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Protein

Palmitoyltransferase ZDHHC6

Gene

ZDHHC6

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

Functioni

Endoplasmic reticulum palmitoyl acyltransferase that mediates palmitoylation of proteins such as AMFR, CALX, ITPR1 and TFRC (PubMed:22314232, PubMed:22728137, PubMed:25368151, PubMed:28826475). Palmitoylates calnexin (CALX), which is required for its association with the ribosome-translocon complex and efficient folding of glycosylated proteins (PubMed:22314232). Mediates palmitoylation of AMFR, promoting AMFR distribution to the peripheral endoplasmic reticulum (PubMed:22728137). Together with SELENOK, palmitoylates ITPR1 in immune cells, leading to regulate ITPR1 stability and function (PubMed:25368151).4 Publications

Catalytic activityi

Palmitoyl-CoA + [protein]-L-cysteine = [protein]-S-palmitoyl-L-cysteine + CoA.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei129S-palmitoyl cysteine intermediateBy similarity1

GO - Molecular functioni

GO - Biological processi

  • protein palmitoylation Source: UniProtKB

Keywordsi

Molecular functionAcyltransferase, Transferase

Names & Taxonomyi

Protein namesi
Recommended name:
Palmitoyltransferase ZDHHC6Curated (EC:2.3.1.2251 Publication)
Alternative name(s):
Transmembrane protein H41 Publication
Zinc finger DHHC domain-containing protein 61 Publication
Short name:
DHHC-61 Publication
Zinc finger protein 376
Gene namesi
Name:ZDHHC6Imported
Synonyms:ZNF376Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000023041.11.
HGNCiHGNC:19160. ZDHHC6.

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
Transmembranei25 – 45HelicalSequence analysisAdd BLAST21
Transmembranei58 – 78HelicalSequence analysisAdd BLAST21
Transmembranei144 – 164HelicalSequence analysisAdd BLAST21
Transmembranei206 – 226HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi328 – 329CC → AA: Abolishes palmitoylation, leading to impaired homooligomeization and decreased catalytic activity; when associated with A-343. 1 Publication2
Mutagenesisi343C → A: Abolishes palmitoylation, leading to impaired homooligomeization and decreased catalytic activity; when associated with 328-A-A-329. 1 Publication1
Mutagenesisi409E → A: Does not affect localization to the endoplasmic reticulum. 1 Publication1
Mutagenesisi410K → A: Impaired localization to the endoplasmic reticulum. 1 Publication1
Mutagenesisi411K → A: Impaired localization to the endoplasmic reticulum. 1 Publication1
Mutagenesisi412N → A: Does not affect localization to the endoplasmic reticulum. 1 Publication1
Mutagenesisi413R → A: Does not affect localization to the endoplasmic reticulum. 1 Publication1

Organism-specific databases

DisGeNETi64429.
OpenTargetsiENSG00000023041.
PharmGKBiPA38803.

Polymorphism and mutation databases

BioMutaiZDHHC6.
DMDMi28202106.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002128711 – 413Palmitoyltransferase ZDHHC6Add BLAST413

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi328S-palmitoyl cysteine1 Publication1
Lipidationi329S-palmitoyl cysteine1 Publication1
Lipidationi343S-palmitoyl cysteine1 Publication1

Post-translational modificationi

Palmitoylated at 3 different sites by ZDHHC16 (PubMed:28826475). The combination of the different palmitoylation events strongly affects the quaternary assembly of ZDHHC6, its localization, stability and function (PubMed:28826475). Palmitoylation at Cys-328 accelerates the turnover of ZDHHC6 (PubMed:28826475). Depalmitoylated by LYPLA2 (PubMed:28826475).1 Publication

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

EPDiQ9H6R6.
MaxQBiQ9H6R6.
PaxDbiQ9H6R6.
PeptideAtlasiQ9H6R6.
PRIDEiQ9H6R6.

PTM databases

iPTMnetiQ9H6R6.
PhosphoSitePlusiQ9H6R6.
SwissPalmiQ9H6R6.

Expressioni

Gene expression databases

BgeeiENSG00000023041.
CleanExiHS_ZDHHC6.
ExpressionAtlasiQ9H6R6. baseline and differential.
GenevisibleiQ9H6R6. HS.

Organism-specific databases

HPAiHPA014357.

Interactioni

Subunit structurei

Homooligomerizes (PubMed:28826475). Interacts with SELENOK (PubMed:25368151).2 Publications

Protein-protein interaction databases

BioGridi122177. 24 interactors.
IntActiQ9H6R6. 1 interactor.
MINTiMINT-1415568.
STRINGi9606.ENSP00000358413.

Structurei

3D structure databases

ProteinModelPortaliQ9H6R6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini99 – 149DHHCPROSITE-ProRule annotationAdd BLAST51
Domaini313 – 398SH3PROSITE-ProRule annotationAdd BLAST86

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi410 – 413Di-lysine motif1 Publication4

Domaini

The DHHC domain is required for palmitoyltransferase activity.By similarity
The C-terminal di-lysine motif confers endoplasmic reticulum localization.1 Publication

Sequence similaritiesi

Belongs to the DHHC palmitoyltransferase family.Curated

Keywords - Domaini

SH3 domain, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1314. Eukaryota.
COG5273. LUCA.
GeneTreeiENSGT00900000140969.
HOGENOMiHOG000017896.
HOVERGENiHBG054221.
InParanoidiQ9H6R6.
KOiK20031.
OMAiFAHQALF.
OrthoDBiEOG091G0HOK.
PhylomeDBiQ9H6R6.
TreeFamiTF320809.

Family and domain databases

InterProiView protein in InterPro
IPR001594. Palmitoyltrfase_DHHC.
IPR001452. SH3_domain.
PfamiView protein in Pfam
PF01529. DHHC. 1 hit.
PF07653. SH3_2. 1 hit.
PROSITEiView protein in PROSITE
PS50216. DHHC. 1 hit.
PS50002. SH3. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H6R6-1) [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
MGTFCSVIKF ENLQELKRLC HWGPIIALGV IAICSTMAMI DSVLWYWPLH
60 70 80 90 100
TTGGSVNFIM LINWTVMILY NYFNAMFVGP GFVPLGWKPE ISQDTMYLQY
110 120 130 140 150
CKVCQAYKAP RSHHCRKCNR CVMKMDHHCP WINNCCGYQN HASFTLFLLL
160 170 180 190 200
APLGCIHAAF IFVMTMYTQL YHRLSFGWNT VKIDMSAARR DPLPIVPFGL
210 220 230 240 250
AAFATTLFAL GLALGTTIAV GMLFFIQMKI ILRNKTSIES WIEEKAKDRI
260 270 280 290 300
QYYQLDEVFV FPYDMGSRWR NFKQVFTWSG VPEGDGLEWP VREGCHQYSL
310 320 330 340 350
TIEQLKQKAD KRVRSVRYKV IEDYSGACCP LNKGIKTFFT SPCTEEPRIQ
360 370 380 390 400
LQKGEFILAT RGLRYWLYGD KILDDSFIEG VSRIRGWFPR KCVEKCPCDA
410
ETDQAPEGEK KNR
Length:413
Mass (Da):47,663
Last modified:March 1, 2001 - v1
Checksum:iE4C6CD875FA03713
GO
Isoform 2 (identifier: Q9H6R6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     90-93: Missing.

Note: No experimental confirmation available.
Show »
Length:409
Mass (Da):47,205
Checksum:iAC56FA6C4DBDE189
GO

Sequence cautioni

The sequence BAB15462 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57N → S in BAD96806 (Ref. 3) Curated1
Sequence conflicti66V → I in BAD96806 (Ref. 3) Curated1
Sequence conflicti78V → A in BAD96806 (Ref. 3) Curated1
Sequence conflicti342P → L in BAB15462 (PubMed:14702039).Curated1
Sequence conflicti370D → G in BAB15462 (PubMed:14702039).Curated1
Sequence conflicti376S → P in BAD96806 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05297441D → N. Corresponds to variant dbSNP:rs34350728Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00693890 – 93Missing in isoform 2. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF267740 mRNA. Translation: AAL56663.1.
AK025605 mRNA. Translation: BAB15187.1.
AK026369 mRNA. Translation: BAB15462.1. Different initiation.
AK223086 mRNA. Translation: BAD96806.1.
CH471066 Genomic DNA. Translation: EAW49526.1.
CH471066 Genomic DNA. Translation: EAW49528.1.
BC007213 mRNA. Translation: AAH07213.1.
BC017434 mRNA. Translation: AAH17434.1.
CCDSiCCDS7574.1. [Q9H6R6-1]
CCDS76335.1. [Q9H6R6-2]
RefSeqiNP_001290063.1. NM_001303134.1. [Q9H6R6-2]
NP_071939.1. NM_022494.2. [Q9H6R6-1]
XP_005270108.1. XM_005270051.4.
XP_006718011.1. XM_006717948.3.
XP_016872050.1. XM_017016561.1.
XP_016872051.1. XM_017016562.1. [Q9H6R6-2]
XP_016872052.1. XM_017016563.1. [Q9H6R6-2]
UniGeneiHs.196990.

Genome annotation databases

EnsembliENST00000369404; ENSP00000358412; ENSG00000023041. [Q9H6R6-2]
ENST00000369405; ENSP00000358413; ENSG00000023041. [Q9H6R6-1]
GeneIDi64429.
KEGGihsa:64429.
UCSCiuc001kzv.3. human. [Q9H6R6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiZDHC6_HUMAN
AccessioniPrimary (citable) accession number: Q9H6R6
Secondary accession number(s): D3DRB6
, Q53G45, Q96IV7, Q9H605
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 2003
Last sequence update: March 1, 2001
Last modified: November 22, 2017
This is version 132 of the entry and version 1 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

Documents

  1. Human chromosome 10
    Human chromosome 10: 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. SIMILARITY comments
    Index of protein domains and families