CEIP2_MOUSE
ID CEIP2_MOUSE Reviewed; 1383 AA.
AC Q5FWI3; Q3UE15; Q3UE98; Q6DFZ0; Q6ZPR7; Q8VE53; Q9QY22;
DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Cell surface hyaluronidase {ECO:0000303|PubMed:10767548};
DE EC=3.2.1.35 {ECO:0000250|UniProtKB:Q9UHN6};
DE AltName: Full=Cell migration-inducing hyaluronidase 2 {ECO:0000250|UniProtKB:Q9UHN6};
DE AltName: Full=Transmembrane protein 2 {ECO:0000303|PubMed:10767548};
GN Name=Cemip2 {ECO:0000312|MGI:MGI:1890373};
GN Synonyms=Kiaa1412 {ECO:0000303|PubMed:14621295},
GN Tmem2 {ECO:0000303|PubMed:10767548};
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, and Czech II; TISSUE=Brain, and 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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-235.
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] OF 415-1383.
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1033-1383, AND TISSUE SPECIFICITY.
RX PubMed=10767548; DOI=10.1016/s0378-1119(00)00090-1;
RA Scott D.A., Drury S., Sundstrom R.A., Bishop J., Swiderski R.E., Carmi R.,
RA Ramesh A., Elbedour K., Srikumari Srisailapathy C.R., Keats B.J.,
RA Sheffield V.C., Smith R.J.H.;
RT "Refining the DFNB7-DFNB11 deafness locus using intragenic polymorphisms in
RT a novel gene, TMEM2.";
RL Gene 246:265-274(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-292 AND ASN-914.
RC TISSUE=Myoblast;
RX PubMed=19656770; DOI=10.1074/mcp.m900195-mcp200;
RA Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D.,
RA Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.;
RT "The mouse C2C12 myoblast cell surface N-linked glycoproteome:
RT identification, glycosite occupancy, and membrane orientation.";
RL Mol. Cell. Proteomics 8:2555-2569(2009).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-292 AND ASN-1234.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-53, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, and Spleen;
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 [9]
RP DEVELOPMENTAL STAGE.
RX PubMed=21896629; DOI=10.1242/dev.065375;
RA Smith K.A., Lagendijk A.K., Courtney A.D., Chen H., Paterson S.,
RA Hogan B.M., Wicking C., Bakkers J.;
RT "Transmembrane protein 2 (Tmem2) is required to regionally restrict
RT atrioventricular canal boundary and endocardial cushion development.";
RL Development 138:4193-4198(2011).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=28246172; DOI=10.1074/jbc.m116.770149;
RA Yamamoto H., Tobisawa Y., Inubushi T., Irie F., Oyama C., Yamaguchi Y.;
RT "A Mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is
RT the long-sought-after cell surface hyaluronidase.";
RL J. Biol. Chem. 292:7304-7313(2017).
CC -!- FUNCTION: Cell surface hyaluronidase that mediates the initial cleavage
CC of extracellular high-molecular-weight hyaluronan into intermediate-
CC size hyaluronan of approximately 5 kDa fragments (By similarity). Acts
CC as a regulator of angiogenesis and heart morphogenesis by mediating
CC degradation of extracellular hyaluronan, thereby regulating VEGF
CC signaling (By similarity). Is very specific to hyaluronan; not able to
CC cleave chondroitin sulfate or dermatan sulfate (By similarity).
CC {ECO:0000250|UniProtKB:A3KPQ7, ECO:0000250|UniProtKB:Q9UHN6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-
CC glucosamine and D-glucuronate residues in hyaluronate.; EC=3.2.1.35;
CC Evidence={ECO:0000250|UniProtKB:Q9UHN6};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q9UHN6};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UHN6};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9UHN6}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10767548,
CC ECO:0000269|PubMed:28246172}.
CC -!- DEVELOPMENTAL STAGE: expressed ubiquitously at early stages of
CC development. Expressed in the endocardial cells lining the ventricles
CC and atria at 9.5 dpc. {ECO:0000269|PubMed:21896629}.
CC -!- SIMILARITY: Belongs to the CEMIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH19745.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC019745; AAH19745.1; ALT_INIT; mRNA.
DR EMBL; BC076570; AAH76570.1; -; mRNA.
DR EMBL; BC089353; AAH89353.1; -; mRNA.
DR EMBL; AK149667; BAE29013.1; -; mRNA.
DR EMBL; AK149803; BAE29096.1; -; mRNA.
DR EMBL; AK129352; BAC98162.1; -; mRNA.
DR EMBL; AF137031; AAF21349.1; -; mRNA.
DR CCDS; CCDS37934.1; -.
DR RefSeq; NP_001028931.1; NM_001033759.2.
DR RefSeq; NP_114386.3; NM_031997.4.
DR RefSeq; XP_006527549.1; XM_006527486.3.
DR RefSeq; XP_006527550.1; XM_006527487.3.
DR AlphaFoldDB; Q5FWI3; -.
DR SMR; Q5FWI3; -.
DR STRING; 10090.ENSMUSP00000093908; -.
DR GlyConnect; 2793; 4 N-Linked glycans (4 sites).
DR GlyGen; Q5FWI3; 5 sites, 4 N-linked glycans (4 sites).
DR iPTMnet; Q5FWI3; -.
DR PhosphoSitePlus; Q5FWI3; -.
DR SwissPalm; Q5FWI3; -.
DR EPD; Q5FWI3; -.
DR jPOST; Q5FWI3; -.
DR MaxQB; Q5FWI3; -.
DR PaxDb; Q5FWI3; -.
DR PeptideAtlas; Q5FWI3; -.
DR PRIDE; Q5FWI3; -.
DR ProteomicsDB; 259253; -.
DR Antibodypedia; 43356; 72 antibodies from 19 providers.
DR DNASU; 83921; -.
DR Ensembl; ENSMUST00000025663; ENSMUSP00000025663; ENSMUSG00000024754.
DR Ensembl; ENSMUST00000096194; ENSMUSP00000093908; ENSMUSG00000024754.
DR GeneID; 83921; -.
DR KEGG; mmu:83921; -.
DR UCSC; uc008gzg.2; mouse.
DR CTD; 23670; -.
DR MGI; MGI:1890373; Cemip2.
DR VEuPathDB; HostDB:ENSMUSG00000024754; -.
DR eggNOG; ENOG502QUM7; Eukaryota.
DR GeneTree; ENSGT00940000153636; -.
DR HOGENOM; CLU_005606_0_0_1; -.
DR InParanoid; Q5FWI3; -.
DR OMA; KDVSNCM; -.
DR OrthoDB; 294134at2759; -.
DR PhylomeDB; Q5FWI3; -.
DR TreeFam; TF316575; -.
DR BioGRID-ORCS; 83921; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Tmem2; mouse.
DR PRO; PR:Q5FWI3; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q5FWI3; protein.
DR Bgee; ENSMUSG00000024754; Expressed in rostral migratory stream and 246 other tissues.
DR ExpressionAtlas; Q5FWI3; baseline and differential.
DR Genevisible; Q5FWI3; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030214; P:hyaluronan catabolic process; ISS:UniProtKB.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; ISS:UniProtKB.
DR CDD; cd13938; PANDER_like_TMEM2; 1.
DR InterPro; IPR019316; G8_domain.
DR InterPro; IPR039477; ILEI/PANDER_dom.
DR InterPro; IPR011050; Pectin_lyase_fold/virulence.
DR InterPro; IPR039473; TMEM2_PANDER-like.
DR Pfam; PF10162; G8; 1.
DR Pfam; PF15711; ILEI; 2.
DR SMART; SM01225; G8; 1.
DR SUPFAM; SSF51126; SSF51126; 1.
DR PROSITE; PS51484; G8; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Cell membrane; Developmental protein; Glycoprotein;
KW Glycosidase; Hydrolase; Membrane; Phosphoprotein; Reference proteome;
KW Repeat; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..1383
FT /note="Cell surface hyaluronidase"
FT /id="PRO_0000289973"
FT TOPO_DOM 1..82
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 83..103
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 104..1383
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 121..245
FT /note="G8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817"
FT REPEAT 669..691
FT /note="PbH1 1"
FT REPEAT 711..733
FT /note="PbH1 2"
FT REPEAT 791..812
FT /note="PbH1 3"
FT REGION 1..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 46..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHN6"
FT MOD_RES 53
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHN6"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973,
FT ECO:0000269|PubMed:19656770"
FT CARBOHYD 914
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19656770"
FT CARBOHYD 1234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CONFLICT 165
FT /note="D -> G (in Ref. 2; BAE29013)"
FT /evidence="ECO:0000305"
FT CONFLICT 1134
FT /note="A -> S (in Ref. 4; AAF21349)"
FT /evidence="ECO:0000305"
FT CONFLICT 1161
FT /note="K -> R (in Ref. 4; AAF21349)"
FT /evidence="ECO:0000305"
FT CONFLICT 1180
FT /note="A -> G (in Ref. 4; AAF21349)"
FT /evidence="ECO:0000305"
FT CONFLICT 1245
FT /note="A -> V (in Ref. 1; AAH19745)"
FT /evidence="ECO:0000305"
FT CONFLICT 1249
FT /note="I -> V (in Ref. 1; AAH19745)"
FT /evidence="ECO:0000305"
FT CONFLICT 1306
FT /note="V -> L (in Ref. 1; AAH19745)"
FT /evidence="ECO:0000305"
FT CONFLICT 1342
FT /note="D -> N (in Ref. 1; AAH19745)"
FT /evidence="ECO:0000305"
FT CONFLICT 1382
FT /note="V -> L (in Ref. 1; AAH76570)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1383 AA; 153801 MW; 7AB8F747A8FC659C CRC64;
MYAAGSRGHS PAFLQPQNGN GHRSPGYVPG KVVPLRPAPP PKNHASAKLT SRSQDAPATF
AFSPEEQRTP SESRKRKRHK NTFICFAITS FSFFVALAVI LGISSKYAPD ENCPDQNPRL
RNWDPGQDSA KHIVIKEGDL FRLTSDATVD SIVIQDGGLL VFGDDKDGSK NITLRTRYIL
IQDGGALHIG AEKCRYRSKA TITLYGKSDE RESMPIFGKK FIGVEAGGTL ELHGAQRTSW
TMLARTLHSS GLPFGSYAFE KDFSRGLNVR VIDQDTARVL ENEKFDTHEY HNESRRLQEF
LRAQEPGRIV AIAVGDSAVK SLLQGTIQMI QDRLGSKLIQ GLGYRQAWAL VGVIDGGSSS
CNESVRNYEN HSTGGKALAQ GEFYTLDGQK FSVTAYSEWS QGISLSGFRV DIADGVKLHL
LDDVSTWEAG DRIVVASTDY SMYQAEELTL LRCPECSRSQ VKVKEIPQYL HVGEIIDGID
MRAEVGLLTR NIVIQGEMED SCYAENHCQF FDYDTFGGHV MIEKNFTSVH LSYVELKHMG
QQHMGRYPVH FHLCGDVDSK GGYSQPASVD GLSVHHSFSR CITVHGTSGL LIKDTIGFDT
LGHCFFLEDG VEQRNILYHN LGLLTKPGTL LPTDRNSSMC TVMRDGVFGN YVPVPTTDCM
AVSTFWIAHP NNHLINNAAA GSQDAGIWYL FHKEPTGESS GLQLLEKPEL TPLGIFYNNR
VHSNFKAGLF VDKGVKTTNA SASDPREYLC LDNSARFRPH QDADPEKPRV AAIIDRLIAF
KNNDNGAWVR GGDIIVQNSA FADNGKGLTF ASDGSFPSDE GSSQEVTESL FVGESRNYGF
QGGQNKYMGT GGIDQKPRTL PRNRTFPIRG FQIYDGPIHL TKSTFKKYVP TPDRYSSAIG
FLMKNSWQTT PRNNVSLVKF GPQVSLNVFF GKPGPWFEDC ELDGDKNSIF HDIDGSVTGY
KDTYVGRMDN YLIRHPNCVN VTKWNAVICS GTYAQVYVQT WNTPNLSMII TRDEYPSHPM
VLRGINQRAI SPQYQPVVML EKGYTIHWNG PAPRTTFLYL VNFNKDDWIR VGLCYPANTS
FQVTVGFLQR QNGSLSRIED YEPARSMEEL QKKPSERKFY FDSGTGLLFL YLRAHSHRDG
HSYCSSQGCE RVKIQAATDS KDISNCMAKA YPQYYKKPSA VKRMPAMLTG LCQGCGTHQM
VFTSDPHKSY LPVRFQSPGK AEIQRGDPSI ISVNGTDFTF RSAGALLLIV DACSVPFRVK
EKRMFLSADV SHMEEYFKAS IPPRSIVLLS TRGEIKQLNI SDSLAVLGLA KPAHLYSKGS
VVFLGFSGNF APSWTKLFTS PDEQGLGVLE QFLPLQMEEY GCSRTGSVHR RDLDLLQQAL
KVL
