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Q8IVH8 (M4K3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 118. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:MAP4K3
Synonyms:RAB8IPL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length894 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Magnesium. Ref.1

Subunit structure

Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation By similarity. UniProtKB Q924I2

Tissue specificity

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. Ref.1

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 CNH domain.

Contains 1 protein kinase domain.

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q8IVH8-1)

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.
Note: No experimental confirmation available.
Isoform 2 Ref.1 (identifier: Q8IVH8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: MNPGFDLSRRNP → MA
Isoform 3 Ref.1 (identifier: Q8IVH8-3)

The sequence of this isoform differs from the canonical sequence as follows:
     352-372: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 894894Mitogen-activated protein kinase kinase kinase kinase 3
PRO_0000086277

Regions

Domain16 – 273258Protein kinase
Domain556 – 867312CNH
Nucleotide binding22 – 309ATP By similarity UniProtKB O00506

Sites

Active site1361Proton acceptor By similarity UniProtKB O00506
Binding site451ATP By similarity
Binding site481ATP Ref.1

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7 Ref.8
Modified residue3981Phosphoserine Ref.6

Natural variations

Alternative sequence1 – 1212MNPGF…SRRNP → MA in isoform 2. Ref.1
VSP_007052
Alternative sequence352 – 37221Missing in isoform 3.
VSP_007053
Natural variant2001V → L. Ref.9
Corresponds to variant rs35957290 [ dbSNP | Ensembl ].
VAR_040743
Natural variant4241H → Q. Ref.9
Corresponds to variant rs56317466 [ dbSNP | Ensembl ].
VAR_040744
Natural variant6691T → S in a lung squamous cell carcinoma sample; somatic mutation. Ref.9
VAR_040745

Experimental info

Mutagenesis481K → E: Loss of kinase activity and ability to activate JNK family. Ref.1
Sequence conflict3921N → D in AAC15472. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 6EB77BBB34E5B733

FASTA894101,316
        10         20         30         40         50         60 
MNPGFDLSRR NPQEDFELIQ RIGSGTYGDV YKARNVNTGE LAAIKVIKLE PGEDFAVVQQ 

        70         80         90        100        110        120 
EIIMMKDCKH PNIVAYFGSY LRRDKLWICM EFCGGGSLQD IYHVTGPLSE LQIAYVSRET 

       130        140        150        160        170        180 
LQGLYYLHSK GKMHRDIKGA NILLTDNGHV KLADFGVSAQ ITATIAKRKS FIGTPYWMAP 

       190        200        210        220        230        240 
EVAAVERKGG YNQLCDLWAV GITAIELAEL QPPMFDLHPM RALFLMTKSN FQPPKLKDKM 

       250        260        270        280        290        300 
KWSNSFHHFV KMALTKNPKK RPTAEKLLQH PFVTQHLTRS LAIELLDKVN NPDHSTYHDF 

       310        320        330        340        350        360 
DDDDPEPLVA VPHRIHSTSR NVREEKTRSE ITFGQVKFDP PLRKETEPHH ELPDSDGFLD 

       370        380        390        400        410        420 
SSEEIYYTAR SNLDLQLEYG QGHQGGYFLG ANKSLLKSVE EELHQRGHVA HLEDDEGDDD 

       430        440        450        460        470        480 
ESKHSTLKAK IPPPLPPKPK SIFIPQEMHS TEDENQGTIK RCPMSGSPAK PSQVPPRPPP 

       490        500        510        520        530        540 
PRLPPHKPVA LGNGMSSFQL NGERDGSLCQ QQNEHRGTNL SRKEKKDVPK PISNGLPPTP 

       550        560        570        580        590        600 
KVHMGACFSK VFNGCPLKIH CASSWINPDT RDQYLIFGAE EGIYTLNLNE LHETSMEQLF 

       610        620        630        640        650        660 
PRRCTWLYVM NNCLLSISGK ASQLYSHNLP GLFDYARQMQ KLPVAIPAHK LPDRILPRKF 

       670        680        690        700        710        720 
SVSAKIPETK WCQKCCVVRN PYTGHKYLCG ALQTSIVLLE WVEPMQKFML IKHIDFPIPC 

       730        740        750        760        770        780 
PLRMFEMLVV PEQEYPLVCV GVSRGRDFNQ VVRFETVNPN STSSWFTESD TPQTNVTHVT 

       790        800        810        820        830        840 
QLERDTILVC LDCCIKIVNL QGRLKSSRKL SSELTFDFQI ESIVCLQDSV LAFWKHGMQG 

       850        860        870        880        890 
RSFRSNEVTQ EISDSTRIFR LLGSDRVVVL ESRPTDNPTA NSNLYILAGH ENSY 

« Hide

Isoform 2 [UniParc].

Checksum: 14839222F5360166
Show »

FASTA884100,133
Isoform 3 [UniParc].

Checksum: 0C7D648387CFFE0C
Show »

FASTA87398,954

References

« Hide 'large scale' references
[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]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. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"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] [Europe PMC] [Abstract]
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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF000145 mRNA. Translation: AAC15472.1.
AF445413 expand/collapse EMBL AC list , 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 expand/collapse EMBL AC list , 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.
CCDSCCDS1803.1. [Q8IVH8-1]
CCDS58707.1. [Q8IVH8-3]
RefSeqNP_001257354.1. NM_001270425.1. [Q8IVH8-3]
NP_003609.2. NM_003618.3. [Q8IVH8-1]
UniGeneHs.655750.

3D structure databases

ProteinModelPortalQ8IVH8.
SMRQ8IVH8. Positions 8-313.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114063. 6 interactions.
DIPDIP-48924N.
IntActQ8IVH8. 10 interactions.
STRING9606.ENSP00000263881.

Chemistry

BindingDBQ8IVH8.
ChEMBLCHEMBL5432.
GuidetoPHARMACOLOGY2087.

PTM databases

PhosphoSiteQ8IVH8.

Polymorphism databases

DMDM29427817.

Proteomic databases

MaxQBQ8IVH8.
PaxDbQ8IVH8.
PRIDEQ8IVH8.

Protocols and materials databases

DNASU8491.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263881; ENSP00000263881; ENSG00000011566. [Q8IVH8-1]
ENST00000341681; ENSP00000345434; ENSG00000011566. [Q8IVH8-3]
GeneID8491.
KEGGhsa:8491.
UCSCuc002rro.4. human. [Q8IVH8-1]
uc002rrp.4. human. [Q8IVH8-3]

Organism-specific databases

CTD8491.
GeneCardsGC02M039476.
H-InvDBHIX0001996.
HGNCHGNC:6865. MAP4K3.
HPAHPA030380.
MIM604921. gene.
neXtProtNX_Q8IVH8.
PharmGKBPA30611.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000230824.
HOVERGENHBG036702.
InParanoidQ8IVH8.
KOK04406.
OMAQNEHRGT.
OrthoDBEOG7WX07M.
PhylomeDBQ8IVH8.
TreeFamTF105121.

Enzyme and pathway databases

SignaLinkQ8IVH8.

Gene expression databases

ArrayExpressQ8IVH8.
BgeeQ8IVH8.
CleanExHS_MAP4K3.
GenevestigatorQ8IVH8.

Family and domain databases

InterProIPR001180. Citron.
IPR011009. Kinase-like_dom.
IPR021160. MAPKKKK.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00780. CNH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF038172. MAPKKKK. 1 hit.
SMARTSM00036. CNH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50219. CNH. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAP4K3. human.
GenomeRNAi8491.
NextBio31767.
PROQ8IVH8.
SOURCESearch...

Entry information

Entry nameM4K3_HUMAN
AccessionPrimary (citable) accession number: Q8IVH8
Secondary accession number(s): Q6IQ39 expand/collapse secondary AC list , Q8IVH7, Q9UDM5, Q9Y6R5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 28, 2003
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM