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Q8IVH8

- M4K3_HUMAN

UniProt

Q8IVH8 - M4K3_HUMAN

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Protein

Mitogen-activated protein kinase kinase kinase kinase 3

Gene

MAP4K3

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

Functioni

May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.1 Publication

Catalytic activityi

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

Cofactori

Mg2+1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei45 – 451ATPPROSITE-ProRule annotation
Binding sitei48 – 481ATP1 PublicationPROSITE-ProRule annotation
Active sitei136 – 1361Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi22 – 309ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. protein kinase activity Source: ProtInc
  3. protein serine/threonine kinase activity Source: UniProtKB
  4. small GTPase regulator activity Source: InterPro

GO - Biological processi

  1. intracellular signal transduction Source: UniProtKB
  2. JNK cascade Source: ProtInc
  3. protein phosphorylation Source: UniProtKB
  4. response to tumor necrosis factor Source: UniProtKB
  5. response to UV Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ8IVH8.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase kinase kinase kinase 3 (EC:2.7.11.1)
Alternative name(s):
Germinal center kinase-related protein kinase
Short name:
GLK
MAPK/ERK kinase kinase kinase 3
Short name:
MEK kinase kinase 3
Short name:
MEKKK 3
Gene namesi
Name:MAP4K3
Synonyms:RAB8IPL1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Unplaced

Organism-specific databases

HGNCiHGNC:6865. MAP4K3.

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi48 – 481K → E: Loss of kinase activity and ability to activate JNK family. 1 Publication

Organism-specific databases

PharmGKBiPA30611.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 894894Mitogen-activated protein kinase kinase kinase kinase 3PRO_0000086277Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine2 Publications
Modified residuei398 – 3981Phosphoserine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ8IVH8.
PaxDbiQ8IVH8.
PRIDEiQ8IVH8.

PTM databases

PhosphoSiteiQ8IVH8.

Expressioni

Tissue specificityi

Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.1 Publication

Gene expression databases

BgeeiQ8IVH8.
CleanExiHS_MAP4K3.
ExpressionAtlasiQ8IVH8. baseline and differential.
GenevestigatoriQ8IVH8.

Organism-specific databases

HPAiHPA030380.

Interactioni

Subunit structurei

Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
GRB2P629932EBI-1758170,EBI-401755
LCP2Q130945EBI-1758170,EBI-346946
PRKCQQ047594EBI-1758170,EBI-374762
PrkcqQ021114EBI-1758170,EBI-2639157From a different organism.

Protein-protein interaction databases

BioGridi114063. 6 interactions.
DIPiDIP-48924N.
IntActiQ8IVH8. 10 interactions.
STRINGi9606.ENSP00000263881.

Structurei

3D structure databases

ProteinModelPortaliQ8IVH8.
SMRiQ8IVH8. Positions 8-313.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini16 – 273258Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini556 – 867312CNHPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 CNH domain.CuratedPROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118848.
HOGENOMiHOG000230824.
HOVERGENiHBG036702.
InParanoidiQ8IVH8.
KOiK04406.
OMAiQNEHRGT.
OrthoDBiEOG7WX07M.
PhylomeDBiQ8IVH8.
TreeFamiTF105121.

Family and domain databases

InterProiIPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
[Graphical view]
PfamiPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038172. MAPKKKK. 1 hit.
SMARTiSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 11 PublicationCurated (identifier: Q8IVH8-1) [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
MNPGFDLSRR NPQEDFELIQ RIGSGTYGDV YKARNVNTGE LAAIKVIKLE
60 70 80 90 100
PGEDFAVVQQ EIIMMKDCKH PNIVAYFGSY LRRDKLWICM EFCGGGSLQD
110 120 130 140 150
IYHVTGPLSE LQIAYVSRET LQGLYYLHSK GKMHRDIKGA NILLTDNGHV
160 170 180 190 200
KLADFGVSAQ ITATIAKRKS FIGTPYWMAP EVAAVERKGG YNQLCDLWAV
210 220 230 240 250
GITAIELAEL QPPMFDLHPM RALFLMTKSN FQPPKLKDKM KWSNSFHHFV
260 270 280 290 300
KMALTKNPKK RPTAEKLLQH PFVTQHLTRS LAIELLDKVN NPDHSTYHDF
310 320 330 340 350
DDDDPEPLVA VPHRIHSTSR NVREEKTRSE ITFGQVKFDP PLRKETEPHH
360 370 380 390 400
ELPDSDGFLD SSEEIYYTAR SNLDLQLEYG QGHQGGYFLG ANKSLLKSVE
410 420 430 440 450
EELHQRGHVA HLEDDEGDDD ESKHSTLKAK IPPPLPPKPK SIFIPQEMHS
460 470 480 490 500
TEDENQGTIK RCPMSGSPAK PSQVPPRPPP PRLPPHKPVA LGNGMSSFQL
510 520 530 540 550
NGERDGSLCQ QQNEHRGTNL SRKEKKDVPK PISNGLPPTP KVHMGACFSK
560 570 580 590 600
VFNGCPLKIH CASSWINPDT RDQYLIFGAE EGIYTLNLNE LHETSMEQLF
610 620 630 640 650
PRRCTWLYVM NNCLLSISGK ASQLYSHNLP GLFDYARQMQ KLPVAIPAHK
660 670 680 690 700
LPDRILPRKF SVSAKIPETK WCQKCCVVRN PYTGHKYLCG ALQTSIVLLE
710 720 730 740 750
WVEPMQKFML IKHIDFPIPC PLRMFEMLVV PEQEYPLVCV GVSRGRDFNQ
760 770 780 790 800
VVRFETVNPN STSSWFTESD TPQTNVTHVT QLERDTILVC LDCCIKIVNL
810 820 830 840 850
QGRLKSSRKL SSELTFDFQI ESIVCLQDSV LAFWKHGMQG RSFRSNEVTQ
860 870 880 890
EISDSTRIFR LLGSDRVVVL ESRPTDNPTA NSNLYILAGH ENSY

Note: No experimental confirmation available.

Length:894
Mass (Da):101,316
Last modified:March 1, 2003 - v1
Checksum:i6EB77BBB34E5B733
GO
Isoform 21 PublicationCurated (identifier: Q8IVH8-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MNPGFDLSRRNP → MA

Show »
Length:884
Mass (Da):100,133
Checksum:i14839222F5360166
GO
Isoform 31 PublicationCurated (identifier: Q8IVH8-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     352-372: Missing.

Note: No experimental confirmation available.

Show »
Length:873
Mass (Da):98,954
Checksum:i0C7D648387CFFE0C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti392 – 3921N → D in AAC15472. (PubMed:9275185)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001V → L.1 Publication
Corresponds to variant rs35957290 [ dbSNP | Ensembl ].
VAR_040743
Natural varianti424 – 4241H → Q.1 Publication
Corresponds to variant rs56317466 [ dbSNP | Ensembl ].
VAR_040744
Natural varianti669 – 6691T → S in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication
VAR_040745

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1212MNPGF…SRRNP → MA in isoform 2. 1 PublicationVSP_007052Add
BLAST
Alternative sequencei352 – 37221Missing in isoform 3. 1 PublicationVSP_007053Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000145 mRNA. Translation: AAC15472.1.
AF445413
, AF445385, AF445386, AF445387, AF445388, AF445390, AF445391, AF445392, AF445393, AF445394, AF445395, AF445396, AF445397, AF445398, AF445399, AF445400, AF445401, AF445402, AF445403, AF445404, AF445405, AF445406, AF445407, AF445408, AF445409, AF445410, AF445411, AF445412 Genomic DNA. Translation: AAN75849.1.
AF445413
, AF445385, AF445386, AF445387, AF445388, AF445390, AF445391, AF445392, AF445393, AF445394, AF445395, AF445397, AF445398, AF445399, AF445400, AF445401, AF445402, AF445403, AF445404, AF445405, AF445406, AF445407, AF445408, AF445409, AF445410, AF445411, AF445412 Genomic DNA. Translation: AAN75850.1.
CH471053 Genomic DNA. Translation: EAX00346.1.
BC071579 mRNA. Translation: AAH71579.1.
AC007684 Genomic DNA. Translation: AAF19240.1.
CCDSiCCDS1803.1. [Q8IVH8-1]
CCDS58707.1. [Q8IVH8-3]
RefSeqiNP_001257354.1. NM_001270425.1. [Q8IVH8-3]
NP_003609.2. NM_003618.3. [Q8IVH8-1]
UniGeneiHs.655750.

Genome annotation databases

GeneIDi8491.
KEGGihsa:8491.
UCSCiuc002rro.4. human. [Q8IVH8-1]
uc002rrp.4. human. [Q8IVH8-3]

Polymorphism databases

DMDMi29427817.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000145 mRNA. Translation: AAC15472.1 .
AF445413
, AF445385 , AF445386 , AF445387 , AF445388 , AF445390 , AF445391 , AF445392 , AF445393 , AF445394 , AF445395 , AF445396 , AF445397 , AF445398 , AF445399 , AF445400 , AF445401 , AF445402 , AF445403 , AF445404 , AF445405 , AF445406 , AF445407 , AF445408 , AF445409 , AF445410 , AF445411 , AF445412 Genomic DNA. Translation: AAN75849.1 .
AF445413
, AF445385 , AF445386 , AF445387 , AF445388 , AF445390 , AF445391 , AF445392 , AF445393 , AF445394 , AF445395 , AF445397 , AF445398 , AF445399 , AF445400 , AF445401 , AF445402 , AF445403 , AF445404 , AF445405 , AF445406 , AF445407 , AF445408 , AF445409 , AF445410 , AF445411 , AF445412 Genomic DNA. Translation: AAN75850.1 .
CH471053 Genomic DNA. Translation: EAX00346.1 .
BC071579 mRNA. Translation: AAH71579.1 .
AC007684 Genomic DNA. Translation: AAF19240.1 .
CCDSi CCDS1803.1. [Q8IVH8-1 ]
CCDS58707.1. [Q8IVH8-3 ]
RefSeqi NP_001257354.1. NM_001270425.1. [Q8IVH8-3 ]
NP_003609.2. NM_003618.3. [Q8IVH8-1 ]
UniGenei Hs.655750.

3D structure databases

ProteinModelPortali Q8IVH8.
SMRi Q8IVH8. Positions 8-313.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114063. 6 interactions.
DIPi DIP-48924N.
IntActi Q8IVH8. 10 interactions.
STRINGi 9606.ENSP00000263881.

Chemistry

BindingDBi Q8IVH8.
ChEMBLi CHEMBL5432.
GuidetoPHARMACOLOGYi 2087.

PTM databases

PhosphoSitei Q8IVH8.

Polymorphism databases

DMDMi 29427817.

Proteomic databases

MaxQBi Q8IVH8.
PaxDbi Q8IVH8.
PRIDEi Q8IVH8.

Protocols and materials databases

DNASUi 8491.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 8491.
KEGGi hsa:8491.
UCSCi uc002rro.4. human. [Q8IVH8-1 ]
uc002rrp.4. human. [Q8IVH8-3 ]

Organism-specific databases

CTDi 8491.
GeneCardsi GC02M039476.
H-InvDB HIX0001996.
HGNCi HGNC:6865. MAP4K3.
HPAi HPA030380.
MIMi 604921. gene.
neXtProti NX_Q8IVH8.
PharmGKBi PA30611.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118848.
HOGENOMi HOG000230824.
HOVERGENi HBG036702.
InParanoidi Q8IVH8.
KOi K04406.
OMAi QNEHRGT.
OrthoDBi EOG7WX07M.
PhylomeDBi Q8IVH8.
TreeFami TF105121.

Enzyme and pathway databases

SignaLinki Q8IVH8.

Miscellaneous databases

ChiTaRSi MAP4K3. human.
GenomeRNAii 8491.
NextBioi 31767.
PROi Q8IVH8.
SOURCEi Search...

Gene expression databases

Bgeei Q8IVH8.
CleanExi HS_MAP4K3.
ExpressionAtlasi Q8IVH8. baseline and differential.
Genevestigatori Q8IVH8.

Family and domain databases

InterProi IPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
[Graphical view ]
Pfami PF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF038172. MAPKKKK. 1 hit.
SMARTi SM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase."
    Diener K., Wang X.S., Chen C., Meyer C.F., Keesler G., Zukowski M., Tan T.-H., Yao Z.
    Proc. Natl. Acad. Sci. U.S.A. 94:9687-9692(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-48.
    Tissue: Macrophage and Skeletal muscle.
  2. "Physical/genetic map of the 2p22-2p21 region on chromosome 2."
    Gorry M.C., Zhang Y., Marks J.J., Suppe B., Hart S., Cortelli J., Pallos D., Hart T.C.
    Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Testis.
  5. Edwards J., Wohldmann P., Hawkins M., Harkins R.
    Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE OF 1-712 (ISOFORM 1).
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-398, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "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.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-200; GLN-424 AND SER-669.

Entry informationi

Entry nameiM4K3_HUMAN
AccessioniPrimary (citable) accession number: Q8IVH8
Secondary accession number(s): Q6IQ39
, Q8IVH7, Q9UDM5, Q9Y6R5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: March 1, 2003
Last modified: November 26, 2014
This is version 121 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 2
    Human chromosome 2: 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

External Data

Dasty 3