HLPDA_HUMAN
ID HLPDA_HUMAN Reviewed; 63 AA.
AC Q9Y5L2; A4D0Z5; Q52LY5; Q53HJ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Hypoxia-inducible lipid droplet-associated protein;
DE AltName: Full=Hypoxia-inducible gene 2 protein;
GN Name=HILPDA; Synonyms=C7orf68, HIG2;
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 [MRNA], AND INDUCTION.
RC TISSUE=Cervix carcinoma;
RX PubMed=10690527;
RA Denko N.C., Schindler C., Koong A., Laderoute K., Green C., Giaccia A.J.;
RT "Epigenetic regulation of gene expression in cervical cancer cells by the
RT tumor microenvironment.";
RL Clin. Cancer Res. 6:480-487(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Coronary artery;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum, and Lung carcinoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15930302; DOI=10.1158/0008-5472.can-05-0120;
RA Togashi A., Katagiri T., Ashida S., Fujioka T., Maruyama O., Wakumoto Y.,
RA Sakamoto Y., Fujime M., Kawachi Y., Shuin T., Nakamura Y.;
RT "Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marker for renal
RT cell carcinoma and potential target for molecular therapy.";
RL Cancer Res. 65:4817-4826(2005).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-44, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION, AND
RP MUTAGENESIS OF 8-TYR-LEU-9; THR-41 AND SER-44.
RX PubMed=20624928; DOI=10.1096/fj.10-159806;
RA Gimm T., Wiese M., Teschemacher B., Deggerich A., Schodel J., Knaup K.X.,
RA Hackenbeck T., Hellerbrand C., Amann K., Wiesener M.S., Honing S.,
RA Eckardt K.U., Warnecke C.;
RT "Hypoxia-inducible protein 2 is a novel lipid droplet protein and a
RT specific target gene of hypoxia-inducible factor-1.";
RL FASEB J. 24:4443-4458(2010).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=21614900;
RA Nishimura S., Tsuda H., Nomura H., Kataoka F., Chiyoda T., Tanaka H.,
RA Tanaka K., Susumu N., Aoki D.;
RT "Expression of hypoxia-inducible 2 (HIG2) protein in uterine cancer.";
RL Eur. J. Gynaecol. Oncol. 32:146-149(2011).
CC -!- FUNCTION: Increases intracellular lipid accumulation. Stimulates
CC expression of cytokines including IL6, MIF and VEGFA. Enhances cell
CC growth and proliferation. {ECO:0000269|PubMed:15930302,
CC ECO:0000269|PubMed:20624928}.
CC -!- INTERACTION:
CC Q9Y5L2; Q9ULW2: FZD10; NbExp=2; IntAct=EBI-8803836, EBI-8803802;
CC Q9Y5L2; O43681: GET3; NbExp=3; IntAct=EBI-8803836, EBI-2515857;
CC -!- SUBCELLULAR LOCATION: Lipid droplet. Secreted. Membrane {ECO:0000305};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in renal cell carcinoma cells but
CC barely detectable in adjacent normal kidney tissue. Detected in some
CC cervical and endometrial cancers. Expression also detected in fetal
CC kidney with little or no expression observed in normal adult heart,
CC liver, lung, pancreas, prostate or spinal cord (at protein level).
CC {ECO:0000269|PubMed:15930302, ECO:0000269|PubMed:20624928,
CC ECO:0000269|PubMed:21614900}.
CC -!- INDUCTION: By hypoxia but highly abundant under normoxic conditions (at
CC protein level). {ECO:0000269|PubMed:10690527,
CC ECO:0000269|PubMed:20624928}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF144755; AAD37585.1; -; mRNA.
DR EMBL; AK222583; BAD96303.1; -; mRNA.
DR EMBL; CH236947; EAL24309.1; -; Genomic_DNA.
DR EMBL; BC001863; AAH01863.1; -; mRNA.
DR EMBL; BC093742; AAH93742.1; -; mRNA.
DR EMBL; BC112183; AAI12184.1; -; mRNA.
DR CCDS; CCDS5802.1; -.
DR RefSeq; NP_001092256.1; NM_001098786.1.
DR RefSeq; NP_037464.1; NM_013332.3.
DR AlphaFoldDB; Q9Y5L2; -.
DR SMR; Q9Y5L2; -.
DR BioGRID; 118964; 4.
DR IntAct; Q9Y5L2; 3.
DR MINT; Q9Y5L2; -.
DR STRING; 9606.ENSP00000257696; -.
DR iPTMnet; Q9Y5L2; -.
DR PhosphoSitePlus; Q9Y5L2; -.
DR BioMuta; HILPDA; -.
DR jPOST; Q9Y5L2; -.
DR MassIVE; Q9Y5L2; -.
DR MaxQB; Q9Y5L2; -.
DR PaxDb; Q9Y5L2; -.
DR PeptideAtlas; Q9Y5L2; -.
DR PRIDE; Q9Y5L2; -.
DR ProteomicsDB; 86439; -.
DR Antibodypedia; 2129; 29 antibodies from 12 providers.
DR DNASU; 29923; -.
DR Ensembl; ENST00000257696.5; ENSP00000257696.4; ENSG00000135245.10.
DR Ensembl; ENST00000435296.2; ENSP00000388871.2; ENSG00000135245.10.
DR GeneID; 29923; -.
DR KEGG; hsa:29923; -.
DR MANE-Select; ENST00000257696.5; ENSP00000257696.4; NM_013332.4; NP_037464.1.
DR UCSC; uc003vne.5; human.
DR CTD; 29923; -.
DR DisGeNET; 29923; -.
DR GeneCards; HILPDA; -.
DR HGNC; HGNC:28859; HILPDA.
DR HPA; ENSG00000135245; Tissue enhanced (esophagus).
DR MIM; 617905; gene.
DR neXtProt; NX_Q9Y5L2; -.
DR OpenTargets; ENSG00000135245; -.
DR PharmGKB; PA164717457; -.
DR VEuPathDB; HostDB:ENSG00000135245; -.
DR eggNOG; ENOG502T735; Eukaryota.
DR GeneTree; ENSGT00390000014201; -.
DR HOGENOM; CLU_192601_0_0_1; -.
DR InParanoid; Q9Y5L2; -.
DR OMA; TIHPEGC; -.
DR OrthoDB; 1628130at2759; -.
DR PhylomeDB; Q9Y5L2; -.
DR PathwayCommons; Q9Y5L2; -.
DR Reactome; R-HSA-8964572; Lipid particle organization.
DR SignaLink; Q9Y5L2; -.
DR BioGRID-ORCS; 29923; 5 hits in 1072 CRISPR screens.
DR GenomeRNAi; 29923; -.
DR Pharos; Q9Y5L2; Tbio.
DR PRO; PR:Q9Y5L2; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y5L2; protein.
DR Bgee; ENSG00000135245; Expressed in vena cava and 203 other tissues.
DR Genevisible; Q9Y5L2; HS.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0030141; C:secretory granule; IDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0035425; P:autocrine signaling; IDA:BHF-UCL.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0010884; P:positive regulation of lipid storage; IDA:UniProtKB.
DR InterPro; IPR026190; Hipoxia_HILPDA.
DR PANTHER; PTHR16886; PTHR16886; 1.
DR Pfam; PF15220; HILPDA; 1.
PE 1: Evidence at protein level;
KW Lipid droplet; Membrane; Phosphoprotein; Reference proteome; Secreted;
KW Stress response; Transmembrane; Transmembrane helix.
FT CHAIN 1..63
FT /note="Hypoxia-inducible lipid droplet-associated protein"
FT /id="PRO_0000083976"
FT TRANSMEM 7..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..37
FT /note="Required for targeting to lipid droplets"
FT REGION 31..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..51
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MUTAGEN 8..9
FT /note="YL->DD: Loss of targeting to lipid droplets and
FT elimination of protein."
FT /evidence="ECO:0000269|PubMed:20624928"
FT MUTAGEN 41
FT /note="T->K: No effect on lipid droplet targeting or
FT protein expression; when associated with K-44."
FT /evidence="ECO:0000269|PubMed:20624928"
FT MUTAGEN 44
FT /note="S->K: No effect on lipid droplet targeting or
FT protein expression; when associated with K-41."
FT /evidence="ECO:0000269|PubMed:20624928"
FT CONFLICT 21
FT /note="V -> T (in Ref. 2; BAD96303)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 63 AA; 6950 MW; 91EA626A511FC8B7 CRC64;
MKHVLNLYLL GVVLTLLSIF VRVMESLEGL LESPSPGTSW TTRSQLANTE PTKGLPDHPS
RSM
