Reviewed,
UniProtKB/Swiss-Prot Q5TCX8 (M3KL4_HUMAN)
Last modified
February 9, 2010.
Version 57.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Mitogen-activated protein kinase kinase kinase EC=2.7.11.25 Alternative name(s): Mixed lineage kinase 4 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1036 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Activates the JUN N-terminal pathway By similarity. UniProtKB Q16584 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium By similarity. UniProtKB P80192 |
| Enzyme regulation | Homodimerization via the leucine zipper domains is required for autophosphorylation and subsequent activation By similarity. UniProtKB Q16584 |
| Subunit structure | Homodimer By similarity. UniProtKB Q16584 |
| Post-translational modification | Autophosphorylation on serine and threonine residues within the activation loop plays a role in enzyme activation By similarity. UniProtKB Q16584 |
| Sequence similarities | Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Contains 1 protein kinase domain. Contains 1 SH3 domain. |
Ontologies
| Keywords | |
|---|---|
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Repeat SH3 domain |
| Ligand | ATP-binding Nucleotide-binding |
| Molecular function | Kinase Serine/threonine-protein kinase Transferase |
| PTM | Phosphoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | activation of JUN kinase activity Inferred from sequence or structural similarity. Source: UniProtKB protein amino acid autophosphorylationInferred from sequence or structural similarity. Source: UniProtKB |
| Molecular function | ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activityInferred from electronic annotation. Source: EC protein homodimerization activityInferred from sequence or structural similarity. Source: UniProtKB protein tyrosine kinase activityInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | |||||||||
| Isoform 1 Ref.6 (identifier: Q5TCX8-1) Also known as: MLK4beta; 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 Ref.6 (identifier: Q5TCX8-2) Also known as: MLK4alpha; The sequence of this isoform differs from the canonical sequence as follows: 559-570: LTSDESNKTWGR → CELSALPRGLLC 571-1036: Missing. | |||||||||
Sequence annotation (Features) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
| Sequence conflict | 566 | 1 | R → P in CAC84639. Ref.1 | ||||||
| Isoform 3 Ref.2 (identifier: Q5TCX8-3) The sequence of this isoform differs from the canonical sequence as follows: 1-554: Missing. 555-559: RAIQL → MFFLVT | |||||||||
| Note: No experimental confirmation available. | |||||||||
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1036 | 1036 | Mitogen-activated protein kinase kinase kinase | PRO_0000086268 | |||||
Regions | |||||||||
| Domain | 38 – 102 | 65 | SH3 | ||||||
| Domain | 124 – 401 | 278 | Protein kinase | ||||||
| Domain | 425 – 446 | 22 | Leucine-zipper 1 | ||||||
| Domain | 460 – 481 | 22 | Leucine-zipper 2 | ||||||
| Nucleotide binding | 130 – 138 | 9 | ATP By similarity UniProtKB Q02779 | ||||||
| Compositional bias | 15 – 37 | 23 | Ser-rich | ||||||
Sites | |||||||||
| Active site | 263 | 1 | Proton acceptor By similarity UniProtKB Q02779 | ||||||
| Binding site | 151 | 1 | ATP By similarity UniProtKB Q02779 | ||||||
Amino acid modifications | |||||||||
| Modified residue | 114 | 1 | Phosphoserine | ||||||
| Modified residue | 299 | 1 | Phosphothreonine; by autocatalysis By similarity UniProtKB Q16584 | ||||||
| Modified residue | 303 | 1 | Phosphoserine; by autocatalysis and MAP4K1 By similarity UniProtKB Q16584 | ||||||
| Modified residue | 455 | 1 | Phosphoserine | ||||||
| Modified residue | 514 | 1 | Phosphoserine Ref.6 | ||||||
| Modified residue | 528 | 1 | Phosphoserine Ref.6 Ref.8 | ||||||
| Modified residue | 543 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 546 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 547 | 1 | Phosphoserine By similarity UniProtKB Q16584 | ||||||
| Modified residue | 592 | 1 | Phosphothreonine | ||||||
| Modified residue | 614 | 1 | Phosphoserine Ref.6 Ref.7 | ||||||
| Modified residue | 732 | 1 | Phosphoserine By similarity UniProtKB Q16584 | ||||||
| Modified residue | 773 | 1 | Phosphoserine | ||||||
| Modified residue | 806 | 1 | Phosphoserine By similarity UniProtKB Q16584 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 554 | 554 | Missing in isoform 3. Ref.2 | VSP_051731 | |||||
| Alternative sequence | 555 – 559 | 5 | RAIQL → MFFLVT in isoform 3. Ref.2 | VSP_051732 | |||||
| Alternative sequence | 559 – 570 | 12 | LTSDE…KTWGR → CELSALPRGLLC in isoform 2. Ref.6 | VSP_051733 | |||||
| Alternative sequence | 571 – 1036 | 466 | Missing in isoform 2. Ref.6 | VSP_051734 | |||||
| Natural variant | 420 | 1 | D → N: dbSNP rs35465006. Ref.10 | VAR_040729 | |||||
| Natural variant | 563 | 1 | E → D: dbSNP rs35758282. Ref.10 | VAR_040730 | |||||
| Natural variant | 597 | 1 | S → F: dbSNP rs34984140. Ref.10 | VAR_040731 | |||||
| Natural variant | 728 | 1 | V → I: dbSNP rs3795375. Ref.10 | VAR_040732 | |||||
| Natural variant | 741 | 1 | E → D: dbSNP rs3795374. Ref.10 | VAR_040733 | |||||
| Natural variant | 784 | 1 | C → G: dbSNP rs963981. Ref.10 | VAR_040734 | |||||
| Natural variant | 892 | 1 | R → W: dbSNP rs55681416. Ref.10 | VAR_040735 | |||||
| Natural variant | 900 | 1 | T → I: dbSNP rs34499091. Ref.10 | VAR_040736 | |||||
| Natural variant | 977 | 1 | R → C: dbSNP rs56065162. Ref.10 | VAR_040737 | |||||
| Natural variant | 982 | 1 | P → L: dbSNP rs34794284. Ref.10 | VAR_040738 | |||||
Experimental info | |||||||||
| Sequence conflict | 274 | 1 | K → E in CAC84639. Ref.1 | ||||||
| Sequence conflict | 274 | 1 | K → E in CAC84640. Ref.1 | ||||||
| Sequence conflict | 330 | 1 | Y → C in CAC84639. Ref.1 | ||||||
| Sequence conflict | 330 | 1 | Y → C in CAC84640. Ref.1 | ||||||
| Sequence conflict | 687 | 1 | E → G in CAC84640. Ref.1 | ||||||
| Sequence conflict | 701 | 1 | S → T in CAC84640. Ref.1 | ||||||
| Sequence conflict | 705 | 1 | T → A in CAC84640. Ref.1 | ||||||
| Sequence conflict | 781 | 1 | P → S in CAC84640. Ref.1 | ||||||
| Sequence conflict | 872 | 1 | Q → R in CAC84640. Ref.1 | ||||||
| Sequence conflict | 1002 | 1 | A → V in CAC84640. Ref.1 | ||||||
| Sequence conflict | 1016 | 1 | C → G in CAC84640. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "MLK4, a new member of mixed lineage kinases." Kvasha S., Protopopov A., Rynditch A., Zabarovsky E., Kashuba V. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Heart. |
| [2] | "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: 11347906] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain. |
| [3] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [6] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514; SER-528 AND SER-614, MASS SPECTROMETRY. |
| [7] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-614, MASS SPECTROMETRY. |
| [8] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528; SER-543 AND SER-546, MASS SPECTROMETRY. |
| [9] | "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: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-455; SER-528; THR-592; SER-614 AND SER-773, MASS SPECTROMETRY. |
| [10] | "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. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-420; ASP-563; PHE-597; ILE-728; ASP-741; GLY-784; TRP-892; ILE-900; CYS-977 AND LEU-982. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AJ311797 mRNA. Translation: CAC84639.1. AJ311798 mRNA. Translation: CAC84640.1. AB058707 mRNA. Translation: BAB47433.1. Different initiation. AL133380 Genomic DNA. Translation: CAI23045.1. AL133380 Genomic DNA. Translation: CAI23046.1. AL133380 Genomic DNA. Translation: CAI23047.1. CH471098 Genomic DNA. Translation: EAW69988.1. BC136648 mRNA. Translation: AAI36649.1. BC136649 mRNA. Translation: AAI36650.1. |
| IPI | IPI00142487. IPI00607654. IPI00607875. |
| RefSeq | NP_115811.2. |
| UniGene | Hs.547779 |
3D structure databases | |
| SMR | Q5TCX8. Positions 42-401. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q5TCX8. 1 interaction. |
| STRING | Q5TCX8. |
PTM databases | |
| PhosphoSite | Q5TCX8. |
Proteomic databases | |
| PRIDE | Q5TCX8. |
Genome annotation databases | |
| Ensembl | ENST00000366624; ENSP00000355583; ENSG00000143674; Homo sapiens. [Genome view] |
| GeneID | 84451. |
| KEGG | hsa:84451. |
| NMPDR | fig|9606.3.peg.3263. |
| UCSC | uc001hvs.1. human. uc001hvt.2. human. uc001hvu.2. human. |
Organism-specific databases | |
| CTD | 84451. |
| GeneCards | GC01P231530. |
| HPA | HPA007636. |
| HUGE | Search... |
Phylogenomic databases | |
| eggNOG | prNOG05813. |
| HOGENOM | HBG716519. |
| HOVERGEN | Q5TCX8. |
| InParanoid | Q5TCX8. |
| OMA | HRKPKQI. |
| OrthoDB | EOG9QC3RC. |
| PhylomeDB | Q5TCX8. |
Enzyme and pathway databases | |
| BRENDA | 2.7.11.25. 247. |
Gene expression databases | |
| ArrayExpress | Q5TCX8. |
| Bgee | Q5TCX8. |
| Genevestigator | Q5TCX8. |
| GermOnline | ENSG00000143674. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR011009. Kinase-like_dom. IPR015785. MAPKKK-like. IPR016231. MAPKKK9/10/11. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR008271. Ser/Thr_prot_kinase_AS. IPR001452. SH3_domain. IPR020473. SH3_region. IPR020635. Tyr_Pkinase_cat_dom. [Graphical view] |
| PANTHER | PTHR23257:SF87. MAPKKK-like. 1 hit. |
| Pfam | PF00018. SH3_1. 1 hit. [Graphical view] |
| PIRSF | PIRSF000556. MAPKKK9_11. 1 hit. |
| PRINTS | PR00452. SH3DOMAIN. |
| SMART | SM00326. SH3. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view] |
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50002. SH3. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 74235. |
Entry information
| Entry name | M3KL4_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q5TCX8 Secondary accession number(s): B2RN34 Q96JM1 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


