Reviewed, UniProtKB/Swiss-Prot O75340 (PDCD6_HUMAN)

Names and origin

Protein names

Recommended name:
    Programmed cell death protein 6
Alternative name(s):
    Apoptosis-linked gene 2 protein
    Probable calcium-binding protein ALG-2

Gene names

Name:	PDCD6
Synonyms:	ALG2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	191 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca2+-regulated signals along the death pathway By similarity.
Subunit structure	Interacts with PEF1. Interacts with SEC31A and PDCD6IP in a calcium-dependent manner. Interacts with RBM22. Ref.6 Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Nucleus. Note: Interaction with RBM22 induces relocalization from the cytoplasm to the nucleus. Ref.9
Sequence similarities	Contains 5 EF-hand domains.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Endoplasmic reticulum Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium
Technical term	3D-structure
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis by extracellular signals Traceable author statement. Source: ProtInc response to calcium ion Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from sequence or structural similarity. Source: UniProtKB calcium-dependent protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAPK1	P53355	3	EBI-352915,EBI-358616
FAS	P25445	1	EBI-352915,EBI-494743
PDCD6IP	Q8WUM4	1	EBI-352915,EBI-310624
SEC31A	O94979	1	EBI-352915,EBI-1767898

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 191	191	Programmed cell death protein 6		PRO_0000073729
Regions
	Domain	23 – 58	36	EF-hand 1
	Domain	59 – 89	31	EF-hand 2
	Domain	90 – 125	36	EF-hand 3
	Domain	126 – 161	36	EF-hand 4
	Domain	162 – 191	30	EF-hand 5
	Calcium binding	36 – 47	12	1 Potential
	Calcium binding	73 – 84	12	2 Potential
	Calcium binding	103 – 114	12	3 Potential
Natural variations
	Natural variant	123	1	G → C in a breast cancer sample; somatic mutation. Ref.11		VAR_035459
Experimental info
	Mutagenesis	47	1	E → A: Loss of interaction with SEC31A and loss of localization to the endoplasmic reticulum; when associated with A-114. Ref.9
	Mutagenesis	114	1	E → A: Loss of interaction with SEC31A and loss if localization to the endoplasmic reticulum; when associated with A-47. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	O75340-1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: D0B5944CF3C696AD	FASTA	191	21,868
	10 20 30 40 50 60 MAAYSYRPGP GAGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDTELQQ ALSNGTWTPF 70 80 90 100 110 120 NPVTVRSIIS MFDRENKAGV NFSEFTGVWK YITDWQNVFR TYDRDNSGMI DKNELKQALS 130 140 150 160 170 180 GFGYRLSDQF HDILIRKFDR QGRGQIAFDD FIQGCIVLQR LTDIFRRYDT DQDGWIQVSY 190 EQYLSMVFSI V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Ganjei J.K., D'Adamio L. Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	Urcelay E., Ibarreta D., Parrilla R., Ayuso M.S. Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[6]	"Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner." Kitaura Y., Matsumoto S., Satoh H., Hitomi K., Maki M. J. Biol. Chem. 276:14053-14058(2001) [PubMed: 11278427] [Abstract] Cited for: INTERACTION WITH PEF1.
[7]	"Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions." Kitaura Y., Satoh H., Takahashi H., Shibata H., Maki M. Arch. Biochem. Biophys. 399:12-18(2002) [PubMed: 11883899] [Abstract] Cited for: INTERACTION WITH PEF1.
[8]	"Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22." Montaville P., Dai Y., Cheung C.Y., Giller K., Becker S., Michalak M., Webb S.E., Miller A.L., Krebs J. Biochim. Biophys. Acta 1763:1335-1343(2006) [PubMed: 17045351] [Abstract] Cited for: INTERACTION WITH RBM22.
[9]	"The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A." Yamasaki A., Tani K., Yamamoto A., Kitamura N., Komada M. Mol. Biol. Cell 17:4876-4887(2006) [PubMed: 16957052] [Abstract] Cited for: INTERACTION WITH SEC31A AND PDCD6IP, MUTAGENESIS OF GLU-47 AND GLU-114, SUBCELLULAR LOCATION.
[10]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[11]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-123.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF035606 mRNA. Translation: AAC27697.1.
U58773 mRNA. Translation: AAF14336.1.
AK315370 mRNA. Translation: BAG37763.1.
BT020072 mRNA. Translation: AAV38875.1.
BC012384 mRNA. Translation: AAH12384.1.
BC106706 mRNA. Translation: AAI06707.1.

IPI

IPI00025277.

RefSeq

NP_037364.1.

UniGene

Hs.50823

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ZN8	X-ray	2.70	A	2-191	[»]
2ZN9	X-ray	2.40	A/B	20-191	[»]
2ZND	X-ray	1.70	A	20-191	[»]
2ZNE	X-ray	2.20	A/B	24-191	[»]
2ZRS	X-ray	3.10	A/B/C/D/E/F/G/H	24-191	[»]
2ZRT	X-ray	3.30	A/B/C/D/E/F/G/H	24-191	[»]

SMR

O75340. Positions 20-188.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75340. 13 interactions.

PTM databases

PhosphoSite

O75340.

Proteomic databases

PRIDE

O75340.

Genome annotation databases

Ensembl

ENSG00000063438. Homo sapiens. [Contig view]

GeneID

10016.

KEGG

hsa:10016.

Organism-specific databases

GeneCards

GC05P000324.

HGNC

HGNC:8765. PDCD6.

MIM

601057. gene.

PharmGKB

PA33115.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

O75340.

OMA

O75340. ISDNELQ.

Gene expression databases

ArrayExpress

O75340.

Bgee

O75340.

CleanEx

HS_ALG2.
HS_PDCD6.

GermOnline

ENSG00000063438. Homo sapiens.

Family and domain databases

InterPro

IPR011992. EF-Hand_type.
IPR018248. EF_hand.
IPR018247. EF_HAND_1.
IPR018249. EF_HAND_2.
IPR002048. EF_hand_Ca_bd.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.

Pfam

PF00036. efhand. 2 hits.
[Graphical view]

ProDom

PD000012. EF-hand. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00054. EFh. 5 hits.
[Graphical view]

PROSITE

PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

37841.

SOURCE

Search...

Entry information

Entry name

PDCD6_HUMAN

Accession

Primary (citable) accession number: O75340
Secondary accession number(s): B2RD16, Q5TZS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)