199Add
BLAST

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_006539829.2. [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

Cross-referencesi

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_006539829.2. [Q8CIP4-2]
UniGeneiMm.260504.

3D structure databases

ProteinModelPortaliQ8CIP4.
SMRiQ8CIP4. Positions 11-369, 653-752.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi231328. 4 interactions.
DIPiDIP-60721N.
STRINGi10090.ENSMUSP00000082862.

PTM databases

iPTMnetiQ8CIP4.
PhosphoSiteiQ8CIP4.

Proteomic databases

MaxQBiQ8CIP4.
PaxDbiQ8CIP4.
PeptideAtlasiQ8CIP4.
PRIDEiQ8CIP4.

Protocols and materials databases

DNASUi232944.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi57787.
MGIiMGI:1920955. Mark4.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
GeneTreeiENSGT00790000122947.
HOGENOMiHOG000233025.
HOVERGENiHBG052453.
InParanoidiQ8CIP4.
KOiK08798.
OMAiLAHEATP.
OrthoDBiEOG091G0D1E.
PhylomeDBiQ8CIP4.
TreeFamiTF315213.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ8CIP4.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000030397.
CleanExiMM_MARK4.
GenevisibleiQ8CIP4. MM.

Family and domain databases

Gene3Di3.30.310.80. 1 hit.
InterProiIPR028375. KA1/Ssp2_C.
IPR001772. KA1_dom.
IPR011009. Kinase-like_dom.
IPR033624. MARK/par1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PANTHERiPTHR24346. PTHR24346. 1 hit.
PfamiPF02149. KA1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00627. UBA. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
SM00165. UBA. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50032. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiMARK4_MOUSE
AccessioniPrimary (citable) accession number: Q8CIP4
Secondary accession number(s): Q80T81
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: March 1, 2003
Last modified: September 7, 2016
This is version 115 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.