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Q9HAP2 (MLXIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
MLX-interacting protein
Alternative name(s):
Class E basic helix-loop-helix protein 36
Short name=bHLHe36
Transcriptional activator MondoA
Gene names
Name:MLXIP
Synonyms:BHLHE36, KIAA0867, MIR, MONDOA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length919 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Binds DNA as a heterodimer with MLX and activates transcription. Binds to the canonical E box sequence 5'-CACGTG-3'. Plays a role in transcriptional activation of glycolytic target genes. Involved in glucose-responsive gene regulation. Ref.5 Ref.6 UniProtKB Q2VPU4

Subunit structure

Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer with MLX. Ref.5 UniProtKB Q2VPU4

Subcellular location

Cytoplasm. Nucleus. Mitochondrion outer membrane. Note: Predominantly cytoplasmic but shuttles between cytoplasm and nucleus when associated with MLX. Also associates with the outer mitochondrial membrane and may shuttle between the outer mitochondrial membrane and the nucleus. Ref.5 Ref.6 UniProtKB Q2VPU4

Tissue specificity

Widely expressed in adult tissues. Most abundant in skeletal muscle. Ref.1

Sequence similarities

Contains 1 bHLH (basic helix-loop-helix) domain.

Sequence caution

The sequence BAA74890.2 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 (identifier: Q9HAP2-1)

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.
Isoform 2 Ref.9 (identifier: Q9HAP2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-393: Missing.
Isoform 3 Ref.4 (identifier: Q9HAP2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     578-628: AAFSGQPQAV...APGVPEFHSS → GEPGGETQCG...HIHLNETKVS
     629-919: Missing.
Note: No experimental confirmation available.
Isoform 4 Ref.9 (identifier: Q9HAP2-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-393: Missing.
     770-772: QQE → LLS
     773-919: Missing.
Isoform 5 Ref.4 (identifier: Q9HAP2-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-393: Missing.
     426-443: Missing.
     578-628: AAFSGQPQAV...APGVPEFHSS → GEPGGETQCG...HIHLNETKVS
     629-919: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9
Chain2 – 919918MLX-interacting protein
PRO_0000298763

Regions

Domain719 – 76951bHLH
Region73 – 327255Required for cytoplasmic localization Ref.5
Region322 – 445124Transactivation domain Ref.5
Region769 – 79022Leucine-zipper
Region832 – 88150Mediates heterotypic interactions between MLXIP and MLX and is required for cytoplasmic localization Ref.5

Amino acid modifications

Modified residue21N-acetylalanine Ref.9
Modified residue271Phosphoserine Ref.7
Modified residue331Phosphoserine Ref.7

Natural variations

Alternative sequence1 – 393393Missing in isoform 2, isoform 4 and isoform 5. Ref.4 Ref.9
VSP_052499
Alternative sequence426 – 44318Missing in isoform 5. Ref.4
VSP_052500
Alternative sequence578 – 62851AAFSG…EFHSS → GEPGGETQCGAPPDPEGCFP IPKAFKLVTTTTTLVCTCMR THIHLNETKVS in isoform 3 and isoform 5. Ref.4
VSP_052501
Alternative sequence629 – 919291Missing in isoform 3 and isoform 5. Ref.4
VSP_052502
Alternative sequence770 – 7723QQE → LLS in isoform 4. Ref.9
VSP_052503
Alternative sequence773 – 919147Missing in isoform 4. Ref.9
VSP_052504
Natural variant3961E → G. Ref.2 Ref.4
Corresponds to variant rs7978353 [ dbSNP | Ensembl ].
VAR_059344
Natural variant5391V → L.
Corresponds to variant rs34702867 [ dbSNP | Ensembl ].
VAR_059345

Sequences

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

Last modified August 21, 2007. Version 2.
Checksum: 47375FCC4333E0C2

FASTA919101,185
        10         20         30         40         50         60 
MAADVFMCSP RRPRSRGRQV LLKPQVSEDD DDSDTDEPSP PPASGAATPA RAHASAAPPP 

        70         80         90        100        110        120 
PRAGPGREEP PRRQQIIHSG HFMVSSPHRE HPPKKGYDFD TVNKQTCQTY SFGKTSSCHL 

       130        140        150        160        170        180 
SIDASLTKLF ECMTLAYSGK LVSPKWKNFK GLKLQWRDKI RLNNAIWRAW YMQYLEKRKN 

       190        200        210        220        230        240 
PVCHFVTPLD GSVDVDEHRR PEAITTEGKY WKSRIEIVIR EYHKWRTYFK KRLQQHKDED 

       250        260        270        280        290        300 
LSSLVQDDDM LYWHKHGDGW KTPVPMEEDP LLDTDMLMSE FSDTLFSTLS SHQPVAWPNP 

       310        320        330        340        350        360 
REIAHLGNAD MIQPGLIPLQ PNLDFMDTFE PFQDLFSSSR SIFGSMLPAS ASAPVPDPNN 

       370        380        390        400        410        420 
PPAQESILPT TALPTVSLPD SLIAPPTAPS LAHMDEQGCE HTSRTEDPFI QPTDFGPSEP 

       430        440        450        460        470        480 
PLSVPQPFLP VFTMPLLSPS PAPPPISPVL PLVPPPATAL NPPAPPTFHQ PQKFAGVNKA 

       490        500        510        520        530        540 
PSVITHTASA TLTHDAPATT FSQSQGLVIT THHPAPSAAP CGLALSPVTR PPQPRLTFVH 

       550        560        570        580        590        600 
PKPVSLTGGR PKQPHKIVPA PKPEPVSLVL KNARIAPAAF SGQPQAVIMT SGPLKREGML 

       610        620        630        640        650        660 
ASTVSQSNVV IAPAAIARAP GVPEFHSSIL VTDLGHGTSS PPAPVSRLFP STAQDPLGKG 

       670        680        690        700        710        720 
EQVPLHGGSP QVTVTGPSRD CPNSGQASPC ASEQSPSPQS PQNNCSGKSD PKNVAALKNR 

       730        740        750        760        770        780 
QMKHISAEQK RRFNIKMCFD MLNSLISNNS KLTSHAITLQ KTVEYITKLQ QERGQMQEEA 

       790        800        810        820        830        840 
RRLREEIEEL NATIISCQQL LPATGVPVTR RQFDHMKDMF DEYVKTRTLQ NWKFWIFSII 

       850        860        870        880        890        900 
IKPLFESFKG MVSTSSLEEL HRTALSWLDQ HCSLPILRPM VLSTLRQLST STSILTDPAQ 

       910 
LPEQASKAVT RIGKRLGES 

« Hide

Isoform 2 [UniParc].

Checksum: 0C3ADBD852823E60
Show »

FASTA52656,822
Isoform 3 [UniParc].

Checksum: 30A3DE477411D863
Show »

FASTA62869,091
Isoform 4 [UniParc].

Checksum: 6EC02D23459161A5
Show »

FASTA37939,808
Isoform 5 [UniParc].

Checksum: CD8533894CB00AB3
Show »

FASTA21722,806

References

« Hide 'large scale' references
[1]"MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a max-like network."
Billin A.N., Eilers A.L., Coulter K.L., Logan J.S., Ayer D.E.
Mol. Cell. Biol. 20:8845-8854(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"Mir, a new bHLHZip protein interacting with Mlx."
Merla G., Cairo S., Reymond A.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), VARIANT GLY-396.
[3]"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[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] (ISOFORMS 1 AND 5), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 176-919 (ISOFORM 3), VARIANT GLY-396.
Tissue: Pancreas and Placenta.
[5]"A novel heterodimerization domain, CRM1, and 14-3-3 control subcellular localization of the MondoA-Mlx heterocomplex."
Eilers A.L., Sundwall E., Lin M., Sullivan A.A., Ayer D.E.
Mol. Cell. Biol. 22:8514-8526(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DNA-BINDING, INTERACTION WITH MLX, SUBCELLULAR LOCATION.
[6]"MondoA-Mlx heterodimers are candidate sensors of cellular energy status: mitochondrial localization and direct regulation of glycolysis."
Sans C.L., Satterwhite D.J., Stoltzman C.A., Breen K.T., Ayer D.E.
Mol. Cell. Biol. 26:4863-4871(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-27 AND SER-33, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"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 ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF312918 mRNA. Translation: AAG34121.1.
AF245480 mRNA. Translation: AAL55689.1.
AF245481 mRNA. Translation: AAL55690.1.
AB020674 mRNA. Translation: BAA74890.2. Different initiation.
BC017656 mRNA. Translation: AAH17656.1.
BC028309 mRNA. Translation: AAH28309.1.
BC039704 mRNA. Translation: AAH39704.1.
BC151841 mRNA. Translation: AAI51842.1.
RefSeqNP_055753.3. NM_014938.5. [Q9HAP2-1]
UniGeneHs.437153.
Hs.721711.
Hs.731847.

3D structure databases

ProteinModelPortalQ9HAP2.
SMRQ9HAP2. Positions 717-773.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116544. 2 interactions.
IntActQ9HAP2. 4 interactions.
MINTMINT-7032145.
STRING9606.ENSP00000312834.

PTM databases

PhosphoSiteQ9HAP2.

Polymorphism databases

DMDM156632588.

Proteomic databases

MaxQBQ9HAP2.
PaxDbQ9HAP2.
PRIDEQ9HAP2.

Protocols and materials databases

DNASU22877.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000319080; ENSP00000312834; ENSG00000175727. [Q9HAP2-1]
ENST00000538698; ENSP00000440769; ENSG00000175727. [Q9HAP2-2]
GeneID22877.
KEGGhsa:22877.
UCSCuc001ubq.3. human. [Q9HAP2-1]
uc001ubr.3. human. [Q9HAP2-3]

Organism-specific databases

CTD22877.
GeneCardsGC12P122516.
H-InvDBHIX0019678.
HGNCHGNC:17055. MLXIP.
HPAHPA023084.
MIM608090. gene.
neXtProtNX_Q9HAP2.
PharmGKBPA128394590.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG276702.
HOVERGENHBG062003.
InParanoidQ9HAP2.
KOK09113.
OMARPMVLST.
OrthoDBEOG7ZD1VF.
PhylomeDBQ9HAP2.
TreeFamTF324749.

Gene expression databases

ArrayExpressQ9HAP2.
BgeeQ9HAP2.
CleanExHS_MLXIP.
GenevestigatorQ9HAP2.

Family and domain databases

Gene3D4.10.280.10. 1 hit.
InterProIPR011598. bHLH_dom.
[Graphical view]
PfamPF00010. HLH. 1 hit.
[Graphical view]
SMARTSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMSSF47459. SSF47459. 1 hit.
PROSITEPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMLXIP. human.
GenomeRNAi22877.
NextBio43439.
PROQ9HAP2.
SOURCESearch...

Entry information

Entry nameMLXIP_HUMAN
AccessionPrimary (citable) accession number: Q9HAP2
Secondary accession number(s): A7MBN0 expand/collapse secondary AC list , O94945, Q7LC47, Q8IXP1, Q8TAH9, Q8WVQ0, Q8WYA5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 21, 2007
Last sequence update: August 21, 2007
Last modified: June 11, 2014
This is version 94 of the entry and version 2 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

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 12

Human chromosome 12: entries, gene names and cross-references to MIM