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Protein

Post-GPI attachment to proteins factor 6

Gene

TMEM8A

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

Functioni

Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchor proteins (GPI-AP). Has phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI. Required for the shedding of the GPI-AP TDGF1, but not CFC1, at the cell surface. Shedding of TDGF1 modulates Nodal signaling by allowing soluble TDGF1 to act as a Nodal coreceptor on other cells (PubMed:27881714). Also indirectly involved in the translocation of RAC1 from the cytosol to the plasma membrane by maintaining the steady state amount of CAV1-enriched plasma membrane subdomains, stabilizing RAC1 at the plasma membrane (PubMed:27835684). In contrast to myomaker (TMEM8C), has no fusogenic activity (PubMed:26858401).3 Publications

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.1 Publication

GO - Molecular functioni

Keywordsi

Molecular functionHydrolase

Protein family/group databases

TCDBi1.N.2.1.6 the myoblast fusion complex (mfc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Post-GPI attachment to proteins factor 61 Publication (EC:3.1.1.41 Publication)
Alternative name(s):
GPI processing phospholipase A21 Publication
Short name:
GPI-PLA21 Publication
Protein M83
Transmembrane protein 6
Transmembrane protein 8
Transmembrane protein 8A
Gene namesi
Name:TMEM8A
Synonyms:PGAP61 Publication, TMEM6, TMEM8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000129925.10
HGNCiHGNC:17205 TMEM8A
neXtProtiNX_Q9HCN3

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini35 – 545ExtracellularSequence analysisAdd BLAST511
Transmembranei546 – 566HelicalSequence analysisAdd BLAST21
Topological domaini567 – 568CytoplasmicSequence analysis2
Transmembranei569 – 589HelicalSequence analysisAdd BLAST21
Topological domaini590 – 605ExtracellularSequence analysisAdd BLAST16
Transmembranei606 – 626HelicalSequence analysisAdd BLAST21
Topological domaini627 – 629CytoplasmicSequence analysis3
Transmembranei630 – 650HelicalSequence analysisAdd BLAST21
Topological domaini651 – 653ExtracellularSequence analysis3
Transmembranei654 – 674HelicalSequence analysisAdd BLAST21
Topological domaini675 – 690CytoplasmicSequence analysisAdd BLAST16
Transmembranei691 – 711HelicalSequence analysisAdd BLAST21
Topological domaini712 – 717ExtracellularSequence analysis6
Transmembranei718 – 738HelicalSequence analysisAdd BLAST21
Topological domaini739 – 771CytoplasmicSequence analysisAdd BLAST33

Keywords - Cellular componenti

Cell membrane, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi584S → A: No effect. 1 Publication1
Mutagenesisi588H → A: Abolishes shedding of TDGF1. 1 Publication1
Mutagenesisi610D → A: Abolishes shedding of TDGF1. 1 Publication1
Mutagenesisi722H → A: Abolishes shedding of TDGF1. 1 Publication1
Mutagenesisi726H → A: Abolishes shedding of TDGF1. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000129925
PharmGKBiPA38211

Polymorphism and mutation databases

BioMutaiTMEM8A
DMDMi296453013

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 34Sequence analysisAdd BLAST34
ChainiPRO_000002253935 – 771Post-GPI attachment to proteins factor 6Add BLAST737

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi407N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi431N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi498 ↔ 508PROSITE-ProRule annotation
Disulfide bondi502 ↔ 521PROSITE-ProRule annotation
Disulfide bondi523 ↔ 532PROSITE-ProRule annotation

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9HCN3
MaxQBiQ9HCN3
PaxDbiQ9HCN3
PeptideAtlasiQ9HCN3
PRIDEiQ9HCN3

PTM databases

iPTMnetiQ9HCN3
PhosphoSitePlusiQ9HCN3

Expressioni

Tissue specificityi

Expressed in pancreas, placenta, spleen, liver, kidney, bone marrow, peripheral blood leukocytes and tonsil.1 Publication

Inductioni

Repressed during activation of CD4+ and CD8+ T-lymphocytes.

Gene expression databases

BgeeiENSG00000129925
CleanExiHS_TMEM8
ExpressionAtlasiQ9HCN3 baseline and differential
GenevisibleiQ9HCN3 HS

Organism-specific databases

HPAiHPA051281
HPA064673

Interactioni

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi12185610 interactors.
IntActiQ9HCN3 10 interactors.
STRINGi9606.ENSP00000401338

Structurei

3D structure databases

ProteinModelPortaliQ9HCN3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini497 – 533EGF-likePROSITE-ProRule annotationAdd BLAST37

Sequence similaritiesi

Belongs to the TMEM8 family.Curated

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IHJ3 Eukaryota
ENOG4111FA8 LUCA
GeneTreeiENSGT00390000004668
InParanoidiQ9HCN3
OMAiCAYVFQP
OrthoDBiEOG091G0KZA
PhylomeDBiQ9HCN3
TreeFamiTF331003

Family and domain databases

InterProiView protein in InterPro
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR021910 NGX6/PGAP6/MYMK
PANTHERiPTHR14319 PTHR14319, 1 hit
PfamiView protein in Pfam
PF12036 DUF3522, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 1 hit
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9HCN3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRAGTGTGG EAVAAVVAGP LLLLLLARPP PASAGYSGKS EVGLVSEHFS
60 70 80 90 100
QAPQRLSFYS WYGSARLFRF RVPPDAVLLR WLLQVSRESG AACTDAEITV
110 120 130 140 150
HFRSGAPPVI NPLGTSFPDD TAVQPSFQVG VPLSTTPRSN ASVNVSHPAP
160 170 180 190 200
GDWFVAAHLP PSSQKIELKG LAPTCAYVFQ PELLVTRVVE ISIMEPDVPL
210 220 230 240 250
PQTLLSHPSY LKVFVPDYTR ELLLELRDCV SNGSLGCPVR LTVGPVTLPS
260 270 280 290 300
NFQKVLTCTG APWPCRLLLP SPPWDRWLQV TAESLVGPLG TVAFSAVAAL
310 320 330 340 350
TACRPRSVTI QPLLQSSQNQ SFNASSGLLS PSPDHQDLGR SGRVDRSPFC
360 370 380 390 400
LTNYPVTRED MDVVSVHFQP LDRVSVRVCS DTPSVMRLRL NTGMDSGGSL
410 420 430 440 450
TISLRANKTE MRNETVVVAC VNAASPFLGF NTSLNCTTAF FQGYPLSLSA
460 470 480 490 500
WSRRANLIIP YPETDNWYLS LQLMCPENAE DCEQAVVHVE TTLYLVPCLN
510 520 530 540 550
DCGPYGQCLL LRRHSYLYAS CSCKAGWRGW SCTDNSTAQT VAQQRAATLL
560 570 580 590 600
LTLSNLMFLA PIAVSVRRFF LVEASVYAYT MFFSTFYHAC DQPGEAVLCI
610 620 630 640 650
LSYDTLQYCD FLGSGAAIWV TILCMARLKT VLKYVLFLLG TLVIAMSLQL
660 670 680 690 700
DRRGMWNMLG PCLFAFVIMA SMWAYRCGHR RQCYPTSWQR WAFYLLPGVS
710 720 730 740 750
MASVGIAIYT SMMTSDNYYY THSIWHILLA GSAALLLPPP DQPAEPWACS
760 770
QKFPCHYQIC KNDREELYAV T
Length:771
Mass (Da):84,761
Last modified:May 18, 2010 - v3
Checksum:i2A21814C449724F8
GO

Sequence cautioni

The sequence BAB14975 differs from that shown. Reason: Erroneous termination at position 750. Translated as Ser.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti460P → A in BAB14975 (PubMed:14702039).Curated1
Sequence conflicti654G → D in BAB16376 (PubMed:11006113).Curated1
Sequence conflicti687S → L in BAB14975 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025307136T → A3 PublicationsCorresponds to variant dbSNP:rs11248931Ensembl.1
Natural variantiVAR_025308310I → V3 PublicationsCorresponds to variant dbSNP:rs2071915Ensembl.1
Natural variantiVAR_057810567R → W1 PublicationCorresponds to variant dbSNP:rs3743887Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB045292 mRNA Translation: BAB16376.1
AE006463 Genomic DNA Translation: AAK61227.1
Z97634 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85824.1
CH471112 Genomic DNA Translation: EAW85825.1
BC021557 mRNA Translation: AAH21557.1
BC004276 mRNA Translation: AAH04276.1
AK024725 mRNA Translation: BAB14975.1 Sequence problems.
CCDSiCCDS10407.1
PIRiJC7388
RefSeqiNP_067082.2, NM_021259.2
UniGeneiHs.288940

Genome annotation databases

EnsembliENST00000431232; ENSP00000401338; ENSG00000129925
GeneIDi58986
KEGGihsa:58986
UCSCiuc002cgu.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTMM8A_HUMAN
AccessioniPrimary (citable) accession number: Q9HCN3
Secondary accession number(s): D3DU49
, Q4TT35, Q8WU24, Q96S25, Q9BR03, Q9BT97, Q9H7B9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: May 18, 2010
Last modified: February 28, 2018
This is version 141 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

Complete proteome, Reference proteome