HPTR_HUMAN
ID HPTR_HUMAN Reviewed; 348 AA.
AC P00739; Q7LE20; Q92658; Q92659; Q9ULB0;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Haptoglobin-related protein;
GN Name=HPR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-339.
RX PubMed=4018023; DOI=10.1002/j.1460-2075.1985.tb02325.x;
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; DOI=10.1016/s0021-9258(18)88836-6;
RA Maeda N.;
RT "Nucleotide sequence of the haptoglobin and haptoglobin-related gene pair.
RT The haptoglobin-related gene contains a retrovirus-like 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 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., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., 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., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., 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 TISSUE
RP 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 G2 and
RT 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., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16778136; DOI=10.1182/blood-2006-05-022327;
RA Nielsen M.J., Petersen S.V., Jacobsen C., Oxvig C., Rees D., Moller H.J.,
RA Moestrup S.K.;
RT "Haptoglobin-related protein is a high-affinity hemoglobin-binding plasma
RT protein.";
RL Blood 108:2846-2849(2006).
RN [8]
RP SIGNAL SEQUENCE.
RX PubMed=25037218; DOI=10.1074/jbc.m114.567578;
RA Harrington J.M., Nishanova T., Pena S.R., Hess M., Scelsi C.L., Widener J.,
RA Hajduk S.L.;
RT "A retained secretory signal peptide mediates high density lipoprotein
RT (HDL) assembly and function of haptoglobin-related protein.";
RL J. Biol. Chem. 289:24811-24820(2014).
CC -!- FUNCTION: Primate-specific plasma protein associated with
CC apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL).
CC This HDL particle, termed trypanosome lytic factor-1 (TLF-1), mediates
CC human innate immune protection against many species of African
CC trypanosomes. Binds hemoglobin with high affinity and may contribute to
CC the clearance of cell-free hemoglobin to allow hepatic recycling of
CC heme iron. {ECO:0000269|PubMed:16778136}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16778136}.
CC Note=Secreted into blood plasma and associated with subtypes of high
CC density lipoproteins (HDL). {ECO:0000269|PubMed:16778136}.
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 the
CC lower limit of detection, therefore the extent of its expression is at
CC most less than 1000-fold that of the HP1F gene. No HPR mRNA can be
CC detected in fetal liver. Expressed in Hep-G2 and leukemia MOLT-4 cell
CC lines. {ECO:0000269|PubMed:8945641}.
CC -!- DOMAIN: The uncleaved signal sequence interacts with HDL fluid lipids
CC and mediates incorporation into the HDL particle.
CC {ECO:0000269|PubMed:25037218}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- CAUTION: Although homologous to serine proteases, it has lost all
CC essential catalytic residues and has no enzymatic activity.
CC {ECO:0000305}.
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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 CCDS; CCDS42193.1; -. [P00739-1]
DR PIR; A00919; HPHUR.
DR RefSeq; NP_066275.3; NM_020995.3. [P00739-1]
DR AlphaFoldDB; P00739; -.
DR SMR; P00739; -.
DR BioGRID; 109487; 17.
DR CORUM; P00739; -.
DR STRING; 9606.ENSP00000441828; -.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR MEROPS; S01.974; -.
DR iPTMnet; P00739; -.
DR PhosphoSitePlus; P00739; -.
DR BioMuta; HPR; -.
DR DMDM; 262527547; -.
DR DOSAC-COBS-2DPAGE; P00739; -.
DR jPOST; P00739; -.
DR MassIVE; P00739; -.
DR MaxQB; P00739; -.
DR PaxDb; P00739; -.
DR PeptideAtlas; P00739; -.
DR PRIDE; P00739; -.
DR ProteomicsDB; 51272; -. [P00739-1]
DR ProteomicsDB; 51273; -. [P00739-2]
DR Antibodypedia; 63671; 238 antibodies from 23 providers.
DR DNASU; 3250; -.
DR Ensembl; ENST00000540303.7; ENSP00000441828.2; ENSG00000261701.9. [P00739-1]
DR GeneID; 3250; -.
DR KEGG; hsa:3250; -.
DR MANE-Select; ENST00000540303.7; ENSP00000441828.2; NM_020995.4; NP_066275.3.
DR UCSC; uc002fby.4; human. [P00739-1]
DR CTD; 3250; -.
DR DisGeNET; 3250; -.
DR GeneCards; HPR; -.
DR HGNC; HGNC:5156; HPR.
DR HPA; ENSG00000261701; Tissue enriched (liver).
DR MIM; 140210; gene.
DR neXtProt; NX_P00739; -.
DR OpenTargets; ENSG00000261701; -.
DR PharmGKB; PA29426; -.
DR VEuPathDB; HostDB:ENSG00000261701; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000159903; -.
DR HOGENOM; CLU_006842_0_0_1; -.
DR InParanoid; P00739; -.
DR OMA; YMKISSY; -.
DR OrthoDB; 798576at2759; -.
DR PhylomeDB; P00739; -.
DR TreeFam; TF334326; -.
DR PathwayCommons; P00739; -.
DR Reactome; R-HSA-2168880; Scavenging of heme from plasma.
DR SignaLink; P00739; -.
DR BioGRID-ORCS; 3250; 27 hits in 1015 CRISPR screens.
DR ChiTaRS; HPR; human.
DR GeneWiki; HPR_(gene); -.
DR GenomeRNAi; 3250; -.
DR Pharos; P00739; Tbio.
DR PRO; PR:P00739; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P00739; protein.
DR Bgee; ENSG00000261701; Expressed in right lobe of liver and 118 other tissues.
DR ExpressionAtlas; P00739; baseline and differential.
DR Genevisible; P00739; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0034366; C:spherical high-density lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0030492; F:hemoglobin binding; NAS:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0002526; P:acute inflammatory response; IBA:GO_Central.
DR GO; GO:0010942; P:positive regulation of cell death; IBA:GO_Central.
DR GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR InterPro; IPR008292; Haptoglobin.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR001254; Trypsin_dom.
DR PANTHER; PTHR24255:SF27; PTHR24255:SF27; 1.
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; PS50240; TRYPSIN_DOM; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Disulfide bond; Hemoglobin-binding;
KW Reference proteome; Secreted; Serine protease homolog; Signal; Sushi.
FT CHAIN 1..348
FT /note="Haptoglobin-related protein"
FT /id="PRO_0000028486"
FT SIGNAL 1..18
FT /note="Not cleaved"
FT /evidence="ECO:0000269|PubMed:25037218"
FT DOMAIN 34..87
FT /note="Sushi"
FT DOMAIN 104..346
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 251..282
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 293..323
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VAR_SEQ 1
FT /note="M -> MHVCVCVCVCVYMPVCVDACMCCEAGRPAFRSFLFSLC (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:8945641"
FT /id="VSP_014529"
FT VARIANT 27
FT /note="T -> M (in dbSNP:rs11642506)"
FT /id="VAR_057161"
FT VARIANT 42
FT /note="N -> H (in dbSNP:rs152832)"
FT /id="VAR_057162"
FT VARIANT 58
FT /note="R -> K (in dbSNP:rs152833)"
FT /id="VAR_057163"
FT VARIANT 156
FT /note="A -> V (in dbSNP:rs1049933)"
FT /id="VAR_059789"
FT VARIANT 203
FT /note="R -> K (in dbSNP:rs2021171)"
FT /id="VAR_057164"
FT VARIANT 283
FT /note="V -> A (in dbSNP:rs1065360)"
FT /id="VAR_057165"
FT VARIANT 339
FT /note="H -> D (in dbSNP:rs12646)"
FT /evidence="ECO:0000269|PubMed:1478675,
FT ECO:0000269|PubMed:2987228, ECO:0000269|PubMed:4018023"
FT /id="VAR_014571"
FT CONFLICT 191
FT /note="L -> I (in Ref. 1; CAA25927)"
FT /evidence="ECO:0000305"
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
