DRP2_MOUSE
ID DRP2_MOUSE Reviewed; 957 AA.
AC Q05AA6; Q61095; Q8C4R1;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 14-NOV-2006, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Dystrophin-related protein 2;
DE Short=DRP-2;
GN Name=Drp2;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 391-862, AND TISSUE SPECIFICITY.
RX PubMed=8640231; DOI=10.1038/ng0696-223;
RA Roberts R.G., Freeman T.C., Kendall E., Vetrie D.L.P., Dixon A.K.,
RA Shaw-Smith C., Bone Q., Bobrow M.;
RT "Characterization of DRP2, a novel human dystrophin homologue.";
RL Nat. Genet. 13:223-226(1996).
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION IN A COMPLEX
RP WITH PRX; UTRN; DMD AND DAG1.
RX PubMed=11430802; DOI=10.1016/s0896-6273(01)00327-0;
RA Sherman D.L., Fabrizi C., Gillespie C.S., Brophy P.J.;
RT "Specific disruption of a Schwann cell dystrophin-related protein complex
RT in a demyelinating neuropathy.";
RL Neuron 30:677-687(2001).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INTERACTION WITH PRX, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION
RP AT SER-748 AND THR-910, DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22764250; DOI=10.1523/jneurosci.1220-12.2012;
RA Sherman D.L., Wu L.M., Grove M., Gillespie C.S., Brophy P.J.;
RT "Drp2 and periaxin form Cajal bands with dystroglycan but have distinct
RT roles in Schwann cell growth.";
RL J. Neurosci. 32:9419-9428(2012).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=23152929; DOI=10.1371/journal.pone.0049722;
RA Fuhrmann-Stroissnigg H., Noiges R., Descovich L., Fischer I.,
RA Albrecht D.E., Nothias F., Froehner S.C., Propst F.;
RT "The light chains of microtubule-associated proteins MAP1A and MAP1B
RT interact with alpha1-syntrophin in the central and peripheral nervous
RT system.";
RL PLoS ONE 7:E49722-E49722(2012).
CC -!- FUNCTION: Required for normal myelination and for normal organization
CC of the cytoplasm and the formation of Cajal bands in myelinating
CC Schwann cells (PubMed:22764250). Required for normal PRX location at
CC appositions between the abaxonal surface of the myelin sheath and the
CC Schwann cell plasma membrane (PubMed:22764250). Possibly involved in
CC membrane-cytoskeleton interactions of the central nervous system.
CC {ECO:0000250, ECO:0000269|PubMed:22764250}.
CC -!- SUBUNIT: Interacts with PRX; this enhances phosphorylation
CC (PubMed:22764250). Identified in a dystroglycan complex that contains
CC at least PRX, DRP2, UTRN, DMD and DAG1 (PubMed:11430802).
CC {ECO:0000269|PubMed:11430802, ECO:0000269|PubMed:22764250}.
CC -!- SUBCELLULAR LOCATION: Postsynaptic density
CC {ECO:0000250|UniProtKB:Q9EPA0}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q9EPA0}. Perikaryon
CC {ECO:0000250|UniProtKB:Q9EPA0}. Cell membrane
CC {ECO:0000269|PubMed:11430802, ECO:0000269|PubMed:22764250,
CC ECO:0000269|PubMed:23152929}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22764250}. Note=Detected in Schwann cells at
CC periaxonal myelin membranes. {ECO:0000269|PubMed:22764250}.
CC -!- TISSUE SPECIFICITY: Detected in quadriceps nerve Schwann cells
CC (PubMed:22764250). Detected in sciatic nerve (PubMed:11430802,
CC PubMed:22764250). Detected in trigeminal nerve Schwann cells (at
CC protein level) (PubMed:11430802). Detected in brain and spinal cord
CC (PubMed:8640231). {ECO:0000269|PubMed:11430802,
CC ECO:0000269|PubMed:22764250, ECO:0000269|PubMed:8640231}.
CC -!- DISRUPTION PHENOTYPE: Mice with a Schwann cell-specific gene disruption
CC show no obvious impairment of nerve conduction velocity and display no
CC visible defects of their motor skills. After six months, about 6% of
CC their nerve fibers present myelination defects, including myelin
CC outfoldings, focal hypermyelination, and onion bulbs with thin myelin
CC and supernumerary Schwann cells. At the molecular level, Schwann cell-
CC specific gene disruption impairs formation of Cajal bands and location
CC of Prx in patches that colocalize with appositions between the abaxonal
CC surface of the myelin sheath and the Schwann cell plasma membrane.
CC Cytoplasm from mutant Schwann cells forms an annulus under the cell
CC membrane, insted of being strictly compartmentalized. Besides, mutant
CC nerves display increased numbers of Schmidt-Lanterman incisures.
CC {ECO:0000269|PubMed:22764250}.
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DR EMBL; AK081426; BAC38217.1; -; mRNA.
DR EMBL; AL672064; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC125345; AAI25346.1; -; mRNA.
DR EMBL; BC125347; AAI25348.1; -; mRNA.
DR EMBL; U43520; AAC52607.1; -; mRNA.
DR CCDS; CCDS30394.1; -.
DR RefSeq; NP_034208.2; NM_010078.3.
DR AlphaFoldDB; Q05AA6; -.
DR SMR; Q05AA6; -.
DR BioGRID; 199313; 4.
DR CORUM; Q05AA6; -.
DR STRING; 10090.ENSMUSP00000115246; -.
DR iPTMnet; Q05AA6; -.
DR PhosphoSitePlus; Q05AA6; -.
DR MaxQB; Q05AA6; -.
DR PaxDb; Q05AA6; -.
DR PRIDE; Q05AA6; -.
DR ProteomicsDB; 277499; -.
DR Antibodypedia; 506; 68 antibodies from 17 providers.
DR DNASU; 13497; -.
DR Ensembl; ENSMUST00000113226; ENSMUSP00000108852; ENSMUSG00000000223.
DR Ensembl; ENSMUST00000113228; ENSMUSP00000108854; ENSMUSG00000000223.
DR Ensembl; ENSMUST00000153424; ENSMUSP00000115246; ENSMUSG00000000223.
DR GeneID; 13497; -.
DR KEGG; mmu:13497; -.
DR UCSC; uc009uga.2; mouse.
DR CTD; 1821; -.
DR MGI; MGI:107432; Drp2.
DR VEuPathDB; HostDB:ENSMUSG00000000223; -.
DR eggNOG; KOG4286; Eukaryota.
DR GeneTree; ENSGT00940000153467; -.
DR HOGENOM; CLU_001187_0_0_1; -.
DR InParanoid; Q05AA6; -.
DR OMA; QADHVMD; -.
DR TreeFam; TF337303; -.
DR BioGRID-ORCS; 13497; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Drp2; mouse.
DR PRO; PR:Q05AA6; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q05AA6; protein.
DR Bgee; ENSMUSG00000000223; Expressed in sciatic nerve and 162 other tissues.
DR ExpressionAtlas; Q05AA6; baseline and differential.
DR Genevisible; Q05AA6; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007417; P:central nervous system development; IEA:InterPro.
DR GO; GO:0050808; P:synapse organization; ISO:MGI.
DR GO; GO:0099536; P:synaptic signaling; IBA:GO_Central.
DR CDD; cd00176; SPEC; 1.
DR CDD; cd00201; WW; 1.
DR Gene3D; 3.30.60.90; -; 1.
DR InterPro; IPR017433; Dystrophin-related_2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR015153; EF-hand_dom_typ1.
DR InterPro; IPR015154; EF-hand_dom_typ2.
DR InterPro; IPR018159; Spectrin/alpha-actinin.
DR InterPro; IPR002017; Spectrin_repeat.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR InterPro; IPR000433; Znf_ZZ.
DR InterPro; IPR043145; Znf_ZZ_sf.
DR Pfam; PF09068; EF-hand_2; 1.
DR Pfam; PF09069; EF-hand_3; 1.
DR Pfam; PF00435; Spectrin; 2.
DR Pfam; PF00397; WW; 1.
DR Pfam; PF00569; ZZ; 1.
DR PIRSF; PIRSF038205; Dystrophin-related_p2; 1.
DR SMART; SM00150; SPEC; 2.
DR SMART; SM00456; WW; 1.
DR SMART; SM00291; ZnF_ZZ; 1.
DR SUPFAM; SSF47473; SSF47473; 2.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
DR PROSITE; PS01357; ZF_ZZ_1; 1.
DR PROSITE; PS50135; ZF_ZZ_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Synapse; Zinc; Zinc-finger.
FT CHAIN 1..957
FT /note="Dystrophin-related protein 2"
FT /id="PRO_0000345015"
FT REPEAT 102..179
FT /note="Spectrin 1"
FT REPEAT 231..337
FT /note="Spectrin 2"
FT DOMAIN 358..383
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT ZN_FING 605..661
FT /note="ZZ-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT REGION 876..923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 879..898
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 610
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 613
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 634
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 637
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT MOD_RES 748
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22764250"
FT MOD_RES 910
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22764250"
FT CONFLICT 362
FT /note="I -> F (in Ref. 1; BAC38217)"
FT /evidence="ECO:0000305"
FT CONFLICT 598
FT /note="V -> VLHRV (in Ref. 4; AAC52607)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 957 AA; 108050 MW; B8F759D964118315 CRC64;
MQPLVMQGCP YTLPRCHEWH AADRFHHSSS LRNTCPQPQV RAAVTIPAPP WDGAGDPCLS
PKLLNGTVGA TGPLEPSAMN LCWNEIKKKS HNLRARLEAF SDLSGKLQLP LREIIDWLSQ
KDEELSAQLP LQGDVALVQQ EKETHAAFME EVKSKGPYIS SVLESAQAFL SQHPFEELEE
SQSESKDTSP RQRIQNLSRF VWKQATVASE LWEKLTARCV DQHRHIEHTL EHLLEIQGAM
EELSSTLTQA EGVRATWEPI GDLFIDSLPE HIQAIKLFKE EFSPVKDGVK LVNDLAHQLA
ISDVHLSMEN SRALEQINIR WKQLQVSVAE RLKQLQDAHR DFGPGSQHFL STSVQVPWER
AISPNKVPYY INHQAQTTCW DHPKMTELYQ TLADLNNIKF SAYRTAMKLR RVQKALRLDL
VTLTTALEIF NEHDLQASEH VMDVVEVIHC LTALYERLEE ERGILVNVPL CVDMSLNWLL
NVFDSGRSGK MRALSFKTGI ACLCGTEVKE KLQYLFSQVA NSGSQCDQRH LGALLHEAIQ
VPRQLGEVAA FGGSNVEPSV RSCFRFSTGK PVIEASQFLE WVNLEPQSMV WLAVLHRVTI
AEQVKHQTKC SICRQCPIKG FRYRSLKQFN VDICQTCFLT GRASKGNKLH YPIMEYYTPT
TSSENMRDFA TTLKNKFRSK QYFSKHPQRG YLPVQSVLES DCSETPASSP MLPHADTHSR
IEHFASRLAE MESQNCSFFN DSLSPDDSID EDQYLLRHSS PITDREPAFG QQAPCSMATE
SKGELEKILA HLEDENRILQ GELRRLKWQH EEAAEAPTLV EGSAEATPDH RNEELLAEAR
ILRQHKSRLE TRMQILEDHN KQLESQLQRL RELLLQPPSE SDGNGSAGSS LASSPRQSEG
SHPREKGQTT PDTEVADDVG SKSQDVSLCL EDIMEKLRHA FPSVRSSDVT ANTLLAS
