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Protein

Pleckstrin homology domain-containing family A member 8

Gene

PLEKHA8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cargo transport protein that is required for apical transport from the Golgi complex. Transports AQP2 from the trans-Golgi network (TGN) to sites of AQP2 phosphorylation. Mediates the non-vesicular transport of glucosylceramide (GlcCer) from the trans-Golgi network (TGN) to the plasma membrane and plays a pivotal role in the synthesis of complex glycosphingolipids. Binding of both phosphatidylinositol 4-phosphate (PIP) and ARF1 are essential for the GlcCer transfer ability. Also required for primary cilium formation, possibly by being involved in the transport of raft lipids to the apical membrane, and for membrane tubulation.3 Publications

GO - Molecular functioni

  • ceramide binding Source: UniProtKB
  • glycolipid binding Source: UniProtKB
  • glycolipid transporter activity Source: UniProtKB
  • phosphatidylinositol-4-phosphate binding Source: UniProtKB

GO - Biological processi

  • ER to Golgi ceramide transport Source: UniProtKB
  • lipid transport Source: UniProtKB
  • protein transport Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Lipid transport, Protein transport, Transport

Keywords - Ligandi

Lipid-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Pleckstrin homology domain-containing family A member 8
Short name:
PH domain-containing family A member 8
Alternative name(s):
Phosphatidylinositol-four-phosphate adapter protein 2
Short name:
FAPP-2
Short name:
Phosphoinositol 4-phosphate adapter protein 2
Short name:
hFAPP2
Serologically defined breast cancer antigen NY-BR-86
Gene namesi
Name:PLEKHA8
Synonyms:FAPP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:30037. PLEKHA8.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: UniProtKB-SubCell
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi18 – 181R → L: Abolishes binding to phosphatylinositol 4-phosphate, less association with Golgi and no preference for TGN location. 1 Publication
Mutagenesisi407 – 4071W → A: Loss of glucosylceramide transfer activity from the TGN to the plasma membrane. 1 Publication

Organism-specific databases

PharmGKBiPA134926954.

Polymorphism and mutation databases

BioMutaiPLEKHA8.
DMDMi387912902.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 519519Pleckstrin homology domain-containing family A member 8PRO_0000306865Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei139 – 1391PhosphothreonineBy similarity
Modified residuei145 – 1451PhosphoserineBy similarity
Modified residuei153 – 1531PhosphothreonineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96JA3.
MaxQBiQ96JA3.
PaxDbiQ96JA3.
PeptideAtlasiQ96JA3.
PRIDEiQ96JA3.

PTM databases

iPTMnetiQ96JA3.
PhosphoSiteiQ96JA3.

Expressioni

Tissue specificityi

Expressed in kidney cell lines.1 Publication

Gene expression databases

BgeeiQ96JA3.
CleanExiHS_PLEKHA8.
ExpressionAtlasiQ96JA3. baseline and differential.
GenevisibleiQ96JA3. HS.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with ARF1; the interaction together with phosphatidylinositol 4-phosphate binding is required for FAPP2 GlcCer transfer ability.By similarity1 Publication

Protein-protein interaction databases

BioGridi124225. 7 interactions.
IntActiQ96JA3. 5 interactions.
STRINGi9606.ENSP00000397947.

Structurei

3D structure databases

ProteinModelPortaliQ96JA3.
SMRiQ96JA3. Positions 1-100, 324-511.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 9393PHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni310 – 519210Glycolipid transfer protein homology domainAdd
BLAST

Domaini

The PH domain of FAPPS binds the small GTPase ARF1 and phosphatidylinositol-4-phosphate (PtdIns4P) with high selectivity, and is required for recruitment of FAPPs to the trans-Golgi network (TGN).1 Publication

Sequence similaritiesi

Contains 1 PH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3221. Eukaryota.
ENOG410YFEA. LUCA.
GeneTreeiENSGT00650000093230.
HOGENOMiHOG000007705.
HOVERGENiHBG108255.
InParanoidiQ96JA3.
KOiK08051.
TreeFamiTF317467.

Family and domain databases

Gene3Di1.10.3520.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR014830. Glycolipid_transfer_prot_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF08718. GLTP. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF110004. SSF110004. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96JA3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEGVLYKWTN YLSGWQPRWF LLCGGILSYY DSPEDAWKGC KGSIQMAVCE
60 70 80 90 100
IQVHSVDNTR MDLIIPGEQY FYLKARSVAE RQRWLVALGS AKACLTDSRT
110 120 130 140 150
QKEKEFAENT ENLKTKMSEL RLYCDLLVQQ VDKTKEVTTT GVSNSEEGID
160 170 180 190 200
VGTLLKSTCN TFLKTLEECM QIANAAFTSE LLYRTPPGSP QLAMLKSSKM
210 220 230 240 250
KHPIIPIHNS LERQMELSTC ENGSLNMEIN GEEEILMKNK NSLYLKSAEI
260 270 280 290 300
DCSISSEENT DDNITVQGEI RKEDGMENLK NHDNNLTQSG SDSSCSPECL
310 320 330 340 350
WEEGKEVIPT FFSTMNTSFS DIELLEDSGI PTEAFLASCY AVVPVLDKLG
360 370 380 390 400
PTVFAPVKMD LVGNIKKVNQ KYITNKEEFT TLQKIVLHEV EADVAQVRNS
410 420 430 440 450
ATEALLWLKR GLKFLKGFLT EVKNGEKDIQ TALNNAYGKT LRQHHGWVVR
460 470 480 490 500
GVFALALRAA PSYEDFVAAL TVKEGDHQKE AFSIGMQRDL SLYLPAMEKQ
510
LAILDTLYEV HGLESDEVV
Length:519
Mass (Da):58,261
Last modified:May 16, 2012 - v3
Checksum:i3E2D0746C00C722B
GO
Isoform 2 (identifier: Q96JA3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     455-455: L → V
     456-519: Missing.

Note: No experimental confirmation available.
Show »
Length:455
Mass (Da):51,141
Checksum:i22F40B4B22AD09E7
GO
Isoform 3 (identifier: Q96JA3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     434-439: NNAYGK → RNPTEN
     441-519: Missing.

Note: No experimental confirmation available.
Show »
Length:440
Mass (Da):49,462
Checksum:i7829E7848E8D5301
GO

Sequence cautioni

The sequence AAG48267.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAK55424.1 differs from that shown. Reason: Erroneous termination at position 508. Translated as Tyr.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti232 – 2321E → G in BAB14449 (PubMed:15489334).Curated
Sequence conflicti287 – 2871T → S in AAK55424 (PubMed:11001876).Curated
Sequence conflicti340 – 3401Y → C in AAK55424 (PubMed:11001876).Curated
Sequence conflicti359 – 3657MDLVGNI → DGSCWKY in AAG48267 (PubMed:12747765).Curated
Sequence conflicti363 – 3631G → E in AAK55424 (PubMed:11001876).Curated
Sequence conflicti370 – 3723QKY → RSI in BAB14449 (PubMed:15489334).Curated
Sequence conflicti460 – 4601A → T in AAK55424 (PubMed:11001876).Curated
Sequence conflicti478 – 4781Q → R in AAK55424 (PubMed:11001876).Curated
Sequence conflicti498 – 4981E → K in AAK55424 (PubMed:11001876).Curated
Sequence conflicti501 – 5011L → M in AAK55424 (PubMed:11001876).Curated
Sequence conflicti506 – 5061T → A in AAK55424 (PubMed:11001876).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti368 – 3681V → E in a breast cancer sample; somatic mutation. 1 Publication
VAR_035444

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei434 – 4396NNAYGK → RNPTEN in isoform 3. 1 PublicationVSP_028543
Alternative sequencei441 – 51979Missing in isoform 3. 1 PublicationVSP_028544Add
BLAST
Alternative sequencei455 – 4551L → V in isoform 2. 1 PublicationVSP_028545
Alternative sequencei456 – 51964Missing in isoform 2. 1 PublicationVSP_028546Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF380162 mRNA. Translation: AAK55424.1. Sequence problems.
AK023180 mRNA. Translation: BAB14449.1.
AK294857 mRNA. Translation: BAG57961.1.
CH471073 Genomic DNA. Translation: EAW93930.1.
BC002838 mRNA. Translation: AAH02838.1.
BC053990 mRNA. Translation: AAH53990.1.
AF308300 mRNA. Translation: AAG48267.1. Different initiation.
CCDSiCCDS5424.1. [Q96JA3-3]
CCDS56473.1. [Q96JA3-1]
RefSeqiNP_001183955.1. NM_001197026.1. [Q96JA3-1]
NP_001183956.1. NM_001197027.1.
NP_116028.1. NM_032639.3. [Q96JA3-3]
XP_011513896.1. XM_011515594.1. [Q96JA3-2]
UniGeneiHs.233495.
Hs.558495.
Hs.734170.

Genome annotation databases

EnsembliENST00000258679; ENSP00000258679; ENSG00000106086. [Q96JA3-3]
ENST00000396257; ENSP00000379556; ENSG00000106086. [Q96JA3-2]
ENST00000449726; ENSP00000397947; ENSG00000106086. [Q96JA3-1]
GeneIDi84725.
KEGGihsa:84725.
UCSCiuc003tan.4. human. [Q96JA3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF380162 mRNA. Translation: AAK55424.1. Sequence problems.
AK023180 mRNA. Translation: BAB14449.1.
AK294857 mRNA. Translation: BAG57961.1.
CH471073 Genomic DNA. Translation: EAW93930.1.
BC002838 mRNA. Translation: AAH02838.1.
BC053990 mRNA. Translation: AAH53990.1.
AF308300 mRNA. Translation: AAG48267.1. Different initiation.
CCDSiCCDS5424.1. [Q96JA3-3]
CCDS56473.1. [Q96JA3-1]
RefSeqiNP_001183955.1. NM_001197026.1. [Q96JA3-1]
NP_001183956.1. NM_001197027.1.
NP_116028.1. NM_032639.3. [Q96JA3-3]
XP_011513896.1. XM_011515594.1. [Q96JA3-2]
UniGeneiHs.233495.
Hs.558495.
Hs.734170.

3D structure databases

ProteinModelPortaliQ96JA3.
SMRiQ96JA3. Positions 1-100, 324-511.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124225. 7 interactions.
IntActiQ96JA3. 5 interactions.
STRINGi9606.ENSP00000397947.

PTM databases

iPTMnetiQ96JA3.
PhosphoSiteiQ96JA3.

Polymorphism and mutation databases

BioMutaiPLEKHA8.
DMDMi387912902.

Proteomic databases

EPDiQ96JA3.
MaxQBiQ96JA3.
PaxDbiQ96JA3.
PeptideAtlasiQ96JA3.
PRIDEiQ96JA3.

Protocols and materials databases

DNASUi84725.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258679; ENSP00000258679; ENSG00000106086. [Q96JA3-3]
ENST00000396257; ENSP00000379556; ENSG00000106086. [Q96JA3-2]
ENST00000449726; ENSP00000397947; ENSG00000106086. [Q96JA3-1]
GeneIDi84725.
KEGGihsa:84725.
UCSCiuc003tan.4. human. [Q96JA3-1]

Organism-specific databases

CTDi84725.
GeneCardsiPLEKHA8.
H-InvDBHIX0010564.
HGNCiHGNC:30037. PLEKHA8.
MIMi608639. gene.
neXtProtiNX_Q96JA3.
PharmGKBiPA134926954.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3221. Eukaryota.
ENOG410YFEA. LUCA.
GeneTreeiENSGT00650000093230.
HOGENOMiHOG000007705.
HOVERGENiHBG108255.
InParanoidiQ96JA3.
KOiK08051.
TreeFamiTF317467.

Miscellaneous databases

GenomeRNAii84725.
PROiQ96JA3.
SOURCEiSearch...

Gene expression databases

BgeeiQ96JA3.
CleanExiHS_PLEKHA8.
ExpressionAtlasiQ96JA3. baseline and differential.
GenevisibleiQ96JA3. HS.

Family and domain databases

Gene3Di1.10.3520.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR014830. Glycolipid_transfer_prot_dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PfamiPF08718. GLTP. 1 hit.
PF00169. PH. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF110004. SSF110004. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities."
    Dowler S.J., Currie R.A., Campbell D.G., Deak M., Kular G., Downes C.P., Alessi D.R.
    Biochem. J. 351:19-31(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "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] (ISOFORM 1).
  3. 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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Tissue: Brain and Placenta.
  5. "Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression."
    Scanlan M.J., Gout I., Gordon C.M., Williamson B., Stockert E., Gure A.O., Jaeger D., Chen Y.-T., Mackay A., O'Hare M.J., Old L.J.
    Cancer Immun. 1:4-4(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-365.
    Tissue: Mammary gland.
  6. "FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P."
    Godi A., Di Campli A., Konstantakopoulos A., Di Tullio G., Alessi D.R., Kular G.S., Daniele T., Marra P., Lucocq J.M., De Matteis M.A.
    Nat. Cell Biol. 6:393-404(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ARF1, DOMAIN, PHOSPHOLIPID-BINDING, FUNCTION, TISSUE SPECIFICITY.
  7. "FAPP2 is involved in the transport of apical cargo in polarized MDCK cells."
    Vieira O.V., Verkade P., Manninen A., Simons K.
    J. Cell Biol. 170:521-526(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. Cited for: FUNCTION, MUTAGENESIS OF ARG-18 AND TRP-407.
  9. Cited for: VARIANT [LARGE SCALE ANALYSIS] GLU-368.

Entry informationi

Entry nameiPKHA8_HUMAN
AccessioniPrimary (citable) accession number: Q96JA3
Secondary accession number(s): B4DH00
, Q7Z5V8, Q9BU78, Q9H274, Q9H8Z7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: May 16, 2012
Last modified: July 6, 2016
This is version 101 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.