Full text data of HPR
HPR
[Confidence: low (only semi-automatic identification from reviews)]
Haptoglobin-related protein; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Haptoglobin-related protein; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P00739
ID HPTR_HUMAN Reviewed; 348 AA.
AC P00739; Q7LE20; Q92658; Q92659; Q9ULB0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-NOV-2009, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Haptoglobin-related protein;
DE Flags: Precursor;
GN Name=HPR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=4018023;
RA Bensi G., Raugei G., Klefenz H., Cortese R.;
RT "Structure and expression of the human haptoglobin locus.";
RL EMBO J. 4:119-126(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=2987228;
RA Maeda N.;
RT "Nucleotide sequence of the haptoglobin and haptoglobin-related gene
RT pair. The haptoglobin-related gene contains a retrovirus-like
RT element.";
RL J. Biol. Chem. 260:6698-6709(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=1478675; DOI=10.1016/S0888-7543(05)80116-8;
RA Erickson L.M., Kim H.S., Maeda N.;
RT "Junctions between genes in the haptoglobin gene cluster of
RT primates.";
RL Genomics 14:948-958(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RX PubMed=8945641; DOI=10.1089/dna.1996.15.1001;
RA Tabak S., Lev A., Valansi C., Shalitin C.;
RT "Transcriptionally active haptoglobin-related (Hpr) gene in Hepatoma
RT G2 and leukamia molt-4 cells.";
RL DNA Cell Biol. 15:1001-1007(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 3-348.
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
CC -!- SUBCELLULAR LOCATION: Secreted (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P00739-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00739-2; Sequence=VSP_014529;
CC -!- TISSUE SPECIFICITY: In adult liver the amount of HPR mRNA is at
CC the lower limit of detection, therefore the extent of its
CC expression is at most less than 1000-fold that of the HP1F gene.
CC No HPR mRNA can be detected in fetal liver. Expressed in Hep-G2
CC and leukemia MOLT-4 cell lines.
CC -!- SIMILARITY: Belongs to the peptidase S1 family.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- SIMILARITY: Contains 1 Sushi (CCP/SCR) domain.
CC -!- CAUTION: Although homologous to serine proteases, it has lost all
CC essential catalytic residues and has no enzymatic activity.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X01794; CAA25927.1; -; Genomic_DNA.
DR EMBL; X01787; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; X01788; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; X01790; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; X01792; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; K03431; AAA88081.1; -; Genomic_DNA.
DR EMBL; M10935; AAA88081.1; JOINED; Genomic_DNA.
DR EMBL; M69197; AAA88079.1; -; Genomic_DNA.
DR EMBL; X89214; CAA61501.1; -; mRNA.
DR EMBL; AC009087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004682; AAC27433.1; -; Genomic_DNA.
DR PIR; A00919; HPHUR.
DR RefSeq; NP_066275.3; NM_020995.3.
DR RefSeq; XP_005255981.1; XM_005255924.1.
DR UniGene; Hs.655361; -.
DR ProteinModelPortal; P00739; -.
DR SMR; P00739; 35-347.
DR STRING; 9606.ENSP00000386047; -.
DR MEROPS; S01.974; -.
DR PhosphoSite; P00739; -.
DR DMDM; 262527547; -.
DR DOSAC-COBS-2DPAGE; P00739; -.
DR PaxDb; P00739; -.
DR PRIDE; P00739; -.
DR DNASU; 3250; -.
DR Ensembl; ENST00000228226; ENSP00000228226; ENSG00000261701.
DR Ensembl; ENST00000356967; ENSP00000349451; ENSG00000261701.
DR Ensembl; ENST00000540303; ENSP00000441828; ENSG00000261701.
DR GeneID; 3250; -.
DR KEGG; hsa:3250; -.
DR UCSC; uc002fby.3; human.
DR CTD; 3250; -.
DR GeneCards; GC16P072097; -.
DR HGNC; HGNC:5156; HPR.
DR HPA; CAB003787; -.
DR HPA; HPA047750; -.
DR MIM; 140210; gene.
DR neXtProt; NX_P00739; -.
DR PharmGKB; PA29426; -.
DR eggNOG; NOG246387; -.
DR HOGENOM; HOG000112945; -.
DR HOVERGEN; HBG005989; -.
DR KO; K14477; -.
DR OMA; SYLPWIH; -.
DR OrthoDB; EOG7DNNV9; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR GeneWiki; HPR_(gene); -.
DR GenomeRNAi; 3250; -.
DR NextBio; 12923; -.
DR PRO; PR:P00739; -.
DR ArrayExpress; P00739; -.
DR Bgee; P00739; -.
DR CleanEx; HS_HPR; -.
DR Genevestigator; P00739; -.
DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0003824; F:catalytic activity; IEA:InterPro.
DR GO; GO:0030492; F:hemoglobin binding; NAS:UniProtKB.
DR GO; GO:0008152; P:metabolic process; IEA:GOC.
DR InterPro; IPR008292; Haptoglobin.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR000436; Sushi_SCR_CCP.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001137; Haptoglobin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS50923; SUSHI; FALSE_NEG.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disulfide bond;
KW Hemoglobin-binding; Polymorphism; Reference proteome; Secreted;
KW Serine protease homolog; Signal; Sushi.
FT SIGNAL 1 19 Potential.
FT CHAIN 20 348 Haptoglobin-related protein.
FT /FTId=PRO_0000028486.
FT DOMAIN 34 87 Sushi.
FT DOMAIN 104 346 Peptidase S1.
FT DISULFID 251 282 By similarity.
FT DISULFID 293 323 By similarity.
FT VAR_SEQ 1 1 M -> MHVCVCVCVCVYMPVCVDACMCCEAGRPAFRSFLFS
FT LC (in isoform 2).
FT /FTId=VSP_014529.
FT VARIANT 27 27 T -> M (in dbSNP:rs11642506).
FT /FTId=VAR_057161.
FT VARIANT 42 42 N -> H (in dbSNP:rs152832).
FT /FTId=VAR_057162.
FT VARIANT 58 58 R -> K (in dbSNP:rs152833).
FT /FTId=VAR_057163.
FT VARIANT 156 156 A -> V (in dbSNP:rs1049933).
FT /FTId=VAR_059789.
FT VARIANT 203 203 R -> K (in dbSNP:rs2021171).
FT /FTId=VAR_057164.
FT VARIANT 283 283 V -> A (in dbSNP:rs1065360).
FT /FTId=VAR_057165.
FT VARIANT 339 339 H -> D (in dbSNP:rs12646).
FT /FTId=VAR_014571.
FT CONFLICT 191 191 L -> I (in Ref. 1; CAA25927).
SQ SEQUENCE 348 AA; 39030 MW; CF9EC3352B8182FA CRC64;
MSDLGAVISL LLWGRQLFAL YSGNDVTDIS DDRFPKPPEI ANGYVEHLFR YQCKNYYRLR
TEGDGVYTLN DKKQWINKAV GDKLPECEAV CGKPKNPANP VQRILGGHLD AKGSFPWQAK
MVSHHNLTTG ATLINEQWLL TTAKNLFLNH SENATAKDIA PTLTLYVGKK QLVEIEKVVL
HPNYHQVDIG LIKLKQKVLV NERVMPICLP SKNYAEVGRV GYVSGWGQSD NFKLTDHLKY
VMLPVADQYD CITHYEGSTC PKWKAPKSPV GVQPILNEHT FCVGMSKYQE DTCYGDAGSA
FAVHDLEEDT WYAAGILSFD KSCAVAEYGV YVKVTSIQHW VQKTIAEN
//
ID HPTR_HUMAN Reviewed; 348 AA.
AC P00739; Q7LE20; Q92658; Q92659; Q9ULB0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 03-NOV-2009, sequence version 2.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Haptoglobin-related protein;
DE Flags: Precursor;
GN Name=HPR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=4018023;
RA Bensi G., Raugei G., Klefenz H., Cortese R.;
RT "Structure and expression of the human haptoglobin locus.";
RL EMBO J. 4:119-126(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=2987228;
RA Maeda N.;
RT "Nucleotide sequence of the haptoglobin and haptoglobin-related gene
RT pair. The haptoglobin-related gene contains a retrovirus-like
RT element.";
RL J. Biol. Chem. 260:6698-6709(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=1478675; DOI=10.1016/S0888-7543(05)80116-8;
RA Erickson L.M., Kim H.S., Maeda N.;
RT "Junctions between genes in the haptoglobin gene cluster of
RT primates.";
RL Genomics 14:948-958(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RX PubMed=8945641; DOI=10.1089/dna.1996.15.1001;
RA Tabak S., Lev A., Valansi C., Shalitin C.;
RT "Transcriptionally active haptoglobin-related (Hpr) gene in Hepatoma
RT G2 and leukamia molt-4 cells.";
RL DNA Cell Biol. 15:1001-1007(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 3-348.
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R.,
RA Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L.,
RA Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E.,
RA Harris P.C., Venter J.C., Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from
RT human chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
CC -!- SUBCELLULAR LOCATION: Secreted (Potential).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P00739-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00739-2; Sequence=VSP_014529;
CC -!- TISSUE SPECIFICITY: In adult liver the amount of HPR mRNA is at
CC the lower limit of detection, therefore the extent of its
CC expression is at most less than 1000-fold that of the HP1F gene.
CC No HPR mRNA can be detected in fetal liver. Expressed in Hep-G2
CC and leukemia MOLT-4 cell lines.
CC -!- SIMILARITY: Belongs to the peptidase S1 family.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- SIMILARITY: Contains 1 Sushi (CCP/SCR) domain.
CC -!- CAUTION: Although homologous to serine proteases, it has lost all
CC essential catalytic residues and has no enzymatic activity.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; X01794; CAA25927.1; -; Genomic_DNA.
DR EMBL; X01787; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; X01788; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; X01790; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; X01792; CAA25927.1; JOINED; Genomic_DNA.
DR EMBL; K03431; AAA88081.1; -; Genomic_DNA.
DR EMBL; M10935; AAA88081.1; JOINED; Genomic_DNA.
DR EMBL; M69197; AAA88079.1; -; Genomic_DNA.
DR EMBL; X89214; CAA61501.1; -; mRNA.
DR EMBL; AC009087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC004682; AAC27433.1; -; Genomic_DNA.
DR PIR; A00919; HPHUR.
DR RefSeq; NP_066275.3; NM_020995.3.
DR RefSeq; XP_005255981.1; XM_005255924.1.
DR UniGene; Hs.655361; -.
DR ProteinModelPortal; P00739; -.
DR SMR; P00739; 35-347.
DR STRING; 9606.ENSP00000386047; -.
DR MEROPS; S01.974; -.
DR PhosphoSite; P00739; -.
DR DMDM; 262527547; -.
DR DOSAC-COBS-2DPAGE; P00739; -.
DR PaxDb; P00739; -.
DR PRIDE; P00739; -.
DR DNASU; 3250; -.
DR Ensembl; ENST00000228226; ENSP00000228226; ENSG00000261701.
DR Ensembl; ENST00000356967; ENSP00000349451; ENSG00000261701.
DR Ensembl; ENST00000540303; ENSP00000441828; ENSG00000261701.
DR GeneID; 3250; -.
DR KEGG; hsa:3250; -.
DR UCSC; uc002fby.3; human.
DR CTD; 3250; -.
DR GeneCards; GC16P072097; -.
DR HGNC; HGNC:5156; HPR.
DR HPA; CAB003787; -.
DR HPA; HPA047750; -.
DR MIM; 140210; gene.
DR neXtProt; NX_P00739; -.
DR PharmGKB; PA29426; -.
DR eggNOG; NOG246387; -.
DR HOGENOM; HOG000112945; -.
DR HOVERGEN; HBG005989; -.
DR KO; K14477; -.
DR OMA; SYLPWIH; -.
DR OrthoDB; EOG7DNNV9; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR GeneWiki; HPR_(gene); -.
DR GenomeRNAi; 3250; -.
DR NextBio; 12923; -.
DR PRO; PR:P00739; -.
DR ArrayExpress; P00739; -.
DR Bgee; P00739; -.
DR CleanEx; HS_HPR; -.
DR Genevestigator; P00739; -.
DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0003824; F:catalytic activity; IEA:InterPro.
DR GO; GO:0030492; F:hemoglobin binding; NAS:UniProtKB.
DR GO; GO:0008152; P:metabolic process; IEA:GOC.
DR InterPro; IPR008292; Haptoglobin.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR000436; Sushi_SCR_CCP.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001137; Haptoglobin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS50923; SUSHI; FALSE_NEG.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Disulfide bond;
KW Hemoglobin-binding; Polymorphism; Reference proteome; Secreted;
KW Serine protease homolog; Signal; Sushi.
FT SIGNAL 1 19 Potential.
FT CHAIN 20 348 Haptoglobin-related protein.
FT /FTId=PRO_0000028486.
FT DOMAIN 34 87 Sushi.
FT DOMAIN 104 346 Peptidase S1.
FT DISULFID 251 282 By similarity.
FT DISULFID 293 323 By similarity.
FT VAR_SEQ 1 1 M -> MHVCVCVCVCVYMPVCVDACMCCEAGRPAFRSFLFS
FT LC (in isoform 2).
FT /FTId=VSP_014529.
FT VARIANT 27 27 T -> M (in dbSNP:rs11642506).
FT /FTId=VAR_057161.
FT VARIANT 42 42 N -> H (in dbSNP:rs152832).
FT /FTId=VAR_057162.
FT VARIANT 58 58 R -> K (in dbSNP:rs152833).
FT /FTId=VAR_057163.
FT VARIANT 156 156 A -> V (in dbSNP:rs1049933).
FT /FTId=VAR_059789.
FT VARIANT 203 203 R -> K (in dbSNP:rs2021171).
FT /FTId=VAR_057164.
FT VARIANT 283 283 V -> A (in dbSNP:rs1065360).
FT /FTId=VAR_057165.
FT VARIANT 339 339 H -> D (in dbSNP:rs12646).
FT /FTId=VAR_014571.
FT CONFLICT 191 191 L -> I (in Ref. 1; CAA25927).
SQ SEQUENCE 348 AA; 39030 MW; CF9EC3352B8182FA CRC64;
MSDLGAVISL LLWGRQLFAL YSGNDVTDIS DDRFPKPPEI ANGYVEHLFR YQCKNYYRLR
TEGDGVYTLN DKKQWINKAV GDKLPECEAV CGKPKNPANP VQRILGGHLD AKGSFPWQAK
MVSHHNLTTG ATLINEQWLL TTAKNLFLNH SENATAKDIA PTLTLYVGKK QLVEIEKVVL
HPNYHQVDIG LIKLKQKVLV NERVMPICLP SKNYAEVGRV GYVSGWGQSD NFKLTDHLKY
VMLPVADQYD CITHYEGSTC PKWKAPKSPV GVQPILNEHT FCVGMSKYQE DTCYGDAGSA
FAVHDLEEDT WYAAGILSFD KSCAVAEYGV YVKVTSIQHW VQKTIAEN
//
MIM
140210
*RECORD*
*FIELD* NO
140210
*FIELD* TI
*140210 HAPTOGLOBIN-RELATED PROTEIN GENE; HPR
*FIELD* TX
CLONING
Bensi et al. (1985) and Maeda (1985) isolated the human HPR gene. Its
read morepredicted amino acid sequence differs by about 8% from that of the
electrophoretically fast-migrating HP variant (HP1F; 140100.0001). The
differences appeared to be located on the surface of the protein
molecule, and the regions and specific residues considered to be
important for binding hemoglobin are identical in the HP and HPR
proteins.
Smithies and Powers (1986) found evidence of gene conversion (see
142200) between the closely linked HP and HPR loci.
GENE FUNCTION
Using immobilized hemoglobin for affinity chromatography, Nielsen et al.
(2006) showed that HPR could bind hemoglobin as efficiently as HP, and
SDS-PAGE showed that HPR migrated as a 45-kD monomer and a 90-kD dimer.
In contrast to HP, HPR did not promote high-affinity binding to CD163
(605545). Western blot analysis of 18 persons with normal HP levels and
13 patients with low HP levels resulting from sickle cell anemia and
extensive intravascular hemolysis indicated that the plasma
concentration of HPR was unaffected by hemolysis, suggesting that
depletion of HP but not HPR in these patients may be a consequence of
the difference in CD163 binding between HP-hemoglobin and HPR-hemoglobin
complexes. Binding of hemoglobin to circulating native HPR incorporated
in the high density lipoprotein (HDL) fraction was indicated by
hemoglobin-affinity precipitation of plasma HPR together with
apolipoprotein-L1 (APOL1; 603743). Nielsen et al. (2006) suggested that
hemoglobin reported to be present in TLF represents HPR-bound
hemoglobin, which may contribute to the biologic activity of circulating
TLF.
The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein
L-I, a component of HDL particles that are also characterized by the
presence of HPR. Vanhollebeke et al. (2008) reported that this process
is mediated by a parasite glycoprotein receptor, which binds the
haptoglobin-hemoglobin complex with high affinity for the uptake and
incorporation of heme into intracellular hemoproteins. In mice, this
receptor was required for optimal parasite growth and the resistance of
parasites to the oxidative burst by host macrophages. In humans, the
trypanosome receptor also recognized the complex between hemoglobin and
HPR, which explains its ability to capture trypanolytic HDLs.
Vanhollebeke et al. (2008) concluded that, in humans, the presence of
HPR has diverted the function of the trypanosome haptoglobin-hemoglobin
receptor to elicit innate host immunity against the parasite.
GENE STRUCTURE
Maeda and Kim (1990) demonstrated that the 2 genes in the human
haptoglobin cluster, HP and HPR, contain 2 retrovirus-like elements. One
(RTVL-Ia) is in the first intron of the HPR gene, and the second
(RTVL-Ic) is at the 3-prime-end of the gene cluster. In the chimpanzee
3-gene cluster (HP-HPR-HPP), there is an additional retrovirus-like
element (RTVL-Ib) in the intergenic region between the chimpanzee HPR
and HPP loci. RTVL-Ia and RTVL-Ib are essentially full size and have the
general structure 5-prime-LTR--gag--pol-env--3-prime-LTR, while RTVL-Ic
lacks about one-third of its 5-prime portion. Although none of the
elements had retained long open reading frames, Maeda and Kim (1990)
detected stretches with amino acids identical to various parts of
proteins of the Moloney murine leukemia virus (Mo-MuLV). They concluded
that the RTVL-I elements were derived from a virus similar in structure
to Mo-MuLV. The DNA sequences surrounding the insertion points of the 3
RTVL-I elements were dissimilar, implying that they integrated into the
haptoglobin gene cluster independently at some time after the initial
formation of the triplicated gene cluster in primates. Comparison of the
nucleotide sequences of the 3 elements suggested that foreign DNA
introduced into the genome can accumulate mutations more rapidly than
the genomic sequences surrounding them. At least 5 other families of
retrovirus-like sequences have been found in the human genome; for a
review, see Cohen and Larsson (1988). In RTVL-I, the tRNA used for the
primer binding site is ile-tRNA. (RTVL-I = retrovirus-like
sequence--isoleucine.)
BIOCHEMICAL FEATURES
During pregnancy, HPR circulates in plasma; furthermore, Kuhajda et al.
(1989) demonstrated that HPR or HPR-like epitopes are expressed in human
breast carcinoma. This led Kuhajda et al. (1989) to examine the
possibility that anti-HPR immunoreactivity of biopsy specimens from
women with primary breast carcinoma might be related to the clinical
behavior of the tumor. They examined the association between the
expression of HPR and the recurrence of cancer in a retrospective study
of 70 patients with early breast cancer treated by mastectomy from
1977-1985 at the Johns Hopkins Hospital. Expression of HPR epitopes was
associated with earlier recurrence, and multivariate analysis showed
that HPR-epitope expression was an independent prognostic factor. The
authors concluded that it is a clinically important predictor of
recurrence, especially in combination with progesterone-receptor status.
MAPPING
The HPR gene maps to chromosome 16q22.1 (Bensi et al., 1985; Maeda,
1985).
Maeda et al. (1986) found that the HPR gene(s) lie on the downstream
side of the HP gene (140100).
EVOLUTION
McEvoy and Maeda (1988) analyzed the evolutionary history of the
haptoglobin gene family by characterizing the haptoglobin genes in
primates. Whereas the HPR gene in the human is 2.2 kb downstream of the
HP gene, chimpanzees, gorillas, orangutans, and Old World monkeys have a
third gene, which McEvoy and Maeda (1988) named HPP for haptoglobin
primate, located 16 kb downstream of HPR. New World monkeys have only 1
haptoglobin gene. McEvoy and Maeda (1988) interpreted these observations
as suggesting triplication of the haptoglobin locus after divergence of
the New World monkeys, followed by deletion of 1 locus in humans. They
stated that, although in vivo transfection experiments indicated that
the HPR promoter is active and cell-specific, no hemoglobin-binding
protein of the expected structure had been detected.
MOLECULAR GENETICS
Maeda et al. (1986) showed that tandemly arranged HPR genes are linked
to the HP2 allele (140100.0002).
Maeda et al. (1986) found polymorphisms for the number of tandemly
arranged HPR genes in the haptoglobin gene cluster in blacks. Such was
not found in 26 whites and 1 Asian; all had a single HPR gene. In 1
black subject, 6 tandemly arranged HPR genes were demonstrated in 1
chromosome 16 by pulsed field gel electrophoresis; his other chromosome
16 had 1 HPR gene.
African trypanosomes cause disease in humans and animals. Trypanosoma
brucei brucei affects cattle but not humans because of its sensitivity
to a subclass of human high density lipoproteins called trypanosome
lytic factor (TLF). TLF contains 2 apolipoproteins that are sufficient
to cause lysis of T. b. brucei in vitro. Smith et al. (1995) identified
these proteins as the human haptoglobin-related protein (HPR) and
paraoxonase-arylesterase (PON; 168820). They found that an antibody to
haptoglobin inhibited TLF activity. TLF was shown to exhibit peroxidase
activity and to be inhibited by catalase. These results suggested that
TLF kills trypanosomes by oxidative damage initiated by its peroxidase
activity. As noted earlier, Maeda et al. (1986) found polymorphism for
the number of tandemly arranged HPR genes in the haptoglobin gene
cluster in blacks, whereas only a single HPR gene was found in other
races. The work of Smith et al. (1995) raised the possibility that the
development of the polymorphism was related to parasite exposure.
*FIELD* SA
Maeda and Smithies (1986)
*FIELD* RF
1. Bensi, G.; Raugei, G.; Klefenz, H.; Cortese, R.: Structure and
expression of the human haptoglobin locus. EMBO J. 4: 119-126, 1985.
2. Cohen, M.; Larsson, E.: Human endogenous retroviruses. BioEssays 9:
191-196, 1988.
3. Kuhajda, F. P.; Piantadosi, S.; Pasternack, G. R.: Haptoglobin-related
protein (Hpr) epitopes in breast cancer as a predictor of recurrence
of the disease. New Eng. J. Med. 321: 636-641, 1989.
4. Maeda, N.: Nucleotide sequence of the haptoglobin and haptoglobin-related
gene pair. J. Biol. Chem. 260: 6698-6709, 1985.
5. Maeda, N.; Kim, H.-S.: Three independent insertions of retrovirus-like
sequences in the haptoglobin gene cluster of primates. Genomics 8:
671-683, 1990.
6. Maeda, N.; McEvoy, S. M.; Harris, H. F.; Huisman, T. H. J.; Smithies,
O.: Polymorphisms in the human haptoglobin gene cluster: chromosomes
with multiple haptoglobin-related (Hpr) genes. Proc. Nat. Acad. Sci. 83:
7395-7399, 1986.
7. Maeda, N.; Smithies, O.: The evolution of multigene families:
human haptoglobin genes. Annu. Rev. Genet. 20: 81-108, 1986.
8. McEvoy, S. M.; Maeda, N.: Complex events in the evolution of the
haptoglobin gene cluster in primates. J. Biol. Chem. 263: 15740-15747,
1988.
9. Nielsen, M. J.; Petersen, S. V.; Jacobsen, C.; Oxvig, C.; Rees,
D.; Moeller, H. J.; Moestrup, S. K.: Haptoglobin-related protein
is a high-affinity hemoglobin-binding plasma protein. Blood 108:
2846-2849, 2006.
10. Smith, A. B.; Esko, J. D.; Hajduk, S. L.: Killing of trypanosomes
by the human haptoglobin-related protein. Science 268: 284-286,
1995.
11. Smithies, O.; Powers, P. A.: Gene conversions and their relation
to homologous chromosome pairing. Phil. Trans. Roy. Soc. London B 312:
291-302, 1986.
12. Vanhollebeke, B.; De Muylder, G.; Nielsen, M. J.; Pays, A.; Tebabi,
P.; Dieu, M.; Raes, M.; Moestrup, S. K.; Pays, E.: A haptoglobin-hemoglobin
receptor conveys innate immunity to Trypanosoma brucei in humans. Science 320:
677-681, 2008.
*FIELD* CN
Ada Hamosh - updated: 6/17/2008
Patricia A. Hartz - updated: 4/3/2007
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 06/20/2008
terry: 6/17/2008
wwang: 4/6/2007
terry: 4/3/2007
mark: 5/3/1995
terry: 5/9/1994
pfoster: 4/21/1994
carol: 4/14/1992
carol: 4/1/1992
supermim: 3/16/1992
*RECORD*
*FIELD* NO
140210
*FIELD* TI
*140210 HAPTOGLOBIN-RELATED PROTEIN GENE; HPR
*FIELD* TX
CLONING
Bensi et al. (1985) and Maeda (1985) isolated the human HPR gene. Its
read morepredicted amino acid sequence differs by about 8% from that of the
electrophoretically fast-migrating HP variant (HP1F; 140100.0001). The
differences appeared to be located on the surface of the protein
molecule, and the regions and specific residues considered to be
important for binding hemoglobin are identical in the HP and HPR
proteins.
Smithies and Powers (1986) found evidence of gene conversion (see
142200) between the closely linked HP and HPR loci.
GENE FUNCTION
Using immobilized hemoglobin for affinity chromatography, Nielsen et al.
(2006) showed that HPR could bind hemoglobin as efficiently as HP, and
SDS-PAGE showed that HPR migrated as a 45-kD monomer and a 90-kD dimer.
In contrast to HP, HPR did not promote high-affinity binding to CD163
(605545). Western blot analysis of 18 persons with normal HP levels and
13 patients with low HP levels resulting from sickle cell anemia and
extensive intravascular hemolysis indicated that the plasma
concentration of HPR was unaffected by hemolysis, suggesting that
depletion of HP but not HPR in these patients may be a consequence of
the difference in CD163 binding between HP-hemoglobin and HPR-hemoglobin
complexes. Binding of hemoglobin to circulating native HPR incorporated
in the high density lipoprotein (HDL) fraction was indicated by
hemoglobin-affinity precipitation of plasma HPR together with
apolipoprotein-L1 (APOL1; 603743). Nielsen et al. (2006) suggested that
hemoglobin reported to be present in TLF represents HPR-bound
hemoglobin, which may contribute to the biologic activity of circulating
TLF.
The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein
L-I, a component of HDL particles that are also characterized by the
presence of HPR. Vanhollebeke et al. (2008) reported that this process
is mediated by a parasite glycoprotein receptor, which binds the
haptoglobin-hemoglobin complex with high affinity for the uptake and
incorporation of heme into intracellular hemoproteins. In mice, this
receptor was required for optimal parasite growth and the resistance of
parasites to the oxidative burst by host macrophages. In humans, the
trypanosome receptor also recognized the complex between hemoglobin and
HPR, which explains its ability to capture trypanolytic HDLs.
Vanhollebeke et al. (2008) concluded that, in humans, the presence of
HPR has diverted the function of the trypanosome haptoglobin-hemoglobin
receptor to elicit innate host immunity against the parasite.
GENE STRUCTURE
Maeda and Kim (1990) demonstrated that the 2 genes in the human
haptoglobin cluster, HP and HPR, contain 2 retrovirus-like elements. One
(RTVL-Ia) is in the first intron of the HPR gene, and the second
(RTVL-Ic) is at the 3-prime-end of the gene cluster. In the chimpanzee
3-gene cluster (HP-HPR-HPP), there is an additional retrovirus-like
element (RTVL-Ib) in the intergenic region between the chimpanzee HPR
and HPP loci. RTVL-Ia and RTVL-Ib are essentially full size and have the
general structure 5-prime-LTR--gag--pol-env--3-prime-LTR, while RTVL-Ic
lacks about one-third of its 5-prime portion. Although none of the
elements had retained long open reading frames, Maeda and Kim (1990)
detected stretches with amino acids identical to various parts of
proteins of the Moloney murine leukemia virus (Mo-MuLV). They concluded
that the RTVL-I elements were derived from a virus similar in structure
to Mo-MuLV. The DNA sequences surrounding the insertion points of the 3
RTVL-I elements were dissimilar, implying that they integrated into the
haptoglobin gene cluster independently at some time after the initial
formation of the triplicated gene cluster in primates. Comparison of the
nucleotide sequences of the 3 elements suggested that foreign DNA
introduced into the genome can accumulate mutations more rapidly than
the genomic sequences surrounding them. At least 5 other families of
retrovirus-like sequences have been found in the human genome; for a
review, see Cohen and Larsson (1988). In RTVL-I, the tRNA used for the
primer binding site is ile-tRNA. (RTVL-I = retrovirus-like
sequence--isoleucine.)
BIOCHEMICAL FEATURES
During pregnancy, HPR circulates in plasma; furthermore, Kuhajda et al.
(1989) demonstrated that HPR or HPR-like epitopes are expressed in human
breast carcinoma. This led Kuhajda et al. (1989) to examine the
possibility that anti-HPR immunoreactivity of biopsy specimens from
women with primary breast carcinoma might be related to the clinical
behavior of the tumor. They examined the association between the
expression of HPR and the recurrence of cancer in a retrospective study
of 70 patients with early breast cancer treated by mastectomy from
1977-1985 at the Johns Hopkins Hospital. Expression of HPR epitopes was
associated with earlier recurrence, and multivariate analysis showed
that HPR-epitope expression was an independent prognostic factor. The
authors concluded that it is a clinically important predictor of
recurrence, especially in combination with progesterone-receptor status.
MAPPING
The HPR gene maps to chromosome 16q22.1 (Bensi et al., 1985; Maeda,
1985).
Maeda et al. (1986) found that the HPR gene(s) lie on the downstream
side of the HP gene (140100).
EVOLUTION
McEvoy and Maeda (1988) analyzed the evolutionary history of the
haptoglobin gene family by characterizing the haptoglobin genes in
primates. Whereas the HPR gene in the human is 2.2 kb downstream of the
HP gene, chimpanzees, gorillas, orangutans, and Old World monkeys have a
third gene, which McEvoy and Maeda (1988) named HPP for haptoglobin
primate, located 16 kb downstream of HPR. New World monkeys have only 1
haptoglobin gene. McEvoy and Maeda (1988) interpreted these observations
as suggesting triplication of the haptoglobin locus after divergence of
the New World monkeys, followed by deletion of 1 locus in humans. They
stated that, although in vivo transfection experiments indicated that
the HPR promoter is active and cell-specific, no hemoglobin-binding
protein of the expected structure had been detected.
MOLECULAR GENETICS
Maeda et al. (1986) showed that tandemly arranged HPR genes are linked
to the HP2 allele (140100.0002).
Maeda et al. (1986) found polymorphisms for the number of tandemly
arranged HPR genes in the haptoglobin gene cluster in blacks. Such was
not found in 26 whites and 1 Asian; all had a single HPR gene. In 1
black subject, 6 tandemly arranged HPR genes were demonstrated in 1
chromosome 16 by pulsed field gel electrophoresis; his other chromosome
16 had 1 HPR gene.
African trypanosomes cause disease in humans and animals. Trypanosoma
brucei brucei affects cattle but not humans because of its sensitivity
to a subclass of human high density lipoproteins called trypanosome
lytic factor (TLF). TLF contains 2 apolipoproteins that are sufficient
to cause lysis of T. b. brucei in vitro. Smith et al. (1995) identified
these proteins as the human haptoglobin-related protein (HPR) and
paraoxonase-arylesterase (PON; 168820). They found that an antibody to
haptoglobin inhibited TLF activity. TLF was shown to exhibit peroxidase
activity and to be inhibited by catalase. These results suggested that
TLF kills trypanosomes by oxidative damage initiated by its peroxidase
activity. As noted earlier, Maeda et al. (1986) found polymorphism for
the number of tandemly arranged HPR genes in the haptoglobin gene
cluster in blacks, whereas only a single HPR gene was found in other
races. The work of Smith et al. (1995) raised the possibility that the
development of the polymorphism was related to parasite exposure.
*FIELD* SA
Maeda and Smithies (1986)
*FIELD* RF
1. Bensi, G.; Raugei, G.; Klefenz, H.; Cortese, R.: Structure and
expression of the human haptoglobin locus. EMBO J. 4: 119-126, 1985.
2. Cohen, M.; Larsson, E.: Human endogenous retroviruses. BioEssays 9:
191-196, 1988.
3. Kuhajda, F. P.; Piantadosi, S.; Pasternack, G. R.: Haptoglobin-related
protein (Hpr) epitopes in breast cancer as a predictor of recurrence
of the disease. New Eng. J. Med. 321: 636-641, 1989.
4. Maeda, N.: Nucleotide sequence of the haptoglobin and haptoglobin-related
gene pair. J. Biol. Chem. 260: 6698-6709, 1985.
5. Maeda, N.; Kim, H.-S.: Three independent insertions of retrovirus-like
sequences in the haptoglobin gene cluster of primates. Genomics 8:
671-683, 1990.
6. Maeda, N.; McEvoy, S. M.; Harris, H. F.; Huisman, T. H. J.; Smithies,
O.: Polymorphisms in the human haptoglobin gene cluster: chromosomes
with multiple haptoglobin-related (Hpr) genes. Proc. Nat. Acad. Sci. 83:
7395-7399, 1986.
7. Maeda, N.; Smithies, O.: The evolution of multigene families:
human haptoglobin genes. Annu. Rev. Genet. 20: 81-108, 1986.
8. McEvoy, S. M.; Maeda, N.: Complex events in the evolution of the
haptoglobin gene cluster in primates. J. Biol. Chem. 263: 15740-15747,
1988.
9. Nielsen, M. J.; Petersen, S. V.; Jacobsen, C.; Oxvig, C.; Rees,
D.; Moeller, H. J.; Moestrup, S. K.: Haptoglobin-related protein
is a high-affinity hemoglobin-binding plasma protein. Blood 108:
2846-2849, 2006.
10. Smith, A. B.; Esko, J. D.; Hajduk, S. L.: Killing of trypanosomes
by the human haptoglobin-related protein. Science 268: 284-286,
1995.
11. Smithies, O.; Powers, P. A.: Gene conversions and their relation
to homologous chromosome pairing. Phil. Trans. Roy. Soc. London B 312:
291-302, 1986.
12. Vanhollebeke, B.; De Muylder, G.; Nielsen, M. J.; Pays, A.; Tebabi,
P.; Dieu, M.; Raes, M.; Moestrup, S. K.; Pays, E.: A haptoglobin-hemoglobin
receptor conveys innate immunity to Trypanosoma brucei in humans. Science 320:
677-681, 2008.
*FIELD* CN
Ada Hamosh - updated: 6/17/2008
Patricia A. Hartz - updated: 4/3/2007
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
alopez: 06/20/2008
terry: 6/17/2008
wwang: 4/6/2007
terry: 4/3/2007
mark: 5/3/1995
terry: 5/9/1994
pfoster: 4/21/1994
carol: 4/14/1992
carol: 4/1/1992
supermim: 3/16/1992