Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O94830 (DDHD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:DDHD2
Synonyms:KIAA0725, SAMWD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length711 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.8 Ref.9

Subunit structure

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

Subcellular location

Cytoplasmcytosol. Endoplasmic reticulum-Golgi intermediate compartment. Golgi apparatuscis-Golgi network. Note: Cycles between the Golgi apparatus and the cytosol. DDHD2 recruitment to the Golgi/endoplasmic reticulum-Golgi intermediate compartment (ERGIC) is regulated by the levels of phosphoinositides, including PI4P. Ref.1 Ref.7 Ref.8

Tissue specificity

Widely expressed (at protein level). Ref.1

Domain

SAM and DDHD domains together are required for phospholipid binding.

Involvement in disease

Spastic paraplegia 54, autosomal recessive (SPG54) [MIM:615033]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the PA-PLA1 family.

Contains 1 DDHD domain.

Contains 1 SAM (sterile alpha motif) domain.

Contains 1 WWE domain.

Caution

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

Sequence caution

The sequence AAH10504.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAB14470.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 711711Phospholipase DDHD2
PRO_0000309330

Regions

Domain30 – 11283WWE
Domain385 – 44864SAM
Domain495 – 700206DDHD

Sites

Active site3511 Probable

Natural variations

Natural variant1861T → M. Ref.5
Corresponds to variant rs2306899 [ dbSNP | Ensembl ].
VAR_036930
Natural variant6601D → H in SPG54. Ref.10
VAR_069574

Experimental info

Mutagenesis3511S → 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. Ref.1 Ref.8 Ref.9
Mutagenesis4341R → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-435 and A-436. Ref.9
Mutagenesis4351K → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-436. Ref.9
Mutagenesis4361K → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-435. Ref.9
Sequence conflict2921S → G in BAB14470. Ref.2
Sequence conflict3761D → G in BAA34445. Ref.5

Sequences

Sequence LengthMass (Da)Tools
O94830 [UniParc].

Last modified November 13, 2007. Version 2.
Checksum: 8C03CD9254B1DBFB

FASTA71181,032
        10         20         30         40         50         60 
MSSVQSQQEQ LSQSDPSPSP NSCSSFELID MDAGSLYEPV SPHWFYCKII DSKETWIPFN 

        70         80         90        100        110        120 
SEDSQQLEEA YSSGKGCNGR VVPTDGGRYD VHLGERMRYA VYWDELASEV RRCTWFYKGD 

       130        140        150        160        170        180 
KDNKYVPYSE SFSQVLEETY MLAVTLDEWK KKLESPNREI IILHNPKLMV HYQPVAGSDD 

       190        200        210        220        230        240 
WGSTPTEQGR PRTVKRGVEN ISVDIHCGEP LQIDHLVFVV HGIGPACDLR FRSIVQCVND 

       250        260        270        280        290        300 
FRSVSLNLLQ THFKKAQENQ QIGRVEFLPV NWHSPLHSTG VDVDLQRITL PSINRLRHFT 

       310        320        330        340        350        360 
NDTILDVFFY NSPTYCQTIV DTVASEMNRI YTLFLQRNPD FKGGVSIAGH SLGSLILFDI 

       370        380        390        400        410        420 
LTNQKDSLGD IDSEKDSLNI VMDQGDTPTL EEDLKKLQLS EFFDIFEKEK VDKEALALCT 

       430        440        450        460        470        480 
DRDLQEIGIP LGPRKKILNY FSTRKNSMGI KRPAPQPASG ANIPKESEFC SSSNTRNGDY 

       490        500        510        520        530        540 
LDVGIGQVSV KYPRLIYKPE IFFAFGSPIG MFLTVRGLKR IDPNYRFPTC KGFFNIYHPF 

       550        560        570        580        590        600 
DPVAYRIEPM VVPGVEFEPM LIPHHKGRKR MHLELREGLT RMSMDLKNNL LGSLRMAWKS 

       610        620        630        640        650        660 
FTRAPYPALQ ASETPEETEA EPESTSEKPS DVNTEETSVA VKEEVLPINV GMLNGGQRID 

       670        680        690        700        710 
YVLQEKPIES FNEYLFALQS HLCYWESEDT VLLVLKEIYQ TQGIFLDQPL Q 

« Hide

References

« Hide 'large scale' references
[1]"A novel phospholipase A1 with sequence homology to a mammalian Sec23p-interacting protein, p125."
Nakajima K., Sonoda H., Mizoguchi T., Aoki J., Arai H., Nagahama M., Tagaya M., Tani K.
J. Biol. Chem. 277:11329-11335(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-351.
[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. expand/collapse author list , 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].
Tissue: Testis.
[3]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:277-286(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 139-711, VARIANT MET-186.
Tissue: Brain.
[6]"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] OF 220-711.
Tissue: Placenta.
[7]"p125 is localized in endoplasmic reticulum exit sites and involved in their organization."
Shimoi W., Ezawa I., Nakamoto K., Uesaki S., Gabreski G., Aridor M., Yamamoto A., Nagahama M., Tagaya M., Tani K.
J. Biol. Chem. 280:10141-10148(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"Golgi-localized KIAA0725p regulates membrane trafficking from the Golgi apparatus to the plasma membrane in mammalian cells."
Sato S., Inoue H., Kogure T., Tagaya M., Tani K.
FEBS Lett. 584:4389-4395(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-351.
[9]"Roles of SAM and DDHD domains in mammalian intracellular phospholipase A1 KIAA0725p."
Inoue H., Baba T., Sato S., Ohtsuki R., Takemori A., Watanabe T., Tagaya M., Tani K.
Biochim. Biophys. Acta 1823:930-939(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHOLIPID-BINDING, INTERACTION WITH DDHD1, HOMOOLIGOMER FORMATION, MUTAGENESIS OF SER-351; ARG-434; LYS-435 AND LYS-436.
[10]"Mutations in DDHD2, encoding an intracellular phospholipase A(1), cause a recessive form of complex hereditary spastic paraplegia."
Schuurs-Hoeijmakers J.H., Geraghty M.T., Kamsteeg E.J., Ben-Salem S., de Bot S.T., Nijhof B., van de Vondervoort I.I., van der Graaf M., Nobau A.C., Otte-Holler I., Vermeer S., Smith A.C., Humphreys P., Schwartzentruber J., Ali B.R., Al-Yahyaee S.A., Tariq S., Pramathan T. expand/collapse author list , Bayoumi R., Kremer H.P., van de Warrenburg B.P., van den Akker W.M., Gilissen C., Veltman J.A., Janssen I.M., Vulto-van Silfhout A.T., van der Velde-Visser S., Lefeber D.J., Diekstra A., Erasmus C.E., Willemsen M.A., Vissers L.E., Lammens M., van Bokhoven H., Brunner H.G., Wevers R.A., Schenck A., Al-Gazali L., de Vries B.B., de Brouwer A.P.
Am. J. Hum. Genet. 91:1073-1081(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG54 HIS-660.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK023218 mRNA. Translation: BAB14470.1. Different initiation.
AK125904 mRNA. Translation: BAG54264.1.
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.
CCDSCCDS34883.1.
RefSeqNP_001157704.1. NM_001164232.1.
NP_056029.2. NM_015214.2.
XP_005273511.1. XM_005273454.1.
XP_005273512.1. XM_005273455.1.
UniGeneHs.434966.

3D structure databases

ProteinModelPortalO94830.
SMRO94830. Positions 386-453.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116862. 2 interactions.
IntActO94830. 2 interactions.
MINTMINT-4649256.
STRING9606.ENSP00000380352.

PTM databases

PhosphoSiteO94830.

Proteomic databases

MaxQBO94830.
PaxDbO94830.
PRIDEO94830.

Protocols and materials databases

DNASU23259.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000397166; ENSP00000380352; ENSG00000085788.
ENST00000520272; ENSP00000429932; ENSG00000085788.
GeneID23259.
KEGGhsa:23259.
UCSCuc003xlb.3. human.

Organism-specific databases

CTD23259.
GeneCardsGC08P038107.
HGNCHGNC:29106. DDHD2.
HPACAB015202.
HPA023143.
HPA023147.
HPA023150.
MIM615003. gene.
615033. phenotype.
neXtProtNX_O94830.
Orphanet320380. Autosomal recessive spastic paraplegia type 54.
PharmGKBPA128394618.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG285690.
HOGENOMHOG000007725.
HOVERGENHBG057256.
InParanoidO94830.
KOK16545.
OMAKDLQEMG.
OrthoDBEOG7JDQWX.
PhylomeDBO94830.
TreeFamTF314133.

Gene expression databases

ArrayExpressO94830.
BgeeO94830.
CleanExHS_DDHD2.
GenevestigatorO94830.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
InterProIPR004177. DDHD.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR004170. WWE-dom.
[Graphical view]
PfamPF02862. DDHD. 1 hit.
PF00536. SAM_1. 1 hit.
PF02825. WWE. 1 hit.
[Graphical view]
SMARTSM00454. SAM. 1 hit.
[Graphical view]
SUPFAMSSF47769. SSF47769. 1 hit.
PROSITEPS51043. DDHD. 1 hit.
PS50918. WWE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi23259.
NextBio44992.
PROO94830.
SOURCESearch...

Entry information

Entry nameDDHD2_HUMAN
AccessionPrimary (citable) accession number: O94830
Secondary accession number(s): B3KWV2, Q9H8X7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: July 9, 2014
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM