Q9NPH2 (INO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Inositol-3-phosphate synthase 1
Short name=IPS 1
EC=5.5.1.4

Alternative name(s):
Myo-inositol 1-phosphate synthase
Short name=MI-1-P synthase
Short name=MIP synthase
Short name=hIPS
Myo-inositol 1-phosphate synthase A1
Short name=hINO1

Gene names

Name:	ISYNA1
Synonyms:	INO1

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	558 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Key enzyme in myo-inositol biosynthesis pathway that catalyzes the conversion of glucose 6-phosphate to 1-myo-inositol 1-phosphate in a NAD-dependent manner. Rate-limiting enzyme in the synthesis of all inositol-containing compounds. Ref.10
Catalytic activity	D-glucose 6-phosphate = 1D-myo-inositol 3-phosphate. Ref.10
Cofactor	NAD. Ref.10
Enzyme regulation	Inhibited by mood-stabilizing drugs such as valproate (VPA) and lithium. Ref.11 Ref.12
Pathway	Polyol metabolism; myo-inositol biosynthesis; myo-inositol from D-glucose 6-phosphate: step 1/2.
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Highly expressed in testis, ovary, heart, placenta and pancreas. Weakly expressed in blood leukocyte, thymus, skeletal muscle and colon. Ref.1
Induction	By glucose and lovastain. Up-regulation is prevented by mevalonic acid, farnesol, and geranylgeraniol. Up-regulated by E2F1. Ref.1 Ref.9 Ref.11 Ref.12
Sequence similarities	Belongs to the myo-inositol 1-phosphate synthase family.
Biophysicochemical properties	Kinetic parameters: KM=0.57 mM for 6-phosphate Ref.10 KM=8 µM for NAD pH dependence: Optimum pH is 8.0.
Sequence caution	The sequence AAP97151.1 differs from that shown. Reason: Frameshift at positions 82, 85 and 496.

Ontologies

Keywords
Biological process	Inositol biosynthesis Lipid biosynthesis Lipid metabolism Phospholipid biosynthesis Phospholipid metabolism
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing
Ligand	NAD
Molecular function	Isomerase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inositol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway phospholipid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	inositol-3-phosphate synthase activity Inferred from electronic annotation. Source: EC nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NPH2-1)

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: Q9NPH2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-128: Missing.

Isoform 3 (identifier: Q9NPH2-3)

The sequence of this isoform differs from the canonical sequence as follows:
     40-93: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 558	558	Inositol-3-phosphate synthase 1		PRO_0000324628
Natural variations
	Alternative sequence	1 – 128	128	Missing in isoform 2.		VSP_032324
	Alternative sequence	40 – 93	54	Missing in isoform 3.		VSP_046065
Experimental info
	Sequence conflict	17	1	G → S in AAP97151. Ref.3
	Sequence conflict	35	1	E → K in AAP97151. Ref.3
	Sequence conflict	57	1	P → T in AAP97151. Ref.3
	Sequence conflict	82	1	R → Q in AAP97151. Ref.3
	Sequence conflict	91	1	Missing in AAP97151. Ref.3
	Sequence conflict	155	1	K → N in AAG35698. Ref.1
	Sequence conflict	193	1	D → N in AAP97151. Ref.3
	Sequence conflict	368	1	P → Q in AAH66902. Ref.8
	Sequence conflict	392	1	S → G in AAH66902. Ref.8
	Sequence conflict	414	1	H → R in BAG52493. Ref.4
	Sequence conflict	471	1	P → R in AAH66902. Ref.8
	Sequence conflict	514	1	S → C in BAA91626. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 3A1009D941A5F87D	FASTA	558	61,068
	10 20 30 40 50 60 MEAAAQFFVE SPDVVYGPEA IEAQYEYRTT RVSREGGVLK VHPTSTRFTF RTARQVPRLG 70 80 90 100 110 120 VMLVGWGGNN GSTLTAAVLA NRLRLSWPTR SGRKEANYYG SLTQAGTVSL GLDAEGQEVF 130 140 150 160 170 180 VPFSAVLPMV APNDLVFDGW DISSLNLAEA MRRAKVLDWG LQEQLWPHME ALRPRPSVYI 190 200 210 220 230 240 PEFIAANQSA RADNLIPGSR AQQLEQIRRD IRDFRSSAGL DKVIVLWTAN TERFCEVIPG 250 260 270 280 290 300 LNDTAENLLR TIELGLEVSP STLFAVASIL EGCAFLNGSP QNTLVPGALE LAWQHRVFVG 310 320 330 340 350 360 GDDFKSGQTK VKSVLVDFLI GSGLKTMSIV SYNHLGNNDG ENLSAPLQFR SKEVSKSNVV 370 380 390 400 410 420 DDMVQSNPVL YTPGEEPDHC VVIKYVPYVG DSKRALDEYT SELMLGGTNT LVLHNTCEDS 430 440 450 460 470 480 LLAAPIMLDL ALLTELCQRV SFCTDMDPEP QTFHPVLSLL SFLFKAPLVP PGSPVVNALF 490 500 510 520 530 540 RQRSCIENIL RACVGLPPQN HMLLEHKMER PGPSLKRVGP VAATYPMLNK KGPVPAATNG 550 CTGDANGHLQ EEPPMPTT
	Isoform 2 [UniParc]. Checksum: 8C21453E5B3E4D88	FASTA	430	47,146
	10 20 30 40 50 60 MVAPNDLVFD GWDISSLNLA EAMRRAKVLD WGLQEQLWPH MEALRPRPSV YIPEFIAANQ 70 80 90 100 110 120 SARADNLIPG SRAQQLEQIR RDIRDFRSSA GLDKVIVLWT ANTERFCEVI PGLNDTAENL 130 140 150 160 170 180 LRTIELGLEV SPSTLFAVAS ILEGCAFLNG SPQNTLVPGA LELAWQHRVF VGGDDFKSGQ 190 200 210 220 230 240 TKVKSVLVDF LIGSGLKTMS IVSYNHLGNN DGENLSAPLQ FRSKEVSKSN VVDDMVQSNP 250 260 270 280 290 300 VLYTPGEEPD HCVVIKYVPY VGDSKRALDE YTSELMLGGT NTLVLHNTCE DSLLAAPIML 310 320 330 340 350 360 DLALLTELCQ RVSFCTDMDP EPQTFHPVLS LLSFLFKAPL VPPGSPVVNA LFRQRSCIEN 370 380 390 400 410 420 ILRACVGLPP QNHMLLEHKM ERPGPSLKRV GPVAATYPML NKKGPVPAAT NGCTGDANGH 430 LQEEPPMPTT
	Isoform 3 [UniParc]. Checksum: 84D7E719BBB98135	FASTA	504	55,136
	10 20 30 40 50 60 MEAAAQFFVE SPDVVYGPEA IEAQYEYRTT RVSREGGVLK EANYYGSLTQ AGTVSLGLDA 70 80 90 100 110 120 EGQEVFVPFS AVLPMVAPND LVFDGWDISS LNLAEAMRRA KVLDWGLQEQ LWPHMEALRP 130 140 150 160 170 180 RPSVYIPEFI AANQSARADN LIPGSRAQQL EQIRRDIRDF RSSAGLDKVI VLWTANTERF 190 200 210 220 230 240 CEVIPGLNDT AENLLRTIEL GLEVSPSTLF AVASILEGCA FLNGSPQNTL VPGALELAWQ 250 260 270 280 290 300 HRVFVGGDDF KSGQTKVKSV LVDFLIGSGL KTMSIVSYNH LGNNDGENLS APLQFRSKEV 310 320 330 340 350 360 SKSNVVDDMV QSNPVLYTPG EEPDHCVVIK YVPYVGDSKR ALDEYTSELM LGGTNTLVLH 370 380 390 400 410 420 NTCEDSLLAA PIMLDLALLT ELCQRVSFCT DMDPEPQTFH PVLSLLSFLF KAPLVPPGSP 430 440 450 460 470 480 VVNALFRQRS CIENILRACV GLPPQNHMLL EHKMERPGPS LKRVGPVAAT YPMLNKKGPV 490 500 PAATNGCTGD ANGHLQEEPP MPTT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning and gene expression analysis of human myo-inositol 1-phosphate synthase." Guan G., Dai P., Shechter I. Arch. Biochem. Biophys. 417:251-259(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION. Tissue: Hepatoma.
[2]	"Mammalian inositol 3-phosphate synthase: its role in the biosynthesis of brain inositol and its clinical use as a psychoactive agent." Parthasarathy L.K., Seelan R.S., Tobias C., Casanova M.F., Parthasarathy R.N. Subcell. Biochem. 39:293-314(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
[3]	"Cloning of a novel human cDNA homology to S.polyrrhiza D-myo-inositol-3-phosphate synthase mRNA." Zhou Y., Yu L., Zhao E.P., Hua Y.M., Xin Y.R., Zhao S.Y. Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). Tissue: Embryo and Teratocarcinoma.
[5]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[6]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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 1). Tissue: Brain and Uterus.
[9]	"E2F1 regulation of the human myo-inositol 1-phosphate synthase (ISYNA1) gene promoter." Seelan R.S., Parthasarathy L.K., Parthasarathy R.N. Arch. Biochem. Biophys. 431:95-106(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[10]	"Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast." Ju S., Shaltiel G., Shamir A., Agam G., Greenberg M.L. J. Biol. Chem. 279:21759-21765(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
[11]	"Human MIP synthase splice variants in bipolar disorder." Shamir A., Shaltiel G., Mark S., Bersudsky Y., Belmaker R.H., Agam G. Bipolar Disord. 9:766-771(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[12]	"Effects of valproate derivatives on human brain myo-inositol-1-phosphate (MIP) synthase activity and amphetamine-induced rearing." Galit S., Shirley M., Ora K., Belmaker R.H., Galila A. Pharmacol. Rep. 59:402-407(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF207640 mRNA. Translation: AAG35698.1. AF220530 mRNA. Translation: AAF26444.1. AF220259 , AF220250, AF220251, AF220252, AF220253, AF220254, AF220255, AF220256, AF220257, AF220258 Genomic DNA. Translation: AAF26739.1. AF086921 mRNA. Translation: AAP97151.1. Frameshift. AK001325 mRNA. Translation: BAA91626.1. AK021526 mRNA. Translation: BAB13837.1. AK092179 mRNA. Translation: BAG52493.1. AL137749 mRNA. Translation: CAB70904.1. AC008397 Genomic DNA. No translation available. CH471106 Genomic DNA. Translation: EAW84703.1. CH471106 Genomic DNA. Translation: EAW84705.1. BC004320 mRNA. Translation: AAH04320.1. BC018952 mRNA. Translation: AAH18952.1. BC066902 mRNA. Translation: AAH66902.1.
IPI	IPI00478861. IPI00549569. IPI00640098.
PIR	T46317.
RefSeq	NP_001164409.1. NM_001170938.1. NP_001240318.1. NM_001253389.1. NP_057452.1. NM_016368.4.
UniGene	Hs.740475.
3D structure databases
HSSP	HSSP built from PDB template 1P1H based on UniProtKB P11986.
ProteinModelPortal	Q9NPH2.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NPH2. 4 interactions.
MINT	MINT-4942504.
STRING	9606.ENSP00000315147.
PTM databases
PhosphoSite	Q9NPH2.
Polymorphism databases
DMDM	74734304.
2D gel databases
REPRODUCTION-2DPAGE	IPI00549569.
Proteomic databases
PaxDb	Q9NPH2.
PRIDE	Q9NPH2.
Protocols and materials databases
DNASU	51477.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338128; ENSP00000337746; ENSG00000105655. ENST00000457269; ENSP00000415458; ENSG00000105655.
GeneID	51477.
KEGG	hsa:51477.
UCSC	uc002nja.2. human.
Organism-specific databases
CTD	51477.
GeneCards	GC19M018545.
HGNC	HGNC:29821. ISYNA1.
HPA	CAB020720. HPA007931. HPA008232.
MIM	611670. gene.
neXtProt	NX_Q9NPH2.
PharmGKB	PA164721116.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1260.
HOVERGEN	HBG061200.
InParanoid	Q9NPH2.
KO	K01858.
OMA	NPVLYAP.
OrthoDB	EOG44F68X.
PhylomeDB	Q9NPH2.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00823; UER00787.
Gene expression databases
ArrayExpress	Q9NPH2.
Bgee	Q9NPH2.
CleanEx	HS_ISYNA1.
Genevestigator	Q9NPH2.
Family and domain databases
Gene3D	3.40.50.720. 2 hits.
InterPro	IPR002587. Myo-inos-1-P_Synthase. IPR013021. Myo-inos-1-P_Synthase_GAPDH. IPR016040. NAD(P)-bd_dom. [Graphical view]
PANTHER	PTHR11510. PTHR11510. 1 hit.
Pfam	PF01658. Inos-1-P_synth. 1 hit. PF07994. NAD_binding_5. 1 hit. [Graphical view]
PIRSF	PIRSF015578. Myoinos-ppht_syn. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	ISYNA1. human.
GenomeRNAi	51477.
NextBio	55121.
SOURCE	Search...

Entry information

Entry name

INO1_HUMAN

Accession

Primary (citable) accession number: Q9NPH2
Secondary accession number(s): B3KRT1 , G5E9U0, Q6NXT5, Q7Z525, Q9BT65, Q9H2Y2, Q9NSU0, Q9NVW7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 102 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.