HUMMR_MOUSE
ID HUMMR_MOUSE Reviewed; 283 AA.
AC Q8VI64; Q96EB2; Q9D9Y5;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Protein MGARP;
DE AltName: Full=Corneal endothelium-specific protein 1;
DE Short=CESP-1;
DE AltName: Full=Hypoxia up-regulated mitochondrial movement regulator protein;
DE AltName: Full=Mitochondria-localized glutamic acid-rich protein;
DE AltName: Full=Ovary-specific acidic protein;
GN Name=Mgarp; Synonyms=Cesp1, Hummr, Osap;
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 [MRNA].
RC TISSUE=Ovary;
RX PubMed=10919256; DOI=10.1210/endo.141.8.7627;
RA Hennebold J.D., Tanaka M., Saito J., Hanson B.R., Adashi E.Y.;
RT "Ovary-selective genes I: the generation and characterization of an ovary-
RT selective complementary deoxyribonucleic acid library.";
RL Endocrinology 141:2725-2734(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye, and Testis;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=16565373; DOI=10.1167/iovs.05-0602;
RA Kinouchi R., Kinouchi T., Hamamoto T., Saito T., Tavares A., Tsuru T.,
RA Yamagami S.;
RT "Distribution of CESP-1 protein in the corneal endothelium and other
RT tissues.";
RL Invest. Ophthalmol. Vis. Sci. 47:1397-1403(2006).
RN [5]
RP FUNCTION IN STEROIDOGENESIS, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=19325000; DOI=10.1210/en.2008-1584;
RA Matsumoto T., Minegishi K., Ishimoto H., Tanaka M., Hennebold J.D.,
RA Teranishi T., Hattori Y., Furuya M., Higuchi T., Asai S., Kim S.H.,
RA Miyakoshi K., Yoshimura Y.;
RT "Expression of ovary-specific acidic protein in steroidogenic tissues: a
RT possible role in steroidogenesis.";
RL Endocrinology 150:3353-3359(2009).
RN [6]
RP FUNCTION IN MITOCHONDRIAL TRANSPORT, INTERACTION WITH RHOT1; RHOT2; TRAK1
RP AND TRAK2, TOPOLOGY, INDUCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RX PubMed=19528298; DOI=10.1083/jcb.200811033;
RA Li Y., Lim S., Hoffman D., Aspenstrom P., Federoff H.J., Rempe D.A.;
RT "HUMMR, a hypoxia- and HIF-1alpha-inducible protein, alters mitochondrial
RT distribution and transport.";
RL J. Cell Biol. 185:1065-1081(2009).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=21447634; DOI=10.1210/en.2011-0050;
RA Zhou M., Wang Y., Qi S., Wang J., Zhang S.;
RT "The expression of a mitochondria-localized glutamic acid-rich protein
RT (MGARP/OSAP) is under the regulation of the HPG axis.";
RL Endocrinology 152:2311-2320(2011).
RN [8]
RP SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=20107910; DOI=10.1007/s11033-010-9948-x;
RA Qi S., Wang Y., Zhou M., Ge Y., Yan Y., Wang J., Zhang S.S., Zhang S.;
RT "A mitochondria-localized glutamic acid-rich protein (MGARP/OSAP) is highly
RT expressed in retina that exhibits a large area of intrinsic disorder.";
RL Mol. Biol. Rep. 38:2869-2877(2011).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION.
RX PubMed=24323429; DOI=10.1007/s12035-013-8602-8;
RA Jia L., Liang T., Yu X., Ma C., Zhang S.;
RT "MGARP regulates mouse neocortical development via mitochondrial
RT positioning.";
RL Mol. Neurobiol. 49:1293-1308(2014).
RN [10]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=31202457; DOI=10.1016/j.bbrc.2019.06.028;
RA Zhang S.;
RT "MGARP is ultrastructurally located in the inner faces of mitochondrial
RT membranes.";
RL Biochem. Biophys. Res. Commun. 516:138-143(2019).
CC -!- FUNCTION: Plays a role in the trafficking of mitochondria along
CC microtubules (PubMed:19325000). Regulates the kinesin-mediated axonal
CC transport of mitochondria to nerve terminals along microtubules during
CC hypoxia (PubMed:19325000). Participates in the translocation of
CC TRAK2/GRIF1 from the cytoplasm to the mitochondrion (PubMed:19325000).
CC Also plays a role in steroidogenesis through maintenance of
CC mitochondrial abundance and morphology (PubMed:19528298). Plays an
CC inhibitory role during neocortex development by regulating
CC mitochondrial morphology, distribution and motility in neocortical
CC neurons (PubMed:24323429). {ECO:0000269|PubMed:19325000,
CC ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:24323429}.
CC -!- SUBUNIT: Interacts with RHOT1/Miro-1, RHOT2/Miro-2, TRAK1/OIP106 and
CC TRAK2/GRIF1. {ECO:0000269|PubMed:19528298}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19325000,
CC ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20107910,
CC ECO:0000269|PubMed:24323429}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:19528298}; Single-pass type IV membrane protein
CC {ECO:0000305|PubMed:19528298}; Cytoplasmic side
CC {ECO:0000305|PubMed:19528298}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:31202457}; Single-pass type IV membrane protein
CC {ECO:0000305|PubMed:31202457}; Cytoplasmic side
CC {ECO:0000305|PubMed:31202457}. Note=Colocalizes with RHOT1, RHOT2,
CC TRAK1 and TRAK2 at the mitochondrion. {ECO:0000269|PubMed:19528298}.
CC -!- TISSUE SPECIFICITY: Expressed in the ovary, testis, brain, adrenal
CC glands and the compartments of the visual nervous system. Expressed in
CC corneal endothelium (CE) (at protein level). Expressed in steroidogenic
CC tissues with the highest level of expression observed in the adrenal
CC gland. Weakly expressed in placenta. Weakly expressed in astrocytes and
CC neurons under normoxia. Strongly expressed in astrocytes and neurons
CC under hypoxia. Expressed in each layer of the retina, with particularly
CC higher staining in the inner segment of the photoreceptor (IS), the
CC outer plexiform layer (OPL) and the ganglion cell layer (GCL).
CC {ECO:0000269|PubMed:16565373, ECO:0000269|PubMed:19325000,
CC ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20107910,
CC ECO:0000269|PubMed:21447634}.
CC -!- INDUCTION: Up-regulated by chorionic gonadotropin in ovary. Up-
CC regulated by hypoxia in a HIF-1A-dependent manner in neurons and
CC astrocytes. Up-regulated during gonad development after birth, probably
CC under the regulation of hormones derived from the hypothalamic-
CC pituitary-gonadal (HPG) axis. {ECO:0000269|PubMed:19325000,
CC ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20107910}.
CC -!- DISRUPTION PHENOTYPE: Reduction of mitochondrial motion in the
CC anterograde direction and increase of mitochondrial motion in the
CC retrograde direction in response to hypoxia (PubMed:19528298). The
CC number of motile mitochondria is not altered (PubMed:19528298).
CC Neocortical neurons exhibit a remarkable increase of the dendritic
CC number and the axon length (PubMed:24323429). Neuronal cells show an
CC increase in the percentage of round mitochondria and a decrease in the
CC percentage of rod or tubular mitochondria (PubMed:24323429).
CC {ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:24323429}.
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DR EMBL; AF228502; AAL55654.1; -; mRNA.
DR EMBL; AK006339; BAB24535.1; -; mRNA.
DR EMBL; AK151401; BAE30369.1; -; mRNA.
DR EMBL; BC012511; AAH12511.1; -; mRNA.
DR EMBL; BC049556; AAH49556.1; -; mRNA.
DR CCDS; CCDS17338.1; -.
DR RefSeq; NP_080634.2; NM_026358.3.
DR AlphaFoldDB; Q8VI64; -.
DR STRING; 10090.ENSMUSP00000040703; -.
DR iPTMnet; Q8VI64; -.
DR PhosphoSitePlus; Q8VI64; -.
DR jPOST; Q8VI64; -.
DR MaxQB; Q8VI64; -.
DR PaxDb; Q8VI64; -.
DR PRIDE; Q8VI64; -.
DR ProteomicsDB; 273354; -.
DR Antibodypedia; 7361; 123 antibodies from 19 providers.
DR Ensembl; ENSMUST00000038154; ENSMUSP00000040703; ENSMUSG00000037161.
DR GeneID; 67749; -.
DR KEGG; mmu:67749; -.
DR UCSC; uc008pdx.2; mouse.
DR CTD; 84709; -.
DR MGI; MGI:1914999; Mgarp.
DR VEuPathDB; HostDB:ENSMUSG00000037161; -.
DR eggNOG; ENOG502S6ZU; Eukaryota.
DR GeneTree; ENSGT00440000037338; -.
DR HOGENOM; CLU_088276_0_0_1; -.
DR InParanoid; Q8VI64; -.
DR OMA; YTYRTVT; -.
DR OrthoDB; 1441982at2759; -.
DR PhylomeDB; Q8VI64; -.
DR TreeFam; TF336324; -.
DR BioGRID-ORCS; 67749; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Mgarp; mouse.
DR PRO; PR:Q8VI64; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8VI64; protein.
DR Bgee; ENSMUSG00000037161; Expressed in epithelium of lens and 113 other tissues.
DR ExpressionAtlas; Q8VI64; baseline and differential.
DR Genevisible; Q8VI64; MM.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0008089; P:anterograde axonal transport; IMP:UniProtKB.
DR GO; GO:0061564; P:axon development; IMP:UniProtKB.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IMP:UniProtKB.
DR GO; GO:0097211; P:cellular response to gonadotropin-releasing hormone; IDA:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IMP:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:2000171; P:negative regulation of dendrite development; IMP:UniProtKB.
DR GO; GO:0010822; P:positive regulation of mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0006626; P:protein targeting to mitochondrion; IDA:UniProtKB.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:UniProtKB.
DR GO; GO:0008090; P:retrograde axonal transport; IMP:UniProtKB.
DR InterPro; IPR026093; MGARP.
DR InterPro; IPR032773; MGARP_N.
DR PANTHER; PTHR22910; PTHR22910; 1.
DR Pfam; PF14962; AIF-MLS; 1.
PE 1: Evidence at protein level;
KW Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..283
FT /note="Protein MGARP"
FT /id="PRO_0000318765"
FT TOPO_DOM 1..41
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:19528298,
FT ECO:0000305|PubMed:31202457"
FT TRANSMEM 42..64
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..283
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305|PubMed:19528298,
FT ECO:0000305|PubMed:31202457"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..283
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 159..187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 196..217
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..249
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..283
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 4
FT /note="R -> S (in Ref. 2; BAB24535)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 283 AA; 29925 MW; AFF16FC5E70536CF CRC64;
MYLRRAVSKT LALPRRAPPG PAPLGKDASL RRMSSRKFPG TSGSNMIYYL VVGVTVSAGG
YYTYKALTSK QVRRTEHVAE PKEQTKAELQ PLPGEKEEHV AEAEQVCSEP GDTAVTEAES
VDAEEVPEAA VVLPEESQAS APSEVPAEAA VVEASLSSSE PELKITEASL VETTESVPES
TQEVESAAPD QDDVCNEGAD TSQEGADTSQ EGADTSQEGA DTTKEEADNS KEAEGTTTED
PRSISEESAE LEESPPLGSE PPAQPESQEE ETQVTEETAS PQG
