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Protein

Pleckstrin homology domain-containing family A member 8

Gene

PLEKHA8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • intermembrane lipid transfer activity Source: InterPro
  • phosphatidylinositol-4-phosphate binding Source: UniProtKB

GO - Biological processi

  • ER to Golgi ceramide transport Source: UniProtKB
  • lipid transport Source: UniProtKB
  • phosphatidylinositol biosynthetic process Source: Reactome
  • protein transport Source: UniProtKB-KW

Keywordsi

Biological processLipid transport, Protein transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-1660499 Synthesis of PIPs at the plasma membrane

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

EuPathDBiHostDB:ENSG00000106086.18
HGNCiHGNC:30037 PLEKHA8
MIMi608639 gene
neXtProtiNX_Q96JA3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi18R → L: Abolishes binding to phosphatylinositol 4-phosphate, less association with Golgi and no preference for TGN location. 1 Publication1
Mutagenesisi407W → A: Loss of glucosylceramide transfer activity from the TGN to the plasma membrane. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000106086
PharmGKBiPA134926954

Polymorphism and mutation databases

BioMutaiPLEKHA8
DMDMi387912902

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003068651 – 519Pleckstrin homology domain-containing family A member 8Add BLAST519

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei139PhosphothreonineBy similarity1
Modified residuei145PhosphoserineBy similarity1
Modified residuei153PhosphothreonineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ96JA3
PaxDbiQ96JA3
PeptideAtlasiQ96JA3
PRIDEiQ96JA3
ProteomicsDBi76918
76919 [Q96JA3-2]
76920 [Q96JA3-3]

PTM databases

iPTMnetiQ96JA3
PhosphoSitePlusiQ96JA3

Expressioni

Tissue specificityi

Expressed in kidney cell lines.1 Publication

Gene expression databases

BgeeiENSG00000106086
CleanExiHS_PLEKHA8
ExpressionAtlasiQ96JA3 baseline and differential
GenevisibleiQ96JA3 HS

Organism-specific databases

HPAiHPA072314

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 interactors
IntActiQ96JA3, 5 interactors
STRINGi9606.ENSP00000397947

Structurei

Secondary structure

1519
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi311 – 313Combined sources3
Turni315 – 317Combined sources3
Helixi319 – 321Combined sources3
Helixi326 – 328Combined sources3
Helixi332 – 340Combined sources9
Helixi343 – 349Combined sources7
Turni351 – 354Combined sources4
Helixi355 – 372Combined sources18
Turni376 – 378Combined sources3
Helixi382 – 391Combined sources10
Helixi401 – 423Combined sources23
Helixi429 – 439Combined sources11
Helixi441 – 444Combined sources4
Helixi447 – 458Combined sources12
Helixi463 – 468Combined sources6
Beta strandi471 – 473Combined sources3
Helixi476 – 478Combined sources3
Helixi480 – 510Combined sources31

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5KDIX-ray1.45A/B309-519[»]
ProteinModelPortaliQ96JA3
SMRiQ96JA3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 93PHPROSITE-ProRule annotationAdd BLAST93

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni310 – 519Glycolipid transfer protein homology domainAdd BLAST210

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

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
InterProiView protein in InterPro
IPR036497 GLTP_sf
IPR014830 Glycolipid_transfer_prot_dom
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
PfamiView protein in Pfam
PF08718 GLTP, 1 hit
PF00169 PH, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SUPFAMiSSF110004 SSF110004, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti232E → G in BAB14449 (PubMed:15489334).Curated1
Sequence conflicti287T → S in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti340Y → C in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti359 – 365MDLVGNI → DGSCWKY in AAG48267 (PubMed:12747765).Curated7
Sequence conflicti363G → E in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti370 – 372QKY → RSI in BAB14449 (PubMed:15489334).Curated3
Sequence conflicti460A → T in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti478Q → R in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti498E → K in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti501L → M in AAK55424 (PubMed:11001876).Curated1
Sequence conflicti506T → A in AAK55424 (PubMed:11001876).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035444368V → E in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028543434 – 439NNAYGK → RNPTEN in isoform 3. 1 Publication6
Alternative sequenceiVSP_028544441 – 519Missing in isoform 3. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_028545455L → V in isoform 2. 1 Publication1
Alternative sequenceiVSP_028546456 – 519Missing in isoform 2. 1 PublicationAdd BLAST64

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
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

Similar proteinsi

Entry informationi

Entry nameiPKHA8_HUMAN
AccessioniPrimary (citable) accession number: Q96JA3
Secondary accession number(s): B4DH00
, Q7Z5V8, Q9BU78, Q9H274, Q9H8Z7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: May 16, 2012
Last modified: June 20, 2018
This is version 115 of the entry and version 3 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

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