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Protein

Mitogen-activated protein kinase kinase kinase 13

Gene

MAP3K13

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B.3 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by autophosphorylation and homodimerization.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei195ATPPROSITE-ProRule annotationBy similarity1
Active sitei279Proton acceptorPROSITE-ProRule annotationBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi174 – 182ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase kinase activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • activation of MAPKK activity Source: UniProtKB
  • JNK cascade Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01117-MONOMER.
SignaLinkiO43283.
SIGNORiO43283.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase 13 (EC:2.7.11.25)
Alternative name(s):
Leucine zipper-bearing kinase
Mixed lineage kinase
Short name:
MLK
Gene namesi
Name:MAP3K13Imported
Synonyms:LZKImported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6852. MAP3K13.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi195K → A: Kinase inactive. Fails to activate NF-kappa-B. 1 Publication1

Organism-specific databases

DisGeNETi9175.
OpenTargetsiENSG00000073803.
PharmGKBiPA30596.

Chemistry databases

ChEMBLiCHEMBL1163124.
GuidetoPHARMACOLOGYi2073.

Polymorphism and mutation databases

BioMutaiMAP3K13.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862641 – 966Mitogen-activated protein kinase kinase kinase 13Add BLAST966

Post-translational modificationi

Autophosphorylated on serine and threonine residues.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO43283.
PeptideAtlasiO43283.
PRIDEiO43283.

PTM databases

iPTMnetiO43283.
PhosphoSitePlusiO43283.

Expressioni

Tissue specificityi

Expressed in the adult brain, liver, placenta and pancreas, with expression strongest in the pancreas.1 Publication

Gene expression databases

BgeeiENSG00000073803.
CleanExiHS_MAP3K13.
ExpressionAtlasiO43283. baseline and differential.
GenevisibleiO43283. HS.

Organism-specific databases

HPAiHPA016497.
HPA036691.
HPA036692.

Interactioni

Subunit structurei

Homodimer; forms dimers through the leucine-zipper motif. Interacts with the C-terminus of MAPK8IP1 through the kinase catalytic domain. Binds PRDX3. Associates with the IKK complex through the kinase domain.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-1168480,EBI-1168480

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114614. 12 interactors.
IntActiO43283. 3 interactors.
MINTiMINT-158088.
STRINGi9606.ENSP00000265026.

Chemistry databases

BindingDBiO43283.

Structurei

3D structure databases

ProteinModelPortaliO43283.
SMRiO43283.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini168 – 409Protein kinasePROSITE-ProRule annotationAdd BLAST242

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni433 – 454Leucine-zipper 1Add BLAST22
Regioni486 – 507Leucine-zipper 2Add BLAST22
Regioni815 – 828AcidicCuratedAdd BLAST14

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4721. Eukaryota.
ENOG410YKX2. LUCA.
GeneTreeiENSGT00760000118807.
HOVERGENiHBG052383.
InParanoidiO43283.
KOiK04422.
OMAiHRRGNSR.
OrthoDBiEOG091G0905.
PhylomeDBiO43283.
TreeFamiTF105119.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017419. MAP3K12_MAP3K13.
IPR027258. MAPKKK13.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR23257:SF336. PTHR23257:SF336. 2 hits.
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF038165. MAPKKK12_MAPKKK13. 1 hit.
PIRSF500742. MAPKKK13. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43283-1) [UniParc]FASTAAdd to basket

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
MANFQEHLSC SSSPHLPFSE SKTFNGLQDE LTAMGNHPSP KLLEDQQEKG
60 70 80 90 100
MVRTELIESV HSPVTTTVLT SVSEDSRDQF ENSVLQLREH DESETAVSQG
110 120 130 140 150
NSNTVDGEST SGTEDIKIQF SRSGSGSGGF LEGLFGCLRP VWNIIGKAYS
160 170 180 190 200
TDYKLQQQDT WEVPFEEISE LQWLGSGAQG AVFLGKFRAE EVAIKKVREQ
210 220 230 240 250
NETDIKHLRK LKHPNIIAFK GVCTQAPCYC IIMEYCAHGQ LYEVLRAGRK
260 270 280 290 300
ITPRLLVDWS TGIASGMNYL HLHKIIHRDL KSPNVLVTHT DAVKISDFGT
310 320 330 340 350
SKELSDKSTK MSFAGTVAWM APEVIRNEPV SEKVDIWSFG VVLWELLTGE
360 370 380 390 400
IPYKDVDSSA IIWGVGSNSL HLPVPSTCPD GFKILMKQTW QSKPRNRPSF
410 420 430 440 450
RQTLMHLDIA SADVLATPQE TYFKSQAEWR EEVKKHFEKI KSEGTCIHRL
460 470 480 490 500
DEELIRRRRE ELRHALDIRE HYERKLERAN NLYMELSAIM LQLEMREKEL
510 520 530 540 550
IKREQAVEKK YPGTYKRHPV RPIIHPNAME KLMKRKGVPH KSGMQTKRPD
560 570 580 590 600
LLRSEGIPTT EVAPTASPLS GSPKMSTSSS KSRYRSKPRH RRGNSRGSHS
610 620 630 640 650
DFAAILKNQP AQENSPHPTY LHQAQSQYPS LHHHNSLQQQ YQQPPPAMSQ
660 670 680 690 700
SHHPRLNMHG QDIATCANNL RYFGPAAALR SPLSNHAQRQ LPGSSPDLIS
710 720 730 740 750
TAMAADCWRS SEPDKGQAGP WGCCQADAYD PCLQCRPEQY GSLDIPSAEP
760 770 780 790 800
VGRSPDLSKS PAHNPLLENA QSSEKTEENE FSGCRSESSL GTSHLGTPPA
810 820 830 840 850
LPRKTRPLQK SGDDSSEEEE GEVDSEVEFP RRQRPHRCIS SCQSYSTFSS
860 870 880 890 900
ENFSVSDGEE GNTSDHSNSP DELADKLEDR LAEKLDDLLS QTPEIPIDIS
910 920 930 940 950
SHSDGLSDKE CAVRRVKTQM SLGKLCVEER GYENPMQFEE SDCDSSDGEC
960
SDATVRTNKH YSSATW
Length:966
Mass (Da):108,296
Last modified:June 1, 1998 - v1
Checksum:i9687F38C8AB20AB1
GO
Isoform 2 (identifier: O43283-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     159-160: DT → VF
     161-966: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:160
Mass (Da):17,575
Checksum:i95152C01C501AEFC
GO
Isoform 3 (identifier: O43283-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-144: Missing.
     145-159: IGKAYSTDYKLQQQD → MSYVECKCLQLENKN

Show »
Length:822
Mass (Da):92,654
Checksum:i22B40649EEF108AB
GO
Isoform 4 (identifier: O43283-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-207: Missing.
     208-220: LRKLKHPNIIAFK → MYCGIQILALWER

Show »
Length:759
Mass (Da):85,404
Checksum:i6E1DCE6581A1A2DC
GO
Isoform 5 (identifier: O43283-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     122-128: RSGSGSG → RYLGSAI
     129-966: Missing.

Show »
Length:128
Mass (Da):14,073
Checksum:i9000EE02899AC48D
GO

Sequence cautioni

The sequence AAI11727 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence BAG59505 differs from that shown. Reason: Erroneous termination at position 740. Translated as Tyr.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106D → G in BAG59505 (PubMed:14702039).Curated1
Sequence conflicti230 – 232CII → YLY in CAA80915 (PubMed:8274451).Curated3
Sequence conflicti268N → D in BAG59505 (PubMed:14702039).Curated1
Sequence conflicti339 – 340FG → MV in CAA80915 (PubMed:8274451).Curated2
Sequence conflicti508E → G in BAG64106 (PubMed:14702039).Curated1
Sequence conflicti821G → R in BAG60014 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05164044E → K.Corresponds to variant rs35266179dbSNPEnsembl.1
Natural variantiVAR_040708517R → G.1 PublicationCorresponds to variant rs56408536dbSNPEnsembl.1
Natural variantiVAR_040709712E → K.1 PublicationCorresponds to variant rs56309231dbSNPEnsembl.1
Natural variantiVAR_040710746P → L in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030577915R → H.Corresponds to variant rs3732576dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0365621 – 207Missing in isoform 4. 1 PublicationAdd BLAST207
Alternative sequenceiVSP_0365631 – 144Missing in isoform 3. 1 PublicationAdd BLAST144
Alternative sequenceiVSP_036564122 – 128RSGSGSG → RYLGSAI in isoform 5. 1 Publication7
Alternative sequenceiVSP_036565129 – 966Missing in isoform 5. 1 PublicationAdd BLAST838
Alternative sequenceiVSP_036566145 – 159IGKAY…LQQQD → MSYVECKCLQLENKN in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_036567159 – 160DT → VF in isoform 2. 1 Publication2
Alternative sequenceiVSP_036568161 – 966Missing in isoform 2. 1 PublicationAdd BLAST806
Alternative sequenceiVSP_036569208 – 220LRKLK…IIAFK → MYCGIQILALWER in isoform 4. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB001872 mRNA. Translation: BAA24817.1.
AK296961 mRNA. Translation: BAG59505.1. Sequence problems.
AK297646 mRNA. Translation: BAG60014.1.
AK302951 mRNA. Translation: BAG64106.1.
AK312714 mRNA. Translation: BAG35589.1.
AC099661 Genomic DNA. No translation available.
AC128680 Genomic DNA. No translation available.
AC132516 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78224.1.
CH471052 Genomic DNA. Translation: EAW78225.1.
BC031677 mRNA. Translation: AAH31677.1.
BC111726 mRNA. Translation: AAI11727.1. Sequence problems.
Z25428 mRNA. Translation: CAA80915.1.
CCDSiCCDS3270.1. [O43283-1]
CCDS56298.1. [O43283-5]
PIRiI38218.
RefSeqiNP_001229243.1. NM_001242314.1. [O43283-1]
NP_001229246.1. NM_001242317.1. [O43283-5]
NP_004712.1. NM_004721.4. [O43283-1]
XP_011511612.1. XM_011513310.2. [O43283-1]
XP_016862945.1. XM_017007456.1. [O43283-1]
UniGeneiHs.591306.
Hs.634586.

Genome annotation databases

EnsembliENST00000265026; ENSP00000265026; ENSG00000073803. [O43283-1]
ENST00000424227; ENSP00000399910; ENSG00000073803. [O43283-1]
ENST00000433092; ENSP00000389798; ENSG00000073803. [O43283-6]
ENST00000438053; ENSP00000403561; ENSG00000073803. [O43283-3]
ENST00000443863; ENSP00000409325; ENSG00000073803. [O43283-4]
ENST00000446828; ENSP00000411483; ENSG00000073803. [O43283-5]
GeneIDi9175.
KEGGihsa:9175.
UCSCiuc003fph.5. human. [O43283-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB001872 mRNA. Translation: BAA24817.1.
AK296961 mRNA. Translation: BAG59505.1. Sequence problems.
AK297646 mRNA. Translation: BAG60014.1.
AK302951 mRNA. Translation: BAG64106.1.
AK312714 mRNA. Translation: BAG35589.1.
AC099661 Genomic DNA. No translation available.
AC128680 Genomic DNA. No translation available.
AC132516 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78224.1.
CH471052 Genomic DNA. Translation: EAW78225.1.
BC031677 mRNA. Translation: AAH31677.1.
BC111726 mRNA. Translation: AAI11727.1. Sequence problems.
Z25428 mRNA. Translation: CAA80915.1.
CCDSiCCDS3270.1. [O43283-1]
CCDS56298.1. [O43283-5]
PIRiI38218.
RefSeqiNP_001229243.1. NM_001242314.1. [O43283-1]
NP_001229246.1. NM_001242317.1. [O43283-5]
NP_004712.1. NM_004721.4. [O43283-1]
XP_011511612.1. XM_011513310.2. [O43283-1]
XP_016862945.1. XM_017007456.1. [O43283-1]
UniGeneiHs.591306.
Hs.634586.

3D structure databases

ProteinModelPortaliO43283.
SMRiO43283.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114614. 12 interactors.
IntActiO43283. 3 interactors.
MINTiMINT-158088.
STRINGi9606.ENSP00000265026.

Chemistry databases

BindingDBiO43283.
ChEMBLiCHEMBL1163124.
GuidetoPHARMACOLOGYi2073.

PTM databases

iPTMnetiO43283.
PhosphoSitePlusiO43283.

Polymorphism and mutation databases

BioMutaiMAP3K13.

Proteomic databases

PaxDbiO43283.
PeptideAtlasiO43283.
PRIDEiO43283.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265026; ENSP00000265026; ENSG00000073803. [O43283-1]
ENST00000424227; ENSP00000399910; ENSG00000073803. [O43283-1]
ENST00000433092; ENSP00000389798; ENSG00000073803. [O43283-6]
ENST00000438053; ENSP00000403561; ENSG00000073803. [O43283-3]
ENST00000443863; ENSP00000409325; ENSG00000073803. [O43283-4]
ENST00000446828; ENSP00000411483; ENSG00000073803. [O43283-5]
GeneIDi9175.
KEGGihsa:9175.
UCSCiuc003fph.5. human. [O43283-1]

Organism-specific databases

CTDi9175.
DisGeNETi9175.
GeneCardsiMAP3K13.
HGNCiHGNC:6852. MAP3K13.
HPAiHPA016497.
HPA036691.
HPA036692.
MIMi604915. gene.
neXtProtiNX_O43283.
OpenTargetsiENSG00000073803.
PharmGKBiPA30596.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4721. Eukaryota.
ENOG410YKX2. LUCA.
GeneTreeiENSGT00760000118807.
HOVERGENiHBG052383.
InParanoidiO43283.
KOiK04422.
OMAiHRRGNSR.
OrthoDBiEOG091G0905.
PhylomeDBiO43283.
TreeFamiTF105119.

Enzyme and pathway databases

BioCyciZFISH:HS01117-MONOMER.
SignaLinkiO43283.
SIGNORiO43283.

Miscellaneous databases

ChiTaRSiMAP3K13. human.
GeneWikiiMAP3K13.
GenomeRNAii9175.
PROiO43283.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073803.
CleanExiHS_MAP3K13.
ExpressionAtlasiO43283. baseline and differential.
GenevisibleiO43283. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR017419. MAP3K12_MAP3K13.
IPR027258. MAPKKK13.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR23257:SF336. PTHR23257:SF336. 2 hits.
PfamiPF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PIRSFiPIRSF038165. MAPKKK12_MAPKKK13. 1 hit.
PIRSF500742. MAPKKK13. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiM3K13_HUMAN
AccessioniPrimary (citable) accession number: O43283
Secondary accession number(s): B2R6U2
, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, Q05BY6, Q15450, Q2NKN3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: June 1, 1998
Last modified: November 2, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.