UniProtKB - Q96L34 (MARK4_HUMAN)
MAP/microtubule affinity-regulating kinase 4
MARK4
Functioni
Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942).
Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762).
Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945).
Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532).
Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999).
Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999).
Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532).
Reduces neuronal cell survival (PubMed:15009667).
Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity).
Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity).
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 (PubMed:23184942).
By similarity6 PublicationsCatalytic activityi
Cofactori
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 88 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 181 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 65 – 73 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- gamma-tubulin binding Source: UniProtKB
- microtubule binding Source: UniProtKB
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
- tau protein binding Source: ARUK-UCL
- tau-protein kinase activity Source: UniProtKB
- ubiquitin binding Source: UniProtKB
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- cell division Source: UniProtKB-KW
- cilium organization Source: ARUK-UCL
- intracellular signal transduction Source: GO_Central
- microtubule bundle formation Source: UniProtKB
- microtubule cytoskeleton organization Source: UniProtKB
- nervous system development Source: UniProtKB
- positive regulation of cell cycle Source: ARUK-UCL
- positive regulation of cilium assembly Source: ARUK-UCL
- positive regulation of programmed cell death Source: UniProtKB
- positive regulation of protein localization to centrosome Source: ARUK-UCL
- protein phosphorylation Source: UniProtKB
- regulation of centrosome cycle Source: ARUK-UCL
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, Cell division, Cilium biogenesis/degradation, Mitosis |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q96L34 |
Reactomei | R-HSA-5620912, Anchoring of the basal body to the plasma membrane |
SignaLinki | Q96L34 |
SIGNORi | Q96L34 |
Names & Taxonomyi
Protein namesi | Recommended name: MAP/microtubule affinity-regulating kinase 4 (EC:2.7.11.13 Publications)Alternative name(s): MAP/microtubule affinity-regulating kinase-like 1 |
Gene namesi | Name:MARK4 Synonyms:KIAA1860, MARKL1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:13538, MARK4 |
MIMi | 606495, gene |
neXtProti | NX_Q96L34 |
VEuPathDBi | HostDB:ENSG00000007047 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Cytoskeleton
- centrosome 1 Publication
- microtubule organizing center 1 Publication
- cilium basal body 1 Publication
- cilium axoneme 1 Publication
Other locations
- dendrite 1 Publication
Note: Localized at the tips of neurite-like processes in differentiated neuroblast cells. Detected in the cytoplasm and neuropil of the hippocampus.2 Publications
Cytoskeleton
- centrosome Source: UniProtKB
- ciliary basal body Source: CACAO
- gamma-tubulin complex Source: ARUK-UCL
- microtubule cytoskeleton Source: UniProtKB
- microtubule organizing center Source: UniProtKB
Cytosol
- cytosol Source: HPA
Other locations
- cytoplasm Source: UniProtKB
- dendrite Source: UniProtKB
- midbody Source: ARUK-UCL
- neuron projection Source: UniProtKB
Keywords - Cellular componenti
Cell projection, Cytoplasm, CytoskeletonPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 214 | T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication | 1 | |
Mutagenesisi | 214 | T → E: Mimicks phosphorylation state, leading to increased activity. Decreases mTORC1 activity. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 57787 |
OpenTargetsi | ENSG00000007047 |
PharmGKBi | PA30641 |
Miscellaneous databases
Pharosi | Q96L34, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5754 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q96L34 |
Genetic variation databases
BioMutai | MARK4 |
DMDMi | 29840797 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086307 | 1 – 752 | MAP/microtubule affinity-regulating kinase 4Add BLAST | 752 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 214 | Phosphothreonine; by LKB11 Publication | 1 | |
Modified residuei | 423 | PhosphoserineBy similarity | 1 | |
Modified residuei | 543 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q96L34 |
jPOSTi | Q96L34 |
MassIVEi | Q96L34 |
MaxQBi | Q96L34 |
PaxDbi | Q96L34 |
PeptideAtlasi | Q96L34 |
PRIDEi | Q96L34 |
ProteomicsDBi | 77145 [Q96L34-1] 77146 [Q96L34-2] |
PTM databases
GlyGeni | Q96L34, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q96L34 |
PhosphoSitePlusi | Q96L34 |
Expressioni
Tissue specificityi
Developmental stagei
Gene expression databases
Bgeei | ENSG00000007047, Expressed in male germ cell and 237 other tissues |
ExpressionAtlasi | Q96L34, baseline and differential |
Genevisiblei | Q96L34, HS |
Organism-specific databases
HPAi | ENSG00000007047, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q96L34
GO - Molecular functioni
- gamma-tubulin binding Source: UniProtKB
- microtubule binding Source: UniProtKB
- tau protein binding Source: ARUK-UCL
- ubiquitin binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121760, 61 interactors |
IntActi | Q96L34, 40 interactors |
MINTi | Q96L34 |
STRINGi | 9606.ENSP00000262891 |
Chemistry databases
BindingDBi | Q96L34 |
Miscellaneous databases
RNActi | Q96L34, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q96L34 |
SMRi | Q96L34 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 59 – 310 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 | |
Domaini | 324 – 368 | UBAPROSITE-ProRule annotationAdd BLAST | 45 | |
Domaini | 703 – 752 | KA1PROSITE-ProRule annotationAdd BLAST | 50 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 36 | DisorderedSequence analysisAdd BLAST | 36 | |
Regioni | 385 – 614 | DisorderedSequence analysisAdd BLAST | 230 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 390 – 413 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 441 – 455 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 459 – 480 | Polar residuesSequence analysisAdd BLAST | 22 | |
Compositional biasi | 494 – 511 | Polar residuesSequence analysisAdd BLAST | 18 | |
Compositional biasi | 527 – 552 | Polar residuesSequence analysisAdd BLAST | 26 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0586, Eukaryota |
GeneTreei | ENSGT00940000159555 |
HOGENOMi | CLU_000288_157_5_1 |
InParanoidi | Q96L34 |
OMAi | CHLPWDK |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q96L34 |
TreeFami | TF315213 |
Family and domain databases
InterProi | View 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 |
Pfami | View protein in Pfam PF02149, KA1, 1 hit PF00069, Pkinase, 1 hit PF00627, UBA, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit SM00165, UBA, 1 hit |
SUPFAMi | SSF103243, SSF103243, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSSRTVLAPG 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
SLTSQKYNEV TATYLLLGRK TEEGGDRGAP GLALARVRAP SDTTNGTSSS
410 420 430 440 450
KGTSHSKGQR SSSSTYHRQR RHSDFCGPSP APLHPKRSPT STGEAELKEE
460 470 480 490 500
RLPGRKASCS TAGSGSRGLP PSSPMVSSAH NPNKAEIPER RKDSTSTPNN
510 520 530 540 550
LPPSMMTRRN TYVCTERPGA ERPSLLPNGK ENSSGTPRVP PASPSSHSLA
560 570 580 590 600
PPSGERSRLA RGSTIRSTFH GGQVRDRRAG GGGGGGVQNG PPASPTLAHE
610 620 630 640 650
AAPLPAGRPR PTTNLFTKLT SKLTRRVADE PERIGGPEVT SCHLPWDQTE
660 670 680 690 700
TAPRLLRFPW SVKLTSSRPP EALMAALRQA TAAARCRCRQ PQPFLLACLH
710 720 730 740 750
GGAGGPEPLS HFEVEVCQLP RPGLRGVLFR RVAGTALAFR TLVTRISNDL
EL
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ6IPE9 | Q6IPE9_HUMAN | MAP/microtubule affinity-regulating... | MARK4 | 97 | Annotation score: | ||
K7EKG8 | K7EKG8_HUMAN | MAP/microtubule affinity-regulating... | MARK4 | 74 | Annotation score: | ||
K7EK17 | K7EK17_HUMAN | MAP/microtubule affinity-regulating... | MARK4 | 62 | Annotation score: | ||
K7EN95 | K7EN95_HUMAN | MAP/microtubule affinity-regulating... | MARK4 | 48 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 70 | F → S in BAB39380 (PubMed:11326310).Curated | 1 | |
Sequence conflicti | 70 | F → S in BAC03375 (PubMed:11326310).Curated | 1 | |
Sequence conflicti | 518 | P → L in BAB55238 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040766 | 377 | R → Q1 PublicationCorresponds to variant dbSNP:rs35070611Ensembl. | 1 | |
Natural variantiVAR_040767 | 418 | R → C in a colorectal adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs780763668Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004946 | 628 – 752 | ADEPE…NDLEL → TLDPSKRQNSNRCVSGASLP QGSKIRSQTNLRESGDLRSQ VAIYLGIKRKPPPGCSDSPG V in isoform 2. 2 PublicationsAdd BLAST | 125 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB049127 mRNA Translation: BAB39380.1 AB088047 mRNA Translation: BAC03375.1 AY057448 mRNA Translation: AAL23683.1 AX305105 mRNA No translation available. AX305106 mRNA No translation available. AY120867 mRNA Translation: AAM55491.1 AB058763 mRNA Translation: BAB47489.1 Different initiation. AK027619 mRNA Translation: BAB55238.1 Different initiation. AK075272 mRNA Translation: BAC11510.1 |
CCDSi | CCDS12658.1 [Q96L34-2] CCDS56097.1 [Q96L34-1] |
RefSeqi | NP_001186796.1, NM_001199867.1 [Q96L34-1] NP_113605.2, NM_031417.3 [Q96L34-2] |
Genome annotation databases
Ensembli | ENST00000262891.9; ENSP00000262891.3; ENSG00000007047.16 ENST00000300843.8; ENSP00000300843.3; ENSG00000007047.16 [Q96L34-2] |
GeneIDi | 57787 |
KEGGi | hsa:57787 |
MANE-Selecti | ENST00000262891.9; ENSP00000262891.3; NM_001199867.2; NP_001186796.1 |
UCSCi | uc002pba.3, human [Q96L34-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB049127 mRNA Translation: BAB39380.1 AB088047 mRNA Translation: BAC03375.1 AY057448 mRNA Translation: AAL23683.1 AX305105 mRNA No translation available. AX305106 mRNA No translation available. AY120867 mRNA Translation: AAM55491.1 AB058763 mRNA Translation: BAB47489.1 Different initiation. AK027619 mRNA Translation: BAB55238.1 Different initiation. AK075272 mRNA Translation: BAC11510.1 |
CCDSi | CCDS12658.1 [Q96L34-2] CCDS56097.1 [Q96L34-1] |
RefSeqi | NP_001186796.1, NM_001199867.1 [Q96L34-1] NP_113605.2, NM_031417.3 [Q96L34-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5ES1 | X-ray | 2.80 | A | 44-370 | [»] | |
AlphaFoldDBi | Q96L34 | |||||
SMRi | Q96L34 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121760, 61 interactors |
IntActi | Q96L34, 40 interactors |
MINTi | Q96L34 |
STRINGi | 9606.ENSP00000262891 |
Chemistry databases
BindingDBi | Q96L34 |
ChEMBLi | CHEMBL5754 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q96L34 |
PTM databases
GlyGeni | Q96L34, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q96L34 |
PhosphoSitePlusi | Q96L34 |
Genetic variation databases
BioMutai | MARK4 |
DMDMi | 29840797 |
Proteomic databases
EPDi | Q96L34 |
jPOSTi | Q96L34 |
MassIVEi | Q96L34 |
MaxQBi | Q96L34 |
PaxDbi | Q96L34 |
PeptideAtlasi | Q96L34 |
PRIDEi | Q96L34 |
ProteomicsDBi | 77145 [Q96L34-1] 77146 [Q96L34-2] |
Protocols and materials databases
Antibodypediai | 31285, 383 antibodies from 37 providers |
DNASUi | 57787 |
Genome annotation databases
Ensembli | ENST00000262891.9; ENSP00000262891.3; ENSG00000007047.16 ENST00000300843.8; ENSP00000300843.3; ENSG00000007047.16 [Q96L34-2] |
GeneIDi | 57787 |
KEGGi | hsa:57787 |
MANE-Selecti | ENST00000262891.9; ENSP00000262891.3; NM_001199867.2; NP_001186796.1 |
UCSCi | uc002pba.3, human [Q96L34-1] |
Organism-specific databases
CTDi | 57787 |
DisGeNETi | 57787 |
GeneCardsi | MARK4 |
HGNCi | HGNC:13538, MARK4 |
HPAi | ENSG00000007047, Low tissue specificity |
MIMi | 606495, gene |
neXtProti | NX_Q96L34 |
OpenTargetsi | ENSG00000007047 |
PharmGKBi | PA30641 |
VEuPathDBi | HostDB:ENSG00000007047 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0586, Eukaryota |
GeneTreei | ENSGT00940000159555 |
HOGENOMi | CLU_000288_157_5_1 |
InParanoidi | Q96L34 |
OMAi | CHLPWDK |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q96L34 |
TreeFami | TF315213 |
Enzyme and pathway databases
PathwayCommonsi | Q96L34 |
Reactomei | R-HSA-5620912, Anchoring of the basal body to the plasma membrane |
SignaLinki | Q96L34 |
SIGNORi | Q96L34 |
Miscellaneous databases
BioGRID-ORCSi | 57787, 11 hits in 1108 CRISPR screens |
ChiTaRSi | MARK4, human |
GeneWikii | MARK4 |
GenomeRNAii | 57787 |
Pharosi | Q96L34, Tchem |
PROi | PR:Q96L34 |
RNActi | Q96L34, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000007047, Expressed in male germ cell and 237 other tissues |
ExpressionAtlasi | Q96L34, baseline and differential |
Genevisiblei | Q96L34, HS |
Family and domain databases
InterProi | View 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 |
Pfami | View protein in Pfam PF02149, KA1, 1 hit PF00069, Pkinase, 1 hit PF00627, UBA, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit SM00165, UBA, 1 hit |
SUPFAMi | SSF103243, SSF103243, 1 hit SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | MARK4_HUMAN | |
Accessioni | Q96L34Primary (citable) accession number: Q96L34 Secondary accession number(s): Q8NG37 Q9BYD8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 28, 2003 |
Last sequence update: | December 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 195 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families