O00562 (PITM1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Membrane-associated phosphatidylinositol transfer protein 1

Alternative name(s):
Drosophila retinal degeneration B homolog
Phosphatidylinositol transfer protein, membrane-associated 1
Short name=PITPnm 1
Pyk2 N-terminal domain-interacting receptor 2
Short name=NIR-2

Gene names

Name:	PITPNM1
Synonyms:	DRES9, NIR2, PITPNM

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	1244 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates RHOA activity, and plays a role in cytoskeleton remodeling. Necessary for normal completion of cytokinesis. Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus. Binds phosphatidyl inositol phosphates (in vitro). May catalyze the transfer of phosphatidylinositol and phosphatidylcholine between membranes By similarity. Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus. Required for protein export from the endoplasmic reticulum and the Golgi. Binds calcium ions. Ref.2 Ref.8 Ref.10 Ref.11
Subunit structure	Interacts with PIK4CA By similarity. Interacts with PTK2B via its C-terminus. Interacts with RHOA. Has higher affinity for the inactive, GDP-bound form of RHOA. The CDK1-phosphorylated form interacts with PLK1. Interacts with VAPB. Ref.2 Ref.8 Ref.9 Ref.10
Subcellular location	Cytoplasm. Golgi apparatus › Golgi stack membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Lipid droplet. Cleavage furrow. Midbody. Note: Peripheral membrane protein associated with Golgi stacks in interphase cells. A minor proportion is associated with the endoplasmic reticulum. Associated with lipid droplets. Dissociates from the Golgi early on in mitosis and localizes to the cleavage furrow and midbody during cytokinesis. Ref.7 Ref.9
Tissue specificity	Ubiquitous. Ref.2
Post-translational modification	Phosphorylated on multiple sites by CDK1 at the onset of mitosis. Phosphorylation facilitates dissociation from the Golgi complex and is required for interaction with PLK1. Ref.2 Ref.7 Ref.9 Phosphorylated on threonine residues upon treatment with oleic acid. Ref.2 Ref.7 Ref.9 Phosphorylated on tyrosine residues by PTK2B. Ref.2 Ref.7 Ref.9
Sequence similarities	Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily. Contains 1 DDHD domain.

Ontologies

Keywords
Biological process	Protein transport Transport
Cellular component	Cytoplasm Endoplasmic reticulum Golgi apparatus Lipid droplet Membrane
Coding sequence diversity	Alternative splicing
Ligand	Calcium Metal-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Traceable author statement PubMed 9245688. Source: ProtInc lipid metabolic process Non-traceable author statement Ref.1. Source: ProtInc phototransduction Traceable author statement Ref.1. Source: ProtInc protein transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi cisterna membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cleavage furrow Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell lipid particle Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Traceable author statement PubMed 9245688. Source: ProtInc midbody Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol transporter activity Traceable author statement PubMed 9245688. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: O00562-1)

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: O00562-2)

The sequence of this isoform differs from the canonical sequence as follows:
     716-716: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1244	1244	Membrane-associated phosphatidylinositol transfer protein 1		PRO_0000232738
Regions
	Domain	686 – 880	195	DDHD
	Compositional bias	310 – 319	10	Poly-Ser
Amino acid modifications
	Modified residue	59	1	Phosphothreonine Probable
	Modified residue	287	1	Phosphothreonine; by CDK1 Ref.9
	Modified residue	300	1	Phosphoserine By similarity
	Modified residue	382	1	Phosphoserine; by CDK1 Ref.9
	Modified residue	896	1	Phosphoserine Ref.9
Natural variations
	Alternative sequence	716	1	Missing in isoform 2.		VSP_021157
Experimental info
	Mutagenesis	59	1	T → A: Prevents association with lipid droplets. Ref.7
	Mutagenesis	59	1	T → E: Causes association with lipid droplets. Ref.7
	Mutagenesis	287	1	T → A: Slightly reduced phosphorylation. Strongly reduced phosphorylation; when associated with A-794 or A-389. Loss of threonine phosphorylation; when associated with A-389; A-793 and A-1222. Ref.9
	Mutagenesis	300	1	S → A: No effect on phosphorylation. Ref.9
	Mutagenesis	326	1	S → A: No effect on phosphorylation. Ref.9
	Mutagenesis	349 – 353	5	EFFDA → ALLAG: Loss of interaction with VAPB. Ref.10
	Mutagenesis	382	1	S → A: Strongly reduced phosphorylation. Ref.9
	Mutagenesis	389	1	T → A: No detectable effect on phosphorylation; when associated with A-793 and A-1222. Strongly reduced phosphorylation; when associated with A-287. Loss of threonine phosphorylation; when associated with A-287; A-794 and A-1222. Ref.9
	Mutagenesis	794	1	T → A: No detectable effect on phosphorylation; when associated with A-389 and A-1222. Strongly reduced phosphorylation; when associated with A-287. Loss of threonine phosphorylation; when associated with A-287; A-389 and A-1222. Ref.9
	Mutagenesis	896	1	S → A: Reduced phosphorylation. Ref.9
	Mutagenesis	1223	1	T → A: No detectable effect on phosphorylation; when associated with A-389 and A-793. Loss of threonine phosphorylation; when associated with A-287; A-389 and A-794. Ref.9
	Sequence conflict	931	1	R → P in AAK01444. Ref.2
	Sequence conflict	1034	1	S → G in AAR06909. Ref.3
	Sequence conflict	1116	1	E → G in CAA67224. Ref.1
	Sequence conflict	1133	1	A → T in CAA67224. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 31, 2006. Version 4. Checksum: F4B66E98B085E9C0	FASTA	1,244	134,848
	10 20 30 40 50 60 MLIKEYHILL PMSLDEYQVA QLYMIQKKSR EESSGEGSGV EILANRPYTD GPGGSGQYTH 70 80 90 100 110 120 KVYHVGSHIP GWFRALLPKA ALQVEEESWN AYPYTRTRYT CPFVEKFSIE IETYYLPDGG 130 140 150 160 170 180 QQPNVFNLSG AERRQRILDT IDIVRDAVAP GEYKAEEDPR LYHSVKTGRG PLSDDWARTA 190 200 210 220 230 240 AQTGPLMCAY KLCKVEFRYW GMQAKIEQFI HDVGLRRVML RAHRQAWCWQ DEWTELSMAD 250 260 270 280 290 300 IRALEEETAR MLAQRMAKCN TGSEGSEAQP PGKPSTEARS AASNTGTPDG PEAPPGPDAS 310 320 330 340 350 360 PDASFGKQWS SSSRSSYSSQ HGGAVSPQSL SEWRMQNIAR DSENSSEEEF FDAHEGFSDS 370 380 390 400 410 420 EEVFPKEMTK WNSNDFIDAF ASPVEAEGTP EPGAEAAKGI EDGAQAPRDS EGLDGAGELG 430 440 450 460 470 480 AEACAVHALF LILHSGNILD SGPGDANSKQ ADVQTLSSAF EAVTRIHFPE ALGHVALRLV 490 500 510 520 530 540 PCPPICAAAY ALVSNLSPYS HDGDSLSRSQ DHIPLAALPL LATSSSRYQG AVATVIARTN 550 560 570 580 590 600 QAYSAFLRSP EGAGFCGQVA LIGDGVGGIL GFDALCHSAN AGTGSRGSSR RGSMNNELLS 610 620 630 640 650 660 PEFGPVRDPL ADGVEGLGRG SPEPSALPPQ RIPSDMASPE PEGSQNSLQA APATTSSWEP 670 680 690 700 710 720 RRASTAFCPP AASSEAPDGP SSTARLDFKV SGFFLFGSPL GLVLALRKTV MPALEAAQMR 730 740 750 760 770 780 PACEQIYNLF HAADPCASRL EPLLAPKFQA IAPLTVPRYQ KFPLGDGSSL LLADTLQTHS 790 800 810 820 830 840 SLFLEELEML VPSTPTSTSG AFWKGSELAT DPPAQPAAPS TTSEVVKILE RWWGTKRIDY 850 860 870 880 890 900 SLYCPEALTA FPTVTLPHLF HASYWESADV VAFILRQVIE KERPQLAECE EPSIYSPAFP 910 920 930 940 950 960 REKWQRKRTQ VKIRNVTSNH RASDTVVCEG RPQVLSGRFM YGPLDVVTLT GEKVDVYIMT 970 980 990 1000 1010 1020 QPLSGKWIHF GTEVTNSSGR LTFPVPPERA LGIGVYPVRM VVRGDHTYAE CCLTVVARGT 1030 1040 1050 1060 1070 1080 EAVVFSIDGS FTASVSIMGS DPKVRAGAVD VVRHWQDSGY LIVYVTGRPD MQKHRVVAWL 1090 1100 1110 1120 1130 1140 SQHNFPHGVV SFCDGLTHDP LRQKAMFLQS LVQEVELNIV AGYGSPKDVA VYAALGLSPS 1150 1160 1170 1180 1190 1200 QTYIVGRAVR KLQAQCQFLS DGYVAHLGQL EAGSHSHASS GPPRAALGKS SYGVAAPVDF 1210 1220 1230 1240 LRKQSQLLRS RGPSQAEREG PGTPPTTLAR GKARSISLKL DSEE
	Isoform 2 [UniParc]. Checksum: 6262539C57A79DA6	FASTA	1,243	134,777
	10 20 30 40 50 60 MLIKEYHILL PMSLDEYQVA QLYMIQKKSR EESSGEGSGV EILANRPYTD GPGGSGQYTH 70 80 90 100 110 120 KVYHVGSHIP GWFRALLPKA ALQVEEESWN AYPYTRTRYT CPFVEKFSIE IETYYLPDGG 130 140 150 160 170 180 QQPNVFNLSG AERRQRILDT IDIVRDAVAP GEYKAEEDPR LYHSVKTGRG PLSDDWARTA 190 200 210 220 230 240 AQTGPLMCAY KLCKVEFRYW GMQAKIEQFI HDVGLRRVML RAHRQAWCWQ DEWTELSMAD 250 260 270 280 290 300 IRALEEETAR MLAQRMAKCN TGSEGSEAQP PGKPSTEARS AASNTGTPDG PEAPPGPDAS 310 320 330 340 350 360 PDASFGKQWS SSSRSSYSSQ HGGAVSPQSL SEWRMQNIAR DSENSSEEEF FDAHEGFSDS 370 380 390 400 410 420 EEVFPKEMTK WNSNDFIDAF ASPVEAEGTP EPGAEAAKGI EDGAQAPRDS EGLDGAGELG 430 440 450 460 470 480 AEACAVHALF LILHSGNILD SGPGDANSKQ ADVQTLSSAF EAVTRIHFPE ALGHVALRLV 490 500 510 520 530 540 PCPPICAAAY ALVSNLSPYS HDGDSLSRSQ DHIPLAALPL LATSSSRYQG AVATVIARTN 550 560 570 580 590 600 QAYSAFLRSP EGAGFCGQVA LIGDGVGGIL GFDALCHSAN AGTGSRGSSR RGSMNNELLS 610 620 630 640 650 660 PEFGPVRDPL ADGVEGLGRG SPEPSALPPQ RIPSDMASPE PEGSQNSLQA APATTSSWEP 670 680 690 700 710 720 RRASTAFCPP AASSEAPDGP SSTARLDFKV SGFFLFGSPL GLVLALRKTV MPALEAQMRP 730 740 750 760 770 780 ACEQIYNLFH AADPCASRLE PLLAPKFQAI APLTVPRYQK FPLGDGSSLL LADTLQTHSS 790 800 810 820 830 840 LFLEELEMLV PSTPTSTSGA FWKGSELATD PPAQPAAPST TSEVVKILER WWGTKRIDYS 850 860 870 880 890 900 LYCPEALTAF PTVTLPHLFH ASYWESADVV AFILRQVIEK ERPQLAECEE PSIYSPAFPR 910 920 930 940 950 960 EKWQRKRTQV KIRNVTSNHR ASDTVVCEGR PQVLSGRFMY GPLDVVTLTG EKVDVYIMTQ 970 980 990 1000 1010 1020 PLSGKWIHFG TEVTNSSGRL TFPVPPERAL GIGVYPVRMV VRGDHTYAEC CLTVVARGTE 1030 1040 1050 1060 1070 1080 AVVFSIDGSF TASVSIMGSD PKVRAGAVDV VRHWQDSGYL IVYVTGRPDM QKHRVVAWLS 1090 1100 1110 1120 1130 1140 QHNFPHGVVS FCDGLTHDPL RQKAMFLQSL VQEVELNIVA GYGSPKDVAV YAALGLSPSQ 1150 1160 1170 1180 1190 1200 TYIVGRAVRK LQAQCQFLSD GYVAHLGQLE AGSHSHASSG PPRAALGKSS YGVAAPVDFL 1210 1220 1230 1240 RKQSQLLRSR GPSQAEREGP GTPPTTLARG KARSISLKLD SEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A mammalian homologue of the Drosophila retinal degeneration B gene: implications for the evolution of phototransduction mechanisms." Rubboli F., Bulfone A., Bogni S., Marchitiello A., Zollo M., Borsani G., Ballabio A., Banfi S. Genes Funct. 1:205-213(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein." Lev S., Hernandez J., Martinez R., Chen A., Plowman G., Schlessinger J. Mol. Cell. Biol. 19:2278-2288(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CALCIUM-BINDING, INTERACTION WITH PTK2B, PHOSPHORYLATION, TISSUE SPECIFICITY. Tissue: Brain.
[3]	"Chromosomal localization, genomic organization and evolution of the genes encoding human phosphatidylinositol transfer protein membrane-associated (PITPNM) 1, 2 and 3." Ocaka L., Spalluto C., Wilson D.I., Hunt D.M., Halford S. Cytogenet. Genome Res. 108:293-302(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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 2). Tissue: Duodenum.
[7]	"Targeting of Nir2 to lipid droplets is regulated by a specific threonine residue within its PI-transfer domain." Litvak V., Shaul Y.D., Shulewitz M., Amarilio R., Carmon S., Lev S. Curr. Biol. 12:1513-1518(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF THR-59, THREONINE PHOSPHORYLATION.
[8]	"Nir2, a novel regulator of cell morphogenesis." Tian D., Litvak V., Toledo-Rodriguez M., Carmon S., Lev S. Mol. Cell. Biol. 22:2650-2662(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RHOA.
[9]	"Mitotic phosphorylation of the peripheral Golgi protein Nir2 by Cdk1 provides a docking mechanism for Plk1 and affects cytokinesis completion." Litvak V., Argov R., Dahan N., Ramachandran S., Amarilio R., Shainskaya A., Lev S. Mol. Cell 14:319-330(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-287; SER-382 AND SER-896, MASS SPECTROMETRY, MUTAGENESIS OF THR-287; SER-300; SER-326; SER-382; THR-389; THR-794; SER-896 AND THR-1223, INTERACTION WITH CDK1 AND PLK1, SUBCELLULAR LOCATION.
[10]	"Differential regulation of endoplasmic reticulum structure through VAP-Nir protein interaction." Amarilio R., Ramachandran S., Sabanay H., Lev S. J. Biol. Chem. 280:5934-5944(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH VAPB, MUTAGENESIS OF 349-GLU--ALA-353.
[11]	"Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function." Litvak V., Dahan N., Ramachandran S., Sabanay H., Lev S. Nat. Cell Biol. 7:225-234(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X98654 mRNA. Translation: CAA67224.1. AF334584 mRNA. Translation: AAK01444.1. AY429102 mRNA. Translation: AAR06909.1. AP001184 Genomic DNA. No translation available. CH471076 Genomic DNA. Translation: EAW74638.1. BC022230 mRNA. Translation: AAH22230.1.
IPI	IPI00307758. IPI00791675.
RefSeq	NP_001124320.1. NM_001130848.1. NP_004901.2. NM_004910.2.
UniGene	Hs.372295.
3D structure databases
ProteinModelPortal	O00562.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00562. 1 interaction.
STRING	9606.ENSP00000348772.
PTM databases
PhosphoSite	O00562.
Proteomic databases
PaxDb	O00562.
PRIDE	O00562.
Protocols and materials databases
DNASU	9600.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000356404; ENSP00000348772; ENSG00000110697. ENST00000436757; ENSP00000398787; ENSG00000110697. ENST00000534749; ENSP00000437286; ENSG00000110697.
GeneID	9600.
KEGG	hsa:9600.
UCSC	uc001olx.3. human. uc001olz.3. human.
Organism-specific databases
CTD	9600.
GeneCards	GC11M067260.
HGNC	HGNC:9003. PITPNM1.
MIM	608794. gene.
neXtProt	NX_O00562.
PharmGKB	PA33337.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5083.
HOGENOM	HOG000294231.
HOVERGEN	HBG052733.
InParanoid	O00562.
OMA	GQQPNVF.
OrthoDB	EOG49W2DK.
Gene expression databases
ArrayExpress	O00562.
Bgee	O00562.
CleanEx	HS_PITPNM1.
Genevestigator	O00562.
GermOnline	ENSG00000110697. Homo sapiens.
Family and domain databases
Gene3D	3.30.530.20. 1 hit. 3.40.50.1000. 1 hit.
InterPro	IPR004177. DDHD. IPR023214. HAD-like_dom. IPR013209. LNS2. IPR001666. PI_transfer. IPR023393. START-like_dom. [Graphical view]
PANTHER	PTHR10658. PTHR10658. 1 hit.
Pfam	PF02862. DDHD. 1 hit. PF02121. IP_trans. 1 hit. PF08235. LNS2. 1 hit. [Graphical view]
PRINTS	PR00391. PITRANSFER.
SMART	SM00775. LNS2. 1 hit. [Graphical view]
SUPFAM	SSF56784. HAD-like_dom. 1 hit.
PROSITE	PS51043. DDHD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1764937.
ChiTaRS	PITPNM1. human.
GenomeRNAi	9600.
NextBio	36015.
SOURCE	Search...

Entry information

Entry name

PITM1_HUMAN

Accession

Primary (citable) accession number: O00562
Secondary accession number(s): A6NME4 , Q6T7X3, Q8TBN3, Q9BZ73

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2006
Last sequence update:	October 31, 2006
Last modified:	May 1, 2013
This is version 98 of the entry and version 4 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.