Q9HAP2 (MLXIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	919 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Membrane Mitochondrion Mitochondrion outer membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	nucleocytoplasmic transport Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	mitochondrial outer membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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.2 (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.2 (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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 919	919	MLX-interacting protein		PRO_0000298763
Regions
	Domain	719 – 769	51	bHLH
	Region	73 – 327	255	Required for cytoplasmic localization Ref.5
	Region	322 – 445	124	Transactivation domain Ref.5
	Region	769 – 790	22	Leucine-zipper
	Region	832 – 881	50	Mediates heterotypic interactions between MLXIP and MLX and is required for cytoplasmic localization Ref.5
Amino acid modifications
	Modified residue	27	1	Phosphoserine Ref.7
	Modified residue	33	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	1 – 393	393	Missing in isoform 2, isoform 4 and isoform 5. Ref.2 Ref.4		VSP_052499
	Alternative sequence	426 – 443	18	Missing in isoform 5. Ref.4		VSP_052500
	Alternative sequence	578 – 628	51	AAFSG…EFHSS → GEPGGETQCGAPPDPEGCFP IPKAFKLVTTTTTLVCTCMR THIHLNETKVS in isoform 3 and isoform 5. Ref.4		VSP_052501
	Alternative sequence	629 – 919	291	Missing in isoform 3 and isoform 5. Ref.4		VSP_052502
	Alternative sequence	770 – 772	3	QQE → LLS in isoform 4. Ref.2		VSP_052503
	Alternative sequence	773 – 919	147	Missing in isoform 4. Ref.2		VSP_052504
	Natural variant	396	1	E → G. Ref.2 Ref.4 Corresponds to variant rs7978353 [ dbSNP | Ensembl ].		VAR_059344
	Natural variant	539	1	V → L. Corresponds to variant rs34702867 [ dbSNP | Ensembl ].		VAR_059345

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 21, 2007. Version 2. Checksum: 47375FCC4333E0C2	FASTA	919	101,185
	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
	Isoform 2 [UniParc]. Checksum: 0C3ADBD852823E60	FASTA	526	56,822
	10 20 30 40 50 60 MDEQGCEHTS RTEDPFIQPT DFGPSEPPLS VPQPFLPVFT MPLLSPSPAP PPISPVLPLV 70 80 90 100 110 120 PPPATALNPP APPTFHQPQK FAGVNKAPSV ITHTASATLT HDAPATTFSQ SQGLVITTHH 130 140 150 160 170 180 PAPSAAPCGL ALSPVTRPPQ PRLTFVHPKP VSLTGGRPKQ PHKIVPAPKP EPVSLVLKNA 190 200 210 220 230 240 RIAPAAFSGQ PQAVIMTSGP LKREGMLAST VSQSNVVIAP AAIARAPGVP EFHSSILVTD 250 260 270 280 290 300 LGHGTSSPPA PVSRLFPSTA QDPLGKGEQV PLHGGSPQVT VTGPSRDCPN SGQASPCASE 310 320 330 340 350 360 QSPSPQSPQN NCSGKSDPKN VAALKNRQMK HISAEQKRRF NIKMCFDMLN SLISNNSKLT 370 380 390 400 410 420 SHAITLQKTV EYITKLQQER GQMQEEARRL REEIEELNAT IISCQQLLPA TGVPVTRRQF 430 440 450 460 470 480 DHMKDMFDEY VKTRTLQNWK FWIFSIIIKP LFESFKGMVS TSSLEELHRT ALSWLDQHCS 490 500 510 520 LPILRPMVLS TLRQLSTSTS ILTDPAQLPE QASKAVTRIG KRLGES
	Isoform 3 [UniParc]. Checksum: 30A3DE477411D863	FASTA	628	69,091
	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 KNARIAPGEP GGETQCGAPP DPEGCFPIPK 610 620 AFKLVTTTTT LVCTCMRTHI HLNETKVS
	Isoform 4 [UniParc]. Checksum: 6EC02D23459161A5	FASTA	379	39,808
	10 20 30 40 50 60 MDEQGCEHTS RTEDPFIQPT DFGPSEPPLS VPQPFLPVFT MPLLSPSPAP PPISPVLPLV 70 80 90 100 110 120 PPPATALNPP APPTFHQPQK FAGVNKAPSV ITHTASATLT HDAPATTFSQ SQGLVITTHH 130 140 150 160 170 180 PAPSAAPCGL ALSPVTRPPQ PRLTFVHPKP VSLTGGRPKQ PHKIVPAPKP EPVSLVLKNA 190 200 210 220 230 240 RIAPAAFSGQ PQAVIMTSGP LKREGMLAST VSQSNVVIAP AAIARAPGVP EFHSSILVTD 250 260 270 280 290 300 LGHGTSSPPA PVSRLFPSTA QDPLGKGEQV PLHGGSPQVT VTGPSRDCPN SGQASPCASE 310 320 330 340 350 360 QSPSPQSPQN NCSGKSDPKN VAALKNRQMK HISAEQKRRF NIKMCFDMLN SLISNNSKLT 370 SHAITLQKTV EYITKLLLS
	Isoform 5 [UniParc]. Checksum: CD8533894CB00AB3	FASTA	217	22,806
	10 20 30 40 50 60 MDEQGCEHTS RTEDPFIQPT DFGPSEPPLS VPPPISPVLP LVPPPATALN PPAPPTFHQP 70 80 90 100 110 120 QKFAGVNKAP SVITHTASAT LTHDAPATTF SQSQGLVITT HHPAPSAAPC GLALSPVTRP 130 140 150 160 170 180 PQPRLTFVHP KPVSLTGGRP KQPHKIVPAP KPEPVSLVLK NARIAPGEPG GETQCGAPPD 190 200 210 PEGCFPIPKA FKLVTTTTTL VCTCMRTHIH LNETKVS

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
+	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.
IPI	IPI00102118. IPI00382754. IPI00795813. IPI00796815. IPI00797501.
RefSeq	NP_055753.3. NM_014938.4.
UniGene	Hs.721711. Hs.731847.
3D structure databases
ProteinModelPortal	Q9HAP2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9HAP2. 3 interactions.
MINT	MINT-7032145.
STRING	9606.ENSP00000312834.
PTM databases
PhosphoSite	Q9HAP2.
Polymorphism databases
DMDM	156632588.
Proteomic databases
PaxDb	Q9HAP2.
PRIDE	Q9HAP2.
Protocols and materials databases
DNASU	22877.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000319080; ENSP00000312834; ENSG00000175727. ENST00000538698; ENSP00000440769; ENSG00000175727.
GeneID	22877.
KEGG	hsa:22877.
UCSC	uc001ubq.3. human. uc001ubr.3. human.
Organism-specific databases
CTD	22877.
GeneCards	GC12P122516.
H-InvDB	HIX0019678.
HGNC	HGNC:17055. MLXIP.
HPA	HPA023084.
MIM	608090. gene.
neXtProt	NX_Q9HAP2.
PharmGKB	PA128394590.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG276702.
HOVERGEN	HBG062003.
InParanoid	Q9HAP2.
KO	K09113.
OMA	NACIAPA.
OrthoDB	EOG4GQQ4B.
Gene expression databases
ArrayExpress	Q9HAP2.
Bgee	Q9HAP2.
CleanEx	HS_MLXIP.
Genevestigator	Q9HAP2.
Family and domain databases
Gene3D	4.10.280.10. 1 hit.
InterPro	IPR011598. bHLH_dom. [Graphical view]
Pfam	PF00010. HLH. 1 hit. [Graphical view]
SMART	SM00353. HLH. 1 hit. [Graphical view]
SUPFAM	SSF47459. HLH_basic. 1 hit.
PROSITE	PS50888. BHLH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MLXIP. human.
GenomeRNAi	22877.
NextBio	43439.
SOURCE	Search...

Entry information

Entry name

MLXIP_HUMAN

Accession

Primary (citable) accession number: Q9HAP2
Secondary accession number(s): A7MBN0 , O94945, Q7LC47, Q8IXP1, Q8TAH9, Q8WVQ0, Q8WYA5

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 21, 2007
Last sequence update:	August 21, 2007
Last modified:	May 1, 2013
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.