O94830 (DDHD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	DDHD2
Synonyms:	KIAA0725, SAMWD1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	711 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Cytoplasm › cytosol. Endoplasmic reticulum-Golgi intermediate compartment. Golgi apparatus › cis-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.
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.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Cytoplasm Golgi apparatus
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell centrosome Inferred from direct assay. Source: HPA cytoplasm Inferred from direct assay. Source: HPA cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum-Golgi intermediate compartment Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	hydrolase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 711	711	Phospholipase DDHD2		PRO_0000309330
Regions
	Domain	30 – 112	83	WWE
	Domain	385 – 448	64	SAM
	Domain	495 – 700	206	DDHD
Sites
	Active site	351	1	Probable
Amino acid modifications
	Modified residue	447	1	Phosphoserine By similarity
Natural variations
	Natural variant	186	1	T → M. Ref.5 Corresponds to variant rs2306899 [ dbSNP | Ensembl ].		VAR_036930
Experimental info
	Mutagenesis	351	1	S → 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
	Mutagenesis	434	1	R → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-435 and A-436. Ref.9
	Mutagenesis	435	1	K → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-436. Ref.9
	Mutagenesis	436	1	K → A: Loss of phospholipid binding and of Golgi/ERGIC localization; when associated with A-434 and A-435. Ref.9
	Sequence conflict	292	1	S → G in BAB14470. Ref.2
	Sequence conflict	376	1	D → G in BAA34445. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	O94830 [UniParc]. Last modified November 13, 2007. Version 2. Checksum: 8C03CD9254B1DBFB	FASTA	711	81,032
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
+	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.
IPI	IPI00871731.
RefSeq	NP_001157704.1. NM_001164232.1. NP_056029.2. NM_015214.2.
UniGene	Hs.434966.
3D structure databases
ProteinModelPortal	O94830.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-4649256.
STRING	9606.ENSP00000380352.
PTM databases
PhosphoSite	O94830.
Proteomic databases
PaxDb	O94830.
PRIDE	O94830.
Protocols and materials databases
DNASU	23259.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000397166; ENSP00000380352; ENSG00000085788. ENST00000520272; ENSP00000429932; ENSG00000085788.
GeneID	23259.
KEGG	hsa:23259.
UCSC	uc003xlb.3. human.
Organism-specific databases
CTD	23259.
GeneCards	GC08P038107.
HGNC	HGNC:29106. DDHD2.
HPA	CAB015202. HPA023143. HPA023147. HPA023150.
MIM	615003. gene.
neXtProt	NX_O94830.
Orphanet	320380. Autosomal recessive spastic paraplegia type 54.
PharmGKB	PA128394618.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG285690.
HOGENOM	HOG000007725.
HOVERGEN	HBG057256.
InParanoid	O94830.
KO	K16545.
OMA	IVQCVND.
OrthoDB	EOG4BK53G.
Gene expression databases
ArrayExpress	O94830.
Bgee	O94830.
CleanEx	HS_DDHD2.
Genevestigator	O94830.
Family and domain databases
Gene3D	1.10.150.50. 1 hit.
InterPro	IPR004177. DDHD. IPR001660. SAM. IPR013761. SAM/pointed. IPR021129. SAM_type1. IPR004170. WWE-dom. [Graphical view]
Pfam	PF02862. DDHD. 1 hit. PF00536. SAM_1. 1 hit. PF02825. WWE. 1 hit. [Graphical view]
SMART	SM00454. SAM. 1 hit. [Graphical view]
SUPFAM	SSF47769. SAM_homology. 1 hit.
PROSITE	PS51043. DDHD. 1 hit. PS50105. SAM_DOMAIN. False negative. PS50918. WWE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	23259.
NextBio	44992.
SOURCE	Search...

Entry information

Entry name

DDHD2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 88 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.