O00470 (MEIS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein Meis1

Gene names

Name:

MEIS1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	390 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias. Ref.5
Subunit structure	Interacts with the N-terminal region of PBX1 to form a heterodimer which binds DNA including a cAMP-responsive sequence in CYP17. Also forms heterodimers with PBX2. Forms heterotrimers with PBX1 or PBX2 and a number of HOX proteins including HOXA9, HOXD4 and HOXD9 where it acts as a non-DNA-binding partner. Also forms heterotrimers with PBX1 and HOX proteins including HOXD9 and HOXD10 where PBX1 is the non-DNA-binding partner. Ref.5
Subcellular location	Nucleus By similarity.
Tissue specificity	Expressed at low level in normal immunohepatopoietic tissues, including the fetal liver. Expressed in a subset of myeloid leukemia cell lines, with the highest expression seen in those with a megakaryocytic-erythroid phenotype. Also expressed at high levels in the cerebellum.
Involvement in disease	Defects in MEIS1 could be a cause of susceptibility to restless legs syndrome type 7 (RLS7) [MIM:612853]. Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation.
Sequence similarities	Belongs to the TALE/MEIS homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
None. [Check GOA]

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CREB1	P16220	9	EBI-1210694,EBI-711855
ETS1	P14921	2	EBI-1210694,EBI-913209

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O00470-1)

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 (identifier: O00470-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MAQR → MQ
     373-390: PMSGMGMNMGMEGQWHYM → LQSMPGEYVA...SGQVMDIHAQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 390	390	Homeobox protein Meis1		PRO_0000049105
Regions
	DNA binding	272 – 334	63	Homeobox; TALE-type
	Region	335 – 390	56	Required for transcriptional activation By similarity
	Compositional bias	194 – 240	47	Ser/Thr-rich
	Compositional bias	242 – 269	28	Asp/Glu-rich (acidic)
	Compositional bias	262 – 269	8	Poly-Asp
Natural variations
	Alternative sequence	1 – 4	4	MAQR → MQ in isoform 2.		VSP_034957
	Alternative sequence	373 – 390	18	PMSGM…QWHYM → LQSMPGEYVARGGPMGVSMG QPSYTQPQMPPHPAQLRHGP PMHTYIPGHPHHPTVMMHGG PPHPGMPMSASSPTVLNTGD PTMSGQVMDIHAQ in isoform 2.		VSP_034958
	Natural variant	272	1	R → H Found in a patient with susceptibility to restless legs syndrome; also found in unaffected persons, although very rare. Ref.6 Corresponds to variant rs61752693 [ dbSNP | Ensembl ].		VAR_063166

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 3B6A0ACCF0C39121	FASTA	390	43,016
	10 20 30 40 50 60 MAQRYDDLPH YGGMDGVGIP STMYGDPHAA RSMQPVHHLN HGPPLHSHQY PHTAHTNAMA 70 80 90 100 110 120 PSMGSSVNDA LKRDKDAIYG HPLFPLLALI FEKCELATCT PREPGVAGGD VCSSESFNED 130 140 150 160 170 180 IAVFAKQIRA EKPLFSSNPE LDNLMIQAIQ VLRFHLLELE KVHELCDNFC HRYISCLKGK 190 200 210 220 230 240 MPIDLVIDDR EGGSKSDSED ITRSANLTDQ PSWNRDHDDT ASTRSGGTPG PSSGGHTSHS 250 260 270 280 290 300 GDNSSEQGDG LDNSVASPST GDDDDPDKDK KRHKKRGIFP KVATNIMRAW LFQHLTHPYP 310 320 330 340 350 360 SEEQKKQLAQ DTGLTILQVN NWFINARRRI VQPMIDQSNR AVSQGTPYNP DGQPMGGFVM 370 380 390 DGQQHMGIRA PGPMSGMGMN MGMEGQWHYM
	Isoform 2 [UniParc]. Checksum: D8F5B46D79D60A71	FASTA	463	50,576
	10 20 30 40 50 60 MQYDDLPHYG GMDGVGIPST MYGDPHAARS MQPVHHLNHG PPLHSHQYPH TAHTNAMAPS 70 80 90 100 110 120 MGSSVNDALK RDKDAIYGHP LFPLLALIFE KCELATCTPR EPGVAGGDVC SSESFNEDIA 130 140 150 160 170 180 VFAKQIRAEK PLFSSNPELD NLMIQAIQVL RFHLLELEKV HELCDNFCHR YISCLKGKMP 190 200 210 220 230 240 IDLVIDDREG GSKSDSEDIT RSANLTDQPS WNRDHDDTAS TRSGGTPGPS SGGHTSHSGD 250 260 270 280 290 300 NSSEQGDGLD NSVASPSTGD DDDPDKDKKR HKKRGIFPKV ATNIMRAWLF QHLTHPYPSE 310 320 330 340 350 360 EQKKQLAQDT GLTILQVNNW FINARRRIVQ PMIDQSNRAV SQGTPYNPDG QPMGGFVMDG 370 380 390 400 410 420 QQHMGIRAPG LQSMPGEYVA RGGPMGVSMG QPSYTQPQMP PHPAQLRHGP PMHTYIPGHP 430 440 450 460 HHPTVMMHGG PPHPGMPMSA SSPTVLNTGD PTMSGQVMDI HAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and mapping of the MEIS1 gene, the human homolog of a murine leukemogenic gene." Smith J.E. Jr., Bollekens J.A., Inghirami G., Takeshita K. Genomics 43:99-103(1997) [PubMed: 9226379] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Full-length cDNA libraries and normalization." Li W.B., Gruber C., Jessee J., Polayes D. Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Placenta.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[5]	"Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene." Okada Y., Nagai R., Sato T., Matsuura E., Minami T., Morita I., Doi T. Blood 101:4748-4756(2003) [PubMed: 12609849] [Abstract] Cited for: FUNCTION, INTERACTION WITH PBX1 AND PBX2.
[6]	"MEIS1 p.R272H in familial restless legs syndrome." Vilarino-Guell C., Chai H., Keeling B.H., Young J.E., Rajput A., Lynch T., Aasly J.O., Uitti R.J., Wszolek Z.K., Farrer M.J., Lin S.-C. Neurology 73:243-245(2009) [PubMed: 19620614] [Abstract] Cited for: VARIANT HIS-272, POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO RESTLESS LEGS SYNDROME TYPE 7.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U85707 mRNA. Translation: AAC51642.1. CR612956 mRNA. No translation available. AC007392 Genomic DNA. No translation available. AC092669 Genomic DNA. No translation available. AC093641 Genomic DNA. No translation available. BC043503 mRNA. Translation: AAH43503.1.
IPI	IPI00011756. IPI00877788.
RefSeq	NP_002389.1. NM_002398.2.
UniGene	Hs.526754. Hs.603755.
3D structure databases
ProteinModelPortal	O00470.
SMR	O00470. Positions 279-334.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00470. 10 interactions.
STRING	O00470.
Proteomic databases
PRIDE	O00470.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000272369; ENSP00000272369; ENSG00000143995.
GeneID	4211.
KEGG	hsa:4211.
UCSC	uc002sdu.1. human.
Organism-specific databases
CTD	4211.
GeneCards	GC02P066660.
H-InvDB	HIX0002114.
HGNC	HGNC:7000. MEIS1.
HPA	CAB011521.
MIM	601739. gene. 612853. phenotype.
neXtProt	NX_O00470.
PharmGKB	PA30740.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19619.
HOVERGEN	HBG055193.
OrthoDB	EOG4XPQFW.
Gene expression databases
ArrayExpress	O00470.
Bgee	O00470.
CleanEx	HS_MEIS1.
Genevestigator	O00470.
GermOnline	ENSG00000143995. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR008422. Homeobox_KN_domain. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
KO	K15613.
Pfam	PF05920. Homeobox_KN. 1 hit. [Graphical view]
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. False negative. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	16590.
SOURCE	Search...

Entry information

Entry name

MEIS1_HUMAN

Accession

Primary (citable) accession number: O00470
Secondary accession number(s): A8MV50

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 1, 1997
Last modified:	January 25, 2012
This is version 95 of the entry and version 1 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.