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Protein

Phospholipase DDHD2

Gene

DDHD2

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

Functioni

Phospholipase that hydrolyzes preferentially phosphatidic acid, including 1,2-dioleoyl-sn-phosphatidic acid, and phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-phosphate (PI3P), phosphatidylinositol 4-phosphate (PI4P), phosphatidylinositol 5-phosphate (PI5P) and possibly phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in the maintenance of the endoplasmic reticulum and/or Golgi structures. May regulate the transport between Golgi apparatus and plasma membrane.3 Publications

Caution

It is uncertain whether Met-1 or Met-31 is the initiator.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei351Curated1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid degradation, Lipid metabolism

Enzyme and pathway databases

ReactomeiR-HSA-1483166 Synthesis of PA

Chemistry databases

SwissLipidsiSLP:000001070

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipase DDHD2 (EC:3.1.1.-)
Alternative name(s):
DDHD domain-containing protein 2
KIAA0725p
SAM, WWE and DDHD domain-containing protein 1
Gene namesi
Name:DDHD2
Synonyms:KIAA0725, SAMWD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000085788.13
HGNCiHGNC:29106 DDHD2
MIMi615003 gene
neXtProtiNX_O94830

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

Cytoplasm, Golgi apparatus

Pathology & Biotechi

Involvement in diseasei

Spastic paraplegia 54, autosomal recessive (SPG54)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. SPG54 patients have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions.
See also OMIM:615033
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069574660D → H in SPG54. 1 PublicationCorresponds to variant dbSNP:rs375168720EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi351S → A: Abolishes phospholipase activity. Loss of efficient targeting to the Golgi apparatus. No effect on PI(3)P-, PI(4)P-, PI(5)P-binding. 3 Publications1
Mutagenesisi434R → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-435 and A-436. 1 Publication1
Mutagenesisi435K → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-436. 1 Publication1
Mutagenesisi436K → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-435. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Neurodegeneration

Organism-specific databases

DisGeNETi23259
MalaCardsiDDHD2
MIMi615033 phenotype
OpenTargetsiENSG00000085788
Orphaneti320380 Autosomal recessive spastic paraplegia type 54
PharmGKBiPA128394618

Polymorphism and mutation databases

BioMutaiDDHD2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003093301 – 711Phospholipase DDHD2Add BLAST711

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei447PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94830
MaxQBiO94830
PaxDbiO94830
PeptideAtlasiO94830
PRIDEiO94830

PTM databases

iPTMnetiO94830
PhosphoSitePlusiO94830

Expressioni

Tissue specificityi

Widely expressed (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000085788
CleanExiHS_DDHD2
ExpressionAtlasiO94830 baseline and differential
GenevisibleiO94830 HS

Organism-specific databases

HPAiCAB015202
HPA023143
HPA023147

Interactioni

Subunit structurei

Forms homooligomers and, to a much smaller extent, heterooligomers with DDHD1.

Protein-protein interaction databases

BioGridi116862, 15 interactors
IntActiO94830, 3 interactors
MINTiO94830
STRINGi9606.ENSP00000380352

Structurei

3D structure databases

ProteinModelPortaliO94830
SMRiO94830
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 112WWEPROSITE-ProRule annotationAdd BLAST83
Domaini385 – 448SAMAdd BLAST64
Domaini495 – 700DDHDPROSITE-ProRule annotationAdd BLAST206

Domaini

SAM and DDHD domains together are required for phospholipid binding.

Sequence similaritiesi

Belongs to the PA-PLA1 family.Curated

Phylogenomic databases

eggNOGiKOG2308 Eukaryota
ENOG410YDSX LUCA
GeneTreeiENSGT00530000063155
HOGENOMiHOG000007725
HOVERGENiHBG057256
InParanoidiO94830
KOiK16545
OMAiNYKFPTC
OrthoDBiEOG091G02T5
PhylomeDBiO94830
TreeFamiTF314133

Family and domain databases

InterProiView protein in InterPro
IPR004177 DDHD_dom
IPR001660 SAM
IPR013761 SAM/pointed_sf
IPR004170 WWE-dom
PfamiView protein in Pfam
PF02862 DDHD, 1 hit
PF00536 SAM_1, 1 hit
PF02825 WWE, 1 hit
SMARTiView protein in SMART
SM01127 DDHD, 1 hit
SM00454 SAM, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
PROSITEiView protein in PROSITE
PS51043 DDHD, 1 hit
PS50918 WWE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: O94830-1) [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
MSSVQSQQEQ LSQSDPSPSP NSCSSFELID MDAGSLYEPV SPHWFYCKII
60 70 80 90 100
DSKETWIPFN SEDSQQLEEA YSSGKGCNGR VVPTDGGRYD VHLGERMRYA
110 120 130 140 150
VYWDELASEV RRCTWFYKGD KDNKYVPYSE SFSQVLEETY MLAVTLDEWK
160 170 180 190 200
KKLESPNREI IILHNPKLMV HYQPVAGSDD WGSTPTEQGR PRTVKRGVEN
210 220 230 240 250
ISVDIHCGEP LQIDHLVFVV HGIGPACDLR FRSIVQCVND FRSVSLNLLQ
260 270 280 290 300
THFKKAQENQ QIGRVEFLPV NWHSPLHSTG VDVDLQRITL PSINRLRHFT
310 320 330 340 350
NDTILDVFFY NSPTYCQTIV DTVASEMNRI YTLFLQRNPD FKGGVSIAGH
360 370 380 390 400
SLGSLILFDI LTNQKDSLGD IDSEKDSLNI VMDQGDTPTL EEDLKKLQLS
410 420 430 440 450
EFFDIFEKEK VDKEALALCT DRDLQEIGIP LGPRKKILNY FSTRKNSMGI
460 470 480 490 500
KRPAPQPASG ANIPKESEFC SSSNTRNGDY LDVGIGQVSV KYPRLIYKPE
510 520 530 540 550
IFFAFGSPIG MFLTVRGLKR IDPNYRFPTC KGFFNIYHPF DPVAYRIEPM
560 570 580 590 600
VVPGVEFEPM LIPHHKGRKR MHLELREGLT RMSMDLKNNL LGSLRMAWKS
610 620 630 640 650
FTRAPYPALQ ASETPEETEA EPESTSEKPS DVNTEETSVA VKEEVLPINV
660 670 680 690 700
GMLNGGQRID YVLQEKPIES FNEYLFALQS HLCYWESEDT VLLVLKEIYQ
710
TQGIFLDQPL Q
Length:711
Mass (Da):81,032
Last modified:November 13, 2007 - v2
Checksum:i8C03CD9254B1DBFB
GO
Isoform 2 (identifier: O94830-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-381: Missing.

Note: No experimental confirmation available.
Show »
Length:330
Mass (Da):37,682
Checksum:i0480B54A739F2ABD
GO

Sequence cautioni

The sequence AAH10504 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB14470 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti292S → G in BAB14470 (PubMed:14702039).Curated1
Sequence conflicti376D → G in BAA34445 (PubMed:9872452).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036930186T → M1 PublicationCorresponds to variant dbSNP:rs2306899EnsemblClinVar.1
Natural variantiVAR_069574660D → H in SPG54. 1 PublicationCorresponds to variant dbSNP:rs375168720EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0560871 – 381Missing in isoform 2. 1 PublicationAdd BLAST381

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK023218 mRNA Translation: BAB14470.1 Different initiation.
AK125904 mRNA Translation: BAG54264.1
AK127040 mRNA Translation: BAG54427.1
AC084024 Genomic DNA No translation available.
AC087362 Genomic DNA No translation available.
AB018268 mRNA Translation: BAA34445.1
CH471080 Genomic DNA Translation: EAW63324.1
BC010504 mRNA Translation: AAH10504.1 Different initiation.
CCDSiCCDS34883.1 [O94830-1]
RefSeqiNP_001157704.1, NM_001164232.1 [O94830-1]
NP_056029.2, NM_015214.2 [O94830-1]
XP_005273511.1, XM_005273454.2 [O94830-1]
XP_005273512.1, XM_005273455.3 [O94830-1]
XP_011542758.1, XM_011544456.1 [O94830-1]
XP_016868741.1, XM_017013252.1 [O94830-1]
XP_016868742.1, XM_017013253.1 [O94830-1]
XP_016868743.1, XM_017013254.1 [O94830-2]
XP_016868744.1, XM_017013255.1 [O94830-2]
XP_016868745.1, XM_017013256.1 [O94830-2]
UniGeneiHs.434966

Genome annotation databases

EnsembliENST00000397166; ENSP00000380352; ENSG00000085788 [O94830-1]
ENST00000517385; ENSP00000429017; ENSG00000085788 [O94830-2]
ENST00000520272; ENSP00000429932; ENSG00000085788 [O94830-1]
GeneIDi23259
KEGGihsa:23259
UCSCiuc003xlb.4 human [O94830-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDDHD2_HUMAN
AccessioniPrimary (citable) accession number: O94830
Secondary accession number(s): B3KWV2, B3KXB5, Q9H8X7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: May 23, 2018
This is version 126 of the entry and version 2 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 8
    Human chromosome 8: 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

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