P30519 (HMOX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Heme oxygenase 2
Short name=HO-2
EC=1.14.99.3

Gene names

Name:	HMOX2
Synonyms:	HO2

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	316 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	Heme oxygenase cleaves the heme ring at the alpha methene bridge to form biliverdin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Under physiological conditions, the activity of heme oxygenase is highest in the spleen, where senescent erythrocytes are sequestrated and destroyed. Heme oxygenase 2 could be implicated in the production of carbon monoxide in brain where it could act as a neurotransmitter.
Catalytic activity	Heme + 3 AH2 + 3 O2 = biliverdin + Fe2+ + CO + 3 A + 3 H2O.
Subcellular location	Microsome. Endoplasmic reticulum.
Induction	Heme oxygenase 2 activity is non-inducible.
Sequence similarities	Belongs to the heme oxygenase family. Contains 2 HRM (heme regulatory motif) repeats.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Microsome
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Heme Iron Metal-binding
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular iron ion homeostasis Traceable author statement. Source: Reactome heme catabolic process Traceable author statement. Source: Reactome heme oxidation Inferred from electronic annotation. Source: InterPro response to hypoxia Inferred from direct assay PubMed 15528406. Source: UniProtKB response to oxidative stress Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome plasma membrane Inferred from direct assay PubMed 15528406. Source: UniProtKB
Molecular_function	heme oxygenase (decyclizing) activity Inferred from direct assay Ref.2. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 316

315

Heme oxygenase 2

PRO_0000209691

Regions

Repeat

264 – 269

6

HRM 1

Repeat

281 – 286

6

HRM 2

Sites

Metal binding

45

1

Iron (heme axial ligand)

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.8

Natural variations

Natural variant

137

1

R → Q. Ref.4
Corresponds to variant rs17884623 [ dbSNP | Ensembl ].

VAR_021067

Natural variant

146

1

P → L. Ref.4
Corresponds to variant rs17880805 [ dbSNP | Ensembl ].

VAR_021068

Experimental info

Sequence conflict

165 – 166

2

QV → KC in AAC05297. Ref.9

Sequence conflict

222

1

Missing in AAB22110. Ref.2

Sequence conflict

276

1

Missing in AAB22110. Ref.2

Sequence conflict

281 – 288

8

SCPFRTAM → LSLPTSY in AAB22110. Ref.2

Secondary structure

1

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316

Helix Strand Turn

Details...

Helix

33 – 40

8

Helix

42 – 49

8

Helix

52 – 58

7

Helix

64 – 87

24

Turn

88 – 90

3

Turn

92 – 94

3

Helix

95 – 97

3

Helix

100 – 103

4

Helix

106 – 117

12

Helix

121 – 124

4

Helix

129 – 144

16

Helix

146 – 148

3

Helix

149 – 175

27

Helix

185 – 187

3

Helix

195 – 208

14

Helix

213 – 238

26

Sequences

	Sequence		Length	Mass (Da)
	P30519 [UniParc]. Last modified November 1, 1995. Version 2. Checksum: BF4B6A341F1A81AC	FASTA	316	36,033
	10 20 30 40 50 60 MSAEVETSEG VDESEKKNSG ALEKENQMRM ADLSELLKEG TKEAHDRAEN TQFVKDFLKG 70 80 90 100 110 120 NIKKELFKLA TTALYFTYSA LEEEMERNKD HPAFAPLYFP MELHRKEALT KDMEYFFGEN 130 140 150 160 170 180 WEEQVQCPKA AQKYVERIHY IGQNEPELLV AHAYTRYMGD LSGGQVLKKV AQRALKLPST 190 200 210 220 230 240 GEGTQFYLFE NVDNAQQFKQ LYRARMNALD LNMKTKERIV EEANKAFEYN MQIFNELDQA 250 260 270 280 290 300 GSTLARETLE DGFPVHDGKG DMRKCPFYAA EQDKGALEGS SCPFRTAMAV LRKPSLQFIL 310 AAGVALAAGL LAWYYM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Heme oxygenase-2. Properties of the heme complex of the purified tryptic fragment of recombinant human heme oxygenase-2." Ishikawa K. J. Biol. Chem. 270:6345-6350(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Human heme oxygenase-2: characterization and expression of a full-length cDNA and evidence suggesting that the two HO-2 transcripts may differ by choice of polyadenylation signal." McCoubrey W.K. Jr., Ewing J.F., Maines M.D. Arch. Biochem. Biophys. 295:13-20(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[3]	"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].
[4]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-137 AND LEU-146.
[5]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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]. Tissue: Lung.
[8]	Bienvenut W.V., Bilsland A.E., Keith W.N. Submitted (JAN-2010) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-17; 30-38; 48-59; 138-168; 206-214 AND 219-246, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: Colon carcinoma and Ovarian carcinoma.
[9]	Follett J., Ahn J.-Y. Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-166. Tissue: Intestine.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Comparison of apo- and heme-bound crystal structures of a truncated human heme oxygenase-2." Bianchetti C.M., Yi L., Ragsdale S.W., Phillips G.N. Jr. J. Biol. Chem. 282:37624-37631(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1-264, HEME-BINDING SITE.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D21243 mRNA. Translation: BAA04789.1.
S34389 mRNA. Translation: AAB22110.2.
BT019788 mRNA. Translation: AAV38591.1.
AY771350 Genomic DNA. Translation: AAV28730.1.
AC007606 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85299.1.
CH471112 Genomic DNA. Translation: EAW85300.1.
BC002396 mRNA. Translation: AAH02396.1.
AF051306 mRNA. Translation: AAC05297.1.

IPI

IPI00026824.

PIR

I60119.
S21700.

RefSeq

NP_001120676.1. NM_001127204.1.
NP_001120677.1. NM_001127205.1.
NP_001120678.1. NM_001127206.1.
NP_002125.3. NM_002134.3.

UniGene

Hs.284279.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q32	X-ray	2.40	A/B	1-264	[»]
2QPP	X-ray	2.61	A/B	1-264	[»]
2RGZ	X-ray	2.61	A/B	1-264	[»]

ProteinModelPortal

P30519.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30519. 15 interactions.

MINT

MINT-1384587.

STRING

9606.ENSP00000219700.

PTM databases

PhosphoSite

P30519.

Polymorphism databases

DMDM

1170328.

Proteomic databases

PaxDb

P30519.

PRIDE

P30519.

Protocols and materials databases

DNASU

3163.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000219700; ENSP00000219700; ENSG00000103415.
ENST00000398595; ENSP00000381595; ENSG00000103415.
ENST00000406590; ENSP00000385100; ENSG00000103415.
ENST00000414777; ENSP00000391637; ENSG00000103415.
ENST00000458134; ENSP00000394103; ENSG00000103415.
ENST00000570646; ENSP00000459214; ENSG00000103415.

GeneID

3163.

KEGG

hsa:3163.

UCSC

uc002cwq.4. human.

Organism-specific databases

CTD

3163.

GeneCards

GC16P004524.

HGNC

HGNC:5014. HMOX2.

HPA

CAB025464.
HPA040611.

MIM

141251. gene.

neXtProt

NX_P30519.

PharmGKB

PA29342.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5398.

HOGENOM

HOG000233221.

HOVERGEN

HBG005982.

InParanoid

P30519.

KO

K00510.

OMA

KQFYRAR.

OrthoDB

EOG4RNB8T.

PhylomeDB

P30519.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpress

P30519.

Bgee

P30519.

CleanEx

HS_HMOX2.

Genevestigator

P30519.

GermOnline

ENSG00000103415. Homo sapiens.

Family and domain databases

Gene3D

1.20.910.10. 1 hit.

InterPro

IPR002051. Haem_Oase.
IPR016053. Haem_Oase-like.
IPR016084. Haem_Oase-like_multi-hlx.
IPR018207. Haem_oxygenase_CS.
[Graphical view]

PANTHER

PTHR10720. PTHR10720. 1 hit.

Pfam

PF01126. Heme_oxygenase. 1 hit.
[Graphical view]

PIRSF

PIRSF000343. Haem_Oase. 1 hit.

PRINTS

PR00088. HAEMOXYGNASE.

SUPFAM

SSF48613. Heme_oxygenase. 1 hit.

PROSITE

PS00593. HEME_OXYGENASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL2546.

ChiTaRS

HMOX2. human.

DrugBank

DB00157. NADH.

EvolutionaryTrace

P30519.

GenomeRNAi

3163.

NextBio

12542.

PMAP-CutDB

P30519.

SOURCE

Search...

Entry information

Entry name

HMOX2_HUMAN

Accession

Primary (citable) accession number: P30519
Secondary accession number(s): A8MT35, D3DUD5, O60605

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 134 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.