HIF1A_MOUSE
ID HIF1A_MOUSE Reviewed; 836 AA.
AC Q61221; O08741; O08993; Q61664; Q61665; Q8C681; Q8CC19; Q8CCB6; Q8R385;
AC Q9CYA8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2003, sequence version 3.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Hypoxia-inducible factor 1-alpha;
DE Short=HIF-1-alpha;
DE Short=HIF1-alpha;
DE AltName: Full=ARNT-interacting protein;
GN Name=Hif1a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Hepatocyte;
RX PubMed=8702901; DOI=10.1074/jbc.271.35.21262;
RA Li H., Ko H.P., Whitlock J.P. Jr.;
RT "Induction of phosphoglycerate kinase 1 gene expression by hypoxia. Roles
RT of Arnt and HIF1alpha.";
RL J. Biol. Chem. 271:21262-21267(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=129/SvJ;
RX PubMed=9368100;
RA Luo G., Gu Y.-Z., Jain S., Chan W.K., Carr K.M., Hogenesch J.B.,
RA Bradfield C.A.;
RT "Molecular characterization of the murine Hif-1 alpha locus.";
RL Gene Expr. 6:287-299(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RC STRAIN=129/Sv;
RX PubMed=9210478; DOI=10.1111/j.1432-1033.1997.t01-1-00155.x;
RA Wenger R.H., Rolfs A., Kvietikova I., Spielmann P., Zimmermann D.R.,
RA Gassmann M.;
RT "The mouse gene for hypoxia-inducible factor-1alpha. Genomic organization,
RT expression and characterization of an alternative first exon and 5'
RT flanking sequence.";
RL Eur. J. Biochem. 246:155-165(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Colon, Diencephalon, Embryo, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Mammary tumor;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 13-822 (ISOFORM 2).
RC TISSUE=Hepatocyte;
RX PubMed=8660378; DOI=10.1006/bbrc.1996.0845;
RA Wenger R.H., Rolfs A., Marti H.H., Guenet J.-L., Gassmann M.;
RT "Nucleotide sequence, chromosomal assignment and mRNA expression of mouse
RT hypoxia-inducible factor-1 alpha.";
RL Biochem. Biophys. Res. Commun. 223:54-59(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 22-85.
RC TISSUE=Hepatocyte;
RA O'Rourke J.F.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INTERACTION WITH COPS5.
RX PubMed=11707426; DOI=10.1074/jbc.c100442200;
RA Bae M.-K., Ahn M.-Y., Jeong J.-W., Bae M.-H., Lee Y.M., Bae S.-K.,
RA Park J.-W., Kim K.-R., Kim K.-W.;
RT "Jab1 interacts directly with HIF-1alpha and regulates its stability.";
RL J. Biol. Chem. 277:9-12(2002).
RN [9]
RP SUMOYLATION, SUBCELLULAR LOCATION, INDUCTION, AND FUNCTION.
RX PubMed=15225651; DOI=10.1016/j.febslet.2004.05.079;
RA Shao R., Zhang F.-P., Tian F., Anders Friberg P., Wang X., Sjoeland H.,
RA Billig H.;
RT "Increase of SUMO-1 expression in response to hypoxia: direct interaction
RT with HIF-1alpha in adult mouse brain and heart in vivo.";
RL FEBS Lett. 569:293-300(2004).
RN [10]
RP INTERACTION WITH TSGA10.
RX PubMed=16777103; DOI=10.1016/j.febslet.2006.05.058;
RA Haegele S., Behnam B., Borter E., Wolfe J., Paasch U., Lukashev D.,
RA Sitkovsky M., Wenger R.H., Katschinski D.M.;
RT "TSGA10 prevents nuclear localization of the hypoxia-inducible factor
RT (HIF)-1alpha.";
RL FEBS Lett. 580:3731-3738(2006).
RN [11]
RP DESUMOYLATION, FUNCTION, AND INTERACTION WITH SENP1.
RX PubMed=17981124; DOI=10.1016/j.cell.2007.08.045;
RA Cheng J., Kang X., Zhang S., Yeh E.T.H.;
RT "SUMO-specific protease 1 is essential for stabilization of HIF1alpha
RT during hypoxia.";
RL Cell 131:584-595(2007).
RN [12]
RP PHOSPHORYLATION BY PLK3.
RX PubMed=20889502; DOI=10.1074/jbc.m110.160325;
RA Xu D., Yao Y., Lu L., Costa M., Dai W.;
RT "Plk3 functions as an essential component of the hypoxia regulatory pathway
RT by direct phosphorylation of HIF-1alpha.";
RL J. Biol. Chem. 285:38944-38950(2010).
RN [13]
RP INTERACTION WITH HIF3A, AND SUBCELLULAR LOCATION.
RX PubMed=21546903; DOI=10.1038/cdd.2011.47;
RA Torii S., Goto Y., Ishizawa T., Hoshi H., Goryo K., Yasumoto K.,
RA Fukumura H., Sogawa K.;
RT "Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative
RT regulator of HIF-1, through binding to pro-survival Bcl-2 family
RT proteins.";
RL Cell Death Differ. 18:1711-1725(2011).
RN [14]
RP FUNCTION.
RX PubMed=22009797; DOI=10.1530/erc-11-0211;
RA Shan B., Gerez J., Haedo M., Fuertes M., Theodoropoulou M., Buchfelder M.,
RA Losa M., Stalla G.K., Arzt E., Renner U.;
RT "RSUME is implicated in HIF-1-induced VEGF-A production in pituitary tumour
RT cells.";
RL Endocr. Relat. Cancer 19:13-27(2012).
RN [15] {ECO:0007744|PDB:4ZPR}
RP X-RAY CRYSTALLOGRAPHY (3.90 ANGSTROMS) OF 13-357 IN COMPLEXES WITH ARNT AND
RP DNA, MUTAGENESIS OF ARG-170 AND VAL-191, REGION, INTERACTION WITH ARNT, AND
RP FUNCTION.
RX PubMed=26245371; DOI=10.1038/nature14883;
RA Wu D., Potluri N., Lu J., Kim Y., Rastinejad F.;
RT "Structural integration in hypoxia-inducible factors.";
RL Nature 524:303-308(2015).
CC -!- FUNCTION: Functions as a master transcriptional regulator of the
CC adaptive response to hypoxia (PubMed:15225651, PubMed:17981124,
CC PubMed:22009797). Under hypoxic conditions, activates the transcription
CC of over 40 genes, including erythropoietin, glucose transporters,
CC glycolytic enzymes, vascular endothelial growth factor, HILPDA, and
CC other genes whose protein products increase oxygen delivery or
CC facilitate metabolic adaptation to hypoxia (PubMed:15225651,
CC PubMed:17981124, PubMed:22009797). Plays an essential role in embryonic
CC vascularization, tumor angiogenesis and pathophysiology of ischemic
CC disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds
CC to core DNA sequence 5'-TACGTG-3' within the hypoxia response element
CC (HRE) of target gene promoters (PubMed:26245371). Activation requires
CC recruitment of transcriptional coactivators such as CREBBP and EP300.
CC Activity is enhanced by interaction with NCOA1 and/or NCOA2.
CC Interaction with redox regulatory protein APEX1 seems to activate CTAD
CC and potentiates activation by NCOA1 and CREBBP. Involved in the axonal
CC distribution and transport of mitochondria in neurons during hypoxia
CC (By similarity). {ECO:0000250|UniProtKB:Q16665,
CC ECO:0000269|PubMed:15225651, ECO:0000269|PubMed:17981124,
CC ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:26245371}.
CC -!- ACTIVITY REGULATION: Induced by reactive oxygen species (ROS).
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- SUBUNIT: Interacts with the ARNT; forms a heterodimer that binds core
CC DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of
CC target gene promoters (PubMed:26245371). Interacts with COPS5; the
CC interaction increases the transcriptional activity of HIF1A through
CC increased stability (PubMed:11707426). Interacts with EP300 (via TAZ-
CC type 1 domains); the interaction is stimulated in response to hypoxia
CC and inhibited by CITED2. Interacts with CREBBP (via TAZ-type 1
CC domains). Interacts with NCOA1, NCOA2, APEX1 and HSP90. Interacts
CC (hydroxylated within the ODD domain) with VHLL (via beta domain); the
CC interaction, leads to polyubiquitination and subsequent HIF1A
CC proteasomal degradation. During hypoxia, sumoylated HIF1A also binds
CC VHL; the interaction promotes the ubiquitination of HIF1A (By
CC similarity). Interacts with SENP1; the interaction desumoylates HIF1A
CC resulting in stabilization and activation of transcription
CC (PubMed:17981124). Interacts (via the ODD domain) with NAA10; the
CC interaction appears not to acetylate HIF1A nor have any affect on
CC protein stability, during hypoxia. Interacts with RWDD3; the
CC interaction enhances HIF1A sumoylation (By similarity). Interacts with
CC TSGA10 (PubMed:16777103). Interacts with HIF3A (PubMed:21546903).
CC Interacts with RORA (via the DNA binding domain); the interaction
CC enhances HIF1A transcription under hypoxia through increasing protein
CC stability. Interaction with PSMA7 inhibits the transactivation activity
CC of HIF1A under both normoxic and hypoxia-mimicking conditions.
CC Interacts with USP20. Interacts with RACK1; promotes HIF1A
CC ubiquitination and proteasome-mediated degradation. Interacts (via N-
CC terminus) with USP19. Interacts with SIRT2. Interacts (deacetylated
CC form) with EGLN1. Interacts with CBFA2T3. Interacts with HSP90AA1 and
CC HSP90AB1. Interacts with DCUN1D1; this interaction increases the
CC interaction between VHL and DCUN1D1. Interacts with HIF1AN (By
CC similarity). {ECO:0000250|UniProtKB:Q16665,
CC ECO:0000269|PubMed:11707426, ECO:0000269|PubMed:16777103,
CC ECO:0000269|PubMed:17981124, ECO:0000269|PubMed:21546903,
CC ECO:0000269|PubMed:26245371}.
CC -!- INTERACTION:
CC Q61221; P35583: Foxa2; NbExp=5; IntAct=EBI-298954, EBI-2893341;
CC Q61221; Q8BIF2: Rbfox3; NbExp=2; IntAct=EBI-298954, EBI-4567146;
CC Q61221; P51450-2: Rorc; NbExp=2; IntAct=EBI-298954, EBI-4422078;
CC Q61221; Q09472: EP300; Xeno; NbExp=2; IntAct=EBI-298954, EBI-447295;
CC Q61221; P40337: VHL; Xeno; NbExp=2; IntAct=EBI-298954, EBI-301246;
CC Q61221-1; P53762: Arnt; NbExp=5; IntAct=EBI-8549331, EBI-78852;
CC Q61221-1; Q6NY15: Tsga10; NbExp=2; IntAct=EBI-8549331, EBI-8549230;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15225651}. Nucleus
CC {ECO:0000269|PubMed:15225651, ECO:0000269|PubMed:21546903}. Nucleus
CC speckle {ECO:0000269|PubMed:21546903}. Note=Colocalizes with HIF3A
CC isoform 2 in the nucleus and speckles (PubMed:21546903). Cytoplasmic in
CC normoxia, nuclear translocation in response to hypoxia (By similarity).
CC {ECO:0000250|UniProtKB:Q16665, ECO:0000269|PubMed:21546903}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q61221-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q61221-2; Sequence=VSP_007739;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- DOMAIN: Contains two independent C-terminal transactivation domains,
CC NTAD and CTAD, which function synergistically. Their transcriptional
CC activity is repressed by an intervening inhibitory domain (ID) (By
CC similarity). {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: S-nitrosylation of Cys-810 may be responsible for increased
CC recruitment of p300 coactivator necessary for transcriptional activity
CC of HIF-1 complex. {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: Requires phosphorylation for DNA-binding. Phosphorylation at Ser-
CC 247 by CSNK1D/CK1 represses kinase activity and impairs ARNT binding
CC (By similarity). Phosphorylation by GSK3-beta and PLK3 promote
CC degradation by the proteasome (PubMed:20889502).
CC {ECO:0000250|UniProtKB:Q16665, ECO:0000269|PubMed:20889502}.
CC -!- PTM: Sumoylated; with SUMO1 under hypoxia (PubMed:15225651,
CC PubMed:17981124). Sumoylation is enhanced through interaction with
CC RWDD3 (By similarity). Both sumoylation and desumoylation seem to be
CC involved in the regulation of its stability during hypoxia
CC (PubMed:15225651, PubMed:17981124). Sumoylation can promote either its
CC stabilization or its VHL-dependent degradation by promoting
CC hydroxyproline-independent HIF1A-VHL complex binding, thus leading to
CC HIF1A ubiquitination and proteasomal degradation (By similarity).
CC Desumoylation by SENP1 increases its stability amd transcriptional
CC activity (PubMed:17981124). There is a disaccord between various
CC publications on the effect of sumoylation and desumoylation on its
CC stability and transcriptional activity (Probable).
CC {ECO:0000250|UniProtKB:Q16665, ECO:0000269|PubMed:15225651,
CC ECO:0000269|PubMed:17981124, ECO:0000305}.
CC -!- PTM: Acetylation of Lys-545 by ARD1 increases interaction with VHL and
CC stimulates subsequent proteasomal degradation (By similarity).
CC Deacetylation of Lys-719 by SIRT2 increases its interaction with and
CC hydroxylation by EGLN1 thereby inactivating HIF1A activity by inducing
CC its proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: Ubiquitinated; in normoxia, following hydroxylation and
CC interaction with VHL. Lys-545 appears to be the principal site of
CC ubiquitination. Clioquinol, the Cu/Zn-chelator, inhibits ubiquitination
CC through preventing hydroxylation at Asn-813 (By similarity).
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC asparagine is (S) stereospecific within HIF CTAD domains.
CC {ECO:0000250|UniProtKB:Q16665}.
CC -!- PTM: In normoxia, is hydroxylated on Pro-402 and Pro-577 in the oxygen-
CC dependent degradation domain (ODD) by EGLN1/PHD2 and EGLN2/PHD1.
CC EGLN3/PHD3 has also been shown to hydroxylate Pro-577. The hydroxylated
CC prolines promote interaction with VHL, initiating rapid ubiquitination
CC and subsequent proteasomal degradation. Deubiquitinated by USP20. Under
CC hypoxia, proline hydroxylation is impaired and ubiquitination is
CC attenuated, resulting in stabilization (By similarity). In normoxia, is
CC hydroxylated on Asn-813 by HIF1AN, thus abrogating interaction with
CC CREBBP and EP300 and preventing transcriptional activation. Repressed
CC by iron ion, via Fe(2+) prolyl hydroxylase (PHD) enzymes-mediated
CC hydroxylation and subsequent proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q16665}.
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DR EMBL; U59496; AAC52730.1; -; Genomic_DNA.
DR EMBL; AF003695; AAC53455.1; -; mRNA.
DR EMBL; AF004155; AAC53461.1; -; Genomic_DNA.
DR EMBL; AF004141; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004142; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004143; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004144; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004145; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004146; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004147; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004148; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004149; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004150; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004151; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004152; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004153; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; AF004154; AAC53461.1; JOINED; Genomic_DNA.
DR EMBL; Y09085; CAA70305.1; -; Genomic_DNA.
DR EMBL; Y09085; CAA70306.1; -; Genomic_DNA.
DR EMBL; Y13656; CAA70306.1; JOINED; Genomic_DNA.
DR EMBL; AK034087; BAC28578.1; -; mRNA.
DR EMBL; AK076395; BAC36320.1; -; mRNA.
DR EMBL; AK033471; BAC28305.1; -; mRNA.
DR EMBL; AK017853; BAB30975.1; -; mRNA.
DR EMBL; BC026139; AAH26139.1; -; mRNA.
DR EMBL; X95580; CAA64833.1; -; mRNA.
DR EMBL; X95002; CAA64458.1; -; mRNA.
DR CCDS; CCDS25977.1; -. [Q61221-1]
DR PIR; JC4837; JC4837.
DR RefSeq; NP_001300848.1; NM_001313919.1.
DR RefSeq; NP_001300849.1; NM_001313920.1.
DR RefSeq; NP_034561.2; NM_010431.2. [Q61221-1]
DR RefSeq; XP_017170450.1; XM_017314961.1. [Q61221-2]
DR PDB; 4ZPR; X-ray; 3.90 A; B=13-357.
DR PDBsum; 4ZPR; -.
DR AlphaFoldDB; Q61221; -.
DR SMR; Q61221; -.
DR BioGRID; 200304; 25.
DR DIP; DIP-31083N; -.
DR IntAct; Q61221; 16.
DR MINT; Q61221; -.
DR STRING; 10090.ENSMUSP00000021530; -.
DR BindingDB; Q61221; -.
DR ChEMBL; CHEMBL6046; -.
DR iPTMnet; Q61221; -.
DR PhosphoSitePlus; Q61221; -.
DR PaxDb; Q61221; -.
DR PRIDE; Q61221; -.
DR ProteomicsDB; 273106; -. [Q61221-1]
DR ProteomicsDB; 273107; -. [Q61221-2]
DR Antibodypedia; 84; 2279 antibodies from 53 providers.
DR DNASU; 15251; -.
DR Ensembl; ENSMUST00000021530; ENSMUSP00000021530; ENSMUSG00000021109. [Q61221-1]
DR GeneID; 15251; -.
DR KEGG; mmu:15251; -.
DR UCSC; uc007nwo.2; mouse. [Q61221-2]
DR UCSC; uc007nwq.2; mouse. [Q61221-1]
DR CTD; 3091; -.
DR MGI; MGI:106918; Hif1a.
DR VEuPathDB; HostDB:ENSMUSG00000021109; -.
DR eggNOG; KOG3558; Eukaryota.
DR GeneTree; ENSGT00940000156774; -.
DR InParanoid; Q61221; -.
DR OMA; TITIFQQ; -.
DR OrthoDB; 547545at2759; -.
DR PhylomeDB; Q61221; -.
DR TreeFam; TF317772; -.
DR Reactome; R-MMU-1234158; Regulation of gene expression by Hypoxia-inducible Factor.
DR Reactome; R-MMU-1234174; Cellular response to hypoxia.
DR Reactome; R-MMU-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8857538; PTK6 promotes HIF1A stabilization.
DR Reactome; R-MMU-8951664; Neddylation.
DR BioGRID-ORCS; 15251; 10 hits in 79 CRISPR screens.
DR ChiTaRS; Hif1a; mouse.
DR PRO; PR:Q61221; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q61221; protein.
DR Bgee; ENSMUSG00000021109; Expressed in pineal body and 284 other tissues.
DR ExpressionAtlas; Q61221; baseline and differential.
DR Genevisible; Q61221; MM.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000791; C:euchromatin; IDA:BHF-UCL.
DR GO; GO:0031514; C:motile cilium; IDA:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0070888; F:E-box binding; IMP:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0002039; F:p53 binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0019896; P:axonal transport of mitochondrion; ISS:UniProtKB.
DR GO; GO:0001922; P:B-1 B cell homeostasis; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0048514; P:blood vessel morphogenesis; IMP:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IGI:MGI.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IGI:MGI.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IGI:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl.
DR GO; GO:0098586; P:cellular response to virus; ISO:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:MGI.
DR GO; GO:0032963; P:collagen metabolic process; IMP:BHF-UCL.
DR GO; GO:0002248; P:connective tissue replacement involved in inflammatory response wound healing; IMP:BHF-UCL.
DR GO; GO:0048546; P:digestive tract morphogenesis; IMP:MGI.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IMP:MGI.
DR GO; GO:0051541; P:elastin metabolic process; IMP:BHF-UCL.
DR GO; GO:0035162; P:embryonic hemopoiesis; IMP:MGI.
DR GO; GO:0001892; P:embryonic placenta development; IMP:MGI.
DR GO; GO:0061030; P:epithelial cell differentiation involved in mammary gland alveolus development; IMP:MGI.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0002067; P:glandular epithelial cell differentiation; IMP:MGI.
DR GO; GO:0002071; P:glandular epithelial cell maturation; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0001947; P:heart looping; IMP:MGI.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; IMP:MGI.
DR GO; GO:0097411; P:hypoxia-inducible factor-1alpha signaling pathway; IDA:MGI.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0060574; P:intestinal epithelial cell maturation; IMP:MGI.
DR GO; GO:0061072; P:iris morphogenesis; IGI:MGI.
DR GO; GO:0006089; P:lactate metabolic process; IMP:MGI.
DR GO; GO:0007595; P:lactation; IMP:MGI.
DR GO; GO:0097152; P:mesenchymal cell apoptotic process; IMP:MGI.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030502; P:negative regulation of bone mineralization; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0045926; P:negative regulation of growth; IMP:MGI.
DR GO; GO:2001054; P:negative regulation of mesenchymal cell apoptotic process; IMP:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; IMP:CACAO.
DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IMP:MGI.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0001755; P:neural crest cell migration; IMP:MGI.
DR GO; GO:0021502; P:neural fold elevation formation; IMP:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IGI:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:MGI.
DR GO; GO:0032364; P:oxygen homeostasis; IMP:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903599; P:positive regulation of autophagy of mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0070101; P:positive regulation of chemokine-mediated signaling pathway; ISO:MGI.
DR GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:BHF-UCL.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:MGI.
DR GO; GO:0046886; P:positive regulation of hormone biosynthetic process; ISO:MGI.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IMP:BHF-UCL.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IGI:MGI.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:1903715; P:regulation of aerobic respiration; IMP:ParkinsonsUK-UCL.
DR GO; GO:0050790; P:regulation of catalytic activity; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006110; P:regulation of glycolytic process; IGI:MGI.
DR GO; GO:2000434; P:regulation of protein neddylation; ISS:UniProtKB.
DR GO; GO:0070243; P:regulation of thymocyte apoptotic process; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0032909; P:regulation of transforming growth factor beta2 production; ISO:MGI.
DR GO; GO:0060992; P:response to fungicide; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IDA:MGI.
DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl.
DR GO; GO:0014850; P:response to muscle activity; IMP:MGI.
DR GO; GO:0000302; P:response to reactive oxygen species; ISS:UniProtKB.
DR GO; GO:0061298; P:retina vasculature development in camera-type eye; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0031929; P:TOR signaling; IMP:MGI.
DR GO; GO:0010573; P:vascular endothelial growth factor production; ISO:MGI.
DR GO; GO:0001944; P:vasculature development; IGI:MGI.
DR GO; GO:0008542; P:visual learning; IMP:MGI.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR001321; HIF-1_alpha.
DR InterPro; IPR014887; HIF-1_TAD_C.
DR InterPro; IPR021537; HIF_alpha_subunit.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF11413; HIF-1; 1.
DR Pfam; PF08778; HIF-1a_CTAD; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR PRINTS; PR01080; HYPOXIAIF1A.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative splicing; Cytoplasm;
KW DNA-binding; Hydroxylation; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; S-nitrosylation; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..836
FT /note="Hypoxia-inducible factor 1-alpha"
FT /id="PRO_0000127221"
FT DOMAIN 17..70
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 80..155
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 228..298
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 302..345
FT /note="PAC"
FT REGION 1..401
FT /note="Interaction with TSGA10"
FT /evidence="ECO:0000269|PubMed:16777103"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 21..30
FT /note="DNA-binding"
FT /evidence="ECO:0000269|PubMed:26245371"
FT REGION 170..191
FT /note="Required for heterodimer formation with ARNT"
FT /evidence="ECO:0000269|PubMed:26245371"
FT REGION 380..417
FT /note="N-terminal VHL recognition site"
FT REGION 401..613
FT /note="ODD"
FT REGION 492..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 544..588
FT /note="NTAD"
FT REGION 569..585
FT /note="C-terminal VHL recognition site"
FT REGION 589..795
FT /note="ID"
FT REGION 593..684
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 707..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 796..836
FT /note="CTAD"
FT MOTIF 728..731
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 593..633
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 649..678
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 707..725
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 247
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 402
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 545
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 564
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 568
FT /note="Phosphothreonine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 577
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 589
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 602
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 668
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 719
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 810
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT MOD_RES 813
FT /note="(3S)-3-hydroxyasparagine"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 391
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 476
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 545
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q16665"
FT CROSSLNK 545
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q16665, ECO:0000305"
FT CROSSLNK 551
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q16665, ECO:0000305"
FT CROSSLNK 560
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q16665, ECO:0000305"
FT VAR_SEQ 512..525
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8660378"
FT /id="VSP_007739"
FT MUTAGEN 170
FT /note="R->A: Decreases heterodimer formation with ARNT.
FT Impairs heterodimer formation with ARNT; when associated
FT with D-191."
FT /evidence="ECO:0000269|PubMed:26245371"
FT MUTAGEN 191
FT /note="V->D: Decreases heterodimer formation with ARNT.
FT Impairs heterodimer formation with ARNT; when associated
FT with A-170."
FT /evidence="ECO:0000269|PubMed:26245371"
FT CONFLICT 12
FT /note="K -> NR (in Ref. 4; BAC28578)"
FT /evidence="ECO:0000305"
FT CONFLICT 31
FT /note="S -> T (in Ref. 1; AAC52730)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="T -> A (in Ref. 1; AAC52730 and 6; CAA64833)"
FT /evidence="ECO:0000305"
FT CONFLICT 351
FT /note="I -> L (in Ref. 1; AAC52730)"
FT /evidence="ECO:0000305"
FT CONFLICT 369
FT /note="M -> K (in Ref. 5; AAH26139)"
FT /evidence="ECO:0000305"
FT CONFLICT 382
FT /note="D -> A (in Ref. 5; AAH26139)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="L -> H (in Ref. 4; BAC28578)"
FT /evidence="ECO:0000305"
FT CONFLICT 569
FT /note="D -> G (in Ref. 4; BAC28578)"
FT /evidence="ECO:0000305"
FT CONFLICT 660
FT /note="Q -> K (in Ref. 4; BAC28305)"
FT /evidence="ECO:0000305"
FT CONFLICT 700
FT /note="N -> K (in Ref. 1; AAC52730 and 2; AAC53455/
FT AAC53461)"
FT /evidence="ECO:0000305"
FT CONFLICT 799
FT /note="E -> V (in Ref. 6; CAA64833)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 836 AA; 93516 MW; 84D64ECAC2CC753B CRC64;
MEGAGGENEK KKMSSERRKE KSRDAARSRR SKESEVFYEL AHQLPLPHNV SSHLDKASVM
RLTISYLRVR KLLDAGGLDS EDEMKAQMDC FYLKALDGFV MVLTDDGDMV YISDNVNKYM
GLTQFELTGH SVFDFTHPCD HEEMREMLTH RNGPVRKGKE LNTQRSFFLR MKCTLTSRGR
TMNIKSATWK VLHCTGHIHV YDTNSNQPQC GYKKPPMTCL VLICEPIPHP SNIEIPLDSK
TFLSRHSLDM KFSYCDERIT ELMGYEPEEL LGRSIYEYYH ALDSDHLTKT HHDMFTKGQV
TTGQYRMLAK RGGYVWVETQ ATVIYNTKNS QPQCIVCVNY VVSGIIQHDL IFSLQQTESV
LKPVESSDMK MTQLFTKVES EDTSCLFDKL KKEPDALTLL APAAGDTIIS LDFGSDDTET
EDQQLEDVPL YNDVMFPSSN EKLNINLAMS PLPSSETPKP LRSSADPALN QEVALKLESS
PESLGLSFTM PQIQDQPASP SDGSTRQSSP ERLLQENVNT PNFSQPNSPS EYCFDVDSDM
VNVFKLELVE KLFAEDTEAK NPFSTQDTDL DLEMLAPYIP MDDDFQLRSF DQLSPLESNS
PSPPSMSTVT GFQQTQLQKP TITATATTTA TTDESKTETK DNKEDIKILI ASPSSTQVPQ
ETTTAKASAY SGTHSRTASP DRAGKRVIEQ TDKAHPRSLN LSATLNQRNT VPEEELNPKT
IASQNAQRKR KMEHDGSLFQ AAGIGTLLQQ PGDCAPTMSL SWKRVKGFIS SEQNGTEQKT
IILIPSDLAC RLLGQSMDES GLPQLTSYDC EVNAPIQGSR NLLQGEELLR ALDQVN
