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Protein

Misshapen-like kinase 1

Gene

MINK1

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

Functioni

Serine/threonine kinase which acts as a negative regulator of Ras-related Rap2-mediated signal transduction to control neuronal structure and AMPA receptor trafficking. Required for normal synaptic density, dendrite complexity, as well as surface AMPA receptor expression in hippocampal neurons. Can activate the JNK and MAPK14/p38 pathways and mediates stimulation of the stress-activated protein kinase MAPK14/p38 MAPK downstream of the Raf/ERK pathway. Phosphorylates: TANC1 upon stimulation by RAP2A, MBP and SMAD1. Has an essential function in negative selection of thymocytes, perhaps by coupling NCK1 to activation of JNK1.
Isoform 4 can activate the JNK pathway. Involved in the regulation of actin cytoskeleton reorganization, cell-matrix adhesion, cell-cell adhesion and cell migration.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.By similarity

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei54ATPPROSITE-ProRule annotation1
Active sitei153Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 39ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • MAP kinase kinase kinase kinase activity Source: GO_Central
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
SignaLinkiQ8N4C8
SIGNORiQ8N4C8

Names & Taxonomyi

Protein namesi
Recommended name:
Misshapen-like kinase 1 (EC:2.7.11.1)
Alternative name(s):
GCK family kinase MiNK
MAPK/ERK kinase kinase kinase 6
Short name:
MEK kinase kinase 6
Short name:
MEKKK 6
Misshapen/NIK-related kinase
Mitogen-activated protein kinase kinase kinase kinase 6
Gene namesi
Name:MINK1Imported
Synonyms:B55, MAP4K6By similarity, MINKImported, YSK2, ZC3
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000141503.15
HGNCiHGNC:17565 MINK1
MIMi609426 gene
neXtProtiNX_Q8N4C8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Golgi apparatus, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Organism-specific databases

DisGeNETi50488
OpenTargetsiENSG00000141503
PharmGKBiPA134910641

Chemistry databases

ChEMBLiCHEMBL5518
GuidetoPHARMACOLOGYi2103

Polymorphism and mutation databases

BioMutaiMINK1
DMDMi296437370

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863291 – 1332Misshapen-like kinase 1Add BLAST1332

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei324PhosphoserineBy similarity1
Modified residuei326PhosphoserineBy similarity1
Modified residuei501Omega-N-methylarginineBy similarity1
Modified residuei509Omega-N-methylarginineCombined sources1
Modified residuei641PhosphoserineCombined sources1
Modified residuei701PhosphoserineCombined sources1
Modified residuei754PhosphoserineCombined sources1
Modified residuei763PhosphoserineCombined sources1
Modified residuei777PhosphoserineCombined sources1
Modified residuei778PhosphoserineCombined sources1
Modified residuei782PhosphoserineCombined sources1
Modified residuei891PhosphothreonineBy similarity1

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ8N4C8
MaxQBiQ8N4C8
PaxDbiQ8N4C8
PeptideAtlasiQ8N4C8
PRIDEiQ8N4C8
ProteomicsDBi71917
71918 [Q8N4C8-2]
71919 [Q8N4C8-3]
71920 [Q8N4C8-4]
71921 [Q8N4C8-5]

PTM databases

iPTMnetiQ8N4C8
PhosphoSitePlusiQ8N4C8

Expressioni

Tissue specificityi

Expressed in the brain, isoform 2 is more abundant than isoform 1. Isoform 3 is ubiquitously expressed. Isoform 1 is most abundant in the skeletal muscle. Isoform 4 is ubiquitously expressed with relative high levels in brain, skeletal muscle, pancreas and testis.1 Publication

Inductioni

Activated after Ras induction via a mechanism involving reactive oxygen species.1 Publication

Gene expression databases

BgeeiENSG00000141503 Expressed in 236 organ(s), highest expression level in CA1 field of hippocampus
CleanExiHS_MINK1
ExpressionAtlasiQ8N4C8 baseline and differential
GenevisibleiQ8N4C8 HS

Organism-specific databases

HPAiHPA056296

Interactioni

Subunit structurei

Interacts with TANC1 (By similarity). Interacts with RAP2A. Isoform 4 interacts with NCK1.By similarity2 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi119075, 20 interactors
IntActiQ8N4C8, 6 interactors
MINTiQ8N4C8
STRINGi9606.ENSP00000347427

Chemistry databases

BindingDBiQ8N4C8

Structurei

3D structure databases

ProteinModelPortaliQ8N4C8
SMRiQ8N4C8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 289Protein kinasePROSITE-ProRule annotationAdd BLAST265
Domaini1019 – 1306CNHPROSITE-ProRule annotationAdd BLAST288

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni866 – 1332Mediates interaction with RAP2A1 PublicationAdd BLAST467

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi359 – 495Gln-richAdd BLAST137
Compositional biasi542 – 729Pro-richAdd BLAST188

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0587 Eukaryota
ENOG410XPHR LUCA
GeneTreeiENSGT00920000148966
HOGENOMiHOG000290708
HOVERGENiHBG036506
InParanoidiQ8N4C8
KOiK04413
OMAiSFTMFVD
OrthoDBiEOG091G018A
PhylomeDBiQ8N4C8
TreeFamiTF105138

Family and domain databases

InterProiView protein in InterPro
IPR001180 CNH_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00780 CNH, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00036 CNH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50219 CNH, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
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 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 31 Publication (identifier: Q8N4C8-1) [UniParc]FASTAAdd to basket
Also known as: MINK-alpha

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
MGDPAPARSL DDIDLSALRD PAGIFELVEV VGNGTYGQVY KGRHVKTGQL
60 70 80 90 100
AAIKVMDVTE DEEEEIKQEI NMLKKYSHHR NIATYYGAFI KKSPPGNDDQ
110 120 130 140 150
LWLVMEFCGA GSVTDLVKNT KGNALKEDCI AYICREILRG LAHLHAHKVI
160 170 180 190 200
HRDIKGQNVL LTENAEVKLV DFGVSAQLDR TVGRRNTFIG TPYWMAPEVI
210 220 230 240 250
ACDENPDATY DYRSDIWSLG ITAIEMAEGA PPLCDMHPMR ALFLIPRNPP
260 270 280 290 300
PRLKSKKWSK KFIDFIDTCL IKTYLSRPPT EQLLKFPFIR DQPTERQVRI
310 320 330 340 350
QLKDHIDRSR KKRGEKEETE YEYSGSEEED DSHGEEGEPS SIMNVPGEST
360 370 380 390 400
LRREFLRLQQ ENKSNSEALK QQQQLQQQQQ RDPEAHIKHL LHQRQRRIEE
410 420 430 440 450
QKEERRRVEE QQRREREQRK LQEKEQQRRL EDMQALRREE ERRQAEREQE
460 470 480 490 500
YKRKQLEEQR QSERLQRQLQ QEHAYLKSLQ QQQQQQQLQK QQQQQLLPGD
510 520 530 540 550
RKPLYHYGRG MNPADKPAWA REVEERTRMN KQQNSPLAKS KPGSTGPEPP
560 570 580 590 600
IPQASPGPPG PLSQTPPMQR PVEPQEGPHK SLVAHRVPLK PYAAPVPRSQ
610 620 630 640 650
SLQDQPTRNL AAFPASHDPD PAIPAPTATP SARGAVIRQN SDPTSEGPGP
660 670 680 690 700
SPNPPAWVRP DNEAPPKVPQ RTSSIATALN TSGAGGSRPA QAVRARPRSN
710 720 730 740 750
SAWQIYLQRR AERGTPKPPG PPAQPPGPPN ASSNPDLRRS DPGWERSDSV
760 770 780 790 800
LPASHGHLPQ AGSLERNRVG VSSKPDSSPV LSPGNKAKPD DHRSRPGRPA
810 820 830 840 850
DFVLLKERTL DEAPRPPKKA MDYSSSSEEV ESSEDDEEEG EGGPAEGSRD
860 870 880 890 900
TPGGRSDGDT DSVSTMVVHD VEEITGTQPP YGGGTMVVQR TPEEERNLLH
910 920 930 940 950
ADSNGYTNLP DVVQPSHSPT ENSKGQSPPS KDGSGDYQSR GLVKAPGKSS
960 970 980 990 1000
FTMFVDLGIY QPGGSGDSIP ITALVGGEGT RLDQLQYDVR KGSVVNVNPT
1010 1020 1030 1040 1050
NTRAHSETPE IRKYKKRFNS EILCAALWGV NLLVGTENGL MLLDRSGQGK
1060 1070 1080 1090 1100
VYGLIGRRRF QQMDVLEGLN LLITISGKRN KLRVYYLSWL RNKILHNDPE
1110 1120 1130 1140 1150
VEKKQGWTTV GDMEGCGHYR VVKYERIKFL VIALKSSVEV YAWAPKPYHK
1160 1170 1180 1190 1200
FMAFKSFADL PHRPLLVDLT VEEGQRLKVI YGSSAGFHAV DVDSGNSYDI
1210 1220 1230 1240 1250
YIPVHIQSQI TPHAIIFLPN TDGMEMLLCY EDEGVYVNTY GRIIKDVVLQ
1260 1270 1280 1290 1300
WGEMPTSVAY ICSNQIMGWG EKAIEIRSVE TGHLDGVFMH KRAQRLKFLC
1310 1320 1330
ERNDKVFFAS VRSGGSSQVY FMTLNRNCIM NW
Length:1,332
Mass (Da):149,822
Last modified:May 18, 2010 - v2
Checksum:i3E3B182CDDB3659C
GO
Isoform 11 Publication (identifier: Q8N4C8-2) [UniParc]FASTAAdd to basket
Also known as: MiNK-1, MINK-delta

The sequence of this isoform differs from the canonical sequence as follows:
     696-732: Missing.

Show »
Length:1,295
Mass (Da):145,806
Checksum:i029AD8C2806C90EE
GO
Isoform 21 Publication (identifier: Q8N4C8-3) [UniParc]FASTAAdd to basket
Also known as: MiNK-2, MINK-gamma

The sequence of this isoform differs from the canonical sequence as follows:
     696-732: Missing.
     800-800: A → ASYKRAIGE

Show »
Length:1,303
Mass (Da):146,711
Checksum:iFD65470BFC6981B2
GO
Isoform 4 (identifier: Q8N4C8-4) [UniParc]FASTAAdd to basket
Also known as: MINK-beta

The sequence of this isoform differs from the canonical sequence as follows:
     581-600: Missing.

Show »
Length:1,312
Mass (Da):147,653
Checksum:iB8D157A582DA5D18
GO
Isoform 5 (identifier: Q8N4C8-5) [UniParc]FASTAAdd to basket
Also known as: MINK-eta

The sequence of this isoform differs from the canonical sequence as follows:
     581-600: Missing.
     696-732: Missing.

Show »
Length:1,275
Mass (Da):143,637
Checksum:i4E992F63A486A95A
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L2I2I3L2I2_HUMAN
Misshapen-like kinase 1
MINK1
381Annotation score:
I3L203I3L203_HUMAN
Misshapen-like kinase 1
MINK1
53Annotation score:
I3L1U1I3L1U1_HUMAN
Misshapen-like kinase 1
MINK1
161Annotation score:
I3L4T2I3L4T2_HUMAN
Misshapen-like kinase 1
MINK1
111Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040799514A → T1 PublicationCorresponds to variant dbSNP:rs56131206Ensembl.1
Natural variantiVAR_046058771V → A2 PublicationsCorresponds to variant dbSNP:rs11556634Ensembl.1
Natural variantiVAR_046059775P → LCombined sources2 PublicationsCorresponds to variant dbSNP:rs11556635Ensembl.1
Natural variantiVAR_046060863V → I1 PublicationCorresponds to variant dbSNP:rs2302319Ensembl.1
Natural variantiVAR_0460611010E → V in a gastric adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0408001200I → V1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041871581 – 600Missing in isoform 4 and isoform 5. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_007059696 – 732Missing in isoform 1, isoform 2 and isoform 5. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_007060800A → ASYKRAIGE in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB041926 mRNA Translation: BAA94838.1
AB035698 mRNA Translation: BAA90753.1
AY775058 mRNA Translation: AAV41830.1
AC233723 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW90401.1
CH471108 Genomic DNA Translation: EAW90403.1
CH471108 Genomic DNA Translation: EAW90399.1
CH471108 Genomic DNA Translation: EAW90400.1
CH471108 Genomic DNA Translation: EAW90402.1
BC034673 mRNA Translation: AAH34673.1
CCDSiCCDS45588.1 [Q8N4C8-1]
CCDS45589.1 [Q8N4C8-3]
CCDS45590.1 [Q8N4C8-4]
RefSeqiNP_001020108.1, NM_001024937.3 [Q8N4C8-4]
NP_001308165.1, NM_001321236.1
NP_056531.1, NM_015716.4 [Q8N4C8-2]
NP_722549.2, NM_153827.4 [Q8N4C8-1]
NP_733763.1, NM_170663.4 [Q8N4C8-3]
UniGeneiHs.443417

Genome annotation databases

EnsembliENST00000347992; ENSP00000269296; ENSG00000141503 [Q8N4C8-3]
ENST00000355280; ENSP00000347427; ENSG00000141503 [Q8N4C8-1]
ENST00000453408; ENSP00000406487; ENSG00000141503 [Q8N4C8-4]
GeneIDi50488
KEGGihsa:50488
UCSCiuc010vsl.3 human [Q8N4C8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB041926 mRNA Translation: BAA94838.1
AB035698 mRNA Translation: BAA90753.1
AY775058 mRNA Translation: AAV41830.1
AC233723 Genomic DNA No translation available.
CH471108 Genomic DNA Translation: EAW90401.1
CH471108 Genomic DNA Translation: EAW90403.1
CH471108 Genomic DNA Translation: EAW90399.1
CH471108 Genomic DNA Translation: EAW90400.1
CH471108 Genomic DNA Translation: EAW90402.1
BC034673 mRNA Translation: AAH34673.1
CCDSiCCDS45588.1 [Q8N4C8-1]
CCDS45589.1 [Q8N4C8-3]
CCDS45590.1 [Q8N4C8-4]
RefSeqiNP_001020108.1, NM_001024937.3 [Q8N4C8-4]
NP_001308165.1, NM_001321236.1
NP_056531.1, NM_015716.4 [Q8N4C8-2]
NP_722549.2, NM_153827.4 [Q8N4C8-1]
NP_733763.1, NM_170663.4 [Q8N4C8-3]
UniGeneiHs.443417

3D structure databases

ProteinModelPortaliQ8N4C8
SMRiQ8N4C8
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119075, 20 interactors
IntActiQ8N4C8, 6 interactors
MINTiQ8N4C8
STRINGi9606.ENSP00000347427

Chemistry databases

BindingDBiQ8N4C8
ChEMBLiCHEMBL5518
GuidetoPHARMACOLOGYi2103

PTM databases

iPTMnetiQ8N4C8
PhosphoSitePlusiQ8N4C8

Polymorphism and mutation databases

BioMutaiMINK1
DMDMi296437370

Proteomic databases

EPDiQ8N4C8
MaxQBiQ8N4C8
PaxDbiQ8N4C8
PeptideAtlasiQ8N4C8
PRIDEiQ8N4C8
ProteomicsDBi71917
71918 [Q8N4C8-2]
71919 [Q8N4C8-3]
71920 [Q8N4C8-4]
71921 [Q8N4C8-5]

Protocols and materials databases

DNASUi50488
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000347992; ENSP00000269296; ENSG00000141503 [Q8N4C8-3]
ENST00000355280; ENSP00000347427; ENSG00000141503 [Q8N4C8-1]
ENST00000453408; ENSP00000406487; ENSG00000141503 [Q8N4C8-4]
GeneIDi50488
KEGGihsa:50488
UCSCiuc010vsl.3 human [Q8N4C8-1]

Organism-specific databases

CTDi50488
DisGeNETi50488
EuPathDBiHostDB:ENSG00000141503.15
GeneCardsiMINK1
H-InvDBiHIX0013452
HGNCiHGNC:17565 MINK1
HPAiHPA056296
MIMi609426 gene
neXtProtiNX_Q8N4C8
OpenTargetsiENSG00000141503
PharmGKBiPA134910641
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0587 Eukaryota
ENOG410XPHR LUCA
GeneTreeiENSGT00920000148966
HOGENOMiHOG000290708
HOVERGENiHBG036506
InParanoidiQ8N4C8
KOiK04413
OMAiSFTMFVD
OrthoDBiEOG091G018A
PhylomeDBiQ8N4C8
TreeFamiTF105138

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
SignaLinkiQ8N4C8
SIGNORiQ8N4C8

Miscellaneous databases

ChiTaRSiMINK1 human
GeneWikiiMINK1
GenomeRNAii50488
PROiPR:Q8N4C8
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141503 Expressed in 236 organ(s), highest expression level in CA1 field of hippocampus
CleanExiHS_MINK1
ExpressionAtlasiQ8N4C8 baseline and differential
GenevisibleiQ8N4C8 HS

Family and domain databases

InterProiView protein in InterPro
IPR001180 CNH_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00780 CNH, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00036 CNH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50219 CNH, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMINK1_HUMAN
AccessioniPrimary (citable) accession number: Q8N4C8
Secondary accession number(s): D3DTK3
, D3DTK4, Q5U8Z0, Q9P1X1, Q9P2R8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: May 18, 2010
Last modified: September 12, 2018
This is version 166 of the entry and version 2 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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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