Q08AM6 (VAC14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein VAC14 homolog

Alternative name(s):
Tax1-binding protein 2

Gene names

Name:	VAC14
Synonyms:	TAX1BP2, TRX

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

General annotation (Comments)

Function	The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2). Acts as a positive activator of PIKfyve kinase activity. Also required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 5-phosphate (PtdIns5P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes. Ref.5 Ref.7
Subunit structure	Forms homooligomers. Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold. Interacts with NOS1. Interacts with HTLV-1 Tax. Ref.3 Ref.6 Ref.8
Subcellular location	Endosome membrane. Microsome membrane By similarity. Note: Mainly associated with membranes of the late endocytic pathway. Ref.5 Ref.7
Tissue specificity	Ubiquitously expressed. Ref.3
Domain	The C-terminal domain (residues 523-782) mediates homomeric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex. Ref.8
Sequence similarities	Belongs to the VAC14 family. Contains 6 HEAT repeats.
Sequence caution	The sequence AAB03813.1 differs from that shown. Reason: Unknown C-terminal region. The sequence BAB15145.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Endoplasmic reticulum Endosome Membrane Microsome
Domain	Repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW signal transduction Non-traceable author statement Ref.3. Source: UniProtKB
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW endosome membrane Inferred from direct assay Ref.7. Source: UniProtKB microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	binding Inferred from electronic annotation. Source: InterPro receptor activity Non-traceable author statement Ref.3. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 782	782	Protein VAC14 homolog		PRO_0000300485
Regions
	Repeat	5 – 42	38	HEAT 1
	Repeat	89 – 126	38	HEAT 2
	Repeat	171 – 208	38	HEAT 3
	Repeat	212 – 249	38	HEAT 4
	Repeat	438 – 475	38	HEAT 5
	Repeat	560 – 598	39	HEAT 6
	Region	773 – 777	5	Mediates interaction with the PDZ domain of NOS1
Amino acid modifications
	Modified residue	11	1	Phosphothreonine Ref.9
	Modified residue	491	1	Phosphoserine Ref.10
	Modified residue	499	1	Phosphothreonine Ref.9
	Modified residue	508	1	Phosphothreonine Ref.10
	Modified residue	770	1	Phosphoserine Ref.10
Experimental info
	Mutagenesis	773	1	G → A: Reduces interaction with NOS1. Ref.6
	Mutagenesis	774	1	D → A: Reduces interaction with NOS1. Ref.6
	Mutagenesis	776	1	L → A: Reduces interaction with NOS1. Ref.6
	Mutagenesis	777	1	D → A: Abolishes interaction with NOS1. Ref.6
	Mutagenesis	780 – 782	3	VVL → AAA: Reduces interaction with NOS1. Ref.6
	Mutagenesis	782	1	L → G: Reduces interaction with NOS1. Ref.6
	Sequence conflict	257	1	A → P in AAB03813. Ref.3
	Sequence conflict	263	1	L → P in AAB03813. Ref.3
	Sequence conflict	352	1	T → A in CAG33624. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q08AM6 [UniParc]. Last modified October 31, 2006. Version 1. Checksum: B39AC1F4D619570F	FASTA	782	87,973
	10 20 30 40 50 60 MNPEKDFAPL TPNIVRALND KLYEKRKVAA LEIEKLVREF VAQNNTVQIK HVIQTLSQEF 70 80 90 100 110 120 ALSQHPHSRK GGLIGLAACS IALGKDSGLY LKELIEPVLT CFNDADSRLR YYACEALYNI 130 140 150 160 170 180 VKVARGAVLP HFNVLFDGLS KLAADPDPNV KSGSELLDRL LKDIVTESNK FDLVSFIPLL 190 200 210 220 230 240 RERIYSNNQY ARQFIISWIL VLESVPDINL LDYLPEILDG LFQILGDNGK EIRKMCEVVL 250 260 270 280 290 300 GEFLKEIKKN PSSVKFAEMA NILVIHCQTT DDLIQLTAMC WMREFIQLAG RVMLPYSSGI 310 320 330 340 350 360 LTAVLPCLAY DDRKKSIKEV ANVCNQSLMK LVTPEDDELD ELRPGQRQAE PTPDDALPKQ 370 380 390 400 410 420 EGTASGGPDG SCDSSFSSGI SVFTAASTER APVTLHLDGI VQVLNCHLSD TAIGMMTRIA 430 440 450 460 470 480 VLKWLYHLYI KTPRKMFRHT DSLFPILLQT LSDESDEVIL KDLEVLAEIA SSPAGQTDDP 490 500 510 520 530 540 GPLDGPDLQA SHSELQVPTP GRAGLLNTSG TKGLECSPST PTMNSYFYKF MINLLKRFSS 550 560 570 580 590 600 ERKLLEVRGP FIIRQLCLLL NAENIFHSMA DILLREEDLK FASTMVHALN TILLTSTELF 610 620 630 640 650 660 QLRNQLKDLK TLESQNLFCC LYRSWCHNPV TTVSLCFLTQ NYRHAYDLIQ KFGDLEVTVD 670 680 690 700 710 720 FLAEVDKLVQ LIECPIFTYL RLQLLDVKNN PYLIKALYGL LMLLPQSSAF QLLSHRLQCV 730 740 750 760 770 780 PNPELLQTED SLKAAPKSQK ADSPSIDYAE LLQHFEKVQN KHLEVRHQRS GRGDHLDRRV VL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]	"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]. Tissue: Brain and Lung.
[3]	"Isolation of a cDNA clone, TRX encoding a human T-cell lymphotrophic virus type-I Tax1 binding protein." Mireskandari A., Reid R.L., Kashanchi F., Dittmer J., Li W.B., Brady J.N. Biochim. Biophys. Acta 1306:9-13(1996) [PubMed: 8611628] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 244-366, TISSUE SPECIFICITY, INTERACTION WITH HTLV-I TAX.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 259-782.
[5]	"A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity." Sbrissa D., Ikonomov O.C., Strakova J., Dondapati R., Mlak K., Deeb R., Silver R., Shisheva A. Mol. Cell. Biol. 24:10437-10447(2004) [PubMed: 15542851] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a new internal PDZ-recognition motif." Lemaire J.F., McPherson P.S. FEBS Lett. 580:6948-6954(2006) [PubMed: 17161399] [Abstract] Cited for: INTERACTION WITH NOS1, MUTAGENESIS OF GLY-773; ASP-774; LEU-776; ASP-777; 780-VAL--LEU-782 AND LEU-782.
[7]	"Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex." Sbrissa D., Ikonomov O.C., Fu Z., Ijuin T., Gruenberg J., Takenawa T., Shisheva A. J. Biol. Chem. 282:23878-23891(2007) [PubMed: 17556371] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX.
[8]	"ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality." Sbrissa D., Ikonomov O.C., Fenner H., Shisheva A. J. Mol. Biol. 384:766-779(2008) [PubMed: 18950639] [Abstract] Cited for: SUBUNIT, IDENTIFICATION IN THE PI(3,5)P2 REGULATORY COMPLEX, DOMAIN.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-11 AND THR-499, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-491; THR-508 AND SER-770, MASS SPECTROMETRY.
[11]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK025479 mRNA. Translation: BAB15145.1. Different initiation. AK056433 mRNA. Translation: BAG51707.1. BC000536 mRNA. Translation: AAH00536.2. BC007214 mRNA. Translation: AAH07214.2. BC125108 mRNA. Translation: AAI25109.1. BC125109 mRNA. Translation: AAI25110.1. U25801 mRNA. Translation: AAB03813.1. Sequence problems. CR457343 mRNA. Translation: CAG33624.1.
IPI	IPI00025160.
PIR	S68091.
RefSeq	NP_060522.3. NM_018052.3.
UniGene	Hs.445061.
3D structure databases
ProteinModelPortal	Q08AM6.
SMR	Q08AM6. Positions 217-242, 415-470.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q08AM6. 1 interaction.
MINT	MINT-3997917.
STRING	Q08AM6.
PTM databases
PhosphoSite	Q08AM6.
Polymorphism databases
DMDM	121940040.
Proteomic databases
PRIDE	Q08AM6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261776; ENSP00000261776; ENSG00000103043.
GeneID	55697.
KEGG	hsa:55697.
UCSC	uc002ezm.1. human.
Organism-specific databases
CTD	55697.
GeneCards	GC16M070721.
H-InvDB	HIX0013204.
HGNC	HGNC:25507. VAC14.
HPA	HPA027766.
MIM	604632. gene.
neXtProt	NX_Q08AM6.
PharmGKB	PA142670633.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG104397.
InParanoid	Q08AM6.
OMA	TAILPCL.
OrthoDB	EOG40K7Z7.
PhylomeDB	Q08AM6.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000103043-MONOMER.
Gene expression databases
ArrayExpress	Q08AM6.
Bgee	Q08AM6.
CleanEx	HS_VAC14.
Genevestigator	Q08AM6.
Family and domain databases
InterPro	IPR011989. ARM-like. IPR016024. ARM-type_fold. IPR021841. DUF3434. [Graphical view]
Gene3D	G3DSA:1.25.10.10. ARM-like. 3 hits.
KO	K15305.
Pfam	PF11916. Vac14_Fig4_bd. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
PROSITE	PS50077. HEAT_REPEAT. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	60525.
SOURCE	Search...

Entry information

Entry name

VAC14_HUMAN

Accession

Primary (citable) accession number: Q08AM6
Secondary accession number(s): B3KPJ5 , Q13174, Q6IA12, Q7L4Y1, Q9BW96, Q9H6V6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	October 31, 2006
Last modified:	January 25, 2012
This is version 53 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.