Reviewed, UniProtKB/Swiss-Prot Q9NR28 (DBLOH_HUMAN)

Names and origin

Protein names

Recommended name:
    Diablo homolog, mitochondrial
Alternative name(s):
    Second mitochondria-derived activator of caspase
      Short name=Smac protein
    Direct IAP-binding protein with low pI

Gene names

Name:	DIABLO
Synonyms:	SMAC

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	239 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Promotes apoptosis by activating caspases in the cytochrome c/Apaf-1/caspase-9 pathway. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP). Ref.1
Subunit structure	Interacts with NGFRAP1/BEX3 By similarity. Homodimer. Interacts with BIRC2, BIRC3, XIAP and BIRC7.
Subcellular location	Mitochondrion. Note: But released into the cytosol when cells undergo apoptosis.
Tissue specificity	Ubiquitously expressed with highest expression in testis. Expression is also high in heart, liver, kidney, spleen, prostate and ovary. Low in brain, lung, thymus and peripheral blood leukocytes. Ref.1
Domain	The mature N-terminus mediates interaction with XIAP.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	activation of caspase activity by cytochrome c Ref.1 Traceable author statement. Source: ProtInc induction of apoptosis via death domain receptors Ref.3 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome mitochondrion Ref.1 Inferred from direct assay. Source: HPA
Molecular function	protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BIRC2	Q13490	2	EBI-517508,EBI-514538
BIRC3	Q13489	1	EBI-517508,EBI-517709
BIRC7	Q96CA5	5	EBI-517508,EBI-517623
XIAP	P98170	5	EBI-517508,EBI-517127
Xiap	Q60989	2	EBI-517508,EBI-517478	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9NR28-1)

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.

Isoform 2 (identifier: Q9NR28-2)

Also known as: Diablo-S;

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: MAALKSWLSRSVTSFFRYRQCLCVPVVANFKKRCFSELIRPWHKTVTIGFGVTLCAVPIA → MKSDFYF

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 55

55

Mitochondrion

Chain

56 – 239

184

Diablo homolog, mitochondrial

PRO_0000021072

Regions

Motif

56 – 60

5

IAP-binding motif By similarity

Natural variations

Alternative sequence

1 – 60

60

MAALK…AVPIA → MKSDFYF in isoform 2.

VSP_004397

Experimental info

Sequence conflict

32

1

K → E in BAB71568. Ref.2

Sequence conflict

44

1

K → R in BAB14994. Ref.2

Sequence conflict

62 – 105

44

Missing in BAB71568. Ref.2

Sequence conflict

165

1

E → K in BAB71568. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

239

Helix Strand Turn

Details...

Helix

68 – 120

53

Beta strand

123 – 125

3

Helix

126 – 173

48

Helix

177 – 236

60

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 70C2AE0DC654D031	FASTA	239	27,131
	10 20 30 40 50 60 MAALKSWLSR SVTSFFRYRQ CLCVPVVANF KKRCFSELIR PWHKTVTIGF GVTLCAVPIA 70 80 90 100 110 120 QKSEPHSLSS EALMRRAVSL VTDSTSTFLS QTTYALIEAI TEYTKAVYTL TSLYRQYTSL 130 140 150 160 170 180 LGKMNSEEED EVWQVIIGAR AEMTSKHQEY LKLETTWMTA VGLSEMAAEA AYQTGADQAS 190 200 210 220 230 ITARNHIQLV KLQVEEVHQL SRKAETKLAE AQIEELRQKT QEEGEERAES EQEAYLRED
	Isoform 2 (Diablo-S). Checksum: FF567F7827AB6108	FASTA	186	21,233
	10 20 30 40 50 60 MKSDFYFQKS EPHSLSSEAL MRRAVSLVTD STSTFLSQTT YALIEAITEY TKAVYTLTSL 70 80 90 100 110 120 YRQYTSLLGK MNSEEEDEVW QVIIGARAEM TSKHQEYLKL ETTWMTAVGL SEMAAEAAYQ 130 140 150 160 170 180 TGADQASITA RNHIQLVKLQ VEEVHQLSRK AETKLAEAQI EELRQKTQEE GEERAESEQE AYLRED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition." Du C., Fang M., Li Y., Li L., Wang X. Cell 102:33-42(2000) [PubMed: 10929711] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, FUNCTION, TISSUE SPECIFICITY.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Stomach.
[3]	"Molecular determinants of the caspase-promoting activity of Smac/DIABLO and its role in the death receptor pathway." Srinivasula S.M., Datta P., Fan X.J., Fernandes-Alnemri T., Huang Z., Alnemri E.S. J. Biol. Chem. 275:36152-36157(2000) [PubMed: 10950947] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), CHARACTERIZATION.
[4]	"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] (ISOFORM 1). Tissue: Muscle and Uterus.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"Structural and biochemical basis of apoptotic activation by Smac/DIABLO." Chai J., Du C., Wu J.W., Kyin S., Wang X., Shi Y. Nature 406:855-862(2000) [PubMed: 10972280] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 56-239.
[7]	"Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain." Liu Z., Sun C., Olejniczak E.T., Meadows R.P., Betz S.F., Oost T., Herrmann J., Wu J.C., Fesik S.W. Nature 408:1004-1008(2000) [PubMed: 11140637] [Abstract] Cited for: STRUCTURE BY NMR OF 56-64 IN COMPLEX WITH XIAP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF262240 mRNA. Translation: AAF87716.1.
AK024768 mRNA. Translation: BAB14994.1.
AK057778 mRNA. Translation: BAB71568.1.
AK315629 mRNA. Translation: BAG37997.1.
AF298770 mRNA. Translation: AAG22077.1.
BC004417 mRNA. Translation: AAH04417.1.
BC011909 mRNA. Translation: AAH11909.1.

IPI

IPI00008418.
IPI00219865.

RefSeq

NP_063940.1.
NP_620307.1.

UniGene

Hs.169611

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FEW	X-ray	2.20	A	56-239	[»]
1G3F	NMR	-	B	56-64	[»]
1G73	X-ray	2.00	A/B	56-217	[»]
1TW6	X-ray	1.71	C/D	56-64	[»]
1XB0	X-ray	2.20	G/H/I/J/K/L	56-62	[»]
1XB1	X-ray	2.70	G/H/I/J/K/L	56-62	[»]
3D9U	X-ray	2.30	B	56-61	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:27627N.

IntAct

Q9NR28. 7 interactions.

Proteomic databases

PRIDE

Q9NR28.

Genome annotation databases

Ensembl

ENSG00000184047. Homo sapiens. [Contig view]

GeneID

56616.

KEGG

hsa:56616.

Organism-specific databases

GeneCards

GC12M121258.

H-InvDB

HIX0018494.

HGNC

HGNC:21528. DIABLO.

HPA

CAB003857.
CAB016688.
HPA001825.

MIM

605219. gene.

PharmGKB

PA134945044.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9NR28.

HOVERGEN

Q9NR28.

OMA

Q9NR28. HIQLVKL.

Enzyme and pathway databases

Pathway_Interaction_DB

caspase_pathway. Caspase cascade in apoptosis.
p75ntrpathway. p75(NTR)-mediated signaling.

Reactome

REACT_578. Apoptosis.

Gene expression databases

Bgee

Q9NR28.

CleanEx

HS_DIABLO.

GermOnline

ENSG00000184047. Homo sapiens.

Family and domain databases

InterPro

IPR015142. Smac_DIABLO.
[Graphical view]

Pfam

PF09057. Smac_DIABLO. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

62059.

PMAP-CutDB

Q9NR28.

SOURCE

Search...

Entry information

Entry name

DBLOH_HUMAN

Accession

Primary (citable) accession number: Q9NR28
Secondary accession number(s): B2RDQ0 , Q96LV0, Q9BT11, Q9HAV6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	October 1, 2000
Last modified:	June 16, 2009
This is version 88 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)