P02790 (HEMO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hemopexin

Alternative name(s):
Beta-1B-glycoprotein

Gene names

Name:

HPX

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	462 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	Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.
Subunit structure	Interacts with HEV ORF3 protein. Interacts with FLVCR1. Ref.12 Ref.15
Subcellular location	Secreted.
Tissue specificity	Expressed by the liver and secreted in plasma.
Post-translational modification	N- and O-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. O-glycosylation in the 30-40 region is minor compared to glycosylation at Thr-24 and Thr-29. Ref.7 Ref.16
Miscellaneous	The isolated N-terminal domain binds one heme. The full-length protein also binds one heme, but at a different site. The physiological significance of this is not clear By similarity.
Sequence similarities	Belongs to the hemopexin family. Contains 5 hemopexin-like domains.
Sequence caution	The sequence CAA26382.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction Transport
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Heme Iron Metal-binding
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular iron ion homeostasis Traceable author statement Ref.5. Source: ProtInc heme metabolic process Inferred from electronic annotation. Source: Compara hemoglobin metabolic process Inferred from electronic annotation. Source: Compara positive regulation of humoral immune response mediated by circulating immunoglobulin Inferred from electronic annotation. Source: Compara positive regulation of immunoglobulin production Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma-mediated signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of tyrosine phosphorylation of Stat1 protein Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular space Inferred from direct assay PubMed 19433579. Source: MGI
Molecular_function	heme transporter activity Traceable author statement Ref.5. Source: ProtInc 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
	Signal peptide	1 – 23	23	Ref.6
	Chain	24 – 462	439	Hemopexin Ref.5		PRO_0000021406
Regions
	Domain	56 – 95	40	Hemopexin-like 1
	Domain	97 – 141	45	Hemopexin-like 2
	Domain	188 – 231	44	Hemopexin-like 3
	Domain	263 – 306	44	Hemopexin-like 4
	Domain	308 – 353	46	Hemopexin-like 5
	Region	30 – 40	11	O-glycosylated at one site
Sites
	Metal binding	79	1	Iron (heme 1 axial ligand) By similarity
	Metal binding	150	1	Iron (heme 1 axial ligand) By similarity
	Metal binding	236	1	Iron (heme 2 axial ligand) By similarity
	Metal binding	293	1	Iron (heme 2 axial ligand) By similarity
Amino acid modifications
	Glycosylation	24	1	O-linked (GalNAc...) Ref.6 Ref.7 Ref.14
	Glycosylation	29	1	O-linked (GalNAc...) Ref.16
	Glycosylation	64	1	N-linked (GlcNAc...) (complex) Ref.7 Ref.10 Ref.14
	Glycosylation	187	1	N-linked (GlcNAc...) (complex) Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14
	Glycosylation	240	1	N-linked (GlcNAc...) Ref.6 Ref.7 Ref.9
	Glycosylation	246	1	N-linked (GlcNAc...) Ref.6 Ref.7 Ref.9
	Glycosylation	453	1	N-linked (GlcNAc...) (complex) Ref.7 Ref.8 Ref.11 Ref.13 Ref.14
	Disulfide bond	50 ↔ 231		Ref.5
	Disulfide bond	149 ↔ 154		Ref.5
	Disulfide bond	188 ↔ 200		Ref.5
	Disulfide bond	257 ↔ 460		Ref.5
	Disulfide bond	366 ↔ 408		Ref.5
	Disulfide bond	418 ↔ 435		Ref.5
Natural variations
	Natural variant	52	1	D → N. Corresponds to variant rs10839564 [ dbSNP | Ensembl ].		VAR_047137
	Natural variant	83	1	R → W. Corresponds to variant rs12117 [ dbSNP | Ensembl ].		VAR_033990
Experimental info
	Sequence conflict	411	1	K → R in BAG36404. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P02790 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: 054B44D0603763B8	FASTA	462	51,676
	10 20 30 40 50 60 MARVLGAPVA LGLWSLCWSL AIATPLPPTS AHGNVAEGET KPDPDVTERC SDGWSFDATT 70 80 90 100 110 120 LDDNGTMLFF KGEFVWKSHK WDRELISERW KNFPSPVDAA FRQGHNSVFL IKGDKVWVYP 130 140 150 160 170 180 PEKKEKGYPK LLQDEFPGIP SPLDAAVECH RGECQAEGVL FFQGDREWFW DLATGTMKER 190 200 210 220 230 240 SWPAVGNCSS ALRWLGRYYC FQGNQFLRFD PVRGEVPPRY PRDVRDYFMP CPGRGHGHRN 250 260 270 280 290 300 GTGHGNSTHH GPEYMRCSPH LVLSALTSDN HGATYAFSGT HYWRLDTSRD GWHSWPIAHQ 310 320 330 340 350 360 WPQGPSAVDA AFSWEEKLYL VQGTQVYVFL TKGGYTLVSG YPKRLEKEVG TPHGIILDSV 370 380 390 400 410 420 DAAFICPGSS RLHIMAGRRL WWLDLKSGAQ ATWTELPWPH EKVDGALCME KSLGPNSCSA 430 440 450 460 NGPGLYLIHG PNLYCYSDVE KLNAAKALPQ PQNVTSLLGC TH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of the human hemopexin gene and evidence for intron-mediated evolution." Altruda F., Poli V., Restagno G., Silengo L. J. Mol. Evol. 27:102-108(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[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: Mammary gland.
[3]	"The hemopexin gene maps to the same location as the beta-globin gene cluster on human chromosome 11." Law M.L., Cai G.Y., Hartz J.A., Jones C., Kao F.T. Genomics 3:48-52(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-462.
[4]	"The primary structure of human hemopexin deduced from cDNA sequence: evidence for internal, repeating homology." Altruda F., Poli V., Restagno G., Argos P., Cortese R., Silengo L. Nucleic Acids Res. 13:3841-3859(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-462.
[5]	"Complete amino acid sequence of human hemopexin, the heme-binding protein of serum." Takahashi N., Takahashi Y., Putnam F.W. Proc. Natl. Acad. Sci. U.S.A. 82:73-77(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF ACTIVE PROTEIN.
[6]	"Amino acid sequence of the N-terminal region of human hemopexin." Frantikova V., Borvak J., Kluh I., Moravek L. FEBS Lett. 178:213-216(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-255.
[7]	"Structure of human hemopexin: O-glycosyl and N-glycosyl sites and unusual clustering of tryptophan residues." Takahashi N., Takahashi Y., Putnam F.W. Proc. Natl. Acad. Sci. U.S.A. 81:2021-2025(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT THR-24; ASN-64; ASN-64; ASN-187; ASN-240; ASN-246 AND ASN-453.
[8]	"A proteomic analysis of human bile." Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A. Mol. Cell. Proteomics 3:715-728(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-187 AND ASN-453, MASS SPECTROMETRY. Tissue: Bile.
[9]	"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry." Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R. Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-187; ASN-240 AND ASN-246, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-64 AND ASN-187, MASS SPECTROMETRY. Tissue: Plasma.
[11]	"Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry." Ramachandran P., Boontheung P., Xie Y., Sondej M., Wong D.T., Loo J.A. J. Proteome Res. 5:1493-1503(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-187 AND ASN-453, MASS SPECTROMETRY. Tissue: Saliva.
[12]	"The ORF3 protein of hepatitis E virus interacts with hemopexin by means of its 26 amino acid N-terminal hydrophobic domain II." Ratra R., Kar-Roy A., Lal S.K. Biochemistry 47:1957-1969(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
[13]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-187 AND ASN-453, MASS SPECTROMETRY. Tissue: Liver.
[14]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-24; ASN-64; ASN-187 AND ASN-453, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[15]	"Kinetics and specificity of feline leukemia virus subgroup C receptor (FLVCR) export function and its dependence on hemopexin." Yang Z., Philips J.D., Doty R.T., Giraudi P., Ostrow J.D., Tiribelli C., Smith A., Abkowitz J.L. J. Biol. Chem. 285:28874-28882(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FLVCR1.
[16]	"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins." Halim A., Ruetschi U., Larson G., Nilsson J. J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-29, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M36803 , M36796, M36799, M36800, M36801, M36802 Genomic DNA. Translation: AAA58678.1. AK313648 mRNA. Translation: BAG36404.1. J03048 mRNA. Translation: AAA52704.1. X02537 mRNA. Translation: CAA26382.1. Different initiation.
IPI	IPI00022488.
PIR	OQHU. I56456.
RefSeq	NP_000604.1. NM_000613.2.
UniGene	Hs.426485.
3D structure databases
ProteinModelPortal	P02790.
ModBase	Search...
Protein-protein interaction databases
IntAct	P02790. 3 interactions.
STRING	9606.ENSP00000265983.
PTM databases
PhosphoSite	P02790.
Polymorphism databases
DMDM	1708182.
2D gel databases
DOSAC-COBS-2DPAGE	P02790.
REPRODUCTION-2DPAGE	IPI00022488.
SWISS-2DPAGE	P02790.
Proteomic databases
PaxDb	P02790.
PeptideAtlas	P02790.
PRIDE	P02790.
Protocols and materials databases
DNASU	3263.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000265983; ENSP00000265983; ENSG00000110169.
GeneID	3263.
KEGG	hsa:3263.
UCSC	uc001mdg.2. human.
Organism-specific databases
CTD	3263.
GeneCards	GC11M006452.
HGNC	HGNC:5171. HPX.
HPA	CAB016725.
MIM	142290. gene.
neXtProt	NX_P02790.
PharmGKB	PA29441.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG251805.
HOGENOM	HOG000112887.
HOVERGEN	HBG005956.
InParanoid	P02790.
OMA	AAVECHR.
OrthoDB	EOG4R502N.
PhylomeDB	P02790.
Gene expression databases
Bgee	P02790.
CleanEx	HS_HPX.
Genevestigator	P02790.
GermOnline	ENSG00000110169. Homo sapiens.
Family and domain databases
Gene3D	2.110.10.10. 2 hits.
InterPro	IPR000585. Hemopexin-like_dom. IPR018487. Hemopexin-like_repeat. IPR016358. Hemopexin_chordata. IPR018486. Hemopexin_CS. [Graphical view]
Pfam	PF00045. Hemopexin. 5 hits. [Graphical view]
PIRSF	PIRSF002551. Hemopexin_chordata. 1 hit.
SMART	SM00120. HX. 5 hits. [Graphical view]
SUPFAM	SSF50923. Hemopexin. 2 hits.
PROSITE	PS00024. HEMOPEXIN. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	HPX. human.
GenomeRNAi	3263.
NextBio	12957.
SOURCE	Search...

Entry information

Entry name

HEMO_HUMAN

Accession

Primary (citable) accession number: P02790
Secondary accession number(s): B2R957

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 136 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.