CEIP2_DANRE
ID CEIP2_DANRE Reviewed; 1378 AA.
AC A3KPQ7;
DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Cell surface hyaluronidase {ECO:0000303|PubMed:21896629, ECO:0000303|PubMed:21896630};
DE EC=3.2.1.35 {ECO:0000305|PubMed:28118600};
DE AltName: Full=Cell migration-inducing hyaluronidase 2 {ECO:0000250|UniProtKB:Q9UHN6};
DE AltName: Full=Protein frozen ventricle {ECO:0000303|PubMed:21896630};
DE AltName: Full=Protein wickham {ECO:0000303|PubMed:21896629};
DE AltName: Full=Transmembrane protein 2 {ECO:0000303|PubMed:21896629, ECO:0000303|PubMed:21896630};
GN Name=cemip2;
GN Synonyms=frv {ECO:0000303|PubMed:21896630},
GN tmem2 {ECO:0000303|PubMed:21896629, ECO:0000303|PubMed:21896630},
GN wkm {ECO:0000303|PubMed:21896629};
GN ORFNames=si:dkey-24k20.1 {ECO:0000303|PubMed:23594743};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND 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 [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=21896630; DOI=10.1242/dev.064261;
RA Totong R., Schell T., Lescroart F., Ryckebusch L., Lin Y.F., Zygmunt T.,
RA Herwig L., Krudewig A., Gershoony D., Belting H.G., Affolter M.,
RA Torres-Vazquez J., Yelon D.;
RT "The novel transmembrane protein Tmem2 is essential for coordination of
RT myocardial and endocardial morphogenesis.";
RL Development 138:4199-4205(2011).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27471259; DOI=10.1242/dev.139485;
RA Ryckebuesch L., Hernandez L., Wang C., Phan J., Yelon D.;
RT "Tmem2 regulates cell-matrix interactions that are essential for muscle
RT fiber attachment.";
RL Development 143:2965-2972(2016).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF VAL-426; TRP-429; ARG-434 AND PHE-608.
RX PubMed=28118600; DOI=10.1016/j.devcel.2016.12.017;
RA De Angelis J.E., Lagendijk A.K., Chen H., Tromp A., Bower N.I., Tunny K.A.,
RA Brooks A.J., Bakkers J., Francois M., Yap A.S., Simons C., Wicking C.,
RA Hogan B.M., Smith K.A.;
RT "Tmem2 regulates embryonic Vegf signaling by controlling hyaluronic acid
RT turnover.";
RL Dev. Cell 40:123-136(2017).
CC -!- FUNCTION: Cell surface hyaluronidase that mediates the initial cleavage
CC of extracellular high-molecular-weight hyaluronan into intermediate-
CC size hyaluronan (PubMed:28118600). Acts as a regulator of angiogenesis
CC in embryos by mediating degradation of extracellular hyaluronan,
CC thereby promoting VEGF signaling (PubMed:28118600). Acts as a regulator
CC of heart development during myocardial and endocardial morphogenesis:
CC involved in the looping stage of heart morphogenesis (PubMed:21896629).
CC Stimulates migration of endocardial cells and increases both myocardial
CC and endocardial fusion (PubMed:21896630). Involved in the restriction
CC of endocardial cushions (ECs) formation to the atrioventricular canal
CC (AVC) (PubMed:21896630). Also required for muscle fiber attachment
CC (PubMed:27471259). Is very specific to hyaluronan; not able to cleave
CC chondroitin sulfate or dermatan sulfate (By similarity).
CC {ECO:0000250|UniProtKB:Q9UHN6, ECO:0000269|PubMed:21896629,
CC ECO:0000269|PubMed:21896630, ECO:0000269|PubMed:27471259,
CC ECO:0000269|PubMed:28118600}.
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:0000305|PubMed:28118600};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q9UHN6};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28118600};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:28118600}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed at the 2 cell stage. Ubiquitously expressed at the 22-somite
CC stage. Expressed in the brain and head mesenchyme, otic vesicles, fin
CC buds, caudal vein and the heart (both myocardial and endocardial cells)
CC at 24 hours post fertilization (hpf). {ECO:0000269|PubMed:21896629,
CC ECO:0000269|PubMed:21896630}.
CC -!- DISRUPTION PHENOTYPE: Embryos show defects in heart morphogenesis:
CC while heart development is normal at the linear heart tube stage,
CC cardiac looping is lost at later developmental stages
CC (PubMed:21896629). Defects during the endocardial morphogenesis,
CC characterized by the formation of ectopic atrioventricular canal in the
CC ventricular myocardium and endocardium (PubMed:21896630). Maternal-
CC zygotic mutants also display muscle fiber detachment, associated with
CC impaired laminin organization and ineffective fibronectin degradation
CC at the myotendinous junction (PubMed:27471259). Defects in
CC angiogenesis, characterized by embryos with no venous sprouting
CC (PubMed:28118600). {ECO:0000269|PubMed:21896629,
CC ECO:0000269|PubMed:21896630, ECO:0000269|PubMed:27471259,
CC ECO:0000269|PubMed:28118600}.
CC -!- SIMILARITY: Belongs to the CEMIP family. {ECO:0000305}.
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; BX294191; CAM56649.1; -; Genomic_DNA.
DR RefSeq; NP_001092919.1; NM_001099449.1.
DR AlphaFoldDB; A3KPQ7; -.
DR SMR; A3KPQ7; -.
DR STRING; 7955.ENSDARP00000082444; -.
DR PaxDb; A3KPQ7; -.
DR PeptideAtlas; A3KPQ7; -.
DR PRIDE; A3KPQ7; -.
DR Ensembl; ENSDART00000133217; ENSDARP00000118976; ENSDARG00000061600.
DR GeneID; 566851; -.
DR KEGG; dre:566851; -.
DR CTD; 23670; -.
DR ZFIN; ZDB-GENE-030131-2179; cemip2.
DR eggNOG; ENOG502QUM7; Eukaryota.
DR GeneTree; ENSGT00940000153636; -.
DR InParanoid; A3KPQ7; -.
DR PhylomeDB; A3KPQ7; -.
DR PRO; PR:A3KPQ7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000061600; Expressed in muscle tissue and 39 other tissues.
DR ExpressionAtlas; A3KPQ7; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0004415; F:hyalurononglucosaminidase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0003190; P:atrioventricular valve formation; IMP:UniProtKB.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:ZFIN.
DR GO; GO:0060974; P:cell migration involved in heart formation; IMP:ZFIN.
DR GO; GO:0003318; P:cell migration to the midline involved in heart development; IMP:UniProtKB.
DR GO; GO:0003143; P:embryonic heart tube morphogenesis; IMP:ZFIN.
DR GO; GO:0003197; P:endocardial cushion development; IMP:ZFIN.
DR GO; GO:0001947; P:heart looping; IMP:UniProtKB.
DR GO; GO:0030214; P:hyaluronan catabolic process; IDA:UniProtKB.
DR GO; GO:0016203; P:muscle attachment; IMP:ZFIN.
DR GO; GO:0060415; P:muscle tissue morphogenesis; IMP:ZFIN.
DR GO; GO:1901203; P:positive regulation of extracellular matrix assembly; IMP:ZFIN.
DR GO; GO:1900748; P:positive regulation of vascular endothelial growth factor signaling pathway; IDA:UniProtKB.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IMP:ZFIN.
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; Reference proteome; Repeat;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..1378
FT /note="Cell surface hyaluronidase"
FT /id="PRO_0000289974"
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..1378
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 121..247
FT /note="G8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00817"
FT REPEAT 672..694
FT /note="PbH1 1"
FT REPEAT 714..736
FT /note="PbH1 2"
FT REGION 1..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..59
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 360
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 527
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 696
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 742
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 854
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 905
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 996
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1069
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 426
FT /note="V->E: In hu4800; defects in angiogenesis."
FT /evidence="ECO:0000269|PubMed:28118600"
FT MUTAGEN 429
FT /note="W->A: Defects in angiogenesis."
FT /evidence="ECO:0000269|PubMed:28118600"
FT MUTAGEN 434
FT /note="R->A: Defects in angiogenesis."
FT /evidence="ECO:0000269|PubMed:28118600"
FT MUTAGEN 608
FT /note="F->A: Defects in angiogenesis."
FT /evidence="ECO:0000269|PubMed:28118600"
SQ SEQUENCE 1378 AA; 152328 MW; 675E1AB8B5650883 CRC64;
MQVNDGPSSH PIFVAPVNGN AQRSSGYVPG RIVPVRSPPP AKAPPPPPLK PPVPPPARPS
VFNLSEDGNR REQAQNQQRK NTYICVGIFF GIFLLILILV LSLTSKDVLD ENCPHQNPAL
RSWKPGHDLK KVVVIHSGEH YRLDSSATLY SITIQAGGSV VFADDKKGSK NITLRTRHIL
IEDGGALHIG APKCRYRSLA TITLVGRSDE TAVTEVPGMG RKFLGVNSGG TLELHGSERM
SWTFLTRTVP ASGLATGDHA FQKNFSRGIN LRVVDQDTAE VLVNERFDTH ESQDDSKRLG
ELLKALPAGR IVALATGDSA VKNLVFETKQ TIHDLLGSNY ISDLKYRDAW ALVSVIGGGN
GSCTEDVREH ENHDTGGKAL ARQDFFTVDG VGFTVTAYSE WSNGYPTTGF QVDAVDKVVL
NLQDDVSSWN PGDRIVVAST DYSMYQAEEF TLLPCPNCNR KQVQIQGKPQ FSHVGEILDG
VDMRAEVALL SRNILIHGEM ENSCYGGNWC QYFSYDTFGG HIKILGNFTS VHLSHIELKH
MGQQREKGRY PLNFHRCGDV DQSGGYSNPA YVDSLSIHHS FSRCVTVHAT NGLLVKDTVG
YDTLGHCFFL KDGIEQRNIF FHNLGLLTRP GTILPTDRND SMCTEITDRV YKGYIPIPAN
ECKAVSSFWI AHPNNHLISN SAAGSQDAGI WYVFHNSSTG DSHGMISETK AELTPLGTFF
NNRVHSNFKA GLFIDRKVKS TNATAADPRE YLCLDNSARF RPHESSDPSR PRVAAIIDTL
ISFKNNDLGA WIRGGDIIIR NSGDGSYPKD EGSSQEVSQS LFIGESRNRG TNGGQNKYWG
IGGVDGKMRT LPRNKTFPIR GFQINDGPVR IFDSTFRAFS PTADRFTMAV GFSLKNIWQL
TPRNNLSALA FHPSVTLRAF FGRPGDWFEQ NDLDGDKNSI FHDLDGSISG YADTYVARAD
NFLIRHPQCV DMPQWNGVVC SGKYSQVYIQ TQAASNLSLS ISRDEYPDKP MVLRGIRTKT
SPSQQYQPVL MMGKSYTMHW NGPAPRETVL SLINFDQDDW ALLGLCYPNE TVFQITSDIY
NKQNNGFEGI EDYGPVTSIA DLEKRQQERK YFFDKSAGLL WLYARARHRR DGNSYCSSAG
CERVKIIATI RANQKTETCN CTANAYPKYS KPASNIVPMP KPNTEPCGAC GASQFAFSSD
PWNSYLQTQI KSLSVKEEQD NDTQAYITVN AQRFDLSQSG FLLVTVDACS GKVTKNSMFS
SLDTKMEQFF KTGIMKRSIV LLATRGQPAS FAGVAQYLES LGSAKTPDLQ NKVAIAFFGF
LGQGGPSPQP WSTLLTCQGA KILGLQERFI PLSLEEYSCP PKKDSPTRMD LELLKKIS
