Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Mitogen-activated protein kinase kinase kinase 13

Gene

MAP3K13

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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
  • identical protein binding Source: IntAct
  • IkappaB kinase complex binding Source: UniProtKB
  • JUN kinase kinase kinase activity Source: ARUK-UCL
  • 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

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000073803.13
HGNCiHGNC:6852 MAP3K13
MIMi604915 gene
neXtProtiNX_O43283

Subcellular locationi

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
ProteomicsDBi48852
48853 [O43283-3]
48854 [O43283-4]
48855 [O43283-5]
48856 [O43283-6]

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 Expressed in 225 organ(s), highest expression level in corpus epididymis
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-protein interaction databases

BioGridi114614, 12 interactors
IntActiO43283, 3 interactors
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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4721 Eukaryota
ENOG410YKX2 LUCA
GeneTreeiENSGT00930000150812
HOVERGENiHBG052383
InParanoidiO43283
KOiK04422
OMAiCAEERGY
OrthoDBiEOG091G0905
PhylomeDBiO43283
TreeFamiTF105119

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017419 MAP3K12_MAP3K13
IPR027258 MAPKKK13
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF038165 MAPKKK12_MAPKKK13, 1 hit
PIRSF500742 MAPKKK13, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

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

This entry has 5 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C459H7C459_HUMAN
Mitogen-activated protein kinase ki...
MAP3K13
246Annotation score:
C9J4W2C9J4W2_HUMAN
Mitogen-activated protein kinase ki...
MAP3K13
137Annotation score:
C9JP65C9JP65_HUMAN
Mitogen-activated protein kinase ki...
MAP3K13
113Annotation score:
F8WF41F8WF41_HUMAN
Mitogen-activated protein kinase ki...
MAP3K13
194Annotation score:
C9IYH2C9IYH2_HUMAN
Mitogen-activated protein kinase ki...
MAP3K13
40Annotation score:

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 dbSNP:rs35266179Ensembl.1
Natural variantiVAR_040708517R → G1 PublicationCorresponds to variant dbSNP:rs56408536Ensembl.1
Natural variantiVAR_040709712E → K1 PublicationCorresponds to variant dbSNP:rs56309231Ensembl.1
Natural variantiVAR_040710746P → L in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_030577915R → H. Corresponds to variant dbSNP:rs3732576Ensembl.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

Similar proteinsi

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
STRINGi9606.ENSP00000265026

Chemistry databases

BindingDBiO43283
ChEMBLiCHEMBL1163124
GuidetoPHARMACOLOGYi2073

PTM databases

iPTMnetiO43283
PhosphoSitePlusiO43283

Polymorphism and mutation databases

BioMutaiMAP3K13

Proteomic databases

PaxDbiO43283
PeptideAtlasiO43283
PRIDEiO43283
ProteomicsDBi48852
48853 [O43283-3]
48854 [O43283-4]
48855 [O43283-5]
48856 [O43283-6]

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
EuPathDBiHostDB:ENSG00000073803.13
GeneCardsiMAP3K13
HGNCiHGNC:6852 MAP3K13
HPAiHPA016497
HPA036691
HPA036692
MIMi604915 gene
neXtProtiNX_O43283
OpenTargetsiENSG00000073803
PharmGKBiPA30596
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4721 Eukaryota
ENOG410YKX2 LUCA
GeneTreeiENSGT00930000150812
HOVERGENiHBG052383
InParanoidiO43283
KOiK04422
OMAiCAEERGY
OrthoDBiEOG091G0905
PhylomeDBiO43283
TreeFamiTF105119

Enzyme and pathway databases

SignaLinkiO43283
SIGNORiO43283

Miscellaneous databases

ChiTaRSiMAP3K13 human
GeneWikiiMAP3K13
GenomeRNAii9175
PROiPR:O43283
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073803 Expressed in 225 organ(s), highest expression level in corpus epididymis
CleanExiHS_MAP3K13
ExpressionAtlasiO43283 baseline and differential
GenevisibleiO43283 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR017419 MAP3K12_MAP3K13
IPR027258 MAPKKK13
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF038165 MAPKKK12_MAPKKK13, 1 hit
PIRSF500742 MAPKKK13, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiM3K13_HUMAN
AccessioniPrimary (citable) accession number: O43283
Secondary accession number(s): B2R6U2
, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, Q05BY6, Q15450, Q2NKN3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: June 1, 1998
Last modified: November 7, 2018
This is version 157 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again