MMRN2_HUMAN
ID MMRN2_HUMAN Reviewed; 949 AA.
AC Q9H8L6; Q504V7; Q6P2N2;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Multimerin-2;
DE AltName: Full=EMILIN-3;
DE AltName: Full=Elastin microfibril interface located protein 3;
DE Short=Elastin microfibril interfacer 3;
DE AltName: Full=EndoGlyx-1 p125/p140 subunit;
DE Flags: Precursor;
GN Name=MMRN2; Synonyms=EMILIN3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, AND VARIANTS SER-49 AND
RP ASP-731.
RX PubMed=11559704; DOI=10.1074/jbc.m106152200;
RA Christian S., Ahorn H., Novatchkova M., Garin-Chesa P., Park J.E.,
RA Weber G., Eisenhaber F., Rettig W.J., Lenter M.C.;
RT "Molecular cloning and characterization of EndoGlyx-1, an EMILIN-like
RT multisubunit glycoprotein of vascular endothelium.";
RL J. Biol. Chem. 276:48588-48595(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-731.
RC TISSUE=Placenta;
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 [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-845.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [6]
RP FUNCTION, AND INTERACTION WITH VEGFA.
RX PubMed=22020326; DOI=10.1038/onc.2011.487;
RA Lorenzon E., Colladel R., Andreuzzi E., Marastoni S., Todaro F.,
RA Schiappacassi M., Ligresti G., Colombatti A., Mongiat M.;
RT "MULTIMERIN2 impairs tumor angiogenesis and growth by interfering with
RT VEGF-A/VEGFR2 pathway.";
RL Oncogene 31:3136-3147(2012).
RN [7]
RP VARIANT [LARGE SCALE ANALYSIS] MET-448.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Inhibits endothelial cells motility and acts as a negative
CC regulator of angiogenesis; it down-regulates KDR activation by binding
CC VEGFA. {ECO:0000269|PubMed:22020326}.
CC -!- SUBUNIT: Heteromer of p110, p125, p140 and p200 subunits; disulfide-
CC linked. Interacts with VEGFA. {ECO:0000269|PubMed:11559704,
CC ECO:0000269|PubMed:22020326}.
CC -!- INTERACTION:
CC Q9H8L6; Q6NTF9-3: RHBDD2; NbExp=3; IntAct=EBI-2623273, EBI-17589229;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:11559704}.
CC -!- TISSUE SPECIFICITY: Endothelium. {ECO:0000269|PubMed:11559704}.
CC -!- PTM: N- and O-glycosylated. {ECO:0000269|PubMed:16335952}.
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DR EMBL; AK023527; BAB14599.1; -; mRNA.
DR EMBL; AC025268; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064415; AAH64415.1; -; mRNA.
DR EMBL; BC094744; AAH94744.1; -; mRNA.
DR CCDS; CCDS7379.1; -.
DR RefSeq; NP_079032.2; NM_024756.2.
DR AlphaFoldDB; Q9H8L6; -.
DR SMR; Q9H8L6; -.
DR BioGRID; 122907; 5.
DR ComplexPortal; CPX-450; Multimerin-2 complex.
DR IntAct; Q9H8L6; 4.
DR STRING; 9606.ENSP00000361097; -.
DR GlyConnect; 1524; 16 N-Linked glycans (6 sites).
DR GlyGen; Q9H8L6; 17 sites, 16 N-linked glycans (6 sites), 1 O-linked glycan (5 sites).
DR iPTMnet; Q9H8L6; -.
DR PhosphoSitePlus; Q9H8L6; -.
DR BioMuta; MMRN2; -.
DR DMDM; 296437373; -.
DR EPD; Q9H8L6; -.
DR jPOST; Q9H8L6; -.
DR MassIVE; Q9H8L6; -.
DR PaxDb; Q9H8L6; -.
DR PeptideAtlas; Q9H8L6; -.
DR PRIDE; Q9H8L6; -.
DR ProteomicsDB; 81216; -.
DR Antibodypedia; 16004; 102 antibodies from 24 providers.
DR DNASU; 79812; -.
DR Ensembl; ENST00000372027.10; ENSP00000361097.4; ENSG00000173269.14.
DR GeneID; 79812; -.
DR KEGG; hsa:79812; -.
DR MANE-Select; ENST00000372027.10; ENSP00000361097.4; NM_024756.3; NP_079032.2.
DR UCSC; uc001kea.4; human.
DR CTD; 79812; -.
DR DisGeNET; 79812; -.
DR GeneCards; MMRN2; -.
DR HGNC; HGNC:19888; MMRN2.
DR HPA; ENSG00000173269; Low tissue specificity.
DR MIM; 608925; gene.
DR neXtProt; NX_Q9H8L6; -.
DR OpenTargets; ENSG00000173269; -.
DR PharmGKB; PA134991578; -.
DR VEuPathDB; HostDB:ENSG00000173269; -.
DR eggNOG; ENOG502QUTH; Eukaryota.
DR GeneTree; ENSGT01030000234633; -.
DR HOGENOM; CLU_012255_1_0_1; -.
DR InParanoid; Q9H8L6; -.
DR OMA; NHMSTSV; -.
DR OrthoDB; 1205089at2759; -.
DR PhylomeDB; Q9H8L6; -.
DR TreeFam; TF336041; -.
DR PathwayCommons; Q9H8L6; -.
DR SignaLink; Q9H8L6; -.
DR BioGRID-ORCS; 79812; 9 hits in 1064 CRISPR screens.
DR ChiTaRS; MMRN2; human.
DR GenomeRNAi; 79812; -.
DR Pharos; Q9H8L6; Tbio.
DR PRO; PR:Q9H8L6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9H8L6; protein.
DR Bgee; ENSG00000173269; Expressed in subcutaneous adipose tissue and 183 other tissues.
DR ExpressionAtlas; Q9H8L6; baseline and differential.
DR Genevisible; Q9H8L6; HS.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:ComplexPortal.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IC:ComplexPortal.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:1903588; P:negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IDA:ComplexPortal.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:ComplexPortal.
DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:ComplexPortal.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; IEA:Ensembl.
DR GO; GO:1905278; P:positive regulation of epithelial tube formation; IDA:ComplexPortal.
DR GO; GO:1905332; P:positive regulation of morphogenesis of an epithelium; IDA:ComplexPortal.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q_dom.
DR InterPro; IPR011489; EMI_domain.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00386; C1q; 1.
DR Pfam; PF07546; EMI; 1.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
DR PROSITE; PS51041; EMI; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Coiled coil; Disulfide bond; Extracellular matrix;
KW Glycoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..949
FT /note="Multimerin-2"
FT /id="PRO_0000007822"
FT DOMAIN 54..132
FT /note="EMI"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT DOMAIN 821..949
FT /note="C1q"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00368"
FT REGION 133..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 779..801
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 167..187
FT /evidence="ECO:0000255"
FT COILED 292..487
FT /evidence="ECO:0000255"
FT COILED 547..596
FT /evidence="ECO:0000255"
FT COILED 688..711
FT /evidence="ECO:0000255"
FT COMPBIAS 780..801
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 249
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 379
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 727
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 845
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT DISULFID 58..122
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT DISULFID 85..92
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT DISULFID 121..130
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00384"
FT VARIANT 49
FT /note="G -> S (in dbSNP:rs3750823)"
FT /evidence="ECO:0000269|PubMed:11559704"
FT /id="VAR_019801"
FT VARIANT 448
FT /note="V -> M (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs748531029)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036362"
FT VARIANT 731
FT /note="H -> D (in dbSNP:rs4934281)"
FT /evidence="ECO:0000269|PubMed:11559704,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_019802"
FT VARIANT 831
FT /note="S -> R (in dbSNP:rs36073867)"
FT /id="VAR_053076"
FT VARIANT 910
FT /note="V -> L (in dbSNP:rs34587013)"
FT /id="VAR_053077"
FT CONFLICT 270
FT /note="R -> H (in Ref. 4; AAH64415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 949 AA; 104409 MW; E4F173CF6A01FA08 CRC64;
MILSLLFSLG GPLGWGLLGA WAQASSTSLS DLQSSRTPGV WKAEAEDTGK DPVGRNWCPY
PMSKLVTLLA LCKTEKFLIH SQQPCPQGAP DCQKVKVMYR MAHKPVYQVK QKVLTSLAWR
CCPGYTGPNC EHHDSMAIPE PADPGDSHQE PQDGPVSFKP GHLAAVINEV EVQQEQQEHL
LGDLQNDVHR VADSLPGLWK ALPGNLTAAV MEANQTGHEF PDRSLEQVLL PHVDTFLQVH
FSPIWRSFNQ SLHSLTQAIR NLSLDVEANR QAISRVQDSA VARADFQELG AKFEAKVQEN
TQRVGQLRQD VEDRLHAQHF TLHRSISELQ ADVDTKLKRL HKAQEAPGTN GSLVLATPGA
GARPEPDSLQ ARLGQLQRNL SELHMTTARR EEELQYTLED MRATLTRHVD EIKELYSESD
ETFDQISKVE RQVEELQVNH TALRELRVIL MEKSLIMEEN KEEVERQLLE LNLTLQHLQG
GHADLIKYVK DCNCQKLYLD LDVIREGQRD ATRALEETQV SLDERRQLDG SSLQALQNAV
DAVSLAVDAH KAEGERARAA TSRLRSQVQA LDDEVGALKA AAAEARHEVR QLHSAFAALL
EDALRHEAVL AALFGEEVLE EMSEQTPGPL PLSYEQIRVA LQDAASGLQE QALGWDELAA
RVTALEQASE PPRPAEHLEP SHDAGREEAA TTALAGLARE LQSLSNDVKN VGRCCEAEAG
AGAASLNASL HGLHNALFAT QRSLEQHQRL FHSLFGNFQG LMEANVSLDL GKLQTMLSRK
GKKQQKDLEA PRKRDKKEAE PLVDIRVTGP VPGALGAALW EAGSPVAFYA SFSEGTAALQ
TVKFNTTYIN IGSSYFPEHG YFRAPERGVY LFAVSVEFGP GPGTGQLVFG GHHRTPVCTT
GQGSGSTATV FAMAELQKGE RVWFELTQGS ITKRSLSGTA FGGFLMFKT
